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Background: Total hip replacement is a common and highly effective operation. All hip replacements would eventually fail if in situ long enough and it is important that patients understand when this might happen. We aimed to answer the question: how long does a hip replacement last?, Methods: We did a systematic review and meta-analysis with a search of MEDLINE and Embase from the start of records to Sept 12, 2017. We included articles reporting 15-year survival of primary, conventional total hip replacement constructs in patients with osteoarthritis. We extracted survival and implant data and used all-cause construct survival as the primary outcome. We also reviewed reports of national joint replacement registries, and extracted data for a separate analysis. In the meta-analyses, we weighted each series and calculated a pooled survival estimate for each source of data. This study was registered with PROSPERO (CRD42018085642)., Findings: We identified 140 eligible articles reporting 150 series, and included 44 of these series (13 212 total hip placements). National joint replacement registries from Australia and Finland provided data for 92 series (215 676 total hip replacements). The 25-year pooled survival of hip replacements from case series was 77·6% (95% CI 76·0-79·2) and from joint replacement registries was 57·9% (95% CI 57·1-58·7)., Interpretation: Assuming that estimates from national registries are less likely to be biased, patients and surgeons can expect a hip replacement to last 25 years in around 58% of patients., Funding: National Institute for Health Research, National Joint Registry for England, Wales, Northern Ireland and Isle of Man, and The Royal College of Surgeons of England., (Copyright © 2019 The Author(s). Published by Elsevier Ltd. This is an Open Access article under the CC BY 4.0 license. Published by Elsevier Ltd.. All rights reserved.)

Background: Knee replacements are the mainstay of treatment for end-stage osteoarthritis and are effective. Given time, all knee replacements will fail and knowing when this failure might happen is important. We aimed to establish how long a knee replacement lasts., Methods: In this systematic review and meta-analysis, we searched MEDLINE and Embase for case series and cohort studies published from database inception until July 21, 2018. Articles reporting 15 year or greater survival of primary total knee replacement (TKR), unicondylar knee replacement (UKR), and patellofemoral replacements in patients with osteoarthritis were included. Articles that reviewed specifically complex primary surgeries or revisions were excluded. Survival and implant data were extracted, with all-cause survival of the knee replacement construct being the primary outcome. We also reviewed national joint replacement registry reports and extracted the data to be analysed separately. In the meta-analysis, we weighted each series and calculated a pooled survival estimate for each data source at 15 years, 20 years, and 25 years, using a fixed-effects model. This study is registered with PROSPERO, number CRD42018105188., Findings: From 4363 references found by our initial search, we identified 33 case series in 30 eligible articles, which reported all-cause survival for 6490 TKRs (26 case series) and 742 UKRs (seven case series). No case series reporting on patellofemoral replacements met our inclusion criteria, and no case series reported 25 year survival for TKR. The estimated 25 year survival for UKR (based on one case series) was 72·0% (95% CI 58·0-95·0). Registries contributed 299 291 TKRs (47 series) and 7714 UKRs (five series). The pooled registry 25 year survival of TKRs (14 registries) was 82·3% (95% CI 81·3-83·2) and of UKRs (four registries) was 69·8% (67·6-72·1)., Interpretation: Our pooled registry data, which we believe to be more accurate than the case series data, shows that approximately 82% of TKRs last 25 years and 70% of UKRs last 25 years. These findings will be of use to patients and health-care providers; further information is required to predict exactly how long specific knee replacements will last., Funding: The National Joint Registry for England, Wales, Northern Ireland, and Isle of Man and the Royal College of Surgeons of England., (Copyright © 2019 Elsevier Ltd. All rights reserved.)

ABSTRACTObjective:Little is known about the current views and practices of healthcare professionals (HCPs) in Sub-Saharan Africa (SSA) regarding delivery of hospital palliative care. The present qualitative study explored the views of nursing staff and medical professionals on providing palliative and end-of-life care (EoLC) to hospital inpatients in Tanzania., Method: Focus group discussions were conducted with a purposive sample of HCPs working on the medical and pediatric wards of the Kilimanjaro Christian Medical Centre, a tertiary referral hospital in northern Tanzania. Transcriptions were coded using a thematic approach., Results: In total, 32 healthcare workers were interviewed via 7 focus group discussions and 1 semistructured interview. Four major themes were identified. First, HCPs held strong views on what factors were important to enable individuals with a life-limiting diagnosis to live and die well. Arriving at a state of "acceptance" was the ultimate goal; however, they acknowledged that they often fell short of achieving this for inpatients. Thus, the second theme involved identifying the "barriers" to delivering palliative care in hospital. Another important factor identified was difficulty with complex communications, particularly "breaking bad news," the third theme. Fourth, participants were divided about their personal preferences for "place of EoLC," but all emphasized the benefits of the hospital setting so as to enable better symptom control., Significance of Results: Despite the fact that all the HCPs interviewed were regularly involved in providing palliative and EoLC, they had received limited formal training in its provision, although they identified such training as a universal requirement. This training gap is likely to be present across much of SSA. Palliative care training, particularly in terms of communication skills, should be comprehensively integrated within undergraduate and postgraduate education. Research is needed to develop culturally appropriate curricula to equip HCPs to manage the complex communication challenges that occur in caring for a diverse inpatient group with palliative care needs.

The calcium sensing receptor (CaSR) in the distal nephron decreases the propensity for calcium stones. Here we investigate if the apical CaSR in the proximal tubule also prevents stone formation acting via regulation of apical dicarboxylate and citrate transport. Urinary citrate, partially reabsorbed as a dicarboxylate in the proximal tubule lumen, inhibits stone formation by complexing calcium. We previously demonstrated a novel apical calcium-sensitive dicarboxylate transport system in OK proximal tubule cells. This calcium-sensitive process has the potential to modulate the amount of citrate available to complex increased urinary calcium. Using isotope labeled succinate uptake in OK cells along with various pharmacologic tools we examined whether the CaSR alters apical dicarboxylate transport and through which signal transduction pathways this occurs. Our results indicate that in the proximal tubule CaSR adjusts apical dicarboxylate transport, and does so via a CaSR → G q  → PKC signaling pathway. Thus, the CaSR may decrease the propensity for stone formation via actions in both proximal and distal nephron segments.

Background: Subtalar arthrodesis through an open approach carries significant risk of complications. An arthroscopic approach aims to minimise damage to the soft tissue envelope to improve recovery, union and complication rates. A two portal approach through the sinus tarsi was used., Methods: A retrospective review of all patients undergoing isolated arthroscopic arthrodesis was performed., Results: Seventy-seven procedures were performed. Successful arthrodesis was achieved in 75 (97.4%). Two patients underwent successful revision arthrodesis for aseptic nonunion. There was one (1.3%) superficial infection and one (1.3%) partial sural nerve injury., Conclusions: Two-portal sinus tarsi arthroscopic subtalar arthrodesis is safe and effective. Advantages over other arthroscopic approaches are the access to all three facets of the joint, avoidance of a posterolateral portal in order to minimise risk to the sural nerve, and the ability to use the same approach to arthrodese the entire triple hindfoot joint complex. Technical tips and pitfalls are discussed., (Copyright © 2017 European Foot and Ankle Society. Published by Elsevier Ltd. All rights reserved.)

ABSTRACTBackground:The number of people living with dementia in sub-Saharan Africa (SSA) is expected to increase rapidly in the coming decades. However, our understanding of how best to reduce dementia risk in the population is very limited. As a first step in developing intervention strategies to manage dementia risk in this setting, we investigated rates of cognitive decline in a rural population in Tanzania and attempted to identify associated factors., Methods: The study was conducted in the rural Hai district of northern Tanzania. In 2014, community-dwelling people aged 65 years and over living in six villages were invited to take part in a cognitive screening program. All participants from four of the six villages were followed-up at two years and cognitive function re-tested. At baseline and follow-up, participants were assessed for functional disability, hypertension, and grip strength (as a measure of frailty). At follow-up, additional assessments of visual acuity, hearing impairment, tobacco and alcohol consumption, and clinical assessment for stroke were completed., Results: Baseline and follow-up data were available for 327 people. Fifty people had significant cognitive decline at two-year follow-up. Having no formal education, low grip strength at baseline, being female and having depression at follow-up were independently associated with cognitive decline., Conclusions: This is one of the first studies of cognitive decline conducted in SSA. Rates of decline at two years were relatively high. Future work should focus on identification of specific modifiable risk factors for cognitive decline with a view to developing culturally appropriate interventions.

Background: Task shifting has been suggested as one way to help manage the increasing burden of dementia in sub-Saharan Africa (SSA). However, brief, easy-to-use and valid screening tools are needed to support this approach. Our team has developed an 11-item questionnaire to assess instrumental activities of daily living (IADLs) in SSA, the Identification and Intervention for Dementia in Elderly Africans (IDEA)-IADL questionnaire. We aimed to externally validate the questionnaire and develop a shorter, more efficient version., Methods: A community-based sample of 329 older adults in 4 rural villages was screened for dementia using the validated IDEA cognitive screen and the 11-item IDEA-IADL questionnaire. A stratified sample was assessed for Diagnostic and Statistical Manual of Mental Disorders (Fourth Edition) dementia by a United Kingdom-based doctor, who was blinded to the results of screening. Area under the receiver operating characteristic (AUROC) curve analysis was used to assess validity, and factor analysis and regression modeling were used to develop a shorter version of the questionnaire., Results: A 3-item IDEA-IADL questionnaire was developed and externally validated in the study sample. The questionnaire was deemed to be valid and enhanced screening performance in 2 villages (AUROC: 0.857 and 0.895) but detracted from the accuracy of the IDEA cognitive screen in the other 2 villages (AUROC: 0.591 and 0.639). These differences appeared to be due to differences in interpretation of responses to questions by the assessors., Conclusions: A brief IDEA-IADLs scale was developed and worked well in some villages. However, our study highlights a training need if brief screening tools to assess IADLs are to be effectively used by nonspecialists in low-resource settings.

By 2030, sub-Saharan Africa is forecast to see the steepest rise in the number of people with hypertension of any world region. Hypertensive retinopathy is known to be a common complication of hypertension in developed countries and some studies suggest it is associated with the presence of other hypertension-related end-organ damage (EOD) such as stroke and cardiovascular disease. In Tanzania hypertension is relatively more common than in other parts of sub-Saharan Africa, especially in the older population; however, the prevalence of hypertensive retinopathy and its association with EOD remain unknown. The authors conducted a cross-sectional study of elderly, community-dwelling, rural Tanzanians to determine the prevalence of hypertensive retinopathy and its association with hypertension and other forms of EOD. Hypertensive retinopathy was diagnosed based on retinal imaging. In a cohort of 61 patients with gradable images, the authors found the overall prevalence of hypertensive retinopathy to be 64% (n = 39), which was strongly associated with hypertension (X 2 [1] = 4.207, P = .004), with a significant trend towards more severe retinopathy with more severe hypertension (r = .377, P = .003). The authors did not find hypertensive retinopathy to be associated with other forms of EOD. Hypertensive retinopathy is highly prevalent in this population and is associated in most but not all cases with hypertension. These findings do not suggest that it could be used as a screening tool for EOD, but it is important to identify and educate patients with retinopathy about possible complications of the condition., (©2018 Wiley Periodicals, Inc.)

Background: In the United Kingdom, people with Parkinson disease (PD) and atypical parkinsonism will require more support with their care needs as the condition progresses. There are few data on the nature of care input required and the amount of informal and formal care needed by people with PD to enable them to remain within their own home., Method: All people with moderate to advanced stage (Hoehn and Yahr III-V) idiopathic PD and atypical parkinsonism under the care of the Northumbria Healthcare NHS Foundation Trust PD service and living in their own home were invited to take part in The Northumbria Care Needs Project, a 10-year prospective longitudinal study. At baseline, data regarding formal (paid) personal and domestic care input and use of respite care, sitting services, and day centers were collected. We also collected data on patient cognitive disability, functional disability, and disease severity and informal carer tasks., Results: Of 162 people with PD included in the study, only 25.2% accessed formal domestic care and the same proportion formal personal care. In contrast, 80.2% identified an informal carer who helped with these tasks. Despite greater level of functional disability in those with an informal carer, levels of formal personal care input were similar to those with and without a formal carer. Levels of formal domestic carer input were higher in those without an informal carer., Conclusions: Use of formal care services was relatively uncommon in our cohort and much of the burden of caring appears to be being met by informal carers.

Alcohol is known to cause elevation of serum total IgE (tIgE). Whether it can predispose to allergic disorders, however, is not clear. To assess whether alcohol can cause sensitization to allergens, we analyzed 100 individuals with alcohol use disorder (AUD) and 50 matched healthy controls. Serum tIgE and specific IgE against environmental allergens were measured. We found 93% of individuals with AUD had raised tIgE compared to only 48% of healthy controls ( p  < 0.0001). Sensitization to aeroallergens was noted in 68% drinkers compared to 24% of controls ( p  < 0.0001). The degree of sensitization was directly proportional to the amount and duration of alcohol intake. There is a possibility of a link between alcohol abuse and allergic sensitization.

Background: Primary immunodeficiency disorders (PID) include a wide spectrum of inherited disorders characterised by functional abnormalities of one or more components of the immune system. Recent updates from the genomic data have contributed significantly to its better understanding with identification of new entities. Diagnosis is always challenging due to their variable clinical presentation. With the evolution of molecular diagnosis, many of these children are being diagnosed early and offered appropriate therapy. However, in developing countries, early diagnosis is still not being made: as a result these patients succumb to their disease. Autopsy data on PID is notably lacking in the literature with histopathological evaluation of PID being limited to rare case reports., Objective: To analyse the clinical, immunologic (including mutational) and morphologic features at autopsy in 10 proven and suspected cases of primary immunodeficiency disorders diagnosed at our Institute over the past decade., Methods: Study includes a detailed clinico-pathological analysis of 10 proven and suspected cases of primary immunodeficiency disorders., Results: A varied spectrum of infectious and non-infectious complications were identified in these cases of which fungal infections were found to be more frequent compared with viral or bacterial infections. Rare and novel morphological findings, like granulomatous involvement of the heart in a patient with chronic granulomatous disease, systemic amyloidosis in a teenage girl with X-linked agammaglobulinemia, are highlighted which is distinctly lacking in the literature., Conclusions: The present study is perhaps the first autopsy series on PID. Even in the molecular era, such analysis is still important, as correlation of pathological features with clinical symptoms provides clues for a timely diagnosis and appropriate therapeutic intervention., Competing Interests: Competing interests: None declared., (© Article author(s) (or their employer(s) unless otherwise stated in the text of the article) 2018. All rights reserved. No commercial use is permitted unless otherwise expressly granted.)

Introduction: Cognitive stimulation therapy is a non-pharmacological intervention for people with dementia. Its use has been associated with substantial improvements in cognition and quality of life in studies from high-income countries, equivalent to those achieved by pharmacological treatments. Cognitive stimulation therapy may be particularly suited to low resource settings, such as sub-Saharan Africa, because it requires little specialist equipment and can be delivered by non-specialist health workers. The aim of this study was to adapt cognitive stimulation therapy for use in sub-Saharan Africa taking into account socio-cultural differences and resource implications., Methods: Cognitive stimulation therapy is a structured programme, originally developed in the United Kingdom. Substantial adaptations were required for use in sub-Saharan Africa. The formative method for adapting psychotherapy was used as a framework for the adaption process. The feasibility of using the adapted cognitive stimulation therapy programme to manage dementia was assessed in Tanzania and Nigeria in November 2013. Further adaptations were made following critical appraisal of feasibility., Results: The adapted cognitive stimulation therapy intervention appeared feasible and acceptable to participants and carers. Key adaptations included identification of suitable treatment settings, task adaptation to accommodate illiteracy and uncorrected sensory impairment, awareness of cultural differences and usage of locally available materials and equipment to ensure sustainability., Conclusions: Cognitive stimulation therapy was successfully adapted for use in sub-Saharan Africa. Future work will focus on a trial of cognitive stimulation therapy in each setting.

2017 marks 200 years since James Parkinson's published his 'Essay on the Shaking Palsy'. Although now most famous for describing the condition that came to bear his name, Parkinson had a wide range of interests and his influence spread beyond medicine. In this review, we provide a biography of James Parkinson's remarkable life.Parkinson's paper not only comprehensively described the symptoms of Parkinson's disease (PD), but challenged his peers to better understand the pathophysiology of the PD. Key observation over the next 2 centuries, included the recognition of the link between the substantia nigra and PD and the discoveries of dopamine deficiency in patients with PD. We review the subsequent development of pharmacological and surgical therapies. Despite great progress over the last 200 years, Parkinson's hopes for a 'cure if employed early enough' or that 'some remedial process may ere long be discovered by which at least the progression of the disease may be stopped' remain apposite today and we reflect on the challenges ahead for the next century.

Background: In sub-Saharan Africa, there are no validated screening tools for delirium in older adults. This study assesses clinical utility of two instruments, the IDEA cognitive screen and the Confusion Assessment Method (CAM) for identification of delirium in older adults admitted to medical wards of a tertiary referral hospital in Tanzania., Method: The IDEA cognitive screen and CAM were administered to a consecutive cohort of older individuals on admission to Kilimanjaro Christian Medical Centre using a blinded protocol. Consensus diagnosis for delirium was established against DSM-5 criteria and dementia by DSM-IV criteria., Results: Of 507 admission assessments, 95 (18.7%) had DSM-5 delirium and 95 (18.7%) had DSM-IV dementia (33 (6.5%) delirium superimposed on dementia). The CAM and IDEA cognitive screen had very good diagnostic accuracy for delirium (AUROC curve 0.94 and 0.87 respectively). However, a number of participants (10.5% and 16.4% respectively) were unable to complete these screening assessments due to reduced consciousness, or other causes of reduced verbal response and were excluded from this analysis; many of whom met DSM-5 criteria for delirium. Secondary analysis suggests that selected cognitive and observational items from the CAM and IDEA cognitive screen may be as effective as the full screening tools in identifying delirium even in unresponsive patients., Conclusion: Both instruments appeared useful for delirium screening in this inpatient setting, but had significant limitations. The combination of assessment items identified may form the basis of a brief, simple delirium screening tool suitable for use by non-specialist clinicians. Further development work is needed., (Copyright © 2017 Elsevier B.V. All rights reserved.)

Few data from sub-Saharan Africa exist on the effects of hypertension on the organs of the human body. We aimed to establish the prevalence of hypertensive end organ damage (EOD) in an elderly cohort of Tanzanians. The population aged 70 years and over of 2 villages in northern Tanzania (n = 246), had blood pressure (BP) data available from 2010 and 2013, and underwent in-depth follow-up for markers of hypertensive EOD in 2016. Assessment included ankle-brachial pressure index, lying-standing BP, electrocardiogram, and mid-stream urine dip. Sustained hypertension (those with hypertension at all 3 assessments) was found in 129 (52.4% subjects). Of the entire cohort, 13.9% had left ventricular hypertrophy and 26.4% had peripheral arterial disease, both of which were associated with sustained hypertension, although orthostatic hypotension, stroke, proteinuria, and arterial stiffening were not. Further investigation, particularly in younger age groups, is merited if hypertension-associated morbidity is to be controlled., (©2018 Wiley Periodicals, Inc.)

Chronic obstructive pulmonary disease (COPD) causes substantial burden of disease in developed countries, but there are limited data from Africa. We aimed to estimate the prevalence of COPD in Tanzania and identify the risk factors associated with it.This was a cross-sectional descriptive survey involving adults aged ≥35 years. We collected data on symptoms and risk factors using the Burden of Obstructive Lung Diseases questionnaire. Spirometry was performed and COPD diagnosed based on post-bronchodilator forced expiratory volume in 1 s/forced vital capacity <70%. We also measured indoor and outdoor carbon monoxide (CO) levels.A total of 869 participants (49.1% females) completed the questionnaires. Of these, 57.1% completed post-bronchodilator spirometry. Of the 25.2% ever-smokers, only 5.4% were current smokers. COPD prevalence was estimated at 17.5% (21.7% in males and 12.9% in females). COPD was associated with a history of cough, phlegm production and wheezing. 51.7% of COPD patients reported cough and 85% had mild to moderate airway limitation. Females had a higher rate of exacerbation. Pulmonary tuberculosis (TB) was reported in 10% of patients. Only 1.7% of patients who were diagnosed as COPD had ever received any medication, with only one female COPD patient having received an inhaler. 99.5% of the population used biomass fuels for cooking. The majority of households had CO levels up to 20 ppm.The prevalence of COPD in Tanzania is high, with a peak at a relatively young age and a preponderance in males. A history of TB, cigarette smoking and male sex are important risk factors. Indoor air pollution coupled with use of biomass fuel for cooking and heating may be an important risk factor for developing COPD in rural Tanzania. However, these factors need to be studied further., Competing Interests: Conflict of interest: None declared., (Copyright ©ERS 2018.)

Purpose: To assess the impact of childhood epilepsy on social transitioning outcomes for young people with epilepsy (YPWE) living in Tanzania, and to explore influences on these outcomes., Methods: At six years from baseline, we followed up 84 YPWE and 79 age- sex- and village- matched controls recruited into a case-control study of childhood epilepsy in rural northern Tanzania. Data were collected from interviews with young people and their carers using a structured questionnaire. Perceived stigma was evaluated using the Kilifi Stigma Score and functional disability using the Barthel Index (BI). The effects of age, gender, functional disability and stigma on selected markers of social transitioning (education, employment and relationships) were estimated using multivariable modelling., Results: Fewer YPWE than controls were in an intimate relationship (42.3% vs. 76.9%) or in education or paid employment (33.3% vs. 91.1%) and they reported elevated perceived stigma scores (27.4% vs. 3.8%). Among YPWE, a positive education or employment outcome was predicted by a lower seizure frequency (adjusted OR 3.79) and a higher BI score (adj. OR 12.12); a positive relationship outcome was predicted by a higher BI score (adj. OR 45.86) and being male (adj. OR 8.55)., Conclusion: YPWE were more likely to experience adverse employment, educational and relationship outcomes in the transition to adult life than controls, with the greatest disadvantage experienced by females, those with greater functional disability and those with poorer seizure control. Markers of social transitioning should be included in any prospective evaluation of interventions designed to support these groups., (Copyright © 2017 British Epilepsy Association. Published by Elsevier Ltd. All rights reserved.)

Aim: To review patients that have undergone correction of a symptomatic femoral malunion using osteotomy combined with decortication., Methods: A retrospective review of all patients who have undergone decortication and multiplanar osteotomy, looking at the pre-operative deformity, correction achieved, time to union and complications., Results: Seven patients underwent correction under the senior author from 2003 to 2012. Average age was 46 years (range 32-60 years). All had femoral shortening deformity (average 2.7 cm, range 2-4 cm). Each also had at least one other plane of deformity with rotation being the next most commonly encountered in 5 out of the 7 (average 33°, range 0°-45°). Two had tri-planar deformity with the five having bi-planar deformity. Average time to union was 16.3 months (range 7-39 months) with an average of 1.5 operations (range 1-3 operations) to union. One patient has a non-union after five corrective operations., Conclusion: Correction of multiplanar deformity of the femur is challenging. Osteotomy with decortication provides a technique to achieve significant femoral multiplanar deformity correction in a single operation. This publication provides technical description of the operative technique, guidance and results.

The colonization of the gut with microbes in early life is critical to the developing newborn immune system, metabolic function and potentially future health. Maternal microbes are transmitted to offspring during childbirth, representing a key step in the colonization of the infant gut. Studies of infant meconium suggest that bacteria are present in the foetal gut prior to birth, meaning that colonization could occur prenatally. Animal studies have shown that prenatal transmission of microbes to the foetus is possible, and physiological changes observed in pregnant mothers indicate that in utero transfer is likely in humans as well. However, direct evidence of in utero transfer of bacteria in humans is lacking. Understanding the timing and mechanisms involved in the first colonization of the human gut is critical to a comprehensive understanding of the early life gut microbiome. This review will discuss the evidence supporting in utero transmission of microbes from mother to infants. We also review sources of transferred bacteria, physiological mechanisms of transfer and modifiers of maternal microbiomes and their potential role in early life infant health. Well-designed longitudinal birth studies that account for established modifiers of the gut microbiome are challenging, but will be necessary to confirm in utero transfer and further our knowledge of the prenatal microbiome., (© 2017 World Obesity Federation.)

Objective: This study aimed to assess the feasibility of a low-literacy adaptation of the Alzheimer's Disease Assessment Scale - Cognitive (ADAS-Cog) for use in rural sub-Saharan Africa (SSA) for interventional studies in dementia. No such adaptations currently exist., Methods: Tanzanian and Nigerian health professionals adapted the ADAS-Cog by consensus. Validation took place in a cross-sectional sample of 34 rural-dwelling older adults with mild/moderate dementia alongside 32 non-demented controls in Tanzania. Participants were oversampled for lower educational level. Inter-rater reliability was conducted by two trained raters in 22 older adults (13 with dementia) from the same population. Assessors were blind to diagnostic group., Results: Median ADAS-Cog scores were 28.75 (interquartile range (IQR), 22.96-35.54) in mild/moderate dementia and 12.75 (IQR 9.08-16.16) in controls. The area under the receiver operating characteristic curve (AUC) was 0.973 (95% confidence interval (CI) 0.936-1.00) for dementia. Internal consistency was high (Cronbach's α 0.884) and inter-rater reliability was excellent (intra-class correlation coefficient 0.905, 95% CI 0.804-0.964)., Conclusion: The low-literacy adaptation of the ADAS-Cog had good psychometric properties in this setting. Further evaluation in similar settings is required.

In the above article (Paddick, 2017) The corresponding author's details were previously listed incorrectly. The correct details are; contact number +44 191 293 2709 and email address William.gray@nhct.nhs.uk. The original article has been updated with the correct contact details. The publishers apologise for any inconvenience and confusion this error has caused.

Background: The majority of older adults with dementia live in low- and middle-income countries (LMICs). Illiteracy and low educational background are common in older LMIC populations, particularly in rural areas, and cognitive screening tools developed for this setting must reflect this. This study aimed to review published validation studies of cognitive screening tools for dementia in low-literacy settings in order to determine the most appropriate tools for use., Method: A systematic search of major databases was conducted according to PRISMA guidelines. Validation studies of brief cognitive screening tests including illiterate participants or those with elementary education were eligible. Studies were quality assessed using the QUADAS-2 tool. Good or fair quality studies were included in a bivariate random-effects meta-analysis and a hierarchical summary receiver operating characteristic (HSROC) curve constructed., Results: Forty-five eligible studies were quality assessed. A significant proportion utilized a case-control design, resulting in spectrum bias. The area under the ROC (AUROC) curve was 0.937 for community/low prevalence studies, 0.881 for clinic based/higher prevalence studies, and 0.869 for illiterate populations. For the Mini-Mental State Examination (MMSE) (and adaptations), the AUROC curve was 0.853., Conclusion: Numerous tools for assessment of cognitive impairment in low-literacy settings have been developed, and tools developed for use in high-income countries have also been validated in low-literacy settings. Most tools have been inadequately validated, with only MMSE, cognitive abilities screening instrument (CASI), Eurotest, and Fototest having more than one published good or fair quality study in an illiterate or low-literate setting. At present no screening test can be recommended.

Background/Study Context: Interest in frailty is growing in low- and middle-income countries, due to demographic aging and resource limitations. However, there is a paucity of data on the nature of frailty in Africa., Methods: The study collected frailty data from people aged 70 years and over living in six villages in the rural Hai District of northern Tanzania. At baseline, a limited data set was collected for 1198 people and a more comprehensive data set for a stratified sample of 296 people. A 40-item frailty index was constructed. Data regarding mortality and dependency were collected at 3-year follow-up., Results: A higher frailty index score was significantly correlated with greater age, never having attended school, falls, mortality, and dependency in activities of daily living. Logistic regression modeling revealed functional disability and cognitive function to be significant independent predictors of the outcome "mortality or dependency.", Conclusions: In resource-poor settings, brief frailty screening assessments may be a useful way of identifying those most in need of support.

Background: Stroke is a major cause of death worldwide and 85.5% of stroke deaths occur in low- and middle-income countries due to stroke. The aim of this study was to investigate correlates and predictors of 30-day mortality in stroke patients in urban Tanzania., Methods: A prospective 30-day follow-up study was conducted at the Muhimbili National Hospital, Dar es Salaam, Tanzania. We recruited all patients with stroke seen at the Emergency Medicine Department and medical wards. Patients underwent medical history and physical examination including full neurological examination. For those who met the criteria for the diagnosis of stroke according to the World Health Organization, further data were collected, including cholesterol, creatinine, fasting blood glucose, full blood picture, human immunodeficiency virus serology, and electrocardiogram. Patients were followed up at 30 days from the date of stroke onset. The date and the cause of death of those participants who died within 30 days of stroke onset were recorded., Results: A total of 224 patients were recruited into the study, with follow-up data available on 186 (83.0%). At 30 days post stroke, 124 patients (66.7%) were still alive. Mortality was significantly higher among stroke patients who were over 65 years of age. Of the 62 who died, 54% died of aspiration pneumonia and 21% of septicemia. Patients with infection were 4.4 times more likely to die than thosewithout (P = .001)., Conclusions: Poststroke mortality rates were high. Many deaths were potentially preventable., (Crown Copyright © 2017. Published by Elsevier Inc. All rights reserved.)

Background: Low diagnostic rates are a barrier to improving care for the growing number of people with dementia in sub-Saharan Africa. Many people with dementia are thought to visit traditional healers (THs) and Christian faith healers (FHs) and these groups may have a role in identifying people with dementia. We aimed to explore the practice and attitudes of these healers regarding dementia in rural Tanzania and investigate attitudes of their patients and their patients’ carers., Methods: This was a qualitative study conducted in Hai district, Tanzania. Semi-structured interviews were conducted with a convenience sample of THs and FHs and a purposive-stratified sample of people with dementia and their carers. Interview guides were devised which included case vignettes. Transcripts of interviews were subject to thematic analysis., Findings: Eleven THs, 10 FHs, 18 people with dementia and 17 carers were recruited. Three themes emerged: (i) conceptualisation of dementia by healers as a normal part of the ageing process and no recognition of dementia as a specific condition; (ii) people with dementia and carer reasons for seeking help and experiences of treatment and the role of prayers, plants and witchcraft in diagnosis and treatment; (iii) willingness to collaborate with allopathic healthcare services. FHs and people with dementia expressed concerns about any collaboration with THs., Conclusions: Although THs and FHs do not appear to view dementia as a specific disease, they may provide a means of identifying people with dementia in this setting.

Investigating genetic architecture of complex traits in ancestrally diverse populations is imperative to understand the etiology of disease. However, the current paucity of genetic research in people of African and Latin American ancestry, Hispanic and indigenous peoples in the United States is likely to exacerbate existing health disparities for many common diseases. The Population Architecture using Genomics and Epidemiology, Phase II (PAGE II), Study was initiated in 2013 by the National Human Genome Research Institute to expand our understanding of complex trait loci in ethnically diverse and well characterized study populations. To meet this goal, the Multi-Ethnic Genotyping Array (MEGA) was designed to substantially improve fine-mapping and functional discovery by increasing variant coverage across multiple ethnicities at known loci for metabolic, cardiovascular, renal, inflammatory, anthropometric, and a variety of lifestyle traits. Studying the frequency distribution of clinically relevant mutations, putative risk alleles, and known functional variants across multiple populations will provide important insight into the genetic architecture of complex diseases and facilitate the discovery of novel, sometimes population-specific, disease associations. DNA samples from 51,650 self-identified African ancestry (17,328), Hispanic/Latino (22,379), Asian/Pacific Islander (8,640), and American Indian (653) and an additional 2,650 participants of either South Asian or European ancestry, and other reference panels have been genotyped on MEGA by PAGE II. MEGA was designed as a new resource for studying ancestrally diverse populations. Here, we describe the methodology for selecting trait-specific content for use in multi-ethnic populations and how enriching MEGA for this content may contribute to deeper biological understanding of the genetic etiology of complex disease., Competing Interests: The authors have declared that no competing interests exist.

Introduction: Current PD assessment methods have inherent limitations. There is need for an objective method to assist clinical decisions and to facilitate evaluation of treatments. Accelerometers, and analysis using artificial neural networks (ANN), have shown potential as a method of motor symptom evaluation. This work describes the development of a novel PD disease state detection system informed by algorithms based on data collected in an unsupervised, home environment. We evaluated whether this approach can reproduce patient-completed symptom diaries and clinical assessment of disease state., Methods: 34 participants with PD wore bilateral wrist-worn accelerometers for 4 h in a research facility (phase 1) and for 7 days at home whilst completing symptom diaries (phase 2). An ANN to predict disease state was developed based on home-derived accelerometer data. Using a leave-one-out approach, ANN performance was evaluated against patient-completed symptom diaries and against clinician rating of disease state., Results: In the clinical setting, specificity for dyskinesia detection was extremely high (0.99); high specificity was also demonstrated for home-derived data (0.93), but with low sensitivity (0.38). In both settings, sensitivity for on/off detection was sub-optimal. ANN-derived values of the proportions of time in each disease state showed strong, significant correlations with patient-completed symptom diaries., Conclusion: Accurate, real-time evaluation of symptoms in an unsupervised, home environment, with this sensor system, is not yet achievable. In terms of the amounts of time spent in each disease state, ANN-derived results were comparable to those of symptom diaries, suggesting this method may provide a valuable outcome measure for medication trials., (Copyright © 2016 Elsevier Ltd. All rights reserved.)

Background: Oncogenic viruses have recently been allied with lung carcinoma, however, the causal association has not been established till date. The study was conducted to determine the prevalence of high-risk Human papillomavirus (HPV; subtypes 16, 18, 31, 33 and 45), Epstein-Barr virus (EBV) and cytomegalovirus (CMV) in lung carcinoma using polymerase chain reaction (PCR) on fine needle aspirates., Methods: Fine needle aspirates of patients with lung carcinoma were included as cases. The control samples included normal lung tissue, collected at the time of medico legal autopsies. DNA was extracted from samples of both cases and controls and analysed by PCR for the presence of HPV, EBV and CMV., Results: A total of 5/73 (6.8%) cases demonstrated the presence of HPV. Of these, 3 were positive for HPV-16 and one each for HPV-18 and HPV-45. A significant association of HPV with squamous cell carcinoma (SCC) (P = 0.01) was observed. Two cases were positive for EBV; however, the difference was not statistically significant for EBV (P = 0.5) as well as CMV. None of the controls were positive for HPV, EBV or CMV., Conclusion: We conclude that fine needle aspirates can serve as reliable sample for PCR based detection of viruses. A significantly higher prevalence of HPV in lung cancer and a significant association with SCC was observed, thereby, indicating a positive link between HPV and etiopathogenesis of lung carcinoma. Diagn. Cytopathol. 2016;44:987-993. © 2016 Wiley Periodicals, Inc., (© 2016 Wiley Periodicals, Inc.)

Large consortia have revealed hundreds of genetic loci associated with anthropometric traits, one trait at a time. We examined whether genetic variants affect body shape as a composite phenotype that is represented by a combination of anthropometric traits. We developed an approach that calculates averaged PCs (AvPCs) representing body shape derived from six anthropometric traits (body mass index, height, weight, waist and hip circumference, waist-to-hip ratio). The first four AvPCs explain >99% of the variability, are heritable, and associate with cardiometabolic outcomes. We performed genome-wide association analyses for each body shape composite phenotype across 65 studies and meta-analysed summary statistics. We identify six novel loci: LEMD2 and CD47 for AvPC1, RPS6KA5/C14orf159 and GANAB for AvPC3, and ARL15 and ANP32 for AvPC4. Our findings highlight the value of using multiple traits to define complex phenotypes for discovery, which are not captured by single-trait analyses, and may shed light onto new pathways., Competing Interests: Kari Stefansson, Valgerdur Steinthorsdottir, Gudmar Thorleifsson and Unnur Thorsteinsdottir are used by deCODE Genetics/Amgen inc. Gérard Waeber and Peter Vollenweider received an unrestricted grant from GSK to build the CoLaus study. Bruce M. Psaty serves on a DSMB for a clinical trial of a device funded by the manufacturer (Zoll LifeCor).

Objectives: The dementia diagnosis gap in sub-Saharan Africa (SSA) is large, partly because of difficulties in screening for cognitive impairment in the community. As part of the Identification and Intervention for Dementia in Elderly Africans (IDEA) study, we aimed to validate the IDEA cognitive screen in a community-based sample in rural Tanzania METHODS: Study participants were recruited from people who attended screening days held in villages within the rural Hai district of Tanzania. Criterion validity was assessed against the gold standard clinical dementia diagnosis using DSM-IV criteria. Construct validity was assessed against, age, education, sex and grip strength and instrumental activities of daily living (IADLs). Internal consistency and floor and ceiling effects were also examined., Results: During community screening, the IDEA cognitive screen had high criterion validity, with an area under the receiver operating characteristic curve of 0.855 (95% CI 0.794 to 0.915). Higher scores on the screen were significantly correlated with lower age, male sex, having attended school, better grip strength and improved performance in activities of daily living. Factor analysis revealed a single factor with an eigenvalue greater than one, although internal consistency was only moderate (Cronbach's alpha = 0.534)., Conclusions: The IDEA cognitive screen had high criterion and construct validity and is suitable for use as a cognitive screening instrument in a community setting in SSA. Only moderate internal consistency may partly reflect the multi-domain nature of dementia as diagnosed clinically. Copyright © 2016 John Wiley & Sons, Ltd., (Copyright © 2016 John Wiley & Sons, Ltd.)

Objectives: Despite an increase in the incidence of systemic connective tissue diseases (CTD), panel testing for detection of antinuclear antibodies (ANA) is not a routine practice in many health centers of the Indian subcontinent. Consequently, the data on its significance is scanty., Methods: To evaluate utility of panel testing, line immunoassay (LIA) and indirect immunofluorescence antinuclear antibody test (IIF-ANA) were performed in 321 cases of CTD., Results: Out of 321 serum samples screened by the above tests, 227 were positive and 18 were negative by both LIA and IIF-ANA. Additional 11/321 (3.4%) cases were picked up by LIA. SSA was most common specificity in these cases followed by SSA/SSB, SSB, Ro-52, Jo-1, dsDNA and nRNP/Sm., Conclusion: Use of LIA along with IF-ANA and ELISA improves sensitivity of CTD screening.

Background: People with Parkinson's disease (PD) and parkinsonism living in care homes (residential or nursing care) in the UK represent around 10-15% of all people with PD and 3-5% of all care home residents. There are few previous data on medication use in those living in care homes with PD. In this study we aimed to compare medication use in a representative cohort of people with PD living in care homes in north-east England with those living in their own homes., Method: All people with late stage (Hoehn and Yahr III-V) idiopathic PD, PD dementia, or atypical parkinsonian syndromes under the care of the Northumbria Healthcare NHS Foundation Trust PD service on 1st January 2015 were identified. Demographic, disease characteristics and medication use data were collected from an audit of medical notes of all those identified., Results: We identified 377 people who met the inclusion criteria, 91 (24.1%) of whom were living in a care home. Disease stage, age and age at disease onset were all significantly higher and levodopa equivalent dose significantly lower in those living in care homes, although disease duration and levodopa dose were not. Greater age, lower levodopa equivalent dose and higher disease stage were independently associated with being in a care home., Conclusions: Although people in care homes had more advanced disease, they were on a significantly lower levodopa equivalent dose. This is likely to be due to the requirement to balance symptom management with drug side-effects., (Copyright © 2016 Elsevier Ltd. All rights reserved.)

Synthetic polymer microarray technology holds remarkable promise to rapidly identify suitable biomaterials for stem cell and tissue engineering applications. However, most of previous microarrayed synthetic polymers do not possess biological ligands (e.g., peptides) to directly engage cell surface receptors. Here, we report the development of peptide-functionalized hydrogel microarrays based on light-assisted copolymerization of poly(ethylene glycol) diacrylates (PEGDA) and methacrylated-peptides. Using solid-phase peptide/organic synthesis, we developed an efficient route to synthesize methacrylated-peptides. In parallel, we identified PEG hydrogels that effectively inhibit non-specific cell adhesion by using PEGDA-700 (M. W.=700) as a monomer. The combined use of these chemistries enables the development of a powerful platform to prepare peptide-functionalized PEG hydrogel microarrays. Additionally, we identified a linker composed of 4 glycines to ensure sufficient exposure of the peptide moieties from hydrogel surfaces. Further, we used this system to directly compare cell adhesion abilities of several related RGD peptides: RGD, RGDS, RGDSG and RGDSP. Finally, we combined the peptide-functionalized hydrogel technology with bioinformatics to construct a library composed of 12 different RGD peptides, including 6 unexplored RGD peptides, to develop culture substrates for hiPSC-derived cardiomyocytes (hiPSC-CMs), a cell type known for poor adhesion to synthetic substrates. 2 out of 6 unexplored RGD peptides showed substantial activities to support hiPSC-CMs. Among them, PMQKMRGDVFSP from laminin β4 subunit was found to support the highest adhesion and sarcomere formation of hiPSC-CMs. With bioinformatics, the peptide-functionalized hydrogel microarrays accelerate the discovery of novel biological ligands to develop biomaterials for stem cell and tissue engineering applications., Statement of Significance: In this manuscript, we described the development of a robust approach to prepare peptide-functionalized synthetic hydrogel microarrays. Combined with bioinformatics, this technology enables us to rapidly identify novel biological ligands for the development of the next generation of functional biomaterials for stem cell and tissue engineering applications., (Copyright © 2016 Acta Materialia Inc. Published by Elsevier Ltd. All rights reserved.)

Background: X-linked agammaglobulinemia (XLA) is an X-linked genetic defect in maturation of B lymphocytes that results in the absence of B lymphocytes in the peripheral blood and profound hypogammaglobulinemia. It is caused by a mutation in the BTK gene located on the X chromosome. There are no large series describing XLA from the developing world., Objective: To analyze the clinical features, immunologic and genetic characteristics, and outcomes of 36 patients with XLA diagnosed and managed for a period of 2 decades., Methods: Diagnosis of XLA was made on the basis of presence of BTK gene mutation or marked reduction of B lymphocytes in peripheral blood with a family history of an affected male relative. The diagnosis was confirmed by genetic mutation studies in 28 patients with 25 unique mutations in the BTK gene., Results: There was a significant delay in diagnosis in most of the patients. The mean (SD) delay in the diagnosis was 4.2 (3.5) years. Point mutations were the most common mutations detected, accounting for 68% of all mutations. Deletions and insertions were also seen in a few cases. Four of the mutations are novel mutations that have not been previously reported. Seven of the 36 patients (19%) were dead at the time of analysis in the present cohort. The mean survival was 137 months (95% confidence interval, 13-163 months)., Conclusion: The present study is perhaps the largest series of patients with XLA from any developing country so far., (Copyright © 2016 American College of Allergy, Asthma & Immunology. Published by Elsevier Inc. All rights reserved.)

Background and Purpose: The burden of stroke is high in sub-Saharan Africa, and improved knowledge of risk factors is needed. Antiphospholipid antibodies are a common acquired stroke risk factor in young individuals. Antiphospholipid antibodies may be induced by infectious diseases. Sub-Saharan Africa has a high infectious burden, and we analyzed the contribution of antiphospholipid antibodies to the risk of stroke in an incident population from rural and urban Tanzania., Methods: Stroke cases and age- and sex-matched community-acquired controls from the rural Hai district and urban Dar-es-Salaam areas of Tanzania were recruited in a wider study of stroke incidence between June 2003 and June 2006. Lupus anticoagulant, anticardiolipin, anti-β2-glycoprotein I, and antiphosphatidylserine/prothrombin antibodies were determined in stored plasma, as well as IgG antibodies against Treponema pallidum., Results: Data from 158 stroke cases and 369 controls were analyzed. Thirty cases (19%) and 4 controls (1%) had a lupus anticoagulant (odds ratio, 20.8; 95% confidence interval, 7.2-60.5). Anticardiolipin IgG was the only other antiphospholipid antibody subtype associated with increased stroke risk (odds ratio, 2.1; 95% confidence interval, 1.0-4.3), but this association disappeared when corrected for IgG antibodies against Treponema pallidum results. The prevalence of anti-β2-glycoprotein I IgG antibodies in the Tanzanian healthy population was high when Dutch cutoff values were applied (67%), whereas presence of anti-β2-glycoprotein I IgM was associated with a reduced stroke risk (odds ratio 0.3; 95% confidence interval, 0.1-1.1)., Conclusions: The presence of lupus anticoagulant is a strong, and to date unrecognized, risk factor for stroke in Tanzania, especially in young and middle-aged individuals., (© 2016 American Heart Association, Inc.)

Autoimmune liver disease (AILD) is a type of chronic liver disease with autoimmune etiology. The diagnosis of the disease is multipronged and detection of autoantibodies in AILDs is an important diagnostic tool and it also helps in the classification of the disease. There are multiple autoantibodies that are detected in AILDs but none is diagnostic. Moreover, these autoantibodies are detected in many other pathological and nonpathological conditions. So the significance of seropositivity for these autoantibodies should be known by both the pathologists as well as the clinicians. In addition, there is prognostic significance associated with some of the antibodies and they also sometimes help in the disease monitoring. The whole array of antibodies detected in AILDs is discussed in detail in this review along with their clinical significance and interpretation., (© The Author(s) 2016.)

Background: Renal involvement is a serious complication of anti-neutrophil cytoplasmic antibody-associated vasculitis (AAV). We describe the pattern of renal involvement and its correlation with outcomes., Patients and Methods: Medical records of 92 patients seen in rheumatology clinic and diagnosed as AAV between January 2007 and June 2014 were analysed. Patients were classified as granulomatosis with polyangiitis (GPA), microscopic polyangiitis (MPA), eosinophilic granulomatosis with polyangiitis (EGPA) and undifferentiated AAV. Overall and renal outcomes were analysed. Patients were classified as advanced renal failure (creatinine >5.7 mg/dl or requiring dialysis), deranged RFT not qualifying the above parameters, and normal renal function., Results: Sixty-seven (72.8 %) patients had GPA, 14 (15.2 %) had MPA, 8 (8.7 %) had EGPA, and 3 (3.3 %) had undifferentiated AAV. Renal involvement was seen in 51 (55.4 %) patients (46.3 % of GPA patients, 78.6 % of MPA, 37.5 % of EGPA and 33.3 % of unclassifiable AAV patients). Renal involvement was more common in males (p = 0.008). Patients with renal involvement had higher mean BVAS scores as compared to patients without renal involvement (p < 0.01). Thirteen patients (25.5 %) presented with advanced renal failure (creatinine >5.7 mg/dl or requiring dialysis), 21 (41.2 %) had deranged renal functions but did not require dialysis, and the rest had proteinuria and active sediments with normal serum creatinine. Twenty-four patients (47.1 %) had good renal outcome with normal creatinine, 12 (23.5 %) had persistent renal insufficiency, 12 (23.5 %) died, and one (2 %) remained dialysis dependent. Mean survival and mortality did not differ in patients with and without renal involvement (p = 0.454, p = 0.388)., Conclusions: Renal involvement was more common in males. BVAS was higher in patients with renal involvement. The mean survival and mortality were similar in patients with or without renal involvement.

Aims: There are few data on the use of hospital services by centenarians living in the UK. In the present study, we recorded the frequency, nature and outcomes of hospital admissions in centenarians in an area of North-East England., Methods: Data regarding hospital attendance in centenarians in Northumberland and North Tyneside, covered by one National Health Service Trust, were collected. For the years 2010-2013, demographics, frequency of admission and length of hospital stay data were collected. Medical notes for those admitted in 2011 were reviewed, and data extracted relating to diagnosis, medications and past medical history., Results: Across the 4 years of the study, there were 349 hospital attendances of centenarians. A total of 264 of these attendances resulted in admission with an overnight stay. In 2011, there were 107 attendances, 75 of which (in 54 unique patents) resulted in admission and an overnight stay. The unique patients admitted represented 41.5% of the centenarians living in the catchment area. The most common primary reason for admission in centenarians was respiratory tract infection, though falls were a primary or secondary reason for admission in 41.3% of centenarians. There were 11 in-hospital deaths in 2011, and a further seven deaths within 30 days of discharge. The median number of medications taken on admission and discharge was six., Conclusions: Almost half of the centenarians living in the catchment area were admitted to hospital during 2011. Over 25% of admissions either died in hospital or within 30 days of discharge. Geriatr Gerontol Int 2016; 16: 969-975., (© 2015 Japan Geriatrics Society.)

[This corrects the article DOI: 10.1371/journal.pgen.1005378.].

We conducted a randomised exploratory trial in children aged between one and sixteen years old to establish the time to achieve an end-tidal oxygen fraction ≥ 0.9 in three different positions: supine, and 30 and 45° head up. We recruited 120 children analysed in two age groups: 1-8 years and 9-16 years. The median (IQR [range]) time to reach the end point was 80 (59-114 [41-295]) s in the younger group and 150 (107-211 [44-405]) s in the older group, regardless of position (p = 0.0001). The end point was reached in 90% of children in approximately 160 s in the younger, and 271 s in the older, groups, respectively. There was no statistical difference between the three positions within each age group in the time to reach the endpoint (p = 0.59). Only two patients in the older age group could not reach the end point, due to poorly fitting facemasks. We conclude that pre-oxygenation can therefore be achieved effectively in most children, and that tilting children head up by 30 or 45° does not significantly reduce the time taken to achieve an end-tidal oxygen fraction of ≥ 0.9. The recommended period for pre-oxygenation in both groups should remain at 3 min but it should be noted that this may be insufficient for many older patients., (© 2016 The Association of Anaesthetists of Great Britain and Ireland.)

Objectives: To conduct a systematic review of frailty screening tools used in low- and middle-income countries (LMICs)., Design: Systematic review., Setting: LMICs, as defined by the World Bank on June 30, 2014., Participants: Elderly adults (as defined by the authors) living in LMICs., Measurements: Studies were included if the population under consideration lived in a LMIC, the study involved an assessment of frailty, the study population was elderly adults, and the full text of the study was available in English. The Medline, Embase, CINAHL and PsychINFO databases were searched up to June 30, 2014., Results: Seventy studies with data from 22 LMICs were included in the review. Brazil, Mexico, and China provided data for 60 of the 70 studies (85.7%), and 15 countries contributed data to only one study. Thirty-six studies used the Fried criteria to assess frailty, 20 used a Frailty Index, and eight used the Edmonton Frailty Scale; none of the assessment tools used had been fully validated for use in a LMIC., Conclusion: There has been a rapid increase in the number of published studies of frailty in LMICs over the last 5 years. Further validation of the assessment tools used to identify frail elderly people in LMICs is needed if they are to be efficient in identifying those most in need of health care in such settings., (© 2016, Copyright the Authors Journal compilation © 2016, The American Geriatrics Society.)

To increase our understanding of the genetic basis of adiposity and its links to cardiometabolic disease risk, we conducted a genome-wide association meta-analysis of body fat percentage (BF%) in up to 100,716 individuals. Twelve loci reached genome-wide significance (P<5 × 10(-8)), of which eight were previously associated with increased overall adiposity (BMI, BF%) and four (in or near COBLL1/GRB14, IGF2BP1, PLA2G6, CRTC1) were novel associations with BF%. Seven loci showed a larger effect on BF% than on BMI, suggestive of a primary association with adiposity, while five loci showed larger effects on BMI than on BF%, suggesting association with both fat and lean mass. In particular, the loci more strongly associated with BF% showed distinct cross-phenotype association signatures with a range of cardiometabolic traits revealing new insights in the link between adiposity and disease risk.

Background: There is a dearth of knowledge about the availability and affordability of the different drug treatments for Parkinson's disease (PD) across sub-Saharan Africa (SSA). We aimed to determine the availability and affordability of drugs for treating PD in Kenya., Methods: A facility-based survey was conducted in selected medicine outlets (pharmacies) in what were formerly the headquarter towns of the eight provinces of Kenya. We used the World Health Organization/Health Action International methodology to obtain data for drugs used to treat PD. Unit price for each drug was obtained., Results: Forty-eight outlets were visited in total, six in each of Kenya's eight provinces. Levodopa (L-dopa) was available in only 24 (50.0%) outlets. Only one public pharmacy sold l-dopa (14 were private and nine were other types of outlet). Ergot-derived dopamine agonists (DAs) and anticholinergics were available in 37 and 35 outlets, respectively. Monoamine-oxidase inhibitors, non-ergot-derived DAs, and catechol- O -methyl transferase inhibitors were available in four, two and zero outlets, respectively. Mean cost of 100 l-dopa tablets was $48.2, though costs varied widely (range, $28.2-$82.4). Only five outlets considered l-dopa affordable, all of which sold 100 tablets for less than $31., Conclusion: There is a lack of availability of PD drugs in Kenya, particularly in public pharmacies, where costs are generally lower. Few pharmacists consider the drugs available to be affordable. If PD is to be effectively managed in Kenya, then strategies are needed to increase the availability and affordability of medication.

Objectives: The burden of stroke on healthcare services in sub-Saharan Africa (SSA) is increasing. However, long-term outcomes from stroke in SSA are not well described. We aimed to investigate case-fatality and health outcomes for stroke survivors at 7- to 10-year follow-up., Materials and Methods: The Tanzanian Stroke Incidence Project (TSIP) recruited incidence stroke cases between 2003 and 2006. We followed up cases in 2013, recording date of death in those who had died., Results: Of 130 stroke cases included in this study, case-fatality and date of death data were available for 124 at 7-10 years post-stroke. Of these, 102 (82.3%) had died by 7 years post-stroke. Functional disability, as measured by the Barthel index immediately post-stroke, was a significant predictor of case-fatality at seven-year follow-up with those with severe disability having an almost four-fold increase in the odds of death compared with those with no, mild or moderate disability., Conclusions: Case-fatality rates are higher than reported in high-income countries, with post-stroke disability a significant predictor of death. Sustainable interventions to reduce post-stroke disability in this setting should be investigated., (© 2015 The Authors. Acta Neurologica Scandinavica published by John Wiley & Sons Ltd.)

Background: Remote monitoring of symptoms in Parkinson's disease (PD) using body-worn sensors would assist treatment decisions and evaluation of new treatments. To date, a rigorous, systematic evaluation of the acceptability of body-worn sensors in PD has not been undertaken., Materials and Methods: Thirty-four participants wore bilateral wrist-worn sensors for 4 h in a research facility and then for 1 week at home. Participants' experiences of wearing the sensors were evaluated using a Likert-style questionnaire after each phase. Qualitative data were collected through free-text responses. Differences in responses between phases were assessed by using the Wilcoxon rank-sum test. Content analysis of qualitative data was undertaken. "Non-wear time" was estimated via analysis of accelerometer data for periods when sensors were stationary., Results: After prolonged wearing there was a negative shift in participants' views on the comfort of the sensor; problems with the sensor's strap were highlighted. However, accelerometer data demonstrated high patient concordance with wearing of the sensors. There was no evidence that participants were less likely to wear the sensors in public. Most participants preferred wearing the sensors to completing symptom diaries., Conclusions: The finding that participants were not less likely to wear the sensors in public provides reassurance regarding the ecological validity of the data captured. The validity of our findings was strengthened by "triangulation" of data sources, enabling patients to express their agenda and repeated assessment after prolonged wearing. Long-term monitoring with wrist-worn sensors is acceptable to this cohort of PD patients. Evaluation of the wearer's experience is critical to the development of remote monitoring technology.

Background: There are few data on mortality rates in the general elderly living in sub-Saharan Africa. We aimed to detail three-year mortality rates in a population of rural community-dwelling older adults in northern Tanzania., Methods: We performed a community-based study of 2232 people aged 70 years and over living in Hai district, Tanzania. At baseline, participants underwent clinical assessment for disability, neurological disorders, hypertension, atrial fibrillation and memory problems. At three-year follow-up mortality data were collected. Mortality rates were compared to UK estimates., Results: At follow-up, data were available for 1873 subjects (83.9%). Of those, 208 (11.1%, 95% CI 9.7-12.5) had died. The age-standardised mortality rate was 10.2% (95% CI 8.8-11.6). Age-standardised mortality rates were lower than estimated for the UK (13.9%). In Cox regression analysis, greater age, higher levels of functional disability, use of a walking aid, subjective report of memory problems, being severely underweight and being normotensive were significant predictors of mortality., Conclusions: Those who survive to old age in Tanzania appear to have relatively low mortality rates. Physical and cognitive disabilities were strongly associated with mortality risk in this elderly community-dwelling population. The association between blood pressure and mortality merits further study., (Copyright © 2015 Elsevier Ireland Ltd. All rights reserved.)

In recognition of the fact that elder abuse is a global problem that doctors underrecognize and underreport, a simulation training session for undergraduate medical students was developed. The primary objective of this qualitative study was to examine barriers to and drivers of medical students making a diagnosis of elder abuse in simulated practice, with the goal of refining teaching methods and informing future teaching sessions for other clinical teachers. Third-year medical students (Newcastle University, United Kingdom) undertook a simulation scenario with a high-fidelity mannequin representing an elder abuse victim. After the simulation scenario, students underwent a semistructured debriefing. A tripartite approach to data collection was employed that included audio recordings of the simulation, data sheets capturing students' thoughts during the scenario, and postscenario debriefing. A different researcher analyzed each data set in isolation before discussions were held to triangulate findings from the data sets. Forty-six students undertook the scenario; none declined to participate. A number of barriers to students diagnosing elder abuse were identified. Students held a low index of suspicion for elder abuse and were overly optimistic regarding the etiology of the individual's injuries. Students lacked the confidence to raise concerns about possible elder abuse, believing that certainty was required before doing so. There was widespread confusion about nomenclature. These findings provide clinical teachers with important topic areas to address in future teaching sessions. Simulation, as a method to teach about elder abuse in a reproducible and immersive fashion, is recommended to clinical teachers., (© 2016, Copyright the Authors Journal compilation © 2016, The American Geriatrics Society.)