A Case of Nongerminomatous Germ Cell Tumor of the Pineal Region: Risks and Advantages of Biopsy by Endoscopic Approach

A 21-year-old male was admitted to our department with headache and drowsiness. CT scan and MRI revealed acute obstructive hydrocephalus caused by a pineal region mass. The serum and CSF levels of beta-human chorionic gonadotropin (beta-hCG) were 215 IU/L and 447 IU/L, respectively, while levels of alpha-fetoprotein (AFP) were normal. A germ cell tumor (GCT) was suspected, and the patient underwent endoscopic third ventriculostomy (ETV) with biopsy. After four days from surgery, the tumor bled with mass expansion and ETV stoma occlusion; thus, a ventriculoperitoneal shunt was positioned. After ten months, the tumor metastasized to the thorax and abdomen with progression of intracerebral tumor mass. Despite the aggressive nature of this tumor, ETV remains a valid approach for a pineal region mass, but in case of GCT, the risk of bleeding should be taken into account, during and after the surgical procedure.

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Higher Growth Rate of Branch Duct Intraductal Papillary Mucinous Neoplasms Associates With Worrisome Features

For patients with branch duct intraductal papillary mucinous neoplasms (BD-IPMNs, cysts), it is a challenge to identify those at high risk for malignant lesions. We sought to identify factors associated with development of pancreatic cancer, focusing on neoplasm growth rate.

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Endoscopic Ultrasound-guided Specimen Collection and Evaluation Techniques Affect Diagnostic Accuracy

Outcomes of endoscopic ultrasound-guided fine needle aspiration (EUS-FNA) evaluation vary with technique, needles, and methods of specimen evaluation. We performed a direct comparison of diagnostic yields of EUS-FNA samples collected using different gauge needles (22- vs 25-gauge), with or without suction.

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No Difference in Effectiveness of 8 vs 12 Weeks of Ledipasvir and Sofosbuvir for Treatment of Hepatitis C in Black Patients

Treatment with the combination of ledipasvir and sofosbuvir for 12 weeks has been approved by the Food and Drug Administration for patients with genotype 1 hepatitis C virus (HCV) infection; some patients can be treated with an 8-week course. Guidelines recommend a 12-week treatment course for black patients, but studies have not compared the effectiveness of 8 vs 12 weeks in black patients who are otherwise eligible for an 8-week treatment regimen.

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Associations of Microscopic Colitis with other Lymphocytic Disorders of the Gastrointestinal Tract

Lymphocytic disorders of the upper and lower gastrointestinal tract seem to cluster in patients. We aimed to assess the frequency of comorbid occurrence of lymphocytic disorders in patients with microscopic colitis (MC).

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Socioeconomic, Cultural, and Ethnoracial Disparities in Inflammatory Bowel Disease

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A case of enteritis induced by nivolumab

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Relapsing Malaria: A Case Report of Primaquine Resistance

Primaquine (an 8-aminoquinoline malarial therapy) is the only FDA-approved therapy to treat the hypnozoite stage of P. vivax. We think of relapse occurring because of parasitic resistance or poor compliance secondary to drug toxicities. However, in patients with repeated treatment failure, we must consider CYP-450 mutations affecting drug metabolism as an important cause of relapse. A 47-year-old man who travelled to a jungle in Venezuela was diagnosed with P. falciparum and P. vivax in July 2015. He was treated with seven rounds of primaquine-based therapy in the following year, all resulted in relapse without further exposure to endemic areas. On his eighth presentation, he was found to have CYP-4502D6 mutation that affected the metabolism and activation of primaquine. Thereafter, he was treated without relapse. Primaquine efficacy depends on many factors. Understanding the mechanism responsible for malaria relapse is paramount for successful treatment and reduction in morbidity and mortality. This case illustrates the importance of considering cytochrome mutations that affect drug efficacy in cases of relapsing malaria.

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Prognostication of superficial Barrett's carcinoma: a Japanese multicenter study

Endoscopic resection (ER) has become the standard therapy for superficial Barrett's carcinoma (BC) in Japan and other countries. Patients undergoing ER sometimes require additional treatment because of recurrence of lymph node metastasis (LNM). We attempted to clarify the histopathologic risk factors for LNM, and the difference between these risk factors for Japanese patients and the conventional risk factors documented for Western patients. This multi-center study included 12 leading institutions belonging to the Japan Research Society for Early Esophageal Cancer and Chromoendoscopy, and was based on a questionnaire designed to gather data on the features of superficial BC cases, except for high-grade intraepithelial neoplasia, treated at those institutions.

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RARA and RARG Gene Downregulation Associated with EZH2 Mutation in Acute Promyelocytic-Like Morphology Leukemia

Most Acute Promyelocytic Leukemia (APL) patients express PML-RARA fusion; in rare cases RARA is rearranged with partner genes other than PML. To date, only two patients presenting features similar to APL showing the RARG gene rearrangement have been described. We report an Acute Myeloid Leukemia (AML) patient with morphology resembling APL without involvement of the RARA gene. Molecular and Fluorescent In Situ Hybridization (FISH) analyses excluded PML-RARA fusion and variant rearrangements involving RARA and RARG loci.

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Extreme delta - with or without brushes: a potential surrogate marker of disease activity in anti-NMDA-receptor encephalitis

NMDARE is a treatable antibody-mediated neurological syndrome resulting in neuropsychiatric disturbances and seizures, which may evolve to severe encephalopathy, autonomic disturbance and orofacial dyskinesias (Dalmau et al. 2011). Clinical seizures are seen in 80% of cases (Dalmau et al. 2011) and EEG abnormalities in 90% (Titulaer et al. 2013), of which the potentially specific EEG pattern of "extreme delta brush" may carry worse prognosis (Schmitt et al. 2012) and may be associated with electrographic seizures (Veciana et al.

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Long Term Electroencephalography in Preterm Neonates: Safety and Quality of Electrode Types

Seizures in preterm neonates have been reported with an incidence ranging between 3.9%-48% (Hellstrom-Westas et al., 1985; Scher et al., 1993; Vesoulis et al., 2014; Lloyd et al., 2017). Seizure incidence varies with the EEG modality utilized- amplitude-integrated EEG (aEEG) versus conventional EEG. Early life seizures in sick premature neonates portend both poor short and long term outcomes. Seizures in extremely low birth weight neonates were associated with short term morbidities such as severe intraventricular hemorrhage, sepsis, meningitis and cystic periventricular leukomalacia (Davis et al., 2010).

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Home remedies to get rid of yellow teeth

A look at how to get rid of yellow teeth using home remedies. Included is detail on why teeth go yellow in the first place and reducing discoloration.

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A Flow Cytometry-based Assay to Identify Compounds That Disrupt Binding of Fluorescently-labeled CXC Chemokine Ligand 12 to CXC Chemokine Receptor 4

A flow cytometry-based cellular binding assay is described that is primarily used as a screening tool to identify compounds that inhibit the binding of a fluorescently labeled CXC chemokine ligand 12 (CXCL12) to the CXC chemokine receptor 4 (CXCR4).

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Are spikes non-inferior to high-frequency oscillations?

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Creative tension and different personalities

The WSJ on the creative tension between Keith Richards and Mick Jagger :

"They're two really different guys, and that's what makes it so powerful. It's like a rubber band pulled really tight. When you release it, it goes flying—that creative tension is what makes it so enduring. They understand that something special happens when the two of them get together. The cognizance of that magic that only comes from the two of them can be frustrating, but also really powerful."

I wish Ritchie Blackmore and Ian Gillan of Deep Purple had recognized this years ago. We would have gotten a few other brilliant albums in the 1970s and 1980s.

"No band has lasted as long as the Rolling Stones."

References:

The Wisdom of Keith Richards https://buff.ly/2FtraJ6

Posted at Clinical Cases and Images. Stay updated and subscribe, follow us on Twitter and connect on Facebook.

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Creation and Implementation of an Outpatient Pathway for Atrial Fibrillation in the Emergency Department Setting: Results of an Expert Panel

Abstract

Atrial fibrillation and flutter (AF) is a common condition among emergency department (ED) patients in the United States (US). Traditionally, ED care for primary complaints related to AF focus on rate control, and patients are often admitted to an inpatient setting for further care. Inpatient care may include further telemetry monitoring and diagnostic testing, rhythm control, a search for identification of AF etiology, and stroke prophylaxis. However, many patients are eligible for safe and effective outpatient management pathways. They are widely used in Canada and other countries but less widely adopted in the US. In this project, we convened an expert panel to create a practical framework for the process of creating, implementing and maintaining an outpatient AF pathway for emergency physicians to assess and treat AF patients, safely reduce hospitalization rates, ensure appropriate stroke prophylaxis, and effectively transition patients to longitudinal outpatient treatment settings from the ED and/or observation unit. To support local pathway creation, the panel also reached agreement on a protocol development plan, a sample pathway, consensus recommendations for pathway components, sample pathway metrics and a structured literature review framework using a modified Delphi technique by a technical expert panel of emergency medicine, cardiology, and other stakeholder groups.

This article is protected by copyright. All rights reserved.

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Knights without Armour

Abstract

Training in Emergency medicine for nearly 5 years, I thought the finish line was getting near and becoming a consultant was just down the corner. I was enjoying work, getting better every day and well appreciated by peers. But little did I know that life had other plans. I ended up in an emergency department presenting with status epilepticus preceded by vague ongoing symptoms lasting for 2 months. I was intubated and transferred to Intensive care and did not receive a formal diagnosis which still remains a mystery. Family, friends and my peers proved to be an essential source of recovery in my time of need, whose presence and importance I didn't appreciate previously. My wife and daughter were my biggest motivation to move forward. I was uncertain whether I would be able to return to work as I was before but never at any point did I feel dejected or depressed, because I knew life had something better in store for me.

This article is protected by copyright. All rights reserved.

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Dual infections of two carbapenemase-producing Acinetobacter baumannii clinical strains isolated from the same blood culture sample of a patient in Iran

In this study, the draft genome sequences of two different carbapenem-resistant Acinetobacter baumannii clinical strains isolated from the same blood culture sample of an Iranian patient were determined. The stra...

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Effectiveness of healthcare worker screening in hospital outbreaks with gram-negative pathogens: a systematic review

Identifying the source of an outbreak is the most crucial aspect of any outbreak investigation. In this review, we address the frequently discussed question of whether (rectal) screening of health care workers...

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Multidrug-resistant gram-negative bacterial infections in a teaching hospital in Ghana

Multidrug-resistant Gram-negative bacteria have emerged as major clinical and therapeutic dilemma in hospitals in Ghana.

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The infection risk scan (IRIS): standardization and transparency in infection control and antimicrobial use

Infection control needs user-friendly standardized instruments to measure the compliance to guidelines and to implement targeted improvement actions. This abstract describes a tool to measure the quality of in...

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Introduction: Interactions Between the Immune System and Parasites Special Issue

Parasitism, in general, means a relationship between two organisms in which 'one organism benefits at the expense of the other' (https://www.britannica.com). In the long term, the benefiting organism, called the parasite, may have the ability to manipulate the other organism, called the host. Humans have evolved under the pressure of unicellular protozoan and multicellular metazoan (worm) parasites. A recent World Health Organization report suggests that about 1.5 billion humans are infected with worms and that 250 million humans are infected with protozoan parasites in total causing about 1 million deaths per year (http://www.who.int/features/2017/year-review/en).

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Host immune responses to Toxoplasma gondii

Abstract

Toxoplasma gondii can infect homoeothermic animals including humans and cause lethal toxoplasmosis in immunocompromised individuals. When hosts are infected with T. gondii, the cells induce immune responses against T. gondii. The pathogen infection is recognized by immune sensors that directly detect T. gondii structural components, leading to production of pro-inflammatory cytokines and chemokines. Antigen-presenting cells such as macrophages and dendritic cells strongly activate T cells and induce development of T_h1 cells and antigen-specific killer CD8 T cells. These T cells and Group 1 innate lymphoid cells are main producers of IFN-γ, which robustly stimulates cell-autonomous immunity in cells infected with T. gondii. IFN-γ-inducible effectors such as IFN-inducible GTPases, inducible nitric oxide synthase and indoleamine-2,3-dioxygenase differentially play important roles in suppression of T. gondii growth and its direct killing in anti-T. gondii cell-autonomous immune responses. In this review, we will describe our current knowledge of innate, adaptive and IFN-γ-mediated cell-autonomous immunity against T. gondii infection.

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Host responses to intestinal nematodes

Abstract

Helminth infection remains common in developing countries, where residents who suffer from the consequences of such infections can develop serious physical and mental disorders and often persist in the face of serious economic problems. Intestinal nematode infection induces the development of T_h2-type immune responses including the B-cell IgE response; additionally, this infection induces an increase in the numbers and activation of various types of effector cells, such as mast cells, eosinophils and basophils, as well as the induction of goblet cell hyperplasia, anti-microbial peptide production and smooth-muscle contraction, all of which contribute to expel nematodes. Innate immunity is important in efforts to eliminate helminth infection; cytokines, including IL-25, IL-33 and thymic stromal lymphopoietin, which are products of epithelial cells and mast cells, induce T_h2 cells and group 2 innate lymphoid cells to proliferate and produce T_h2 cytokines. Nematodes also facilitate chronic infection by suppression of immune reactions through an increased number of T_reg cells. Immunosuppression by parasite infection may ultimately be beneficial for the host animals; indeed, a negative correlation has been found between parasite infection and the prevalence of inflammatory disease in humans.

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Unforeseen pathologies caused by malaria

Abstract

Individuals from malaria-endemic regions often acquire partial immunity after multiple repeated infections throughout their lives. This partial immunity prevents them from developing severe complications and they often remain asymptomatic with a persistent, low parasite density in the blood, and therefore the necessity for treatment is neglected. These patients with chronic, asymptomatic malaria serve as a reservoir for Plasmodium parasite transmission, becoming a major obstacle for eradication efforts. The constant exposure to malaria infection may have benefits in the short term by conferring protection from acute, severe malaria; however, it may cause substantially more harm in the long term. Rather than the parasite burden itself, the complications induced by the dysregulated immune responses and the tissue damage done by the parasites and their products can cause chronic and irreversible suffering. Furthermore, the complete clearance of parasites in the body may not lead to complete recovery from the disease as complications can still persist. The fact that there are chronic pathologies caused by malaria that mostly remain obscure and have the potential to cause a serious burden has recently been gaining attention. Here, we present and discuss the evidence of unforeseen pathologies and the risks associated with malaria.

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How to master the host immune system? Leishmania parasites have the solutions!

Abstract

Infection by protozoan parasites of the genus Leishmania results in the development of leishmaniasis, an increasingly prevalent group of diseases affecting over 12 million people worldwide. Leishmaniasis can have very different outcomes ranging from cutaneous lesions, mucosal lesions to visceralization depending on the species of the infecting parasite and on the immune response developed by the host. As an obligate intracellular parasite, residing within macrophages, Leishmania evolved in strict contact with the host immune system, developing different mechanisms to evade or modulate the immune response. Various types of immune responses are observed during different Leishmania spp. infections, resulting in parasite clearance but also contributing to the pathogenesis, thus increasing the complexity of the course of the disease. Interestingly, depending on the type of leishmaniasis developed, opposite treatment strategies, which either boost or inhibit the inflammatory response, have shown efficacy. In this review, we summarize the contribution of different immune cell types to the development of the anti-leishmanial immune response and the parasite strategies to evade and modulate host immunity. Further, we discuss the involvement of co-infecting pathogens in the determination of the outcome of leishmaniasis and on the effectiveness of treatment and the implication of the immune response for treatment and vaccine development.

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What is periodontal surgery?

Learn all about gum surgery, including the conditions it is used for and the different types that are available. We also look at preparation and recovery times.

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Spinal meningioma, aortic aneurysms and the missing link of observation: the anchoring heuristic approach

Over the last three decades, the development of systematic and protocol-based algorithms, and advances in available diagnostic tests have become the indispensable parts of practising medicine. Naturally, despite the implementation of meticulous protocols involving diagnostic tests or even trials of empirical therapies, the cause of one's symptoms may still not be obvious. We herein report a case of chronic back pain, which took about 5 years to get accurately diagnosed. The case challenges the diagnostic assumptions and sets ground of discussion for the diagnostic reasoning pitfalls and heuristic biases that mislead the caring physicians and cost years of low quality of life to our patient. This case serves as an example of how anchoring heuristics can interfere in the diagnostic process of a complex and rare entity when combined with a concurrent potentially life-threatening condition.

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Development of a Core Outcome Set for Clinical Effectiveness Trials in Esophageal Cancer Resection Surgery

Objective: Development of a core outcome set (COS) for clinical effectiveness trials in esophageal cancer resection surgery. Background: Inconsistency and heterogeneity in outcome reporting after esophageal cancer resection surgery hampers comparison of trial results and undermines evidence synthesis. COSs provide an evidence-based approach to these challenges. Methods: A long list of clinical and patient-reported outcomes was identified and categorized into outcome domains. Domains were operationalized into a questionnaire and patients and health professionals rated the importance of items from 1 (not important) to 9 (extremely important) in 2 Delphi survey rounds. Retained items were discussed at a consensus meeting and a final COS proposed. Professionals were surveyed to request endorsement of the COS. Results: A total of 68 outcome domains were identified and operationalized into a questionnaire; 116 (91%) of consenting patients and 72 (77%) of health professionals completed round 1. Round 2 response rates remained high (87% patients, 93% professionals). Rounds 1 and 2 prioritized 43 and 19 items, respectively. Retained items were discussed at a patient consensus meeting and a final 10-item COS proposed, endorsed by 61/67 (91%) professionals and including: overall survival; in-hospital mortality; inoperability; need for another operation; respiratory complications; conduit necrosis and anastomotic leak; severe nutritional problems; ability to eat/drink; problems with acid indigestion or heartburn; and overall quality of life. Conclusions: The COS is recommended for all pragmatic clinical effectiveness trials in esophageal cancer resection surgery. Further work is needed to delineate the definitions and parameters and explore best methods for measuring the individual outcomes.

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Radiomics and Deep Learning in Clinical Imaging: What Should We Do?

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A case of acute necrotizing pancreatitis complicated with non ST elevation myocardial infarction

Acute pancreatitis is an inflammatory condition with varying severity and a range of local and systemic complications. Here we report a patient with acute necrotizing pancreatitis complicated with a true non S...

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A young female presenting with heart failure secondary to eosinophilic myocarditis: a case report and review of the literature

Eosinophilic myocarditis is one of the fatal complications of idiopathic hypereosinophilic syndromes. Given the rarity of this form of myocarditis, it is often under-recognized. We describe a young girl who pr...

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A digital assessment system for evaluating kinetic tremor in essential tremor and Parkinson’s disease

Spiral drawing on papers is a common tremor evaluation tool for diagnosing patients with essential tremor (ET) or Parkinson's disease (PD). No standard drawing methods and parameters that use graphic tablets a...

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Prognostic models for complete recovery in ischemic stroke: a systematic review and meta-analysis

Prognostic models have been increasingly developed to predict complete recovery in ischemic stroke. However, questions arise about the performance characteristics of these models. The aim of this study was to ...

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Pediatric multiple sclerosis: a review

Pediatric-onset multiple sclerosis (POMS) prevalence and incidence rates are increasing globally. No disease-modifying therapy are approved for MS pediatric population. Hence, we aim to review the literature o...

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Integrin αVβ3 can substitute for collagen-binding β1-integrins in vivo to maintain a homeostatic interstitial fluid pressure

New Findings

• What is the central question of this study?

  Collagen-binding β₁-integrins function physiologically in cellular control of dermal interstitial fluid pressure (P_IF) in vivo and thereby participate in control of extravascular fluid volume. During anaphylaxis, simulated by injection of Compound 48/80 integrin α_Vβ₃ takes over this physiological function. Here we addressed the question whether integrin α_Vβ₃ can replace collagen-binding β₁-integrin to maintain a long-term homeostatic P_IF.

• What is the main finding and its importance?

  Mice lacking the collagen-binding integrin α₁₁β₁ show a complex dermal phenotype with regard to the interstitial physiology apparent in the control of P_IF. Notably dermal P_IF is not lowered with Compound 48/80 in these animals. Our present data infer the integrin α_Vβ₃ to be the likely candidate that has taken over the role of collagen-binding β₁-integrins for maintaining a steady-state homeostatic P_IF. A better understanding of molecular processes involved in control of P_IF is instrumental for establishing novel treatment regimens for control of edema formation in anaphylaxis and septic shock.

Abstract

Accumulated data indicate that cell-mediated contraction of reconstituted collagenous gels in vitro can serve as a model for cell-mediated control of interstitial fluid pressure (P_IF) in vivo. A central role for collagen-binding β₁-integrins in both processes has been established. Furthermore, integrin α_Vβ₃ takes over the role of collagen-binding β₁-integrins in mediating contraction after perturbations of collagen-binding β₁-integrins in vitro. Integrin α_Vβ₃ is also instrumental for normalization of dermal P_IF that has been lowered due to mast cell degranulation with Compound 48/80 (C48/80) in vivo. Here we demonstrate a role of integrin α_Vβ₃ in maintaining a long term homeostatic dermal P_IF in mice lacking the collagen-binding integrin  α₁₁β₁ (α11^−/- mice). Measurements of P_IF were performed after circulatory arrest. Furthermore, cell-mediated integrin α_Vβ₃-directed contraction of collagenous gels in vitro depends on free access of a collagen-site known to bind several ECM proteins that form substrates for α_Vβ₃-directed cell attachment, such as fibronectin and fibrin. A streptococcal collagen-binding protein, CNE, specifically binds to and block this site on the collagen triple helix. Here we show that whereas CNE perturbed α_Vβ₃-directed and PDGF-BB induced normalization of dermal P_IF after C48/80 it did not affect α_Vβ₃-dependent maintenance of a homeostatic dermal P_IF. These data imply that dynamic modifications of the ECM structure is needed during acute patho-physiologic modulations of P_IF but not for long-term maintenance of a homeostatic P_IF. Our data thus show that collagen-binding β₁-integrins, integrin α_Vβ₃ and ECM-structure are potential targets for novel therapy aimed to modulate edema formation and hypovolemic shock during anaphylaxis.

This article is protected by copyright. All rights reserved

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Anaphylactic hypotension causes renal and adrenal sympathoexcitaion and induces c-fos in the hypothalamus and medulla oblongata

New Findings

• What is the central question of this study?

  Whether anaphylaxis affects sympathetic outflows to the brown adipose tissue (BAT) and adrenal grand is not known. Moreover, it is unknown whether anaphylaxis affects some brain areas in association with sympathetic regulation.

• What is the main finding and its importance?

  We showed that sympathoexcitatory responses to anaphylaxis regionally occurred in the kidney and adrenal grand, but not in the thermogenesis-related BAT. Further, anaphylactic hypotension also caused increase in c-fos immunoreactivity in the hypothalamic and medullary areas. Moreover, catecholaminergic neurons of the brain stem causes adrenal sympathoexcitation in a baroreceptor-independent manner.

Abstract

We previously reported that sympathetic nerve activity (SNA) to the kidney and the hind limb increases during anaphylactic hypotension in anesthetized rats. Based on this evidence, we examined effects of anaphylactic hypotension on SNA to the brown adipose tissue (BAT), and the adrenal gland and kidney in anesthetized rats. We demonstrated that adrenal and renal SNA, but not BAT-SNA, were stimulated. In addition, the effects of anaphylaxis on neural activities of the hypothalamic and medullary nuclei, which are candidates for relaying efferent SNA to the peripheral organs, were investigated via immunohistochemical staining of c-fos. Anaphylaxis increased c-fos expression in the neurons of the paraventricular nucleus (PVN) of the hypothalamus and in those of the nucleus tractus solitarius (NTS) and rostral ventrolateral medulla (RVLM) of the medulla oblongata; c-fos was expressed in gamma-aminobutyric acid (GABA)-ergic neurons of the NTS and in the catecholaminergic neurons of the RVLM. In addition, c-fos expression in the rostral NTS and mid NTS during anaphylaxis were reduced by sinoaortic baroreceptor denervation, however increased c-fos expression in the caudal NTS and RVLM or adrenal sympathoexcitation were not affected by sinoaortic baroreceptor denervation. These results indicated that anaphylactic hypotension activates the hypothalamic PVN, and the medullary NTS and RVLM, independently of the baroreflex pathway. Further, it stimulated efferent SNA to the adrenal grand and kidney to restore blood pressure.

This article is protected by copyright. All rights reserved

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Prevalence and correlates of herbal medicine use among type 2 diabetic patients in Teaching Hospital in Ethiopia: a cross-sectional study

Type 2 Diabetes Mellitus (T2DM) patients are increasingly using herbal remedies due to the fact that sticking to the therapeutic regimens is becoming awkward. However, studies towards herbal medicine use by di...

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Crude extract and fractions from Eugenia uniflora Linn leaves showed anti-inflammatory, antioxidant, and antibacterial activities

This study showed phytochemical composition and evaluates the anti-inflammatory, and analgesic activities of crude extract (CE) and fractions from E. uniflora Linn leaves.

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Phenolic compounds as antioxidants and chemopreventive drugs from Streptomyces cellulosae strain TES17 isolated from rhizosphere of Camellia sinensis

Oxidative stress in an intracellular environment created by the accumulation of reactive oxygen species results in oxidative damage to biomolecules which ultimately become a hallmark for severe diseases like c...

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Extract from Astragalus membranaceus inhibit breast cancer cells proliferation via PI3K/AKT/mTOR signaling pathway

Astragalus membranaceus (AM) is a commonly used herb in traditional Chinese medicine (TCM), which has been used as an essential tonic to treat various diseases for more than 2000 years. In this study, we aimed to...

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Abstract from the Chinese Journal of Hypertension

The Effects of Renal Sympathetic Denervation on Hypothalamic Mitogen-Activated Protein Kinase and NF-κB in Spontaneously Hypertensive Rats

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Abstract from the Chinese Journal of Hypertension

Arachidonic Acid Induces Human Podocyte Apoptosis

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Erratum

"Antihypertensive Medications and Falls in the Elderly" by Cai, Anping and David A. Calhoun (Am J Hypertens 2018; 31: 281–283). doi: 10.1093/ajh/hpx203

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In Memoriam Jacques Genest Sr, C.C., MD, MACP, FRCPC 1919–2018

Dr Jacques Genest Sr, a "great" of hypertension research in the 20^th Century, passed away peacefully on 5 January 2018, in Montreal, Quebec, Canada, at the age of 98. He is survived by Estelle, his wife, and his children Paul, Suzanne, Jacques Jr, Marie and Hélène, 12 grandchildren and 7 great-grandchildren. Jacques Genest Sr was born in Montreal and having finished his medical studies at the University of Montreal, specialized in endocrinology and nephrology at Harvard hospitals in Boston, at Johns Hopkins in Baltimore, and at the Rockefeller University in New York.

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Response to “Associations Among Plasma Total Homocysteine Levels, Circadian Blood Pressure Variation, and Endothelial Function in Hypertension”

To the Editor:

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Renal Considerations in the Treatment of Hypertension

Abstract

There are renal implications when employing intensive blood pressure control strategies. While this approach provides cardiovascular benefit in patients with and without chronic kidney disease, the impact on renal disease progression differs according to the pattern of underlying renal injury. In the setting of proteinuria, stringent blood pressure control has generally conferred a protective effect on renal disease progression, but in the absence of proteinuria, this benefit tends to be much less impressive. Thiazide diuretics are frequently part of the regimen to achieve intensive blood pressure control. These drugs can cause hyponatremia and present with biochemical evidence mimicking the syndrome of inappropriate antidiuretic hormone secretion. Altered prostaglandin transport may explain the unique susceptibility to this complication observed in some patients. Hyperkalemia is also a complication of intensive blood pressure lowering particularly in the setting of renin–angiotensin–aldosterone blockade. There are strategies and new drugs now available that can allow use of these blockers and at the same time ensure a normal plasma potassium concentration.

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Mineralocorticoid Receptor Antagonists Treatment in Resistant Hypertension and HFpEF: Evidence and Courage

Heart failure is a complex syndrome and associated with a major health-economic burden due the high hospital readmission rate. During the last decade heart failure management has been more focused on heart failure with preserved ejection fraction (HFpEF).¹ There are some limitations in the classification and recognizing the different phenotypes within HFpEF. Consequently, this may lead to more tailored therapy for heart failure. Hypertension, diabetes beyond age and gender play an important role in the development of HFpEF.² Resistant hypertension increases the risk for development of HFpEF and may aggravate the HFpEF process. It is evident that resistant hypertension needs to be treated appropriately.^3,4 A few studies like ASCOT and PATHWAY-2 have shown that mineralocorticoid receptor antagonists (MRA), especially spironolactone are very effective in blood pressure lowering.^5,6 There is still therapeutic inertia in the treatment of resistant hypertension,⁷ which lead unfortunately to worsening of the heart failure condition.

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Associations Among Plasma Total Homocysteine Levels, Circadian Blood Pressure Variation, and Endothelial Function in Hypertension

To the Editor:

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Hypertension Control in Adults With CKD in China: Baseline Results From the Chinese Cohort Study of Chronic Kidney Disease (C-STRIDE)

Abstract

BACKGROUND

Hypertension contributes to increased morbidity and mortality in the chronic kidney disease (CKD) population. Studies on blood pressure control in CKD patients in China are limited. In this study, we aimed to describe the status of blood pressure control in Chinese CKD patients based on the first national prospective CKD cohort data.

METHODS

A subgroup of Chinese Cohort Study of Chronic Kidney Disease participants with hypertension at baseline was included in the present study. Uncontrolled blood pressure was defined as systolic blood pressure ≥140 mm Hg and/or diastolic blood pressure ≥90 mm Hg. Defined daily doses (DDDs) are used as a standard measurement of drug utilization in this population. Factors associated with uncontrolled blood pressure were analyzed using multivariable logistic regression.

RESULTS

There were 2,251 hypertensive CKD subjects among 2,873 predialysis CKD participants. The awareness, treatment, and control rates of hypertension were 80.7%, 95.6%, and 57.1%, respectively. Factors independently associated with uncontrolled blood pressure were overweight, obesity, albuminuria, decreased estimated glomerular filtration rate (eGFR), and diabetes. Over 50% of study subjects were prescribed 2 or more antihypertensive medications and only 7% were prescribed diuretics. Uncontrolled hypertensive patients were prescribed less antihypertensive medication than controlled hypertensives (DDD 1.3 [1.0–2.3] vs. 2.0 [1.0–3.1], P < 0.001).

CONCLUSIONS

Hypertension control was suboptimal among hypertensive CKD patients in China, especially among those overweight or with obesity, albuminuria, lower eGFR, and diabetes. Patients with uncontrolled hypertension should undergo treatment regimen evaluation to select the appropriate dosage and type of antihypertensive medications.

http://ift.tt/2Dga9jM

Spironolactone and Resistant Hypertension in Heart Failure With Preserved Ejection Fraction

Abstract

BACKGROUND

Recent evidence suggests that the mineralocorticoid receptor antagonist spironolactone should be the preferred fourth-line antihypertensive treatment in resistant hypertension (RHTN). Whether spironolactone improves blood pressure (BP) control in heart failure with preserved ejection fraction (HFpEF) and RHTN is unknown.

METHODS

We identified patients with RHTN, defined as baseline systolic blood pressure (SBP) between 140 and 160 mm Hg on 3 or more medications, in the Americas cohort of the Treatment of Preserved Cardiac Function Heart Failure with an Aldosterone Antagonist trial, in which patients with HFpEF were randomized to spironolactone vs. placebo. We evaluated the effects of spironolactone vs. placebo on BP reduction in this group and related this to the primary composite outcome of death from cardiovascular causes, aborted cardiac arrest, or hospitalization for heart failure.

RESULTS

We identified 403 participants in the Americas with RHTN. Compared to people without RHTN, those with RHTN were more frequently women, non-White, diabetics, with a higher left ventricular ejection fraction and body mass index, and a lower hemoglobin concentration. In the RHTN group, spironolactone resulted in a decrease of SBP: −6.1 (−8.9, −3.3); P < 0.001 and diastolic BP: −2.9 (−4.6, −1.2); P = 0.001 mm Hg during the first 8 months. BP became controlled after 4 weeks in 63% of patients receiving spironolactone vs. 46% receiving placebo (P = 0.003), with similar responses at 8 weeks, 4 and 8 months. Patients with RHTN derived similar overall benefit from spironolactone on the primary outcomes as those without.

CONCLUSIONS

In HFpEF patients with RHTN, spironolactone lowered BP substantially and was associated with similar benefit as those without RHTN.

CLINICAL TRIALS REGISTRATION

Trial Number NCT00094302 (ClinicalTrials.gov identifier)

http://ift.tt/2Ij0rRq

Human Immunodeficiency Virus Infection And Hypertension. Is There a Connection?

Abstract

Data support that hypertension (HTN) is prevalent among human immunodeficiency virus (HIV) patients contributing to increased risk of cardiovascular disease. Immunodeficiency and prolonged antiretroviral treatment along with common risk factors including older age, male gender, and high body mass index might conduce to greater incidence of HTN. The purpose of this review was to summarize recent evidence of the increased cardiovascular risk in these patents linking HIV infection to HTN.

http://ift.tt/2p70WoG

Benzodiazepines: An Old Class of New Antihypertensive Drugs?

The role of the γ-aminobutyric acid (GABA) signaling in blood pressure regulation is complex and only partially characterized. Old studies on anesthetized animals reported that GABA injection in the central nervous system (CNS) decreased blood pressure, heart rate, and renal sympathetic nerve activity,¹ but did not attenuate blood pressure elevation induced by a salt load.² Other studies demonstrated that the GABAergic activity of different areas of the CNS could affect the neural regulation of blood pressure through sympathoinhibitory signals and that stimulation of GABA-type A receptors in the posterior hypothalamus of spontaneously hypertensive rats decreased blood pressure more than in control animals (Wistar-Kyoto rats).³ The GABA_A-receptors are chloride ion channels whose major function is inhibition of neurotransmission in specific areas of the CNS of vertebrates.

http://ift.tt/2IhQ5kW

Reproducibility of Retinal Microvascular Traits Decoded by the Singapore I Vessel Assessment Software Across the Human Age Range

Abstract

BACKGROUND

Retinal microvascular traits predict adverse health outcomes. The Singapore I Vessel Assessment (SIVA) software improved automated postprocessing of retinal photographs. In addition to microvessel caliber, it generates measures of arteriolar and venular geometry. Few studies addressed the reproducibility of SIVA measurements across a wide age range.

METHODS

In the current study, 2 blinded graders read images obtained by nonmydriatic retinal photography twice in 20 11-year-old children, born prematurely (n = 10) or at term (n = 10) and in 60 adults (age range, 18.9–86.1 years).

RESULTS

Former preterm compared with term children had lower microvessel diameter and disorganized vessel geometry with no differences in intraobserver and interobserver variability. Among adults, microvessel caliber decreased with age and blood pressure and arteriolar geometry was inversely correlated with female sex and age. Intraobserver differences estimated by the Bland–Altman method did not reach significance for any measurement. Across measurements, median reproducibility (RM) expressed as percent of the average trait value was 8.8% in children (median intraclass correlation coefficient [ICC], 0.94) and 8.0% (0.97) in adults. Likewise, interobserver differences did not reach significance with RM (ICC) of 10.6% (0.85) in children and 10.4% (0.93) in adults. Reproducibility was best for microvessel caliber (intraobserver/interobserver RM, 4.7%/6.0%; ICC, 0.98/0.96), worst for venular geometry (17.0%/18.8%; 0.93/0.84), and intermediate for arteriolar geometry (10.9%/14.9%; 0.95/0.86).

CONCLUSIONS

SIVA produces repeatable measures of the retinal microvasculature in former preterm and term children and in adults, thereby proving its usability from childhood to old age.

http://ift.tt/2p5NGkf

Genetic Variation in SLC8A1 Gene Involved in Blood Pressure Responses to Acute Salt Loading

Abstract

BACKGROUND

Salt sensitivity of blood pressure (SSBP) increases the risk of cardiovascular complications, and the heritability of SSBP is about 50% in Chinese population. However, studies identifying genes involved in BP responses to acute sodium loading and diuresis shrinkage are still limited.

METHOD

A total of 342 essential hypertensives from Beijing were recruited in our study. A modified Sullivan's acute oral saline load and diuresis shrinkage test was conducted to each individual. Medical history and lifestyle risk factors were obtained by questionnaire. Generalized linear model was used to examine the associations of 29 single-nucleotide polymorphisms (SNPs) with SSBP and false discovery rate (FDR) was used to correct P values for multiple testing.

RESULTS

In the process of acute sodium loading, after adjusting for age and 24-hour urinary sodium concentration, SNPs in CYP11B2, PRKG1, SLC8A1 genes were significantly associated with systolic BP (SBP) rising in the additive and recessive model; SNPs in CYP4A11, PRKG1, SLC8A1, and ADRB2 genes were significantly associated with diastolic BP (DBP) rising. In the process of diuresis shrinkage, SNPs of CLCNKA, eNOS, PRKG1 gene were associated with SBP and DBP decreasing. After FDR correction, rs434082 in SLC8A1 gene was still significantly associated with blood pressure rising during salt load. In the additive model, A allele increased DBP of 2.8 mm Hg (FDR_q = 0.029) and MAP of 3.1 mm Hg (FDR_q = 0.029) after adjusting for age and 24-hour urinary sodium concentration.

CONCLUSION

SLC8A1 gene may contribute to BP change in the process of acute sodium loading in a Han Chinese population.

http://ift.tt/2IgSPih

Long-Term Improvement in Aortic Pulse Wave Velocity After Weight Loss Can Be Predicted by White Adipose Tissue Factors

Abstract

BACKGROUND

Arterial stiffness, measured by pulse wave velocity (PWV), is linked to obesity, cardiovascular disease, and all-cause mortality. Short-term weight loss improves PWV, but the long-term effects are unknown. We investigated the effect of pronounced long-term weight loss on PWV and whether anthropometric/metabolic parameters and/or white adipose tissue (WAT) phenotype could predict this change in PWV.

METHODS

Eighty-two obese subjects were examined before and 2 years after Roux-en-Y gastric bypass. Analyses included anthropometrics, routine clinical chemistry, and hyperinsulinemic-euglycemic clamp. Arterial stiffness was measured as aortic PWV (aPWV) using the Arteriograph device. WAT mass and distribution were assessed by dual-X-ray absorptiometry. Baseline visceral and subcutaneous WAT samples were obtained to measure adipocyte cell size. Transcriptomic profiling of subcutaneous WAT was performed in a subset of subjects (n = 30).

RESULTS

At the 2-year follow-up, there were significant decreases in body mass index (39.4 ± 3.5 kg/m² vs. 26.6 ± 3.4 kg/m²; P < 0.0001) and aPWV (7.8 ± 1.5 m/s vs. 7.2 ± 1.4 m/s; P = 0.006). Multiple regression analyses showed that baseline subcutaneous adipocyte volume was associated with a reduction in aPWV (P = 0.014), after adjusting for confounders. Expression analyses of 52 genes implicated in arterial stiffness showed that only one, COL4A1, independently predicted improvements in aPWV after adjusting for confounders (P = 0.006).

CONCLUSIONS

Bariatric surgery leads to long-term reduction in aPWV. This improvement can be independently predicted by subcutaneous adipocyte volume and WAT COL4A1 expression, which suggests that subcutaneous WAT has a role in regulating aPWV.

CLINICAL TRIALS REGISTRATION

Trial Number NCT01727245 (clinicaltrials.gov)

http://ift.tt/2p4Idu1

The State of Hypertension in Sub-Saharan Africa: Review and Commentary

Ischemic heart disease is the leading cause of death globally, accounting for almost 9 million deaths annually as of 2015.¹ According to World Health Organization (WHO) data, the number of deaths as a result of ischemic heart disease has increased by almost 2 million per year since 2000.¹ In developing regions around the world, as defined by World Bank groupings, cardiovascular disease is now the number one killer in all regions with the exception of sub-Saharan Africa, where it ranks second. However, with sub-Saharan Africans above the age of 30, cardiovascular disease again rises to the top as the leading cause of death.² The WHO identifies hypertension as the leading risk factor for cardiovascular disease.³ The incidence of hypertension globally was around 1 billion people in 2008, an increase from 600 million in 1980.⁴ Across all WHO regions, including the Americas, Africa has the highest prevalence of hypertension where 46% of the entire population over 25 years of age is estimated to be hypertensive. In the INTERHEART Africa study, we learned that the age at which sub-Saharan Africans present with first myocardial infarction is significantly younger than any other global region using comparison data from the global INTERHEART study. Further, 5 modifiable risk factors, with hypertension as the most profound, is attributed to 89.2% of acute myocardial infarctions in sub-Saharan Africans.^5,6 This problem is projected to continue to worsen and without intervention could become epidemic.⁵ Given all of this, the WHO has put forth a Global Action Plan including the following goals by 2020: (i) a 25% relative reduction in the prevalence of raised blood pressure or contain the prevalence of raised blood pressure, according to national circumstances; (ii) a 30% relative reduction in mean population intake of salt/sodium; at least 50% of eligible people receive drug therapy and counseling to prevent heart attacks and strokes; (iii) an 80% availability of the affordable basic technologies and essential medicines, including generics, required to treat major noncommunicable diseases.⁷

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Insulin-Like Growth Factor-1 and Receptor Contribute Genetic Susceptibility to Hypertension in a Han Chinese Population

Abstract

BACKGROUND

Insulin-like growth factor 1 (IGF-1) and IGF-1 receptor (IGF-1R) have been suggested to mediate the pathophysiological response to elevated blood pressure. This study aims to evaluate the association of IGF-1 and IGF-1R with hypertension.

METHODS

Overall, 2,012 hypertensive cases and 2,210 controls were included in a case–control study, and 10 tagging single nucleotide polymorphisms (tagSNPs) were selected. The association of these SNPs with hypertension was further evaluated in a follow-up analysis and in an adolescent population.

RESULTS

A case–control study indicated that rs1815009 and rs2654981 in IGF-1R were significantly associated with hypertension, with odds ratios of 0.89 (P = 0.009) and 1.19 (P = 0.034), respectively, after adjusting for covariates. Stratification analyses revealed significant associations with hypertension (P < 0.05) for rs35767 in normal weight and obese populations; for rs2229765 in individuals <55 years of age and in overweight and nondrinking populations; and for rs2002880 in overweight and drinking populations. In a follow-up study, rs13379905 in IGF-1R was associated with hypertension incidence (hazard ratio, HR = 1.24, P = 0.042). This association was more significant in individuals with a hypertensive family history (HR = 2.10, P = 0.001). The association of rs13379905 with prehypertension and hypertension was further replicated in adolescent males (P = 0.005). Significant associations with hypertension incidence (P < 0.05) were observed for rs6219 in individuals <55 years of age and among those with obesity and a hypertensive family history as well as rs2002880 in obese individuals.

CONCLUSIONS

Our findings suggest that IGF-1R may contribute to the genetic susceptibility to hypertension, with BMI, age, and family history of hypertension all potentially modulating the genetic effects of IGF-1 on hypertension.

http://ift.tt/2DgjPL1

The Impact of Intradialytic Pedaling Exercise on Arterial Stiffness: A Pilot Randomized Controlled Trial in a Hemodialysis Population

Abstract

OBJECTIVES

Regular exercise is known to reduce arterial stiffness (AS) in hemodialysis patients. However, the impact of a more realistic intradialytic form of exercise, such as pedaling, is unclear. We aimed to examine (i) the effect of intradialytic pedaling exercise on AS over 4 months and (ii) the longer term effect of pedaling on AS 4 months after exercise cessation.

METHODS

Patients on stable in-center hemodialysis (3 x/week) were randomly assigned 1:1 to either intradialytic pedaling exercise (EX) or to a control group receiving usual hemodialysis (nonEX) for 4 months. At baseline and 4 months, peripheral and central blood pressure (BP) indices, heart rate (HR), augmentation index HR corrected (AIx75), and carotid-femoral pulse wave velocity (cfPWV) were assessed (applanation tonometry). Measurements were repeated in the EX group 4 months postexercise cessation.

RESULTS

As per protocol analysis was completed in 10 EX group participants (58 ± 17 years, body mass index 26 ± 4 kg/m²) and 10 nonEX group participants (53 ± 15 years, body mass index 27 ± 6 kg/m²). Peripheral and central BP was unchanged in both groups. AIx75 was unchanged in the EX group, however, a significant median increase of 3.5% [interquartile range, IQR 1.0, 8.5] was noted in the nonEX group (P = 0.009). We noted a significantly greater absolute decrease in cfPWV in the EX group compared to controls: −1.00 [IQR −1.95, 0.05] vs. 0.20 [IQR −0.10, 0.90] (P = 0.033). Interestingly, the decrease in cfPWV observed in the EX group was partially reversed 4 months after exercise cessation.

CONCLUSION

Intradialytic pedaling exercise has a beneficial impact on AS. This relationship warrants further investigation.

CLINICAL TRIALS REGISTRATION

Trial Number #NCT03027778 (clinicaltrials.gov)

http://ift.tt/2IgVvfJ

Association Between Chronic or Acute Use of Antihypertensive Class of Medications and Falls in Older Adults. A Systematic Review and Meta-Analysis

Abstract

BACKGROUND

Evaluating effect of acute or chronic use of antihypertensives on risk of falls in older adults.

METHODS

Data sources: Systematic search of primary research articles in CINAHL, Cochrane, EBM, EMBASE, and MEDLINE databases from January 1 2007 to June 1 2017. Study selection: Research studies of cohort, case-control, case-crossover, cross-sectional, or randomized controlled trial (RCT) design examining association between antihypertensives and falls in people older than 60 years were evaluated. Data synthesis: Twenty-nine studies (N = 1,234,667 participants) were included. Study quality was assessed using the Newcastle–Ottawa Scale (NOS). PRISMA and MOOSE guidelines were used for abstracting data and random-effects inverse-variance meta-analysis was conducted on 26 articles examining chronic antihypertensive use, with odds ratios (ORs) and hazards ratios (HRs) analyzed separately. Time-risk analysis was performed on 5 articles examining acute use of antihypertensives. Outcomes: Pooled ORs and HRs were calculated to determine the association between chronic antihypertensive use and falls. For time-risk analysis, OR was plotted with respect to number of days since antihypertensive commencement, change, or dose increase.

RESULTS

There was no significant association between risk of falling and chronic antihypertensive medication use (OR = 0.97, 95% confidence interval [CI] 0.93–1.01, I² = 64.1%, P = 0.000; and HR = 0.96, 95% CI 0.92–1.00, I² = 0.0%, P = 0.706). The time-risk analysis demonstrated a significantly elevated risk of falling 0–24 hours after antihypertensive initiation, change, or dose increase. When diuretics were used, the risk remained significantly elevated till day 21.

CONCLUSIONS

There is no significant association between chronic use of antihypertensives and falls in older adults. Risk of falls is highest on day zero for all antihypertensive medications.

http://ift.tt/2p5Rlyz

Benzodiazepine Consumption Is Associated With Lower Blood Pressure in Ambulatory Blood Pressure Monitoring (ABPM): Retrospective Analysis of 4938 ABPMs

Abstract

BACKGROUND

The effect of chronic benzodiazepine use on blood pressure has not been documented. We aimed to evaluate whether regular benzodiazepine use can be associated to the results of ambulatory blood pressure monitoring (ABPM).

METHODS

A retrospective analysis of the ABPM database between 2009 and 2015 was performed. The study groups were divided according to benzodiazepine treatment at least 3 months before ABPM. Generalized estimating equation (GEE) model analysis was conducted to estimate the association between benzodiazepine treatment and ABPM test measurements. Multivariable COX regression survival analysis model for mortality and cardiovascular (CV) events was performed.

RESULTS

A total of 4,938 ABPM studies were included in final analysis, 670 ABPMs of benzodiazepine-treated patients, and 4,268 of untreated patients. The benzodiazepine-treated group was significantly older, with a predominance of female patients, comprised more diabetic patients and consumed more antihypertensive medications. Adjustment for age, gender, diabetes mellitus, and number of antihypertensive medications, showed an association between benzodiazepine treatment and significantly lower ABPM measurements. When the analysis was split into those ≥60 years old and the other <60 years old, regular benzodiazepine consumption was associated with lower ABPM measurements only among ≥60 years old. Multivariable Cox regression survival analysis showed that regular benzodiazepine consumption was not associated with increased mortality or CV events (mean follow-up period of 42.4 ± 19.8 and 42.1 ± 20.0 months, respectively).

CONCLUSIONS

Long-term use of benzodiazepines by ≥60 years old was independently associated with lower diastolic and systolic blood pressure in all parameters of ABPM, but not among younger patients.

http://ift.tt/2IgSBYt

Intratumoural expression of deoxycytidylate deaminase or ribonuceotide reductase subunit M1 expression are not related to survival in patients with resected pancreatic cancer given adjuvant chemotherapy

Intratumoural expression of deoxycytidylate deaminase or ribonuceotide reductase subunit M1 expression are not related to survival in patients with resected pancreatic cancer given adjuvant chemotherapy

Intratumoural expression of deoxycytidylate deaminase or ribonuceotide reductase subunit M1 expression are not related to survival in patients with resected pancreatic cancer given adjuvant chemotherapy, Published online: 09 March 2018; doi:10.1038/s41416-018-0005-1

Intratumoural expression of deoxycytidylate deaminase or ribonuceotide reductase subunit M1 expression are not related to survival in patients with resected pancreatic cancer given adjuvant chemotherapy

http://ift.tt/2tABDky

Changes in MLST profiles and biotypes of Corynebacterium diphtheriae isolates from the diphtheria outbreak period to the period of invasive infections caused by nontoxigenic strains in Poland (1950–2016)

Corynebacterium diphtheriae is a re-emerging pathogen in Europe causing invasive infections in vaccinated persons and classical diphtheria in unvaccinated persons. In the presented study we analysed genetic chang...

http://ift.tt/2FyGeFC

Continuous hypoxia reduces the concentration of streptomycin in the blood

A high incidence and mortality of plague in the past two decades occurred in the Qinghai-Tibet Plateau, China. High dose streptomycin (6–8 g/d) remained the first practical strategy for controlling the progres...

http://ift.tt/2GgRjfC

A Review of the Current Evidence on Gadolinium Deposition in the Brain

Abstract

Over the past 3 years, gadolinium-based contrast agents have been linked to MRI signal changes in the brain, which have been found to be secondary to gadolinium deposition in the brain, particularly in the dentate nuclei and globus pallidus even in patients having an intact blood-brain barrier and a normal renal function. This tends to occur more in linear agents than with macrocyclic agents. Nonetheless, there has been no significant evidence that this has any clinical consequence. We reviewed the current evidence related to this new phenomenon and the precautionary approach taken by regulatory agencies.

http://ift.tt/2IfahUk

Prognostic Value of EEG in Patients after Cardiac Arrest—An Updated Review

Abstract

Purpose of Review

This paper aims to review and summarize the key contributions of EEG to prognostication after cardiac arrest (CA).

Recent Findings

While there are more EEG patterns predicting poor than good outcome, even EEG patterns previously considered to be "very malignant" may result in survival with a meaningful neurological outcome depending on their underlying etiology as well as the continuity and reactivity of the EEG background. Regardless of the potentially confounding factors, EEG patterns are highly specific with a relatively low false-positive rate. The development of more complex and comprehensive approaches to quantitative EEG analysis could help improve the prognostic value of EEG, but this approach has its own limitations. Seizures and status epilepticus in the setting of CA predict poor outcomes, but it is not clear whether treating them prevents additional brain damage and results in improved outcome.

Summary

Either continuous EEG or frequent intermittent EEGs should be obtained within the first 12–24 h of return of spontaneous circulation in order to capture highly dynamic and prognostic patterns. Even though EEG has high predictive value for outcomes after cardiac arrest, it should not be the only prognostic tool. Rather, to improve prognostication, EEG should be used in combination with the neurological examination and other ancillary tests.

http://ift.tt/2FCUkJh

When the Ends Are Really the Beginnings: Targeting Telomerase for Treatment of GBM

Abstract

Purpose of Review

High-throughput genomic sequencing has identified alterations in the gene encoding human telomerase reverse transcriptase (TERT) as points of interest for elucidating the oncogenic mechanism of multiple different cancer types, including gliomas. In gliomas, the TERT promoter mutation (TPM) and resultant overexpression of TERT are observed mainly in the most aggressive (primary glioblastoma/grade IV astrocytoma) and the least aggressive (grade II oligodendroglioma) cases. This article reviews recent research on (1) the mechanism of TERT activation in glioma, (2) downstream consequences of TERT overexpression on glioma pathogenesis, and (3) targeting TPMs as a therapeutic strategy.

Recent Findings

New molecular classifications for gliomas include using TPMs, where the mutant group demonstrates the worst prognosis. Though a canonical function of TERT is established in regard to telomere maintenance, recent studies on non-canonical functions of TERT explore varied roles of telomerase in tumor progression and maintenance.

Summary

Somatic alterations of the TERT promoter present a promising target for novel therapeutics development in primary glioma treatment.

http://ift.tt/2FI5f4e

Transition of Children with Neurological Disorders

Abstract

Purpose of the Review

The goal of the article is to describe a systematic approach through core principles and steps for the transition of the patient with a neurological disorder to the adult model of care, to provide steps and principles to help receiving providers successfully integrate the patient into their practice, and to discuss cultural, systemic, and discipline-based barriers to transition.

Recent Finding

The literature has expanded rapidly. The recent publications help define the barriers to the process and are currently exploring the best methods to evaluate readiness, needs, barriers, and develop solutions for best practices. There is a consensus that there is a need for a systematic approach to transition and integration of the patient with a neurological disorder.

Summary

The transition of the child and youth with special health care needs (CYSHCN) is complex with multiple barriers. An important concept is that these patients, their families, and medical care providers all benefit from a coordinated and collaborative methodology.

http://ift.tt/2tybJh9

Insights into the Mechanisms That May Clarify Obesity as a Risk Factor for Multiple Sclerosis

Abstract

Purpose of Review

The proportion to which genetic and environmental factors contribute to the etiology of multiple sclerosis (MS) is still incompletely understood. An interesting association between MS etiology and obesity has recently been shown although the mechanisms underlying this association are still unknown. We propose deregulated gut microbiota and increased leptin levels as possible mechanisms underlying MS etiology in obese individuals.

Recent Findings

Alterations in the human gut microbiota and leptin levels have recently been established as immune modulators in both MS patients and obese individuals. A resemblance between pro-inflammatory bacterial profiles in MS and obese individuals was observed. Furthermore, elevated leptin levels push the immune system towards a more pro-inflammatory state and inhibit the regulatory immune response.

Summary

Deregulated gut microbiota and elevated leptin levels may explain the increased risk of developing MS in obese individuals. Further research to confirm causality is warranted.

http://ift.tt/2FGmZNj

Mild Cognitive Impairment in Parkinson’s Disease—What Is It?

Abstract

Purpose of Review

Mild cognitive impairment is a common feature of Parkinson's disease, even at the earliest disease stages, but there is variation in the nature and severity of cognitive involvement and in the risk of conversion to Parkinson's disease dementia. This review aims to summarise current understanding of mild cognitive impairment in Parkinson's disease. We consider the presentation, rate of conversion to dementia, underlying pathophysiology and potential biomarkers of mild cognitive impairment in Parkinson's disease. Finally, we discuss challenges and controversies of mild cognitive impairment in Parkinson's disease.

Recent Findings

Large-scale longitudinal studies have shown that cognitive involvement is important and common in Parkinson's disease and can present early in the disease course. Recent criteria for mild cognitive impairment in Parkinson's provide the basis for further study of cognitive decline and for the progression of different cognitive phenotypes and risk of conversion to dementia.

Summary

Improved understanding of the underlying pathology and progression of cognitive change are likely to lead to opportunities for early intervention for this important aspect of Parkinson's disease.

http://ift.tt/2tx0gi7

Cell Cycle Markers in the Evaluation of Bladder Cancer

Abstract

Bladder cancer (BC) is a heterogeneous neoplasia characterized by a high number of recurrences. Standardized clinical and morphological parameters are not always sufficient to predict individual tumor behavior. The aim of this study was to evaluate the expression of cell cycle regulators proteins as potential adjuvant in prognosis and monitoring of this disease. Block paraffin samples from patients with urothelial bladder carcinoma treated by transurethral resection (TUR) were collected to immunohistochemistry analysis for proteins p16, p21, p27, p53, pRb and Ki-67. Chisquare, logistic regression and Kaplan-Meier curve were used to analyze the prognostic value of these markers. Of the 93 patients included in the study, the main categories of staging observed were T1 (53%) and Ta (29%), and the distribution between tumor grades was 58% of patients with low grade to 42% of patients with high grade. The expressions of p16, p21, p27, p53, pRb and Ki-67 were altered in 31%, 42%, 60%, 91%, 27% and 56% of patients, respectively. The immunohistochemical expression of Ki-67 was associated with tumor histological grade (p = 0.016), and expression of pRb with recurrence-free survival (p = 0.035), but no isolated marker was significant associated with recurrence and progression in multivariate analysis. More than two markers abnormally expressed were associated with presence of recurrence (p = 0.005) and lower recurrence-free surviva (p = 0.004). Our panel marker has important prognostic value for BC, especially when more than two have altered expression predicting good clinical recurrence implication.

http://ift.tt/2GbYGEP

Cancer screening policy in Hungary

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Author's reply to: Cancer screening policy in Hungary

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Associations between Statin Use and Risk of Non-Hodgkin Lymphomas by Subtype

Abstract

Non-Hodgkin lymphomas (NHL) are a group of cancers with highly heterogeneous biology and clinical features. Statins are increasingly prescribed to prevent cardiovascular diseases. Early evidence shows a preventive effect of statins for some cancers, but their effect on NHL risk is unclear.

We conducted a population-based nested case-control study involving 5,541 NHL cases and 27,315 controls matched for gender, age, place of residence, and length of period of available prescription drug data. We assessed the use of statins prior to diagnosis (excluding the 12 months prior to the index date). We used conditional logistic regression models to estimate odds ratio (OR) and 95% confidence interval (CI) for use of any statin, adjusting for medical conditions, number of family physician visits for 5 years prior to index date, healthcare utilization, income, and use of other medications.

Over one-quarter of cases and controls were prescribed statins. Ever-use of any statin was associated with lower risk of Total NHL (OR=0.82, 95% CI 0.76-0.89) and of certain subtypes including diffuse large B-cell lymphomas (DLBCL, OR=0.77, 95% CI 0.65-0.92), plasma cell neoplasms (PCN, OR=0.76, 95% CI 0.63-0.91) and other B-cell NHL (0.75, 0.59-0.95). Analysis by statin type suggested that the association was limited to high potency statin and lipophilic statin users. No clear duration- or dose-response relationships were observed.

Our findings provide evidence that statin use can reduce the risk of DLBCL and plasma cell lymphomas, but not other NHL types. Further studies are warranted to verify these associations and to examine the biological mechanisms. This article is protected by copyright. All rights reserved.

http://ift.tt/2oZiZOu

Caspase-3 regulates the migration, invasion, and metastasis of colon cancer cells

Caspase-3 (CASP3) is a major mediator of apoptosis activated during cellular exposure to cytotoxic drugs, radiotherapy, or immunotherapy. It is often used as a marker for efficacy of cancer therapy. However, recent reports indicate that caspase-3 also has non-apoptotic roles such as promotion of tumor relapse and tumor angiogenesis. Therefore, the roles of caspase-3 in tumor progression remains to be defined clearly. In this study, we established caspase-3 knockout (KO) colon cancer cell lines by use of the CRISPR technology. In vitro, caspase-3 knockout HCT116 cells were significantly less clonogenic in soft agar assays. They were also significantly less invasive and more sensitive to radiation and mitomycin C than control cells. In vivo, CASP3KO cells formed tumors at rates similar to control cells but were significantly more sensitive to radiotherapy. They were also less prone to pulmonary metastasis when inoculated either subcutaneously or intravenously. At the mechanistic level, caspase-3 gene knockout appeared to cause reduced EMT phenotypes when compared with parental HCT116 cells. Indeed, they showed significantly increased E-cadherin expression, reduced N-cadherin, Snail, Slug, and ZEB1 expression than control cells. Therefore, therapeutic targeting of caspase-3 may not only increase the sensitivity of cancer cell to chemotherapy and radiotherapy, but also inhibit cancer cell invasion and metastases. This article is protected by copyright. All rights reserved.

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Correction to: Biological/pathological functions of the CXCL12/CXCR4/CXCR7 axes in the pathogenesis of bladder cancer

Following the publication from the original article, it came to our attention that we unintentionally neglected to acknowledge some text overlap with previous publications.

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Intratumoural expression of deoxycytidylate deaminase or ribonuceotide reductase subunit M1 expression are not related to survival in patients with resected pancreatic cancer given adjuvant chemotherapy

http://ift.tt/2oYdMXm

Lactate gap as a tool in identifying ethylene glycol poisoning

Ethylene glycol toxicity is a known cause of anion gap metabolic acidosis, with the presence of an osmolar gap and the right clinical context suggesting to the diagnosis. Rapid recognition and early treatment is crucial. Unfortunately, ethylene glycol levels are not readily available and must be performed at a reference laboratory. We present a case where recognising the significance of the 'lactate gap' assisted in identifying ethylene glycol poisoning.

http://ift.tt/2IheOFU

Pancytopenia: a rare complication of Graves disease

A 27-year-old male patient who presented to the emergency room with complaints of sweating, palpitations, heat intolerance, insomnia and weight loss for the last 3 months. His medical history was significant for hypertension. On examination, he was tachycardic, hypertensive, had tremors of the upper extremities and a smooth goitre with a thyroid bruit. Laboratory assessment revealed a suppressed thyroid-stimulating hormone, high free thyroxine and positive thyroid receptor antibodies. Complete blood count showed pancytopenia. As part of the work-up for pancytopenia, haptoglobin, ferritin, Coombs test, reticulocyte count hepatitis B and C antibodies were done, all of which were normal. Patient was started on methimazole, propranolol and hydrocortisone. His symptoms improved through the hospital course and he was subsequently discharged. Thyroidectomy was done once the patient's hyperthyroidism was controlled. Levothyroxine was started for the control of postsurgical hypothyroidism. Six months after thyroidectomy, the patient was euthyroid and the pancytopenia resolved.

http://ift.tt/2DhcP0l

Renocolic fistula secondary to urothelial carcinoma

A 77-year-old man presented with watery, bloody diarrhoea, symptomatic anaemia and signs of sepsis. He was well known to our unit with a history of extensive low-grade urothelial carcinoma involving a solitary kidney. CT performed on admission demonstrated a new finding of renocolic fistula. Due to his multiple medical and surgical comorbidities conservative management was elected. He passed away after 1 year of follow-up.

http://ift.tt/2IeWo8R

The novel use of botulinum toxin A for the treatment of Raynauds phenomenon in the toes

Raynaud's phenomenon is a vasospastic disorder of the digital vessels triggered by exposure to cold or stress. It is most commonly observed in the hands, but also frequently affects the toes. We present three cases of patients with severe Raynaud's phenomenon in the toes, secondary to scleroderma. The diagnosis of Raynaud's syndrome and scleroderma was established according to the 2010 American College of Rheumatology and European League Against Rheumatism criteria. Patients were treated with 10 units of botulinum toxin injected into each foot. Two millilitres was injected into the base of each toe in both the left and right feet. Six weeks postinjection into the toes, patients reported an improvement of cold intolerance, colour change and frequency and severity of Raynaud's attacks. The effects were reported to last up to 5 months. To our knowledge, these are the first reported cases of the treatment of Raynaud's phenomenon in the toes with botulinum toxin A.

http://ift.tt/2p3rJT3

Atrial myxoma presenting as infective endocarditis

A 23-year-old Asian student presented to our service with a 1-month history of fever, weight loss of 10 kg, night sweats, fatigue and general malaise. He was previously well with no significant medical or family history. He had a low-grade pyrexia and cardiac auscultation revealed a diastolic murmur consistent with 'tumour plop'. He had no sequelae of endocarditis. He had low-grade pyrexia of 37.7°C, and ECG showed sinus tachycardia at 130 bpm. He had raised inflammatory markers and was started on broad spectrum antibiotics. Blood cultures grew Streptococcus viridans twice. Transthoracic and transo-oesophageal echocardiography revealed a large mobile mass attached to the interatrial septum, suspicious for atrial myxoma, flopping into the left ventricle but not causing left ventricular outflow tract obstruction. All valves looked normal in appearance. He was treated with antibiotics for 2 weeks until inflammatory markers normalised. The patient was referred for cardiothoracic surgery where a large atrial myxoma (5 cmx3 cm) was excised just superior to the mitral valve. It had areas of necrosis and was colonised with S. viridans. He had an unremarkable postoperative course and made a complete recovery.

http://ift.tt/2IcUMw5

Rare case of thoracic endometriosis presenting with lung nodules and pneumothorax

We present the case of a 34-year-old Nigerian woman who was referred to the Respiratory team with a 12-month history of breathlessness. She was concurrently being investigated for an abdominal mass and rectal and vaginal bleeding. Consequently, she underwent cross-sectional imaging of her chest, abdomen and pelvis, revealing a small right-sided pneumothorax and right lower lobe pleural-based lesion. Shortly thereafter, she was admitted to the hospital with chest pain and required chest drain insertion. This partially treated her pneumothorax but she required referral to a cardiothoracic centre for definitive diagnosis and to manage her non-resolving pneumothorax. Biopsies from the video-assisted thoracoscopic surgery confirmed the very rare diagnosis of thoracic endometriosis.

http://ift.tt/2DhcJ8Z

Spontaneous renal infarct heralding bowel ischaemia in an adult male: lessons to learn from a rare clinical association

Spontaneous renal artery dissection (SRAD) is a rare entity with less than 200 cases reported in literature. It usually affects middle-aged men and the clinical presentation is non-specific. Many times it is associated with conditions such as hypertension, fibromuscular dysplasia or vasculitides. We report the case of a patient who initially had renal infarct due to SRAD and then progressed to have bowel ischaemia. The renal infarct preceded bowel ischaemia in this patient and to the best of our knowledge this is the first such association reported in literature. Our report emphasises the point that whenever this condition is diagnosed in a patient one should be vigilant for other vascular disorders.

http://ift.tt/2IeWihv

Evaluation of the district health management fellowship training programme: a case study in Iran

Objective

To evaluate the district health management fellowship training programme in the north-west of Iran.

Data sources/study setting

The programme was introduced to build the managerial capacity of district health managers in Iran. Eighty-nine heads of units in the province's health centre, district health managers and the health deputies of the district health centres in the north-west provinces of Iran had registered for the district health management fellowship training programme in Tabriz in 2015–2016.

Study design

This was an educational evaluation study to evaluate training courses to measure participants' reactions and learning and, to a lesser extent, application of training to their job and the organisational impact.

Data collection/extraction methods

Valid and reliable questionnaires were used to assess learning techniques and views towards the fellowship, and self-assessment of health managers' knowledge and skills. Also, pretest and post-test examinations were conducted in each course and a portfolio was provided to the trainees to be completed in their work settings.

Principal findings

About 63% of the participants were medical doctors and 42.3% of them had over 20 years of experience. Learning by practice (scored 18.37 out of 20) and access to publications (17.27) were the most useful methods of training in health planning and management from the participants' perspective. Moreover, meeting peers from other districts and the academic credibility of teachers were the most important features of the current programme. Based on the managers' self-assessment, they were most skilful in quality improvement, managing, planning and evaluation of the district. The results of the post-test analysis on data collected from district health managers showed the highest scores in managing the district (77 out of 100) and planning and evaluation (69) of the courses.

Conclusion

The results of this study indicated that training courses, methods and improvement in managers' knowledge about the health system and the skills necessary to manage their organisation were acceptable.

http://ift.tt/2oYN2FZ

Impact of particulate matter on mothers and babies in Antwerp (IPANEMA): a prospective cohort study on the impact of pollutants and particulate matter in pregnancy

Introduction

Air pollution is a hot topic and is known to cause multiple health issues. Especially pregnant women seem to be vulnerable to environmental issues. There are data suggesting that exposure contributes to hypertensive disorders.

This study aims to evaluate the effects of exposure to particulate matter (PM) and outdoor air pollutants on the clinical pregnancy outcome for mother and child and to determine which biochemical changes in maternal, placental and cord blood best explain this effect.

Methods and analysis

This study is a prospective cohort study. We aim to recruit 200 pregnant women. The outcome measurements will include maternal parameters, labour parameters and neonatal parameters.

Multiple samples will be analysed such as maternal urine samples (8-oxo-deoxyguanosine), maternal blood samples (routine blood sampling, biomarkers of pre-eclampsia and transcript markers), maternal hair samples, neonatal blood samples (transcript markers) combined with extensive questionnaires.

Ethics and dissemination

We obtain informed consent from each participant prior to enrolment in the study.

The study has received approval by the Ethical Committee of the Antwerp University Hospital (14/40/411).

IPANEMA is the first prospective study to assess the impact of PM on mothers and babies in Antwerp, Belgium.

Findings from this study will contribute to improve knowledge on the impact of exposure to air pollution on mothers and babies and will also define biomarkers as predictors for pregnant women at risk.

Trial registration

ClinicalTrials.gov: 14/40/411. Registered 22-10-2015.

http://ift.tt/2DfMK22

Consumption of ultra-processed foods and associated sociodemographic factors in the USA between 2007 and 2012: evidence from a nationally representative cross-sectional study

Objectives

To compare ultra-processed food consumption across sociodemographic groups and over time (2007–2008, 2009–2010, 2011–2012) in the USA.

Design

Cross-sectional study.

Setting

National Health and Nutrition Examination Survey (NHANES) 2007–2012.

Participants

All individuals aged ≥2 years with at least one 24-hour dietary recall were included (n=23 847).

Main outcome measures

Average dietary contribution of ultra-processed foods (expressed as a percentage of the total caloric value of the diet), obtained after classifying all food items according to extent and purpose of industrial food processing using NOVA classification.

Data analysis

Linear regression was used to evaluate the association between sociodemographic characteristics or NHANES cycles and dietary contribution of ultra-processed foods.

Results

Almost 60% of calories consumed in the period 2007–2012 came from ultra-processed foods. Consumption of ultra-processed foods decreased with age and income level, was higher for non-Hispanic whites or non-Hispanic blacks than for other race/ethnicity groups and lower for people with college than for lower levels of education, all differences being statistically significant. Overall contribution of ultra-processed foods increased significantly between NHANES cycles (nearly 1% point per cycle), the same being observed among males, adolescents and high school education-level individuals.

Conclusions

Ultra-processed food consumption in the USA in the period 2007–2012 was overall high, greater among non-Hispanic whites or non-Hispanic blacks, less educated, younger, lower-income strata and increased across time.

http://ift.tt/2oZbVBD

Organisational perspectives on addressing differential attainment in postgraduate medical education: a qualitative study in the UK

Objectives

To explore how representatives from organisations with responsibility for doctors in training perceive risks to the educational progression of UK medical graduates from black and minority ethnic groups (BME UKGs), and graduates of non-UK medical schools (international medical graduates (IMGs)). To identify the barriers to and facilitators of change.

Design

Qualitative semistructured individual and group interview study.

Setting

Postgraduate medical education in the UK.

Participants

Individuals with roles in examinations and/or curriculum design from UK medical Royal Colleges. Employees of NHS Employers.

Results

Representatives from 11 medical Royal Colleges (n=29) and NHS Employers (n=2) took part (55% medically qualified, 61% male, 71% white British/Irish, 23% Asian/Asian British, 6% missing ethnicity). Risks were perceived as significant, although more so for IMGs than for BME UKGs. Participants based significance ratings on evidence obtained largely through personal experience. A lack of evidence led to downgrading of significance. Participants were pessimistic about effecting change, two main barriers being sensitivities around race and the isolation of interventions. Participants felt that organisations should acknowledge problems, but felt concerned about being transparent without a solution; and talking about race with trainees was felt to be difficult. Participants mentioned 63 schemes aiming to address differential attainment, but these were typically local or specialty-specific, were not aimed at BME UKGs and were largely unevaluated. Participants felt that national change was needed, but only felt empowered to effect change locally or within their specialty.

Conclusions

Representatives from organisations responsible for training doctors perceived the risks faced by BME UKGs and IMGs as significant but difficult to change. Strategies to help organisations address these risks include: increased openness to discussing race (including ethnic differences in attainment among UKGs); better sharing of information and resources nationally to empower organisations to effect change locally and within specialties; and evaluation of evidence-based interventions.

http://ift.tt/2HmyzKM

Is it feasible to conduct a randomised controlled trial of pretransplant exercise (prehabilitation) for patients with multiple myeloma awaiting autologous haematopoietic stem cell transplantation? Protocol for the PREeMPT study

Introduction

While myeloma is an incurable malignancy, developments in disease management have led to increased life expectancy in recent years. Treatment typically involves stem-cell transplantation. Increased survival rates equate to more patients living with the burden of both the disease and its treatment for increasing number of years, rendering myeloma a long-term condition.

Evidence exists to demonstrate the benefits of exercise for patients recovering from stem-cell transplantation, and prehabilitation—exercise before treatment—has been shown to be effective in other disease areas. To date there has been no research into prehabilitation in patients with myeloma awaiting transplantation treatment.

Our objective is to determine whether it is feasible to conduct a randomised controlled trial into pretransplant exercise for patients with multiple myeloma who are awaiting autologous stem-cell transplantation.

Methods and analysis

This mixed methods study identifies patients with diagnosis of multiple myeloma who have been assigned to the autologous transplantation list and invites them to participate in six weekly sessions of individualised, supervised exercise while awaiting transplantation.

Quantitative data to determine feasibility targets include rates of recruitment, adherence and adverse events, and outcome measures including 6 min walking distance test and quality of life.

Qualitative interviews are undertaken with a purposive sample of patients to capture their experiences of the study and the intervention.

Ethics and dissemination

Ethics committee approval has been obtained. Dissemination will be through open-access publications and presentations and will seek to reach multiprofessional bases as well as patients and carer groups, addressing the widespread interest in this area of research.

Trial registration number

NCT03135925; Pre-results.

http://ift.tt/2FoTOPQ

Steps Towards Alcohol Misuse Prevention Programme (STAMPP): a school-based and community-based cluster randomised controlled trial

Objectives

To assess the effectiveness of a combined classroom curriculum and parental intervention (the Steps Towards Alcohol Misuse Prevention Programme (STAMPP)), compared with alcohol education as normal (EAN), in reducing self-reported heavy episodic drinking (HED) and alcohol-related harms (ARHs) in adolescents.

Setting

105 high schools in Northern Ireland (NI) and in Scotland.

Participants

Schools were stratified by free school meal provision. Schools in NI were also stratified by school type (male/female/coeducational). Eligible students were in school year 8/S1 (aged 11–12 years) at baseline (June 2012).

Intervention

A classroom-based alcohol education intervention, coupled with a brief alcohol intervention for parents/carers.

Primary outcomes

(1) The prevalence of self-reported HED in the previous 30 days and (2) the number of self-reported ARHs in the previous 6 months. Outcomes were assessed using two-level random intercepts models (logistic regression for HED and negative binomial for number of ARHs).

Results

At 33 months, data were available for 5160 intervention and 5073 control students (HED outcome), and 5234 and 5146 students (ARH outcome), respectively. Of those who completed a questionnaire at either baseline or 12 months (n=12 738), 10 405 also completed the questionnaire at 33 months (81.7%). Fewer students in the intervention group reported HED compared with EAN (17%vs26%; OR=0.60, 95% CI 0.49 to 0.73), with no significant difference in the number of self-reported ARHs (incident rate ratio=0.92, 95% CI 0.78 to 1.05). Although the classroom component was largely delivered as intended, there was low uptake of the parental component. There were no reported adverse effects.

Conclusions

Results suggest that STAMPP could be an effective programme to reduce HED prevalence. While there was no significant reduction in ARH, it is plausible that effects on harms would manifest later.

Trial registration number

ISRCTN47028486; Post-results.

http://ift.tt/2HoGg3b

Using an internet intervention to support self-management of low back pain in primary care: findings from a randomised controlled feasibility trial (SupportBack)

Objective

To determine the feasibility of a randomised controlled trial of an internet intervention for low back pain (LBP) using three arms: (1) usual care, (2) usual care plus an internet intervention or (3) usual care plus an internet intervention with additional physiotherapist telephone support.

Design and setting

A three-armed randomised controlled feasibility trial conducted in 12 general practices in England.

Participants

Primary care patients aged over 18 years, with current LBP, access to the internet and without indicators of serious spinal pathology or systemic illness.

Interventions

The 'SupportBack' internet intervention delivers a 6-week, tailored programme, focused on graded goal setting, self-monitoring and provision of tailored feedback to encourage physical activity. Additional physiotherapist telephone support consisted of three brief telephone calls over a 4-week period, to address any concerns and provide reassurance.

Outcomes

The primary outcomes were the feasibility of the trial design including recruitment, adherence and retention at follow-up. Secondary descriptive and exploratory analyses were conducted on clinical outcomes including LBP-related disability at 3 months follow-up.

Results

Primary outcomes: 87 patients with LBP were recruited (target 60–90) over 6 months, and there were 3 withdrawals. Adherence to the intervention was higher in the physiotherapist-supported arm, compared with the stand-alone internet intervention. Trial physiotherapists adhered to the support protocol. Overall follow-up rate on key clinical outcomes at 3 months follow-up was 84%.

Conclusions

This study demonstrated the feasibility of a future definitive randomised controlled trial to determine the clinical and cost-effectiveness of the SupportBack intervention in primary care patients with LBP.

Trial registration number

ISRCTN31034004; Results.

http://ift.tt/2FqKgUn

Effectiveness of evidence-based treatments of fetal alcohol spectrum disorders in children and adolescents: a systematic review protocol

Introduction

The aim of this paper is to provide a protocol for a systematic review assessing the effectiveness of evidence from randomised controlled trials comparing fetal alcohol spectrum disorders pharmacological and non-pharmacological interventions with placebo/dummy interventions or usual standards of care in children and adolescents (<18 years old).

Methods and analysis

The following electronic databases will be searched: Medline (Ovid), Cumulative Index of Nursing and Allied Health Plus with Full text (EBSCO), Cochrane Central Register of Controlled Trials (Cochrane Library—Wiley), PsycINFO (ProQuest) and Proquest DissertationsandTheses will be searched from inception to March 2017 for relevant citations of published trials using individualised search strategies prepared for database. We will also search the reference lists of relevant articles and conference proceedings. Two reviewers will independently assess each study against predetermined inclusion/exclusion criteria and extract data including population characteristics, types and duration of interventions and outcomes from included trials. Internal validity will be assessed using the Cochrane Risk of Bias Tool. Primary outcome measures will be improvements in symptoms, including: hyperactivity, impulsivity and attention as measured by standard rating scales. Secondary outcome measures will include improvements in physical and mental health domains, as well as cognitive, behavioural, social and educational skills as measured by rating scales, standardised psychometric tests of IQ and memory, grade repetition, literacy tests and diagnosis of mental health disorder.

Ethics and dissemination

Ethical approval will not be obtained since it is not required for systematic reviews as there are no concerns regarding patient privacy. The results of this review will be disseminated through publication in a peer-review journal and presented at relevant conferences.

PROSPERO registration number

CRD42013005996.

http://ift.tt/2HoGdo1