A widespread visually-sensitive functional network relates to symptoms in essential tremor

Abstract

Essential tremor is a neurological syndrome of heterogeneous pathology and aetiology that is characterized by tremor primarily in the upper extremities. This tremor is commonly hypothesized to be driven by a single or multiple neural oscillator(s) within the cerebello-thalamo-cortical pathway. Several studies have found an association of blood-oxygen level-dependent (BOLD) signal in the cerebello-thalamo-cortical pathway with essential tremor, but there is behavioural evidence that also points to the possibility that the severity of tremor could be influenced by visual feedback. Here, we directly manipulated visual feedback during a functional MRI grip force task in patients with essential tremor and control participants, and hypothesized that an increase in visual feedback would exacerbate tremor in the 4–12 Hz range in essential tremor patients. Further, we hypothesized that this exacerbation of tremor would be associated with dysfunctional changes in BOLD signal and entropy within, and beyond, the cerebello-thalamo-cortical pathway. We found that increases in visual feedback increased tremor in the 4–12 Hz range in essential tremor patients, and this increase in tremor was associated with abnormal changes in BOLD amplitude and entropy in regions within the cerebello-thalamo-motor cortical pathway, and extended to visual and parietal areas. To determine if the tremor severity was associated with single or multiple brain region(s), we conducted a birectional stepwise multiple regression analysis, and found that a widespread functional network extending beyond the cerebello-thalamo-motor cortical pathway was associated with changes in tremor severity measured during the imaging protocol. Further, this same network was associated with clinical tremor severity measured with the Fahn, Tolosa, Marin Tremor Rating Scale, suggesting this network is clinically relevant. Since increased visual feedback also reduced force error, this network was evaluated in relation to force error but the model was not significant, indicating it is associated with force tremor but not force error. This study therefore provides new evidence that a widespread functional network is associated with the severity of tremor in patients with essential tremor measured simultaneously at the hand during functional imaging, and is also associated with the clinical severity of tremor. These findings support the idea that the severity of tremor is exacerbated by increased visual feedback, suggesting that designers of new computing technologies should consider using lower visual feedback levels to reduce tremor in essential tremor.

http://ift.tt/2DBmG2P

Cutaneous infection with paucibacillary Mycobacterium tuberculosis treated successfully with a modified antituberculous drug regimen

Tuberculosis is a serious infection that is increasing in prevalence, affecting many people worldwide. The diagnosis of cutaneous tuberculosis is challenging and requires the correlation of clinical findings with often inconclusive diagnostic testing. Extrapulmonary tuberculosis comprises approximately 10% of all cases of tuberculosis, and cutaneous tuberculosis makes up only a small proportion of these cases. Discussed here is the case of a 61-year-old immunocompetent female with a large cutaneous lesion on her index finger secondary to Mycobacterium tuberculosis. Tissue cultures taken at biopsy were negative; however, empiric antimycobacterial therapy was initiated. The initial regimen was not tolerated, and antituberculous therapy was substituted for moxifloxacin and clarithromycin. The lesion improved significantly with a concurrent improvement in function.

http://ift.tt/2C2d1nI

Maxillary chondrosarcoma mimicking torus palatinus

Description 

An 88-year-old man was referred to the head and neck surgery clinic for investigation of a painless hard palate lesion. The mass had been present for several months and was identified incidentally by the general practitioner. There were no oral or sinonasal symptoms. On examination, a 3x2 cm hard palatal swelling, covered by normal mucosa and resembling a torus palatinus was identified (figure 1). Flexible nasal endoscopy revealed the tumour to involve the floor of the nasal cavity bilaterally, displacing the inferior nasal turbinates. Examination of the neck was normal.

Figure 1

Midline palatal swelling covered by mucosa.

A biopsy was taken, and histological analysis described a welldifferentiated cartilaginous lesion consistent with a grade 1 chondrosarcoma. A CT scan was performed (figure 2). The regional head and neck and regional sarcoma multidisciplinary team meetings recommended surgical management. The patient underwent...

http://ift.tt/2C27EEY

Intractable hyperemesis gravidarum in a patient with type 1 diabetes

Hyperemesis gravidarum is not uncommon. Its pathogenies is multifactorial but not fully understood. We present a case of a middle class, Caucasian pregnant woman aged 24 years with coexisting type 1 diabetes, who had severe hyperemesis gravidarum from the sixth week of pregnancy and was resistant to all standard and off-the-label treatments raising questions about the pathogenesis of hyperemesis gravidarum. She was managed with a multidisciplinary approach and was supported with total parenteral nutrition till she had an emergency caesarean section in the 29th week of pregnancy. Her vomiting stopped as soon as a small for gestational age but otherwise healthy male baby was delivered.

http://ift.tt/2Bp06sE

Shah-Waardenburg syndrome: a case highlighting the importance of a holistic approach to assessing a child

We present the case of a 45-day-old child with the chief complaint of failure to pass stools for 10 days. After initial investigation, the patient was found to have Hirschsprung's disease. However, with further examination and analysis, the extremely rare diagnosis of type 4 Waardenburg syndrome was made (also known as Shah-Waardenburg syndrome or Waardenburg-Hirschsprung's disease).

http://ift.tt/2BnWsza

Unusual case of anxiety: trichloroethylene neurotoxicity

I present an uncommon case of recurrent, intractable anxiety that was presented acutely and slowly evolved into a chronic debilitating condition. A young previously fit and healthy 24-year-old patient presents with somewhat atypical symptoms of anxiety. Full medical work-up including examination, blood, ECG electrocardiogram, electroencephalogram and CT of the head was unremarkable. When the history was explored in detail, it was revealed he worked in the navy and was exposed to a neurotoxic solvent, trichloroethylene. This case highlights the importance of eliciting a detailed occupational history, particularly paying attention to patient demographics such as occupation and presenting symptoms that do not readily fit into diagnostic criteria.

http://ift.tt/2BrX1Ih

Short-course high-dose ibuprofen causing both early and delayed jejunal perforations in a non-smoking man

Description

A 48-year-old non-smoking man underwent laparotomy for peritonitis immediately after taking ibuprofen 800 mg 6 hourly for 14 days for back pain. His only other medication was long-term omeprazole 20 mg per day. At operation he had three separate perforations in his proximal jejunum. Fifteen centimetres of jejunum were resected with primary anastomosis. Histology showed focal mucosal ischaemic changes with normal mucosa between. There was no vasculitis. The perforations were attributed to ibuprofen intake. He made an uneventful recovery and was instructed to refrain from non-steroidal anti-inflammatory drug (NSAID) intake.

He was readmitted 5 months later with abdominal pain. He had continued omeprazole but had taken no further NSAID. CT showed extensive free intra-abdominal fluid with free gas adjacent to his proximal jejunum (figure 1), indicating a further perforation. This was confirmed at laparotomy when a 5 mm perforated ulcer was found in his proximal jejunum (figure...

http://ift.tt/2BoTGJW

Oyster-related tenosynovitis: a rare case of Mycobacterium szulgai in the immunocompromised

A 66-year-old man with a history of renal transplant on chronic immunosuppression presented to his primary care physician with a swollen right index finger. On examination, mild swelling was present. Conservative management failed and initial plain films were negative. Corticosteroid injection was performed by orthopaedics, but symptoms recurred several months later and an MRI showed flexor digitorum tenosynovitis and abscesses of the superficialis and profundus tendons. A flexor tenolysis was performed with cultures positive for Mycobacterium szulgai, a rare, non-tuberculous mycobacterial infection. Treatment was initiated with moxifloxacin, ethambutol and azithromycin daily for nearly 4 months. Repeat MRI 3 months after completion of antibiotics showed near resolution of the tenosynovitis.

http://ift.tt/2C2cWQW

HHV-8-associated haemophagocytic lymphohistiocytosis in a patient with advanced AIDS

We present a patient with advanced AIDS admitted with recurrent shock of unclear aetiology, fevers, altered mental status and refractory cytopenias. His case posed a diagnostic challenge because evaluation of septic shock in the setting of advanced AIDS requires a time-consuming work-up for broad infectious aetiologies that can delay consideration of other diagnoses, including primary or secondary haemophagocytic lymphohistiocytosis (HLH). After this patient did not improve with supportive care and empiric antimicrobials, there was concern for HLH given that he met ≥5 of the HLH consortium criteria. He underwent bone marrow biopsy, which was non-diagnostic. Empiric therapy for HLH was initiated, but unfortunately, the patient died. Autopsy revealed extensive haemophagocytosis in the spleen, bone marrow and liver, confirming the diagnosis of HLH. Postmortem, his soluble CD-25 returned 18 890 pg/mL (<1033 pg/mL), and his serum HHV-8 PCR resulted positive. The diagnosis was HLH secondary to Human Herpes Virus 8 (HHV-8) in a patient with advanced AIDS.

http://ift.tt/2BoOo1d

Chickenpox: an ageless disease

A 97-year-old woman presented with 4-day history of vesicular rash, initially at the feet but then spread up to the thighs bilaterally, abdomen and trunk. The initial differentials included bullous pemphigus and cellulitis by the emergency department. She was then managed as bullous pemphigus by the acute medical team and started on high-dose steroids, with no other differentials considered. When her care was taken over by the general medical team, varicella zoster virus (VZV) infection was suspected. After confirmation by the dermatology team regarding the clinical diagnosis and the positive VZV DNA swabs, she was started on acyclovir.

http://ift.tt/2C2cQZA

Osteoid bezoar: a rare case causing small bowel obstruction

Acute intestinal obstruction due to foreign bodies or bezoar is a rare occurrence in an adult. We report an unusual case of a 27-year-old male patient with no previous history of abdominal surgery or other medical disease, who presented with an acute episode of intestinal obstruction due to ingestion of a bone piece which was managed surgically by enterotomy, and the patient had an uneventful postoperative course. He was advised regular follow-up once in 2 weeks initially and once a month subsequently. He had no problems at the end of 6 months.

http://ift.tt/2BoTGcU

Idiopathic bilateral hypertrophic olivary degeneration

Description

A 55-year-old man presented with involuntary movements of the tongue and soft palate associated with unsteadiness in walking for a period of 3 months. The patient did not complain of ear clicking. Examination revealed palatal myoclonus, tongue fasciculation and ataxic gait. MRI of the brain showed increased T2 and Fluid Attenuation Inversion recovery (FLAIR) signal intensities in the bilateral inferior olivary complex without diffusion restriction (figure 1). Midbrain, pons, and cerebral and cerebellar parenchyma were normal (figure 2). Imaging features were consistent with bilateral hypertrophic olivary degeneration. Hypertrophic olivary degeneration is a unique type of trans-synaptic neuronal degeneration caused by damage to the dentatorubral pathway or the triangle of Guillain and Mollaret (figure 3). Focal lesions like infarction, haemorrhage, demyelination  and trauma involving this neuronal pathway lead to interruption, and following sequential pathological changes are described (table 1).1

Figure 1

Coronal T2 (A), axial T2 (B),...

http://ift.tt/2BoNXE7

Contemporary non-surgical approach for faecal diversion in a case of Fourniers gangrene

Fournier's gangrene is a fatal necrotising fasciitis of the perineum, genitals and lower abdomen. Patients often need an aggressive surgical debridement, and in few cases, a diverting colostomy. We report the case of a 70-year-old man with multiple comorbidities diagnosed with Fournier's gangrene, who underwent debridement and had a wound complication due to faecal contamination. A novel, self-retaining rectal device was used to perform faecal diversion, which subsequently showed wound healing within a week, hence avoiding the need of a colostomy.

http://ift.tt/2C2chiq

Variant of Lemierres syndrome with internal jugular vein aneurysm

Internal jugular vein (IJV) aneurysm is a rare entity, and a thrombosed aneurysm poses diagnostic and management challenges. We came across a 53-year-old woman who presented with fever, vomiting and right neck swelling for a week. Laboratory investigations showed neutrophilic leucocytosis, raised acute phase reactant and blood culture yielded Klebsiella pneumoniae. Ultrasound and contrast-enhanced CT neck revealed a large fusiform aneurysm of the right IJV with filling defect extending from the aneurysm into the right transverse sinus. There was a cavity at the right lower third molar tooth. MRI confirmed the findings with additional enhancing focus at right lower periodontal region. The swelling reduced after 2 weeks of medical therapy, and follow-up imaging 4 months later showed complete resolution of the aneurysm with residual thrombosis. After extensive workup, dental infection remains the only identifiable primary source leading to thrombophlebitis of the right IJV and subsequent sequelae.

http://ift.tt/2BpRbqG

Correction: Gangrenous digital infarcts in a severe case of cutaneous polyarteritis nodosa

The correct order of authors is as follows:

Hamzah Mahmood-Rao, Nirav Gandhi, Tina Ding

http://ift.tt/2C2clPc

Double hit! A unique case of resistant hypertension

A middle-aged woman with obesity, hyperlipidaemia and diet-controlled diabetes was referred for resistant hypertension. Her blood pressure (BP) was uncontrolled on five medications, including a diuretic. Physical exam revealed a systolic ejection murmur, and ECHO demonstrated moderate hypertrophy. Laboratory examination revealed elevated aldosterone level (20.7 ng/dL) and elevated aldosterone:renin ratio (41.4 (ng/dL)/(ng/mL/h)), meeting criteria for primary aldosteronism (PA), and confirmed by saline infusion testing. CT scan of the adrenals was non-localising. Adrenal venous sampling confirmed bilateral idiopathic adrenal hyperplasia. Concurrent primary hyperparathyroidism was demonstrated by elevated calcium and parathyroid hormone levels and localised by sestamibi scan. Idiopathic adrenal hyperplasia was treated medically with spironolactone. Her BP remained elevated until postparathyroidectomy. Evidence shows that a hyperfunctioning parathyroid gland may contribute to maintaining hyperaldosteronism in PA making this bidirectional link unique. The significance of this case is in the potential for further understanding of the pathophysiology of common causes of secondary hypertension.

http://ift.tt/2Bo3FPv

Cost comparison by treatment arm and center-level variations in cost and inpatient days on the phase III high-risk B acute lymphoblastic leukemia trial AALL0232

Abstract

The Children's Oncology Group (COG) develops and implements multi-institutional clinical trials with the primary goal of assessing the efficacy and safety profile of treatment regimens for various pediatric cancers. However, the monetary costs of treatment regimens are not measured. AALL0232 was a COG randomized phase III trial for children with acute lymphoblastic leukemia that found that dexamethasone (DEX) was a more effective glucocorticoid than prednisone (PRED) in patients younger than 10 years, but PRED was equally effective and less toxic in older patients. In addition, high-dose methotrexate (HD-MTX) led to better survival than escalating doses of methotrexate (C-MTX). Cost data from the Pediatric Health Information System database were merged with clinical data from the COG AALL0232 trial. Total and component costs were compared between treatment arms and across hospitals. Inpatient costs were higher in the HD-MTX and DEX arms when compared to the C-MTX and PRED arms at the end of therapy. There was no difference in cost between these arms at last follow-up. Considerable variation in total costs existed across centers to deliver the same therapy that was driven by differences in inpatient days and pharmacy costs. The more effective regimens were found to be more expensive during therapy but were ultimately cost-neutral in longer term follow-up. The variations in cost across centers suggest an opportunity to standardize resource utilization for patients receiving similar therapies, which could translate into reduced healthcare expenditures.

When comparing costs between treatment arms of the high-risk B acute lymphoblastic leukemia pediatric trial, high-dose methotrexate and dexamethasone arms were associated with higher costs when compared to the escalating methotrexate and prednisone arms during protocol therapy, but there was no difference in cost between the methotrexate or steroid arms at time of last follow up. We also found that costs vary significantly across hospitals to deliver identical therapy.

http://ift.tt/2BDVTFo

Correction: Geographical prevalence and risk factors for pterygium: a systematic review and meta-analysis

Liu L, Wu J, Geng J, et al. Geographical prevalence and risk factors for pterygium: a systematic review and meta-analysis. BMJ Open 2013;3:e003787. doi: 10.1136/bmjopen-2013-003787

In the abstract, the sentence:

"We found a trend that the higher pooled prevalence of pterygium was associated with increasing geographical latitude and age in the world."

should read:

"We found a trend that the higher pooled prevalence of pterygium was associated with decreasing geographical latitude and age in the world."

http://ift.tt/2BoQH4c

Effects of a 12-week cardiovascular rehabilitation programme on systemic inflammation and traditional coronary artery disease risk factors in patients with rheumatoid arthritis (CARDIA trial): a randomised controlled trial

Introduction

Patients with systemic inflammatory diseases such as rheumatoid arthritis (RA) have an increased risk of cardiovascular disease (CVD) above the baseline risk attributable to traditional CVD risk factors seen in the general population. Exercise in cardiac rehabilitation (CR) is designed specifically for high-risk primary prevention and those with established CVD. Even though the European League Against Rheumatism guidelines state that exercise is safe for individuals with RA and exercise can reduce CVD risk, patients with RA rarely participate in CR. Thus, little is known about CR's impact on inflammatory and CVD risk in the RA population. The purpose of this trial is to determine the feasibility of a 12-week CR programme for patients with RA and whether it decreases CVD risk without exacerbating RA.

Methods and analysis

This is a randomised controlled trial whereby 60 participants with RA will be recruited and randomly assigned to either standard of care (SOC) treatment or SOC plus a 12-week CR programme (60 min of education plus two 60 min aerobic exercise sessions/week). Exercise will be performed at 60%–80% of heart rate reserve. Outcome measures (Framingham Risk Score, resting heart rate, blood pressure, blood lipids, markers of systemic inflammation (ie, interleukin (IL) 6 and tumour necrosis factor-α (TNF-α), Clinical Disease Assessment Index, Disease Activity Score-28, physical activity levels and peak cardiorespiratory fitness) will be assessed preintervention (week-0), postintervention (week-13) and 6 months postintervention.

Ethics and dissemination

Ethical approval was obtained from the Nova Scotia Health Authority Research Ethics Board. Results will be submitted for publication in an appropriate peer-reviewed journal.

Trial registration number

NCT01534871; Pre-results

http://ift.tt/2C2frCT

Correction: A qualitative study exploring the social and environmental context of recently-acquired HIV infection among men who have sex with men in South-East England

Gourlay A, Fox J, Gafos M, et al. A qualitative study exploring the social and environmental context of recently acquired HIV infection among men who have sex with men in South-East England. BMJ Open 2017;7:e016494. doi: 10.1136/bmjopen-2017-016494.

The current email address of corresponding author Annabelle Gourlay is annabelle.gourlay@lshtm.ac.uk.

Mitzy Gafos is also affiliated to the Department of Global Health and Development, Faculty of Public Health and Policy, London School of Hygiene and Tropical Medicine, London.

http://ift.tt/2C2FpWY

Association between serum uric acid and atrial fibrillation: a cross-sectional community-based study in China

Objectives

To investigate the effects of gender on the association of serum uric acid (SUA) levels and atrial fibrillation (AF) prevalence in a community-based Chinese population.

Setting

Data were obtained from annual Jidong Oilfield employee and family member health checkups. The Jidong community is geographically located in Tangshan City in northern China.

Participants

A total of 9078 residents were invited to take part in the survey and provided informed consents. Individuals without data of ECG or SUA were excluded, leaving 8937 residents in our study.

Primary and secondary outcome measures

SUA was measured at baseline using the uricase-peroxidase method. Hyperuricaemia was defined as a SUA level >7.0 mg/dL in men and >5.7 mg/dL in women. AF was diagnosed based on ECG findings and/or any medical history of AF from referring physicians. The crude and independent association between SUA levels and AF prevalence was evaluated with logistic regression analysis.

Results

AF prevalence was 0.6% (53/8937). Participants with hyperuricaemia had a higher AF prevalence compared with those with normal SUA levels (1.1% vs 0.5%; P=0.02). Hyperuricaemia was correlated with AF after adjustment for various cardiovascular risk factors in all participants (P=0.03, OR 2.051, 95% CI 1.063 to 3.856). This correlation was particularly stronger in women compared with men (P<0.001, OR 6.366, 95% CI 2.553 to 15.871 in women and P=0.96, OR 1.025, 95% CI 0.400 to 2.626 in men).

Conclusions

We demonstrated a significant association between increased SUA levels and AF prevalence in a Chinese population. Our data indicate that there is a gender-specific mechanism underlying the relationship between SUA and AF.

http://ift.tt/2Bphnlo

Preoxygenation with non-invasive ventilation versus high-flow nasal cannula oxygen therapy for intubation of patients with acute hypoxaemic respiratory failure in ICU: the prospective randomised controlled FLORALI-2 study protocol

Introduction

Endotracheal intubation in intensive care unit (ICU) is a procedure at high risk of life-threatening complications. Among them, severe oxygen desaturation, usually defined as a drop of pulse oxymetry (SpO₂) below 80%, is the most common. Preoxygenation enables delaying oxygen desaturation occurring during apnea induced by anaesthetic drugs. Data suggest that non-invasive ventilation (NIV) or high-flow nasal cannula (HFNC) oxygen therapy could further increase PaO₂ before intubation procedure and prevent oxygen desaturation episodes as compared with standard oxygen. However, no recommendation favours one technique rather than the other, since they have never been compared. Hence, whether a strategy of preoxygenation with NIV or HFNC is more effective than the other in patients with acute hypoxaemic respiratory failure remains to be established.

Methods and analysis

The FLORALI-2 study is a multicentre randomised controlled trial comparing a preoxygenation strategy with either NIV or HFNC in patients with acute hypoxaemic respiratory failure needing intubation in ICU. The 320 patients will be randomised with a ratio 1:1 in two groups according to the strategy of preoxygenation. The primary outcome is the occurrence of an episode of severe oxygen desaturation defined by a drop of SpO₂ below 80% during the intubation procedure. Secondary outcomes include feasibility of the two strategies, immediate and late complications related to intubation.

Ethics and dissemination

The study has been approved by the central ethics committee (Ethics Committee Ouest-III, Poitiers, France) and patients will be included after informed consent. The results will be submitted for publication in peer-reviewed journals.

Trial registration number

NCT02668458; Pre-results.

http://ift.tt/2C3PHpC

Determinants of immunisation coverage of children aged 12-59 months in Indonesia: a cross-sectional study

Objectives

Despite the adoption of WHO's Expanded Programme on Immunisation in Indonesia since 1977, a large proportion of children are still completely unimmunised or only partly immunised. This study aimed to assess factors associated with low immunisation coverage of children in Indonesia.

Setting

Children aged 12–59 months in Indonesia.

Participant

The socioeconomic characteristics and immunisation status of the children were obtained from the most recent Demographic and Health Survey, the 2012 Indonesia Demographic and Health Survey. Participants were randomly selected through a two-stage stratified sampling design. Data from 14 401 children aged 12–59 months nested within 1832 census blocks were included in the analysis. Multilevel logistic regression models were constructed to account for hierarchical structure of the data.

Results

The mean age of the children was 30 months and they were equally divided by sex. According to the analysis, 32% of the children were fully immunised in 2012. Coverage was significantly lower among children who lived in Maluku and Papua region (adjusted OR: 1.94; 95% CI 1.42 to 2.64), were 36–47 months old (1.39; 1.20 to 1.60), had higher birth order (1.68; 1.28 to 2.19), had greater family size (1.47; 1.11 to 1.93), whose mother had no education (2.13; 1.22 to 3.72) and from the poorest households (1.58; 1.26 to 1.99). The likelihood of being unimmunised was also higher among children without health insurance (1.16; 1.04 to 1.30) and those who received no antenatal (3.28; 2.09 to 5.15) and postnatal care (1.50; 1.34 to 1.69).

Conclusions

Socioeconomic factors were strongly associated with the likelihood of being unimmunised in Indonesia. Unimmunised children were geographically clustered and lived among the most deprived population. To achieve WHO target of protective coverage, public health interventions must be designed to meet the needs of these high-risk groups.

http://ift.tt/2BrPglm

Correction: Cost-utility and budget impact analyses of the use of NEPA for chemotherapy-induced nausea and vomiting prophylaxis in Italy

Restelli U, Saibene G, Nardulli P, et al. Cost-utility and budget impact analyses of the use of NEPA for chemotherapy-induced nausea and vomiting prophylaxis in Italy. BMJ Open 2017;7:e015645. doi: 10.1136/bmjopen-2016-015645.

There is an error in Supplementary file 1. In the first table of the supplementary material, Annex 1, in row MEC, –2.5 and –4.4 in column ' NEPA – APR+PALO (%)' should be +2.5 and +4.4, respectively.

http://ift.tt/2BY3GgV

Risk of autism spectrum disorder in offspring following paternal use of selective serotonin reuptake inhibitors before conception: a population-based cohort study

Objective

The present study aimed to examine the association between paternal selective serotonin reuptake inhibitor (SSRI) use before conception and the risk of autism spectrum disorder (ASD) in offspring.

Design

A population-based cohort study.

Methods

We conducted a cohort study of 669 922 children born from 1998 to 2008, with follow-up throughout 2013. Based on Danish national registers, we linked information on paternal use of SSRIs, ASD diagnosed in children and a range of potential confounders. The children whose fathers used SSRIs during the last 3 months prior to conception were identified as the exposed. Cox regression model was used to estimate the HR for ASD in children.

Results

Compared with unexposed children, the exposed had a 1.62-fold higher risk of ASD (95% CI 1.33 to 1.96) and the risk attenuated after adjusting for potential confounders, especially fathers' psychiatric conditions (HR=1.43, 95% CI 1.18 to 1.74). When extending the exposure window to 1 year before conception, the increased risk persisted in children of fathers using SSRIs only from the last year until the last 3 months prior to conception (HR=1.54, 95% CI 1.21 to 1.94) but not in children of fathers using SSRIs only during the last 3 months prior to conception (HR=1.17, 95% CI 0.75 to 1.82). We also performed stratified analyses according to paternal history of affective disorders and observed no increased ASD risk among children whose father had affective disorders. Besides, the sibling analysis showed that the ASD risk did not increase among exposed children compared with their unexposed siblings.

Conclusions

The mildly increased risk of ASD in the offspring associated with paternal SSRI use before conception may be attributable to paternal underlying psychiatric indications related to SSRI use or other unmeasured confounding factors.

http://ift.tt/2Boxujf

Two-epoch cross-sectional case record review protocol comparing quality of care of hospital emergency admissions at weekends versus weekdays

Introduction

The mortality associated with weekend admission to hospital (the 'weekend effect') has for many years been attributed to deficiencies in quality of hospital care, often assumed to be due to suboptimal senior medical staffing at weekends. This protocol describes a case note review to determine whether there are differences in care quality for emergency admissions (EAs) to hospital at weekends compared with weekdays, and whether the difference has reduced over time as health policies have changed to promote 7-day services.

Methods and analysis

Cross-sectional two-epoch case record review of 20 acute hospital Trusts in England. Anonymised case records of 4000 EAs to hospital, 2000 at weekends and 2000 on weekdays, covering two epochs (financial years 2012–2013 and 2016–2017). Admissions will be randomly selected across the whole of each epoch from Trust electronic patient records. Following training, structured implicit case reviews will be conducted by consultants or senior registrars (senior residents) in acute medical specialities (60 case records per reviewer), and limited to the first 7 days following hospital admission. The co-primary outcomes are the weekend:weekday admission ratio of errors per case record, and a global assessment of care quality on a Likert scale. Error rates will be analysed using mixed effects logistic regression models, and care quality using ordinal regression methods. Secondary outcomes include error typology, error-related adverse events and any correlation between error rates and staffing. The data will also be used to inform a parallel health economics analysis.

Ethics and dissemination

The project has received ethics approval from the South West Wales Research Ethics Committee (REC): reference 13/WA/0372. Informed consent is not required for accessing anonymised patient case records from which patient identifiers had been removed. The findings will be disseminated through peer-reviewed publications in high-quality journals and through local High-intensity Specialist-Led Acute Care (HiSLAC) leads at the 121 hospitals that make up the HiSLAC Collaborative.

http://ift.tt/2C3PH96

Rationale and design of the violence, injury and trauma observatory (VITO): the Cape Town VITO pilot studies protocol

The establishment of violence and injury observatories elsewhere has been found to reduce the burden within a relatively short period. Currently no integrated system exists in South Africa to provide collated data on violence, to allow for targeted interventions and routine monitoring and evaluation.This research seeks to identify if bringing multiple data sources, including but not limited to data from the South African Police Service (SAPS), Forensic Pathology Services (FPS), Emergency Medical Services (EMS) and local hospital clinical databases, together are (1) feasible; (2) able to generate data for action, that is valid, reliable and robust and (3) able to lead to interventions.

The violence, injury and trauma observatory (VITO) is a planned collaborative, multicentre study of clinical, police and forensic data for violence and injury in the City of Cape Town, where a local context exists of access to multiple source of health and non-health data. The VITO will initially be piloted in Khayelitsha, a periurban community characterised by increased rates of violence, where fatal and non-fatal injury data will be sourced from within the community for the period 2012–2015 and subjected to descriptive statistics and time-trend analyses. Analysed data will be visualised using story maps, data clocks, web maps and other geographical information systems-related products.

This study has been approved by the University of Cape Town's Human Research Ethics Committee (HREC 861/2016). We intend to disseminate our findings among stakeholders within the local government safety cluster, non-governmental organisations working within the violence prevention sector and the afflicted communities through the SAPS and violence prevention through urban upgrading community forums. Findings from this work will serve to identify important issues and trends, influence public policy and develop evidence-based interventions.

http://ift.tt/2BnZqn3

Results of physician licence examination and scholarship contract compliance by the graduates of regional quotas in Japanese medical schools: a nationwide cross-sectional survey

Objectives

Responding to the serious shortage of physicians in rural areas, the Japanese government has aggressively increased the number of entrants to medical schools since 2008, mostly as a chiikiwaku, entrants filling a regional quota. The quota has spread to most medical schools, and these entrants occupied 16% of all medical school seats in 2016. Most of these entrants were admitted to medical school with a scholarship with the understanding that after graduation they will practise in designated areas of their home prefectures for several years. The quota and scholarship programmes will be revised by the government starting in 2018. This study evaluates the intermediate outcomes of these programmes.

Design

Cross-sectional survey to all prefectural governments and medical schools every year from 2014 to 2017 to obtain data on medical graduates.

Settings

Nationwide.

Participants

All quota and non-quota graduates with prefecture scholarship in each prefecture, and all the quota graduates without scholarship in each medical school.

Primary outcome measures

Passing rate of the National License Examination for Physicians and the percentage of graduates who have not bought out the scholarship contract after graduation.

Results

Most prefectures and medical schools in Japan participated in this study (97.8%–100%). Quota graduates with scholarship were significantly more likely to pass the National License Examination for Physicians than the other medical graduates in Japan at all the years (97.9%, 96.7%, 97.4% and 94.7% vs 93.9%, 94.5%, 94.3% and 91.8%, respectively). The percentage of quota graduates with scholarship who remained in the scholarship contract 3 years after graduation was 92.2% and 89.9% for non-quota graduates with scholarship.

Conclusions

Quota entrants showed better academic performance than their peers. Most of the quota graduates remained in the contractual workforce. The imminent revision of the national policy regarding quota and scholarship programmes needs to be based on this evidence.

http://ift.tt/2BZEZ3t

Health impact of objective burden, subjective burden and positive aspects of caregiving: an observational study among caregivers in Switzerland

Objective

To investigate associations of objective caregiver burden, subjective caregiver burden and positive aspects of caregiving with self-reported health indicators in caregiving partners of persons with a severe physical disability (spinal cord injury).

Design

Cross-sectional, observational.

Setting

Community, Switzerland.

Participants

Caregiving partners of persons with spinal cord injury (n=118, response rate 19.7%).

Outcome measures

General health, role limitations due to physical health, role limitations due to mental health, pain intensity, mental health and vitality were assessed using items from the 36-Item Short Form Health Survey (SF-36). Three items were used to assess the frequency of different types of sleep problems.

Results

Subjective caregiver burden was associated to all self-reported health indicators. A high subjective burden was linked to poorer general health (OR 6.5, 95% CI 2.0 to 21.5), more role limitations due to physical health (OR 4.2, 95% CI 1.4 to 12.8), more role limitations due to mental health (OR 3.6, 95 % CI 1.1 to 11.7), higher pain intensity (OR 4.0, 95% CI 1.4 to 11.5), poorer mental health (coefficient –17.9, 95% CI –24.5 to –11.2), lower vitality (coefficient –20.3, 95% CI –28.4 to –12.1), and more frequent sleep problems (OR 5.3, 95% CI 1.6 to 18.4). Partners who indicated positive aspects of caregiving further reported better mental health (coefficient 6.5, 95% CI 0.2 to 12.8). Objective burden was not related to any health indicator.

Conclusions

Subjective burden and lack of positive aspects of caregiving were associated with poorer physical and mental health. Caregiver health may be promoted through the strengthening of psychological and psychosocial resources.

http://ift.tt/2Brcfxj

Correction: Patient preferences for venous thromboembolism prophylaxis after injury: a discrete choice experiment

Haac BE, O'Hara NN, Mullins CD, et al. Patient preferences for venous thromboembolism prophylaxis after injury: a discrete choice experiment. BMJ Open 2017;7:e016676. doi: 10.1136/bmjopen-2017-016676

The last author's first name should be 'Gerard', not 'Gerald'. Also, the corresponding author 'Dr Nathan N O'Hara' should be listed 'Mr Nathan N O'Hara'.

http://ift.tt/2C04JNe

Anticipated health behaviour changes and perceived control in response to disclosure of genetic risk of breast and ovarian cancer: a quantitative survey study among women in the UK

Background

Genetic risk assessment for breast cancer and ovarian cancer (BCOC) is expected to make major inroads into mainstream clinical practice. It is important to evaluate the potential impact on women ahead of its implementation in order to maximise health benefits, as predictive genetic testing without adequate support could lead to adverse psychological and behavioural responses to risk disclosure.

Objective

To examine anticipated health behaviour changes and perceived control to disclosure of genetic risk for BCOC and establish demographic and person-specific correlates of adverse anticipated responses in a population-based sample of women.

Design

Cross-sectional quantitative survey study carried out by the UK Office for National Statistics in January and March 2014.

Setting

Face-to-face computer-assisted interviews conducted by trained researchers in participants' homes.

Participants

837 women randomly chosen from households across the UK identified from the Royal Mail's Postcode Address File.

Outcome measures

Anticipated health behaviour change and perceived control to disclosure of BCOC risk.

Results

In response to a genetic test result, most women (72%) indicated 'I would try harder to have a healthy lifestyle', and over half (55%) felt 'it would give me more control over my life'. These associations were independent of demographic factors or perceived risk of BCOC in Bonferroni-corrected multivariate analyses. However, a minority of women (14%) felt 'it isn't worth making lifestyle changes' and that 'I would feel less free to make choices in my life' (16%) in response to BCOC risk disclosure. The former belief was more likely to be held by women who were educated below university degree level (P<0.001) after adjusting for other demographic and person-specific correlates.

Conclusion

These findings indicate that women in the UK largely anticipate that they would engage in positive health behaviour changes in response to BCOC risk disclosure.

http://ift.tt/2BnEZqu

Clinical features and prognosis of patients with acute non-specific chest pain in emergency and cardiology departments after the introduction of high-sensitivity troponins: a prospective cohort study

Objectives

To determine the incidence of clinical, cardiac-related endpoints and mortality among patients presenting to an emergency or cardiology department with non-specific chest pain (NSCP), and who receive testing with a high-sensitivity troponin. A second objective was to identify risk factors for the above-noted endpoints during 12 months of follow-up.

Design

A prospective multicentre study.

Setting

Emergency and cardiology departments in Southern Denmark.

Subjects

The study enrolled 1027 patients who were assessed for acute chest pain in an emergency or cardiology department, and in whom a myocardial infarction or another obvious reason for chest pain had been ruled out. Patients were enrolled from September 2014 to June 2015 and followed for 1 year.

Main outcome measures

Clinical, cardiac-related endpoints (cardiac-related death, acute myocardial infarction, unstable angina and coronary revascularisation) and all-cause mortality.

Results

Over a period of 1 year, cardiac-related endpoints were found in 19 patients (1.9%): 0 patients experienced cardiac-related death, 2 (0.2%) had myocardial infarction, 4 (0.4%) had unstable angina pectoris and 17 (1.7%) underwent coronary revascularisation. All-cause mortality was observed in seven patients (0.7%). When compared with the general population, the standardised mortality ratio did not differ. The risk factors associated with the study endpoints included male gender, body mass index >25 kg/m², previous known coronary artery disease, hypertension, hypercholesterolaemia, diabetes mellitus and the use of statins. A total of 73% of the endpoints occurred in males.

Conclusion

The prognosis for patients with NSCP is favourable, with a 1-year mortality after discharge that is comparable with the background population. Few clinical endpoints took place during follow-up, and those that did were predominantly in males.

http://ift.tt/2C04RMI

Qualitative and quantitative assessment of posterior segment optical coherence tomography images using standard photos: the Liwan Eye Study

Background/aims

To develop a standardised grading scheme, using standard photos, for spectral-domain ocular coherence tomography (SD-OCT) images of the posterior eye and evaluate the interobserver agreement among trained ophthalmologists in identifying pathological changes.

Methods

Subjects were recruited from Liwan District, Guangzhou, with SD-OCT data collection from June 2013 to November 2013 as part of 10-year follow-up visits from the Liwan Eye Study. All subjects underwent SD-OCT imaging of the macula with scanning lines analysed by two ophthalmologists to assess for the presence of 12 different posterior segment lesions. Per cent agreement for each lesion between the graders and quantitative measures of dome-shaped macula (DSM) height and choroidal thickness were calculated.

Results

A total of 679 SD-OCT images from 679 subjects were independently evaluated by the two graders. Each of the 12 lesions was successfully graded as present or absent in over 96% of images. For all lesions, per cent agreement between observers was over 90%, ranging from 90.7% for epiretinal membranes and retinal pigment epithelium thickenings to 99.7% for full thickness macular holes and retinal detachments. Quantitative measurements of DSM height and choroidal thickness at three locations of the eye all exhibited intraclass correlation scores between the two graders of greater than 0.9.

Conclusion

Our study demonstrates high concordance between graders in characterising posterior segment lesions using SD-OCT images, validating the continued use of this imaging modality in the diagnosis of posterior eye disease.

http://ift.tt/2BnFNMe

Subgrouping and TargetEd Exercise pRogrammes for knee and hip OsteoArthritis (STEER OA): a systematic review update and individual participant data meta-analysis protocol

Introduction

Knee and hip osteoarthritis (OA) is a leading cause of disability worldwide. Therapeutic exercise is a recommended core treatment for people with knee and hip OA, however, the observed effect sizes for reducing pain and improving physical function are small to moderate. This may be due to insufficient targeting of exercise to subgroups of people who are most likely to respond and/or suboptimal content of exercise programmes. This study aims to identify: (1) subgroups of people with knee and hip OA that do/do not respond to therapeutic exercise and to different types of exercise and (2) mediators of the effect of therapeutic exercise for reducing pain and improving physical function. This will enable optimal targeting and refining the content of future exercise interventions.

Methods and analysis

Systematic review and individual participant data meta-analyses. A previous comprehensive systematic review will be updated to identify randomised controlled trials that compare the effects of therapeutic exercise for people with knee and hip OA on pain and physical function to a non-exercise control. Lead authors of eligible trials will be invited to share individual participant data. Trial-level and participant-level characteristics (for baseline variables and outcomes) of included studies will be summarised. Meta-analyses will use a two-stage approach, where effect estimates are obtained for each trial and then synthesised using a random effects model (to account for heterogeneity). All analyses will be on an intention-to-treat principle and all summary meta-analysis estimates will be reported as standardised mean differences with 95% CI.

Ethics and dissemination

Research ethical or governance approval is exempt as no new data are being collected and no identifiable participant information will be shared. Findings will be disseminated via national and international conferences, publication in peer-reviewed journals and summaries posted on websites accessed by the public and clinicians.

PROSPERO registration number

CRD42017054049.

http://ift.tt/2BYKakq

Prevalence and possible factors associated with anaemia, and vitamin B12 and folate deficiencies in women of reproductive age in Pakistan: analysis of national-level secondary survey data

Objective

To determine the prevalence and possible factors associated with anaemia, and vitamin B₁₂ and folate deficiencies in women of reproductive age (WRA) in Pakistan.

Methods

A secondary analysis was conducted on data collected through the large-scale National Nutrition Survey in Pakistan in 2011. Anaemia was defined as haemoglobin levels <12 g/dL, vitamin B₁₂ deficiency as serum vitamin B₁₂ levels of <203 pg/mL (150 pmol/L) and folate deficiency as serum folate levels <4 ng/mL (10 nmol/L).

Results

A total of 11 751 blood samples were collected and analysed. The prevalence of anaemia, vitamin B₁₂ deficiency and folate deficiency was 50.4%, 52.4% and 50.8%, respectively. After adjustment, the following factors were positively associated with anaemia: living in Sindh province (RR 1.07; 95% CI 1.04 to 1.09) P<0.00, food insecure with moderate hunger (RR 1.03; 95% CI 1.00 to 1.06) P=0.02, four or more pregnancies (RR 1.03; 95% CI 1.01 to 1.05) P<0.00, being underweight (RR 1.03; 95% CI 1.00 to 1.05) P=0.02, being overweight or obese (RR 0.95; 95% CI 0.93 to 0.97) P<0.00 and weekly intake of leafy green vegetables (RR 0.98; 95% CI 0.95 to 1.00) P=0.04. For vitamin B₁₂ deficiency, a positive association was observed with rural population (RR 0.81; 95% CI 0.66 to 1.00) P=0.04, living in Khyber Pakhtunkhwa province (RR 1.25; 95% CI 1.11 to 1.43) P<0.00 and living in Azad Jammu and Kashmir (RR 1.50; 95% CI 1.08 to 2.08) P=0.01. Folate deficiency was negatively associated with daily and weekly intake of eggs (RR 0.89; 95% CI 0.81 to 0.98) P=0.02 and (RR 0.88; 95% CI 0.78 to 0.99) P=0.03.

Conclusions

In Pakistan, anaemia, and vitamin B₁₂ and folate deficiencies are a severe public health concern among WRA. Our findings suggest that further research is needed on culturally appropriate short-term and long-term interventions within communities and health facilities to decrease anaemia, and vitamin B₁₂ and folate deficiencies among Pakistani women.

http://ift.tt/2C04vWo

Workflow interruptions and stress atwork: a mixed-methods study among physicians and nurses of a multidisciplinary emergency department

Objectives

Dealing with multiple workflow interruptions is a major challenge in emergency department (ED) work. This study aimed to establish a taxonomy of workflow interruptions that takes into account the content and purpose of interruptive communication. It further aimed to identify associations of workflow interruptions with ED professionals' work stress.

Design

Combined data from expert observation sessions and concomitant self-evaluations of ED providers.

Setting

ED of an academic community hospital in Germany.

Participants

Multidisciplinary sample of ED physicians and nurses. 77 matched observation sessions of interruptions and self-evaluations of work stress were obtained on 20 randomly selected days.

Outcome measures

ED professionals' stress evaluations were based on standardised measures. ED workload data on patient load, patient acuity and staffing were included as control variables in regression analyses.

Results

Overall mean rate was 7.51 interruptions/hour. Interruptions were most frequently caused by ED colleagues of another profession (27.1%; mean interruptions/hour rate: 2.04), by ED colleagues of the same profession (24.1%; 1.81) and by telephone/beeper (21%; 1.57). Concerning the contents of interruption events, interruptions most frequently occurred referring to a parallel case under care (30.3%, 2.07), concerning the current case (19.1%; 1.28), or related to coordination activities (18.2%, 1.24). Regression analyses revealed that interruptive communication related to parallel cases significantly increased ED providers' stress levels (β=0.24, P=0.03). This association remained significant after controlling for ED workload.

Discussion

Interruptions that refer to parallel cases under care were associated with increased stress among ED physicians and nurses. Our approach to distinguish between sources and contents of interruptions contributes to an improved understanding of potential benefits and risks of workflow interruptions in ED work environments. Despite some limitations, our findings add to future research on the implications of interruptions for effective and safe patient care and work in complex and dynamic care environments.

http://ift.tt/2Bn6rVf

Assessment of medium-term cardiovascular disease risk after Japans 2011 Fukushima Daiichi nuclear accident: a retrospective analysis

Objective

To assess the medium-term indirect impact of the 2011 Fukushima Daiichi nuclear accident on cardiovascular disease (CVD) risks and to identify whether risk factors for CVD changed after the accident.

Participants

Residents aged 40 years and over participating in annual public health check-ups from 2009 to 2012, administered by Minamisoma city, located about 10 to 40 km from the Fukushima Daiichi nuclear plant.

Methods

The sex-specific Framingham CVD risk score was considered as the outcome measure and was compared before (2009–2010) and after the accident (2011–2012). A multivariate regression analysis was employed to evaluate risk factors for CVD.

Results

Data from 563 individuals (60.2% women) aged 40 to 74 years who participated in the check-ups throughout the study period was analysed. After adjusting for covariates, no statistically significant change was identified in the CVD risk score postaccident in both sexes, which may suggest no obvious medium-term health impact of the Fukushima nuclear accident on CVD risk. The risk factors for CVD and their magnitude and direction (positive/negative) did not change after the accident.

Conclusions

There was no obvious increase in CVD risks in Minamisoma city, which may indicate successful management of health risks associated with CVD in the study sample.

http://ift.tt/2BYK3p0

Acquired Resistance of PTEN-Deficient Cells to PARP Inhibitor and Ara-C Mediated by 53BP1 Loss and SAMHD1 Overexpression

Summary

With increasing uses of PARP inhibitors (PARPis) for cancer therapy, understanding their resistance is becoming urgent. However, acquired PARPi resistance in the PTEN-deficient background is poorly understood. We generated 3 PARPi-resistant PTEN-deficient glioblastoma U251 variants separately with olaparib (U251/OP), talazoparib (U251/TP) and simmiparib (U251/SP). These variants displayed consistent resistance (2.46~71.78-fold) to all 5 PARPis including niraparib and rucaparib and showed higher degrees of resistance to the PARPis to which the parental cells were more sensitive. The resistance was characteristic of fast emergence and high stability. However, the resistance acquirement did not cause an increasingly aggressive phenotype. The resistance was not correlated to various factors including PTEN mutations. The PARPi-treated variants produced less γH2AX and G2/M arrest. Consistently, loss of 53BP1 occurred in all variants and its compensation enhanced their sensitivity to PARPis by ~76%. The variants revealed slightly different cross-resistance profiles to 13 non-PARPi anticancer drugs. All were resistant to Ara-C (6~8-fold) but showed differential resistance to 5-fluorouracil, gemcitabine and paclitaxel. Almost no resistance was observed to the rest drugs including cisplatin. SAMHD1 was overexpressed in all the variants and its knockout completely restored their sensitivity to Ara-C but did not affect their PARPi sensitivity. This study demonstrates a consistent resistance profile to PARPis and a unique cross-resistance profile to non-PARPi drugs in different PARPi-resistant U251 cells and reveals 53BP1 loss and SAMHD1 overexpression as the primary mechanisms responsible for their resistance to PARPis and Ara-C, respectively. These effects probably result from heritable gene change(s) caused by persistent PARPi exposure.

This article is protected by copyright. All rights reserved.

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SLC35F2 is indispensable for papillary thyroid carcinoma progression via activation of TGFBR1/ASK-1/MAPK signaling axis

Summary

Solute carrier family control essential physiological functions and are tightly linked to human diseases. Solute carrier family 35 member F2 (SLC35F2) is aberrantly activated in several malignancies. However, the biological function and molecular mechanism of SLC35F2 in papillary thyroid carcinoma (PTC) are yet to be fully explored. Here, we showed that SLC35F2 was prominently up-regulated in PTC tissues at both protein and mRNA expression level compared with matched adjacent normal tissues. Besides, the high expression of SLC35F2 was significantly associated with lymph node metastasis in patients with PTC. CRISPR/Cas9-mediated knockout of SLC35F2 attenuated the tumorigenic properties of PTC, including cell proliferation, migration and invasion and induced G1 phase arrest. In contrast, ectopic expression of SLC35F2 brought about aggressive malignant phenotypes of PTC cells. Moreover, SLC35F2 expedited the proliferation and migration of PTC cells by targeting TGFBR1 and p-ASK-1, thereby activating the mitogen-activated protein kinase (MAPK) signaling pathway. Besides, the malignant behaviors induced by over-expression of SLC35F2 could be abrogated by silencing of TGFBR1 using a specific inhibitor. We conducted the first study on SLC35F2 in thyroid cancer with the aim of elucidating the functional significance and molecular mechanism of SLC35F2. Our findings suggest that SLC35F2 exerts its oncogenic effect on PTC progression through the MAPK pathway, with dependence on activation of TGFBR-1 and ASK-1.

This article is protected by copyright. All rights reserved.

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FDA Approves Trastuzumab Biosimilar [News in Brief]

Second biosimilar approved for cancer will be used for HER2-positive breast and stomach cancers.

http://ift.tt/2ziHEjg

Contents

http://ift.tt/2BR9oyD

Neurophysiology and cognitive reserve: A promising path

In the summer of 2017, a Lancet commission on Dementia prevention, intervention, and care (Livingston et al., 2017) identified nine risk factors for dementia that are potentially modifiable. Further, it estimated that if these nine factors are eliminated, one in three cases of dementia could be prevented. Among these nine factors, several are conceptually linked to cognitive reserve. Cognitive reserve refers to the brain capacity to cope with damage or diseases towards maintaining a stable level of function (Stern, 2002).

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Editorial Board

http://ift.tt/2BRBxp7

Correlations between MUNIX and adapted multiple point stimulation MUNE methods

Motor unit number estimate (MUNE) usually represents the ratio of the maximal compound muscle action potential (CMAP) divided by the average surface-recorded motor unit potential (SMUP). MUNE techniques differ in how single motor units (MU) are obtained. McComas et al. (1971) introduced the first MUNE technique, referred as the incremental technique. Incremental stimulation was applied at one stimulation point on the nerve and the stimulus intensity was gradually increased from a subthreshold value until 11 increments in the muscle response were obtained.

http://ift.tt/2D1tt4A

Tumor-associated CD204+ M2 macrophages is an unfavorable prognosticator in uterine cervical adenocarcinoma

Abstract

Uterine cervical adenocarcinoma is rare, but its prevalence has increased. To improve outcomes and ensure the suitability of recent immunotherapies, the aim of the study was to evaluate the clinicopathological impact of the tumor immune microenvironment of uterine cervical adenocarcinoma. We investigated 148 adenocarcinoma cases, including 21 cases of adenocarcinoma in situ (AIS) and 127 cases of invasive adenocarcinoma, using immunohistochemistry to detect tumor-infiltrating immune cells and the expression of PD-L1 and p16 on tumor cells, and we then conducted correlation and survival analyses. The density of immune cells and expression levels were compared between the tumor cell nest and stroma and between AIS and invasive adenocarcinoma using digital image analysis. A higher density of tumor-infiltrating CD204⁺ M2 macrophages was significantly associated with shorter disease-free survival, although no other tumor-infiltrating immune cells were prognostic, including CD4⁺, CD8⁺, FOXP3⁺, and PD-1⁺ lymphocytes and CD68⁺ macrophages. The density of stroma-infiltrating lymphocytes and macrophages was significantly higher in invasive adenocarcinoma than in AIS. The density of tumor-infiltrating lymphocytes in p16-expressing human papillomavirus (HPV)-positive tumors was significantly higher than that in HPV-negative tumors. HPV status was not associated with patient outcome. Expression of PD-L1 on tumor cells was found only in invasive adenocarcinoma cases (17.3%). A higher density of stroma-infiltrating lymphocytes and macrophages was found in PD-L1-positive tumors than in negative tumors. Patients with PD-L1-positive tumors tended to experience longer survival. It is suggested that tumor-infiltrating CD204⁺ M2 macrophages may predict poor prognoses in patients with cervical adenocarcinoma.

This article is protected by copyright. All rights reserved.

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Interventions are needed to support patient–provider decision-making for DCIS: a scoping review

Abstract

Purpose

Prognostic and treatment uncertainty make ductal carcinoma in situ (DCIS) complex to manage. The purpose of this study was to describe research that evaluated DCIS communication experiences, needs and interventions among DCIS patients or physicians.

Methods

MEDLINE, EMBASE, CINAHL and The Cochrane Library were searched from inception to February 2017. English language studies that evaluated patient or physician DCIS needs, experiences or behavioural interventions were eligible. Screening and data extraction were done in duplicate. Summary statistics were used to describe study characteristics and findings.

Results

A total of 51 studies published from 1997 to 2016 were eligible for review, with a peak of 8 articles in year 2010. Women with DCIS lacked knowledge about the condition and its prognosis, although care partners were more informed, desired more information and experienced decisional conflict. Many chose mastectomy or prophylactic mastectomy, often based on physician's recommendation. Following treatment, women had anxiety and depression, often at levels similar to those with invasive breast cancer. Disparities were identified by education level, socioeconomic status, ethnicity and literacy. Physicians said that they had difficulty explaining DCIS and many referred to DCIS as cancer. Despite the challenges reported by patients and physicians, only two studies developed interventions designed to improve patient–physician discussion and decision-making.

Conclusions

As most women with DCIS undergo extensive treatment, and many experience treatment-related complications, the paucity of research on PE to improve and support informed decision-making for DCIS is profound. Research is needed to improve patient and provider discussions and decision-making for DCIS management.

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Population exposure–safety analysis of cediranib for Phase I and II studies in patients with cancer

Summary

Aims

A multistudy analysis of cediranib, a potent, selective inhibitor of all three vascular endothelial growth factor receptors (VEGFR-1, -2 and -3), was conducted to establish population exposure–safety models for the relationship of cediranib exposure to the safety endpoints, diastolic and systolic blood pressure (DBP and SBP) and diarrhoea in cancer patients. These models were applied to predict safety outcomes for different cediranib dose regimens.

Methods

Models for hypertension and diarrhoea were constructed based on data from 10 Phase I and three Phase II studies comprising 631 cancer patients following cediranib once-daily oral dosing. Daily DBP and SBP were simultaneously characterized using indirect response models for predicted cediranib concentration–time courses, while daily diarrhoea events were modelled as ordered categorical variables with a proportional odds model with a Markov element for predicted average cediranib concentrations.

Results

For 20 mg cediranib once-daily oral administration, the mean increase in DBP and SBP was predicted to be 7 (95% CI 3–13) and 8 mmHg (95% CI 3–16), respectively, while the probability of mild diarrhoea, but not the severity, was predicted to increase over time. Severe diarrhoea was predicted to be resolved rapidly upon discontinuation of cediranib treatment.

Conclusions

Maximum blood pressure increase was observed within the first few days of cediranib treatment, consistent with the pharmacokinetic profile of cediranib reaching steady state in about 5 days. The probability of diarrhoea increased with cediranib concentration but was far more dependent on the status of diarrhoea predicted on the previous day.

http://ift.tt/2l14Hdi

Oncogenic Ras Isoforms Signaling Specificity at the Membrane

How do Ras isoforms attain oncogenic specificity at the membrane? Oncogenic KRas, HRas, and NRas (K-Ras, H-Ras, and N-Ras) differentially populate distinct cancers. How they selectively activate effectors and why is KRas4B the most prevalent are highly significant questions. Here, we consider determinants that may bias isoform-specific effector activation and signaling at the membrane. We merge functional data with a conformational view to provide mechanistic insight. Cell-specific expression levels, pathway cross-talk, and distinct interactions are the key, but conformational trends can modulate selectivity. There are two major pathways in oncogenic Ras-driven proliferation: MAPK (Raf/MEK/ERK) and PI3Kα/Akt/mTOR. All membrane-anchored, proximally located, oncogenic Ras isoforms can promote Raf dimerization and fully activate MAPK signaling. So why the differential statistics of oncogenic isoforms in distinct cancers and what makes KRas so highly oncogenic? Many cell-specific factors may be at play, including higher KRAS mRNA levels. As a key factor, we suggest that because only KRas4B binds calmodulin, only KRas can fully activate PI3Kα/Akt signaling. We propose that full activation of both MAPK and PI3Kα/Akt proliferative pathways by oncogenic KRas4B—but not by HRas or NRas—may help explain why the KRas4B isoform is especially highly populated in certain cancers. We further discuss pharmacologic implications. Cancer Res; 1–10. ©2017 AACR.

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Folliculotropism in pigmented facial macules: Differential diagnosis with Reflectance confocal microscopy

Abstract

Pigmented facial macules are common on sun damage skin. The diagnosis of early stage lentigo maligna (LM) and lentigo maligna melanoma (LMM) is challenging. Reflectance confocal microscopy (RCM) has been proven to increase diagnostic accuracy of facial lesions.

A total 154 pigmented facial macules, retrospectively collected, were evaluate for the presence of already described RCM features and new parameters depicting aspects of the follicle .

Melanocytic nests, roundish pagetoid cells, follicular infiltration, bulgings from the follicles and many bright dendrites, and infiltration of the hair follicle (i.e. folliculotropism) were found to be indicative of LM/LMM compared to non-melanocytic skin neoplasms, with an overall sensitivity of 96% and specificity of 83%. Concerning non-melanocytic skin neoplasms, solar lentigo and lichen planus-like keratosis resulted better distinguishable from LM/LMM because usually lacking malignant features and presenting characteristic diagnostic parameters, such as cepidermal cobblestone pattern and polycyclic papillary contours. On the other hand, distinction of pigmented actinic keratosis (PAK) resulted more difficult, and needing evaluation of hair follicle infiltration and bulging structures, due to the frequent observation of few bright dendrites in the epidermis, but predominantly not infiltrating the hair follicle (estimated specificity for PAK 53%). .

A detailed evaluation of the components of the folliculotropism may help to improve the diagnostic accuracy. The classification of the type, distribution and amount of cells, and the presence of bulging around the follicles seem to represent important tools for the differentiation between PAK and LM/LMM at RCM analysis.

This article is protected by copyright. All rights reserved.

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Illuminating the covert mission of mononuclear phagocytes in their regional niches

Shu Zhen Chong | Maximilien Evrard | Chi Ching Goh | Lai Guan Ng

http://ift.tt/2ph0yHB

Intraoperative cortico-cortical evoked potentials shows disconnection of the motor cortex from the epileptogenic network during subtotal hemispherotomy

Epileptic spasms (ES) are a unique seizure type, comprising of sudden tonic movements of predominantly proximal and truncal muscles. In the revised operational classification of seizure types by the International League Against Epilepsy (ILAE) (Fisher et al., 2017), ES are classified as into focal, generalized, and unknown onset categories. Iimura et al. reported that ten of 23 patients who underwent subtotal hemispherectomy or multilobar resection presented with ES (Iimura et al., 2017). They found extensively distributed interictal epileptogenic high-frequency oscillations (HFOs) which skipped the motor area.

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Tumour-like giant nerves in entrapment neuropathies

High resolution ultrasound has recently become a useful complementary method to electrophysiology for the confirmation of various entrapment neuropathies. The ultrasonographic signs of entrapment neuropathies include the segmental enlargement of the cross-sectional area (CSA) and the change of the echotexture of the nerve proximal and sometimes distal to the site of compression (Cartwright and Walker, 2013; Csillik et al., 2016). On longitudinal scans, an abrupt caliber change and a spindle-like segmental swelling of the nerve is typically seen.

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Differential changes in the spinal segmental locomotor output in Hereditary Spastic Paraplegia

Hereditary spastic paraplegia (HSP) includes a heterogeneous group of inherited neurodegenerative disorders resulting from primary retrograde degeneration of corticospinal fibers originating from many areas of the brain (de Souza et al., 2016). Most of the corticospinal neurons originate in the primary motor cortex and premotor frontal areas. Corticospinal axons originating from layer V pyramidal neurons synapse directly or via spinal interneurons with alpha-motor neurons (MN) innervating skeletal muscles and controlling movements of the limbs and trunk.

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Cyclin D1 mRNA as a molecular marker for minimal residual disease monitoring in patients with mantle cell lymphoma

Abstract

Chromosomal translocation t(11;14)(q13;q32) is a characteristic molecular marker of mantle cell lymphoma (MCL) and leads to the fusion of the immunoglobulin heavy chain enhancer-promoter with the cyclin D1 gene. Both aberrant cyclin D1 expression and underlying chromosomal aberration may be used as molecular targets for monitoring minimal residual disease (MRD). The present study aims to assess the usefulness of quantitative cyclin D1 gene expression compared to the standardised but more technologically demanding DNA-based method for immunoglobulin heavy chain (IGH) or t(11;14) clone-specific gene rearrangement quantification in a cohort of bone marrow (BM) and peripheral blood (PB) samples from patients with MCL. We simultaneously evaluated DNA-MRD and cyclin D1 expression levels in 234 samples from 57 patients. We observed that both in DNA-MRD positive and negative BM/PB pairs from the same time points the expression levels of cyclin D1 are lower in PB than in BM (median 19×, BM/PB range 0.41–352). The correlation of cyclin D1 transcript levels with DNA-MRD or with flow cytometry was good only in samples with a very high infiltration. In DNA-MRD-negative BM samples, we observed a significant heterogeneity of cyclin D1 expression (in the range of more than three orders of magnitude). This is in contrast to previous reports demonstrating the usefulness of cyclin D1 for MRD monitoring that did not use DNA-based method as a reference. In PB, the specificity of cyclin D1 expression was better due to a lower physiological background. In conclusion, we show that cyclin D1 is unsuitable for MRD monitoring in BM.

http://ift.tt/2pb71Uu

Re-bleeding and Mortality After Lower Gastrointestinal Bleeding in Patients Taking Anti-platelets or Anti-coagulants

Patients who develop lower gastrointestinal bleeding (LGIB) while receiving anti-coagulants or anti-platelets have increased severity of bleeding and risk of re-bleeding. We compared outcomes of patients receiving anti-platelets, anti-coagulants, or direct oral anti-coagulants (DOACs) who develop LGIB, as well as the effects of withholding these drugs on their course of bleeding.

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Epithelioid Granulomas Associate with Increased Severity and Progression of Crohn’s Disease, Based on 6-year Follow Up

Epithelioid granulomas are characteristics of a subset of patients with Crohn's disease (CD), but their significance, with regard to disease progression and severity, is unclear. We investigated the relationship between granulomas and CD severity over a 6-year time period in a large cohort of patients.

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Increasing Prevalence of Primary Biliary Cholangitis and Reduced Mortality with Treatment

There are few data from longitudinal studies of trends in primary biliary cholangitis (PBC) among patients under routine clinical care in the United States (US). We collected data from the Fibrotic Liver Disease consortium to investigate changes in incidence and prevalence of PBC and the effects of patient demographics, clinical features, and treatment on mortality.

http://ift.tt/2zhwjQP

National Early Warning Score accurately discriminates the risk of serious adverse events in patients with liver disease

The National Early Warning Score (NEWS) is used to identify deteriorating adult hospital inpatients. However, it includes physiological parameters frequently altered in patients with cirrhosis. We aimed to assess the performance of the NEWS in acute and chronic liver diseases.

http://ift.tt/2BCp1ge

Local Control and Toxicity of External Beam Reirradiation with Pulsed Low-Dose-Rate Technique

To evaluate the efficacy and toxicity of external beam reirradiation using pulsed low-dose-rate (PLDR) technique.

http://ift.tt/2DzHYNU

EMS1 Editorial Advisory Board reflects on 2017 and the year ahead

It was a big year for EMS, and for EMS1. EMS providers made big strides for patient care and promoting the profession in 2017. Community paramedic Lisa Cassidy with the St. Charles County Ambulance District launched the #StopHeroin campaign for opioid abuse prevention and treatment. Charles Avery, an EMS program director at Bainbridge State College, made it possible for a young woman with Down Syndrome ...

http://ift.tt/2kFV44G

Variation in Positive End-Expiratory Pressure Levels for Mechanically Ventilated Extremely Low Birth Weight Infants

To test the hypothesis that significant positive end-expiratory pressure (PEEP) level variation exists between neonatal centers.

http://ift.tt/2BRtd8V

Systolic Blood Pressure Elevation in Children with Obstructive Sleep Apnea Is Improved with Positive Airway Pressure Use

To evaluate the effect of continuous positive airway pressure (CPAP) treatment on blood pressure (BP) in children with obstructive sleep apnea (OSA).

http://ift.tt/2BSPovz

Utility of Early-Onset Sepsis Risk Calculator for Neonates Born to Mothers with Chorioamnionitis

To evaluate the performance of the early-onset sepsis (EOS) risk calculator in a cohort of neonates born to mothers with clinical chorioamnionitis, and to compare the diagnostic utility of the EOS calculator, clinical signs, and laboratory evaluations for correctly identifying EOS in this cohort.

http://ift.tt/2CZosJZ

Pyridostigmine for the Reversal of Severe Adverse Reactions to Botulinum Toxin in Children

Therapeutic botulinum toxin injections are commonly performed in pediatric otolaryngology. Aerodigestive complications from botulinum toxin injections, although rare, may be serious. Oral pyridostigmine is effective in the symptomatic treatment of these complications. We report 2 cases of aerodigestive complications arising from injection of botulinum toxin that were successfully treated with pyridostigmine.

http://ift.tt/2CZooKf

Osmotic Demyelination Unrelated to Hyponatremia

Osmotic demyelination unrelated to hyponatremia is rarely reported. We present a case of osmotic demyelination in a patient with hypernatremia in the absence of preceding hyponatremia and review previously reported cases of osmotic demyelination in nonhyponatremic patients. We conclude that a rapid increase in serum sodium concentration and plasma tonicity even in the absence of preceding hyponatremia may surpass the brain's capacity for adaptation to hypertonicity and lead to osmotic demyelination in predisposed individuals.

http://ift.tt/2Bnhv4Q

Health Insurance and the Use of Peritoneal Dialysis in the United States

Many patients in the United States have limited or no health insurance at the time they develop end-stage renal disease (ESRD). We examined whether health insurance limitations affected the likelihood of peritoneal dialysis (PD) use.

http://ift.tt/2C1J3jS

High-Output Cardiac Failure and Coronary Steal With an Arteriovenous Fistula

Creation of an arteriovenous access for hemodialysis can provoke a sequence of events that significantly affects cardiovascular hemodynamics. We present a 78-year-old man with end-stage renal disease and concomitant coronary artery disease previously requiring coronary artery bypass grafting including a left internal mammary graft to the left anterior descending artery, ischemic cardiomyopathy with left ventricular systolic dysfunction, and severe aortic stenosis who developed hypotension unresponsive to medical therapy after recent angioplasty of his ipsilateral arteriovenous fistula for high-grade outflow stenosis.

http://ift.tt/2BnM7TQ

HLA-DQA1 and APOL1 as Risk Loci for Childhood-Onset Steroid-Sensitive and Steroid-Resistant Nephrotic Syndrome

Few data exist for the genetic variants underlying the risk for steroid-sensitive nephrotic syndrome (SSNS) in children. The objectives of this study were to evaluate HLA-DQA1 and APOL1 variants as risk factors for SSNS in African American children and use classic HLA antigen types and amino acid inference to refine the HLA-DQA1 association.

http://ift.tt/2C1nqjB

Mortality and Allograft Loss Trends Among US Pediatric Kidney Transplant Recipients With and Without Focal Segmental Glomerulosclerosis

Pediatric patients with focal segmental glomerulosclerosis (FSGS) have high rates of disease recurrence and allograft failure after kidney transplantation, but there are few data for long-term survival posttransplantation.

http://ift.tt/2BnLVnA

Risk Predictors and Causes of Technique Failure Within the First Year of Peritoneal Dialysis: An Australia and New Zealand Dialysis and Transplant Registry (ANZDATA) Study

Concern regarding technique failure is a major barrier to increased uptake of peritoneal dialysis (PD), and the first year of therapy is a particularly vulnerable time.

http://ift.tt/2C1jAH8

Characterization of adherence and persistence profile in a real-life population of patients treated with adalimumab

Abstract

Background

Published data on long term adherence and persistence with Adalimumab (Humira®) in clinical practice are scarce and often limited to selected patient populations. This study assessed adherence with adalimumab across different indications and identified correlates and outcomes of poor adherence.

Methods

We analyzed data originating from the electronic database of Maccabi Healthcare Services (MHS) that includes 2.1 million enrollees. We randomly selected patients with at least one dispense of adalimumab since it was included in the local health basket in Israel in 2008 until the end of 2013. Patients with the following indications (n=1339) were included: Crohn's disease (CD), ulcerative colitis (UC), rheumatoid arthritis (RA), psoriatic arthritis i(PSA), ankylosing spondylitis (AS) and psoriasis.

Adherence with therapy was assessed by the medication possession ratio (MPR) during follow-up period.

Results

Good adherence (MPR≥80%) was observed among 80% of study patients and was associated with lower risk for ≥1 hospitalization per year of follow-up (adjusted-OR=1.94, 95% CI:1.15-3.28). Patients with AS and CD persisted on adalimumab therapy the most, reaching median use of 27.0 and 26.7 months, respecti vely. Half (52.4%) of the patients discontinued treatment during a mean (SD) follow-up of 3.07 (1.71) years. High socioeconomic status was associated with lower risk for discontinuation (adjusted-HR=0.74; 0.60-0.91). UC and concomitant prednisolone use were associated with increased risk for treatment discontinuation (HR=1.31; 1.00-1.72, and HR=1.40; 1.17-1.68, respectively).

Conclusion

Our results indicate encouraging persistence and adherence with adalimumab of patients with inflammatory conditions.

http://ift.tt/2kZXJoY

Bone marrow edema associated with everolimus [Case Report]

Purpose

The case of a patient who experienced bone marrow edema and pain in both feet and a compression fracture of one heel bone after several months of everolimus use is reported.

Summary

A 62-year-old woman with a grade 1 metastatic pancreatic neuroendocrine tumor (pNET) developed bilateral lower extremity edema and pain approximately 4 months after initiation of treatment with everolimus, an inhibitor of mammalian (or mechanistic) target of rapamycin (mTOR). The patient was referred for orthopedic evaluation, which resulted in diagnosis of bone marrow edema and a compression fracture of the calcaneus on the basis of magnetic resonance imaging results. The case was discussed with a clinical pharmacist, and after an in-depth analysis to rule out potential alternative causes for the patient's edema and pain, everolimus was discontinued. The patient had a full recovery from the presenting symptoms within 10 days of discontinuation of everolimus. Analysis of this case using the adverse drug reaction probability scale of Naranjo et al. yielded a score of 6, indicating a probable adverse reaction to everolimus. A hypothesized mechanism for everolimus-induced bone pain includes marrow edema and hyperemia from reduced intraosseous perfusion, which have been previously reported in association with mTOR inhibitor use.

Conclusion

Bone marrow edema developed and a fracture occurred in a patient taking everolimus for a metastatic pNET, with complete resolution of lower extremity swelling and pain within 2 weeks of everolimus discontinuation.

http://ift.tt/2DxNxwG

New drugs and dosage forms [News]

http://ift.tt/2pgXZ8F

Implementation of a prioritized scoring tool to improve time to pharmacist intervention [Case Study]

Purpose

The implementation of a prioritized scoring tool to improve time to pharmacist intervention is described.

Summary

At the Ohio State University Wexner Medical Center, pharmacists are accepted providers of therapeutic drug monitoring of vancomycin and aminoglycosides. At the onset of this initiative and despite the implementation of an integrated electronic medical record (EMR), management of pharmacokinetically monitored medications was conducted using a paper monitoring form. The potential for transcription errors during this process provided an opportunity for improvement. For these reasons, the department of pharmacy focused its initial efforts for a patient scoring system on the pharmacokinetics scoring module. Adjustment of associated medications based on pharmacokinetic values was a core function of pharmacists of the institution and was expected to be conducted without fail. Vancomycin was used as the index surrogate pharmacokinetically monitored medication within the module for testing and validation because of the clear expectations and standardized resources available to pharmacists to complete the task. The pharmacokinetics scoring module was designed specifically for the function of dosing management, searching throughout the EMR and concisely displaying the information a pharmacist needs to make a clinical decision. Importantly, integration of the scoring module reduced the time to intervention from hours to minutes. The median time to intervention was reduced to within a clinical working shift (8 hours) with the scoring module versus 24 hours or longer with the paper monitoring system.

Conclusion

The implementation of an internally developed pharmacokinetics scoring module built into the EMR substantially reduced the time to clinical intervention for pharmacokinetic monitoring of vancomycin drug levels.

http://ift.tt/2DzqMYS

User fee act, pending legislation focus on drug costs [News]

http://ift.tt/2peEHAO

Physical compatibility of fosfomycin for injection with select i.v. drugs during simulated Y-site administration [Practice Research Report]

Purpose

The results of a study to determine the physical compatibility of ZTI-01 (fosfomycin for injection) in 0.9% sodium chloride or 5% dextrose during simulated Y-site administration with 37 i.v. antimicrobials and 58 nonantimicrobials are reported.

Methods

Fosfomycin, an epoxide antibiotic with broad-spectrum activity against multidrug-resistant bacteria, is marketed in the United States only in an oral formulation with limited bioavailability, but an i.v. formulation is in development. Fosfomycin for injection and other evaluated drugs were reconstituted according to manufacturer recommendations and further diluted with 0.9% sodium chloride or 5% dextrose to the final desired concentrations. Y-site administration was simulated in glass culture tubes. Incompatibility was defined as changes in visual characteristics or a change in turbidity of >0.5 nephelometric turbidity units over the 120-minute observation period.

Results

Of the 95 drugs tested, 16 were incompatible with fosfomycin in 0.9% sodium chloride, and 18 were incompatible with fosfomycin in 5% dextrose; incompatibility was observed with 10 of 37 antimicrobials, including the 3 commercially available amphotericin B products, anidulafungin, caspofungin, ceftaroline, ciprofloxacin, daptomycin, doxycycline, and isavuconazonium sulfate.

Conclusion

Fosfomycin for injection at a concentration of 30 mg/mL was physically compatible with 73 of 95 (77%) of the i.v. drugs tested at concentrations used clinically in both 0.9% sodium chloride injection and 5% dextrose injection. Twenty-two drugs were deemed incompatible in at least 1 of the 2 diluents.

http://ift.tt/2DzqC3I

Pharmacists, technicians will soon need LGBTQ education to practice in D.C. [News]

http://ift.tt/2peBMbn

Regulators seek input on reasons for high drug costs [News]

http://ift.tt/2Dzqyku

News brief [News]

http://ift.tt/2pbvKIc

Stability of extemporaneously prepared preservative-free prochlorperazine nasal spray [Practice Research Report]

Purpose

The stability of an extemporaneously prepared preservative-free prochlorperazine 5-mg/mL nasal spray was evaluated.

Methods

The preservative-free prochlorperazine nasal spray was prepared by adding 250 mg of prochlorperazine edisylate to 50 mL of citrate buffer in a low-density polyethylene nasal spray bottle. A stability-indicating high-performance liquid chromatography (HPLC) method was developed and validated using the major degradant prochlorperazine sulfoxide and by performing forced-degradation studies. For chemical stability studies, 3 100-μL samples of the preservative-free prochlorperazine from 5 nasal spray bottles stored at room temperature were collected at days 0, 20, 30, 45, and 60 and were assayed in triplicate using the stability-indicating HPLC method. Microbiological testing involved antimicrobial effectiveness testing based on United States Pharmacopeia (USP) chapter 51 and quantitative microbiological enumeration of aerobic bacteria, yeasts, and mold based on USP chapter 61. Samples for microbiological testing were collected at days 0, 30, and 60.

Results

The stability-indicating HPLC method clearly identified the degradation product prochlorperazine sulfoxide without interference from prochlorperazine. All tested solutions retained over 90% of the initial prochlorperazine concentration for the 60-day study period. There were no detectable changes in color, pH, and viscosity in any sample. There was no growth of bacteria, yeast, and mold for 60 days in all samples tested.

Conclusion

An extemporaneously prepared preservative-free nasal spray solution of prochlorperazine edisylate 5 mg/mL was physically, chemically, and microbiologically stable for 60 days when stored at room temperature in low-density polyethylene bottles.

http://ift.tt/2Dy8N56

Benzodiazepine use and cognitive decline in the elderly [Clinical Review]

Purpose

Published evidence on the relationship between benzodiazepine exposure and altered cognition in the geriatric population is reviewed.

Summary

Benzodiazepines constitute one of the most commonly prescribed medication classes and are used primarily for management of anxiety and insomnia. Despite strong recommendations based on high-quality evidence warning of the potential cognitive adverse effects of benzodiazepine use, particularly in patients 65 years of age or older, published literature suggests that a substantial proportion of the U.S. geriatric population use these medications in a chronic fashion. The body of evidence suggesting that benzodiazepine use may be a modifiable risk factor for dementia continues to grow. Evidence exists to suggest that benzodiazepine use in the elderly population is associated with cognitive decline, dementia, and Alzheimer's disease, although evidence regarding the correlation between benzodiazepine use and dementia is conflicting; the more recent studies in this area have focused on eliminating causation bias. Pharmacists in a variety of settings can educate patients and assist providers in selecting an appropriate medication regimen for anxiety or insomnia that is tailored to each elderly patient's needs and takes into account the immediate and long-term safety of the patient.

Conclusion

Investigations of the association between benzodiazepine therapy and cognitive decline in elderly patients have yielded mixed findings. Stronger links have emerged from studies examining longer- rather than shorter-acting benzodiazepines, longer rather than shorter durations of use, or earlier rather than later exposure. Questions remain about causality and the impact of confounders on study interpretation.

http://ift.tt/2peEGge

Interprofessional care collaboration for patients with heart failure [Note]

Purpose

An innovative collaborative care model to improve transitions of care (TOC) for patients with heart failure (HF) is described.

Summary

As part of a broad effort by New Hanover Regional Medical Center (NHRMC) to reduce avoidable 30-day hospital readmissions and decrease associated healthcare costs through a team-centered, value-based approach to patient care, an interprofessional team was formed to help reduce hospital readmissions among discharged patients with HF. The team consists of 5 TOC pharmacists, 4 community paramedics, and 4 advanced care practitioners (ACPs) who collaborate to coordinate care and prevent 30-day readmissions among patients with HF transitioning from the hospital to the community setting. Each team member plays an integral role in providing high-quality postdischarge care. The TOC pharmacist ensures that patients have access to all needed medications, provides in-home medication reconciliation services, makes medication recommendations, and alerts the team of potential medication-related issues. Community paramedics conduct home visits consisting of physical and mental health assessments, diet and disease state education, reviews of medication bottles and education on proper medication use, and administration of i.v. diuretics to correct volume status under provider orders. The ACPs offer close clinic follow-up (typically initiated within 7 days of discharge) as well as long-term HF management and education.

Conclusion

At NHRMC, collaboration among healthcare professionals, including a TOC pharmacist, community paramedics, and ACPs, has assisted in the growth and expansion of services provided to patients with HF.

http://ift.tt/2DyCsLC

Topiramate in the treatment of cocaine use disorder [Clinical Consultation]

Purpose

The literature on topiramate use in cocaine-dependent patients was reviewed.

Summary

Six randomized, double-blind, controlled clinical trials evaluating the use of topiramate in patients who were cocaine dependent were analyzed. The results from the studies indicated that topiramate, when used in combination with cognitive behavioral therapy, may be effective in reducing short-term cocaine use and should be considered as a possible treatment option. Other trials suggested that topiramate was not effective in patients with a dual diagnosis of opioid and cocaine dependence. Two trials suggested that short-term abstinence assisted by pharmacotherapy is a predictor of longer-term (6 months and 1 year, respectively) abstinence. Cocaine use is dependent on multiple factors; therefore, a reduction in use or craving is not definitively associated with abstinence. However, decreased use reduces potential patient harm and the amount of money spent on illicit cocaine. The findings of this literature review should be used to encourage the completion of more trials that are appropriately designed. Topiramate was shown to be effective for increasing cocaine abstinence, the proportion of cocaine nonuse days, and the proportion of patients to attain 3 consecutive weeks of cocaine abstinence and decreasing the abuse liability of cocaine. Conflicting results in clinical trials do not provide a definitive answer regarding topiramate's efficacy in managing cocaine dependence.

Conclusion

Available research neither validates nor invalidates the hypothesis that topiramate is efficacious in attaining abstinence in cocaine-dependent patients.

http://ift.tt/2pdzRDW

Pharmacy in Israel [Pharmacy Abroad]

http://ift.tt/2Dy8Ldu

Microprobe Capillary Electrophoresis Mass Spectrometry for Single-cell Metabolomics in Live Frog (Xenopus laevis) Embryos

We describe steps that enable fast in situ sampling of a small portion of an individual cell with high precision and minimal invasion using capillary-based micro-sampling, to facilitate chemical characterization of a snapshot of metabolic activity in live embryos using a custom-built single cell capillary electrophoresis and mass spectrometry platform.

http://ift.tt/2pfq3cu

Generation and Culturing of Primary Human Keratinocytes from Adult Skin

The human skin acts as a first line of defense against the external environment. We present a method for isolating primary human keratinocytes from adult skin. These isolated keratinocytes are useful in numerous experimental setups, and are a highly suitable model for studying molecular mechanisms in cutaneous biology in vitro.

http://ift.tt/2zgDkkC

Design Principles for Building a Leadership Development Program in a Department of Surgery

No abstract available

http://ift.tt/2p7fMz7

Magnetic Surgery: Results From First Prospective Clinical Trial in 50 Patients

Objective: To evaluate a new magnetic surgical system during reduced-port laparoscopic cholecystectomy in a prospective, multicenter clinical trial. Background: Laparoscopic instrumentation coupled by magnetic fields may enhance surgeon performance by allowing for shaft-less retraction and mobilization. The movements can be performed under direct visualization, generating different angles of traction and reducing the number of trocars to perform the procedure. This may reduce well-known associated complications of trocars, including incisional pain, scarring, infection, bowel, and vascular injuries, among others. Methods: A prospective, multicenter, single-arm, open-label study was performed to assess the safety and performance of a magnetic surgical system (Levita Magnetics' Surgical System). The investigational device was used during a 3-port laparoscopic technique. The primary endpoints evaluated were safety and feasibility of the device to adequately mobilize the gallbladder to achieve effective exposure of the targeted surgical site. Patients were followed for 30 days postprocedure. Results: Between January 2014 and March 2015, 50 patients presenting with benign gallbladder disease were recruited. Forty-five women and 5 men with an average age of 39 years (18–59), average body mass index of 27 kg/m2 (20.4–34.1) and an average abdominal wall thickness of 2.6 cm (1.8–4.6). The procedures were successfully performed in all 50 patients. No device-related serious adverse events were reported. Surgeons rated as "excellent" (90%) or "sufficient" (10%) the exposure of the surgical site. Conclusions: This clinical trial shows that this new magnetic surgical system is safe and effective in reduced-port laparoscopic cholecystectomy.

http://ift.tt/2p9IK19

In the Next Issue

No abstract available

http://ift.tt/2kUSQO4

Minimally Invasive Thoracic Surgery 3.0: Lessons Learned From the History of Lung Cancer Surgery

No abstract available

http://ift.tt/2p8NDY7

Anti-stress and neuronal cell differentiation induction effects of Rosmarinus officinalis L. essential oil

Mood disorder accounts for 13 % of global disease burden. And while therapeutic agents are available, usually orally administered, most have unwanted side effects, and thus making the inhalation of essential o...

http://ift.tt/2DvOWn8

Stenosis of the Inferior Vena Cava: A Murine Model of Deep Vein Thrombosis

We describe here stenosis in the inferior vena cava as a murine model of deep vein thrombosis. This model recapitulates blood flow restriction, one of the major triggers of venous thrombosis in humans.

http://ift.tt/2BSi3kl

Comprehensive Workflow for the Genome-wide Identification and Expression Meta-analysis of the ATL E3 Ubiquitin Ligase Gene Family in Grapevine

This article describes the procedure for the identification and characterization of a gene family in grapevine applied to the family of Arabidopsis Tóxicos in Levadura (ATL) E3 ubiquitin ligases.

http://ift.tt/2CWZXge

Impact of HPV vaccination with Gardasil® in Switzerland

Gardasil®, a quadrivalent vaccine targeting low-risk (6, 11) and high-risk (16, 18) human papillomaviruses (HPV), has been offered to 11–14 year-old schoolgirls in Switzerland since 2008. To evaluate its succe...

http://ift.tt/2BPN8VH

Genetic diversity of Leishmania donovani that causes cutaneous leishmaniasis in Sri Lanka: a cross sectional study with regional comparisons

Leishmania donovani is the etiological agent of visceral leishmaniasis (VL) in the Indian subcontinent. However, it is also known to cause cutaneous leishmaniasis (CL) in Sri Lanka. Sr...

http://ift.tt/2CYJvfH

Primary care challenges of an obscure case of “Alice in Wonderland” syndrome in a patient with severe malaria in a resource-constrained setting: a case report

"Alice in Wonderland" syndrome (AIWS) is a rare neurological abnormality characterized by distortions of visual perceptions, body schema and experience of time. AIWS has been reported ...

http://ift.tt/2BPMXcZ

Examining the online approaches used by hospitals in Sydney, Australia to inform patients about healthcare associated infections and infection prevention strategies

Provision of information plays a critical role in supporting patients to be engaged or empowered to be involved with infection prevention measures in hospitals. This explorative study evaluated the suitability...

http://ift.tt/2CZK4WC

Long-term proton pump inhibitor use is a risk factor of gastric cancer after treatment for Helicobacter pylori: a retrospective cohort analysis

We read with interest the recent publication by Cheung et al. The authors conclude that proton pump inhibitor (PPI) use is associated with a 2.4-fold increase in the risk of gastric cancer in patients who received Helicobacter pylori eradication therapy.1 This is an important finding given that the safety of long-term PPI use remains unclear. Notably, no significant association between histamine-2 receptor antagonist (H2RA) use and gastric cancer was observed, which suggests a PPI-specific effect in this context.

Cheung et al used a large population-based database to select patients after eradication and performed propensity score adjustment analysis. However, as the authors described in the Discussion section, we have concerns about the limitations of this study, in particular the lack of endoscopic and histological examinations, the results of which could influence the association between PPI use and gastric cancer. The presence of gastric atrophy and intestinal metaplasia (IM) in H. pylori-infected...

http://ift.tt/2BQTlRu

A Compartment-Quasi3D multiscale approach for drug absorption, transport, and retention in the human lungs.

Abstract

The majority of current models used for modeling the pulmonary drug absorption, transport, and retention are 0D compartmental models where the airways are generally split into the airways and alveolar sections. Such block models deliver low fidelity solutions and the spatial lung drug concentrations cannot be obtained. Other approaches utilize high fidelity CFD models with limited capabilities due to their exorbitant computational cost. Recently, we presented a novel, fast-running and robust Quasi-3D (Q3D) model for modeling the pulmonary airflow. This Q3D method preserved the 3D lung geometry, delivered extremely accurate solutions and was 25,000 times faster in comparison to the CFD methods. In this paper, we present a Q3D-compartment multiscale combination to model the pulmonary drug absorption, transport, and retention. The initial deposition is obtained from CFD simulations. The lung absorption compartment model of Yu and Rosania is adapted to this multiscale format. The lung is modeled in the Q3D format till 8^th airway generation. The remainder of the lung along with the systemic circulation and elimination processes were modeled using compartments. The Q3D model is further adapted, by allowing for various heterogeneous annular lung layers. This allows us to model the drug transport across the layers and along the lung. Using this multiscale model, the spatio-temporal drug concentrations in the different lung layers and the temporal concentration in the plasma are obtained. The concentration profile in the plasma was found to be better aligned with the experimental findings in comparison with compartmental model for the standard test cases. Thus, this multiscale model can be used to optimize the target-specific drug delivery, increase the localized bio-availability, thereby facilitating applications from the bench to bedside for various patient/lung-disease variations.

http://ift.tt/2CVZRFN

Adaptive immune response to Clostridium difficile infection: A perspective for prevention and therapy

Abstract

Clostridium difficile infection (CDI) is one of the most important nosocomial illnesses and a major cause of morbidity and mortality. While initial treatment of CDI is usually successful, unprovoked relapses remain an important and frustrating problem. This review examines the literature describing the natural immune response to CDI, and to what extent it can explain the propensity for relapses. In particular, we discuss studies on antibody and, to a lesser extent, B cell and T cell responses in CDI. Despite years of study, there remains incomplete understanding of the natural antibody response to the major pathogenic toxins, TcdA and TcdB, and other bacterial antigens, in CDI. Recent literature suggests that a specific subset of neutralizing antibodies that target the putative carbohydrate-binding domains of TcdB and possibly TcdA have the greatest protective ability. This is further supported by recent successful clinical trials of a humanized monoclonal antibody to the major toxin TcdB. A better understanding of how and why the most protective adaptive immune response develops may lead to improved vaccine and therapeutic targets for recurrent CDI.

This article is protected by copyright. All rights reserved

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Modification of pomegranate waste with iron ions a green composite for removal of Pb from aqueous solution: equilibrium, thermodynamic and kinetic studies

Pomegranate waste modified with Fe2+ and Fe3+ ions followed with carbonization were used as an adsorbent to remove the Pb2+ ions from aqueous solution. To optimum the highest adsorption efficiency, adsorption exp...

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Microbial diversity of saline environments: searching for cytotoxic activities

In order to select halophilic microorganisms as a source of compounds with cytotoxic activities, a total of 135 bacterial strains were isolated from water and sediment samples collected from the Zipaquirá salt...

http://ift.tt/2DvIUTv