Antihypertensive drug class and dyslipidemia: risk association among Chinese patients with uncomplicated hypertension

Factors associated with dyslipidemia in Chinese patients with uncomplicated hypertension were investigated in 1,139 patients newly prescribed a single antihypertensive drug in the public primary healthcare setting in Hong Kong, where their fasting lipid profiles were measured 4 to 16 weeks after the first prescription. Multivariate logistic regression showed that thiazide users were more likely (OR 3.67, 95% C.I. 1.13, 11.88, p=0.030) to have adverse (> 6.2mmol/l) total cholesterol (TC) compared with drugs acting on the renin angiotensin system (RAS), but the absolute difference in mean TC between thiazide users and all patients was small ( 0.14 mmol/l), while advanced age and male gender were also associated with some aspects of dyslipidemia. Clinicians should be aware of the increased risk of dyslipidemia in these groups, but the mild dyslipidemic profile associated with thiazides should not in itself deter its use as a possible first-line antihypertensive agent among Chinese patients

Prevalence of under and over weight in children with neurodisability, using body composition measures

We aimed to compare rates of under and overweight in children with different neurodevelopmental disorders (NDD) by measuring weight, height/length, arm-to-leg bioelectrical impedance (BIA) and subscapular and triceps skinfolds in 146 children aged 4-16 years attending special schools. Z scores were calculated and skinfolds and lean mass Z scores were further adjusted for height. Underweight was found in 9% (14) children (body mass index (BMI) < 2nd) but only 3% (4) had skinfolds <5th centile. Overweight was much commoner, with 41% (58) children having BMI > 95th and 20% (14) had skinfolds >95th centile. Children with cerebral palsy were very short with low BMI and lean mass, but only 8% (3) had skinfolds <5th centile. The children with Down syndrome were also very short and once adjusted for height, half had skinfolds >95th centile. We conclude that overweight and raised body fat is now common in children with NDD, even when the BMI is low

Etiologic workup in cases of cryptogenic stroke: protocol for a systematic review and comparison of international clinical practice guidelines

Background Stroke is a leading cause of death and disability worldwide. Identifying the aetiology of ischaemic stroke is essential in order to initiate appropriate and timely secondary prevention measures to reduce the risk of recurrence. For the majority of ischaemic strokes, the aetiology can be readily identified, but in at least 30% of cases the exact aetiology cannot be determined using existing investigative protocols. Such strokes are classed as ‘cryptogenic’ or as a stroke of unknown origin. However, there exists substantial variation in clinical practice when investigating cases of seemingly cryptogenic stroke, often reflecting local service availability and the preferences of treating clinicians. This variation in practice is compounded by the lack of international consensus as to the optimum level and timing of investigations required following a stroke. To address this gap, we aim to systematically review and compare recommendations in evidence-based clinical practice guidelines (CPGs) that relate to the assessment and investigation of the aetiology of ischaemic stroke, and any subsequent diagnosis of cryptogenic stroke. Method We will search for CPGs using electronic databases (MEDLINE, Health Management Information Consortium (HMIC), EMBASE, and CINAHL); relevant websites and search engines (e.g. guideline specific websites, governmental, charitable, professional practice organisations); and hand-searching of bibliographies and reference lists. Two reviewers will independently screen titles, abstracts and CPGs using a pre-defined relevance criteria form. From each included CPG we will extract definitions and terms for cryptogenic stroke; recommendations related to assessment and investigation of the aetiology of stroke, including grade of recommendations and underpinning evidence. Quality of the included CPGs will be assessed using the AGREE II (Appraisal of Guidelines for Research & Evaluation) tool. Recommendations across the CPGs will be summarised descriptively highlighting areas of convergence and divergence between CPGs. Discussion To our knowledge this will be the first review to systematically compare recommendations of international CPGs on investigating the aetiology of ischaemic stroke. The findings will allow for a better understanding of international perspectives on the optimum level of investigations required following a stroke, and thus contribute to achieving greater international consensus on best practice in this important and complex area

Proteostasis Dysregulation in Pancreatic Cancer

The most common form of pancreatic cancer, pancreatic ductal adenocarcinoma (PDAC), has a dismal 5-year survival rate of less than 5%. Radical surgical resection, in combination with adjuvant chemotherapy, provides the best option for long-term patient survival. However, only approximately 20% of patients are resectable at the time of diagnosis, due to locally advanced or metastatic disease. There is an urgent need for the identification of new, specific, and more sensitive biomarkers for diagnosis, prognosis, and prediction to improve the treatment options for pancreatic cancer patients. Dysregulation of proteostasis is linked to many pathophysiological conditions, including various types of cancer. In this review, we report on findings relating to the main cellular protein degradation systems, the ubiquitin-proteasome system (UPS) and autophagy, in pancreatic cancer. The expression of several components of the proteolytic network, including E3 ubiquitinligases and deubiquitinating enzymes, are dysregulated in PDAC, which accounts for approximately 90% of all pancreatic malignancies. In the future, a deeper understanding of the emerging role of proteostasis in pancreatic cancer has the potential to provide clinically relevant biomarkers and new strategies for combinatorial therapeutic options to better help treat the patients.Peer reviewe

Stroke in women — from evidence to inequalities

Stroke is the second largest cause of disability-adjusted life-years lost worldwide. The prevalence of stroke in women is predicted to rise rapidly, owing to the increasing average age of the global female population. Vascular risk factors differ between women and men in terms of prevalence, and evidence increasingly supports the clinical importance of sex differences in stroke. The influence of some risk factors for stroke — including diabetes mellitus and atrial fibrillation — are stronger in women, and hypertensive disorders of pregnancy also affect the risk of stroke decades after pregnancy. However, in an era of evidence-based medicine, women are notably under-represented in clinical trials — despite governmental actions highlighting the need to include both men and women in clinical trials — resulting in a reduced generalizability of study results to women. The aim of this Review is to highlight new insights into specificities of stroke in women, to plan future research priorities, and to influence public health policies to decrease the worldwide burden of stroke in women

Global variation in anastomosis and end colostomy formation following left-sided colorectal resection

Background End colostomy rates following colorectal resection vary across institutions in high-income settings, being influenced by patient, disease, surgeon and system factors. This study aimed to assess global variation in end colostomy rates after left-sided colorectal resection. Methods This study comprised an analysis of GlobalSurg-1 and -2 international, prospective, observational cohort studies (2014, 2016), including consecutive adult patients undergoing elective or emergency left-sided colorectal resection within discrete 2-week windows. Countries were grouped into high-, middle- and low-income tertiles according to the United Nations Human Development Index (HDI). Factors associated with colostomy formation versus primary anastomosis were explored using a multilevel, multivariable logistic regression model. Results In total, 1635 patients from 242 hospitals in 57 countries undergoing left-sided colorectal resection were included: 113 (6·9 per cent) from low-HDI, 254 (15·5 per cent) from middle-HDI and 1268 (77·6 per cent) from high-HDI countries. There was a higher proportion of patients with perforated disease (57·5, 40·9 and 35·4 per cent; P < 0·001) and subsequent use of end colostomy (52·2, 24·8 and 18·9 per cent; P < 0·001) in low- compared with middle- and high-HDI settings. The association with colostomy use in low-HDI settings persisted (odds ratio (OR) 3·20, 95 per cent c.i. 1·35 to 7·57; P = 0·008) after risk adjustment for malignant disease (OR 2·34, 1·65 to 3·32; P < 0·001), emergency surgery (OR 4·08, 2·73 to 6·10; P < 0·001), time to operation at least 48 h (OR 1·99, 1·28 to 3·09; P = 0·002) and disease perforation (OR 4·00, 2·81 to 5·69; P < 0·001). Conclusion Global differences existed in the proportion of patients receiving end stomas after left-sided colorectal resection based on income, which went beyond case mix alone