Transforming Parkinson's Care in Africa (TraPCAf): protocol for a multimethodology National Institute for Health and Care Research Global Health Research Group project.

BACKGROUND: Parkinson's disease (PD) is the second most common neurodegenerative disorder and, according to the Global Burden of Disease estimates in 2015, was the fastest growing neurological disorder globally with respect to associated prevalence, disability, and deaths. Information regarding the awareness, diagnosis, phenotypic characteristics, epidemiology, prevalence, risk factors, treatment, economic impact and lived experiences of people with PD from the African perspective is relatively sparse in contrast to the developed world, and much remains to be learned from, and about, the continent. METHODS: Transforming Parkinson's Care in Africa (TraPCAf) is a multi-faceted, mixed-methods, multi-national research grant. The study design includes multiple sub-studies, combining observational (qualitative and quantitative) approaches for the epidemiological, clinical, risk factor and lived experience components, as appropriate, and interventional methods (clinical trial component). The aim of TraPCAf is to describe and gain a better understanding of the current situation of PD in Africa. The countries included in this National Institute for Health and Care Research (NIHR) Global Health Research Group (Egypt, Ethiopia, Ghana, Kenya, Nigeria, South Africa and Tanzania) represent diverse African geographies and genetic profiles, with differing resources, healthcare systems, health and social protection schemes, and policies. The research team is composed of experts in the field with vast experience in PD, jointly led by a UK-based and Africa-based investigator. DISCUSSION: Despite the increasing prevalence of PD globally, robust data on the disease from Africa are lacking. Existing data point towards the poor awareness of PD and other neurological disorders on the continent and subsequent challenges with stigma, and limited access to affordable services and medication. This multi-site study will be the first of its kind in Africa. The data collected across the proposed sub-studies will provide novel and conclusive insights into the situation of PD. The selected country sites will allow for useful comparisons and make results relevant to other low- and middle-income countries. This grant is timely, as global recognition of PD and the public health challenge it poses builds. The work will contribute to broader initiatives, including the World Health Organization's Intersectoral global action plan on epilepsy and other neurological disorders. TRIAL REGISTRATION: https://doi.org/10.1186/ISRCTN77014546 .

The Coronary Sinus Reducer; 5-year Dutch experience.

BACKGROUND: Refractory angina is a growing and major health-care problem affecting millions of patients with coronary artery disease worldwide. The Coronary Sinus Reducer (CSR) is a device that may be considered for the relief of symptoms of refractory angina. It causes increased venous pressure leading to a dilatation of arterioles and reduced arterial vascular resistance in the sub-endocardium. This study describes the 5­year Dutch experience regarding safety and efficacy of the CSR. METHODS: One hundred and thirty-two patients with refractory angina were treated with the CSR. The primary efficacy endpoint of the study was Canadian Cardiovascular Society (CCS) class improvement between baseline and 6­month follow-up. The primary safety endpoint was successful CSR implantation in the absence of any device-related events. RESULTS: Eighty-five patients (67%) showed improvement of at least 1 CCS class and 43 patients (34%) of at least 2 classes. Mean CCS class improved from 3.17 ± 0.61 to 2.12 ± 1.07 after implantation (P < 0.001). The CSR was successfully implanted in 99% of the patients and only minor complications during implantation were reported. CONCLUSION: The CSR is a simple, safe, and effective option for most patients with refractory angina. However, approximately thirty percent of the patients showed no benefit after implantation. Future studies should focus on the exact underlying mechanisms of action and reasons for non-response to better identify patients that could benefit most from this therapy.

BMI-for-age in South Asian children of 0-20 years in the Netherlands: secular changes and misclassification by WHO growth references.

BACKGROUND: South Asians are prone to cardiometabolic disease at lower BMI levels than most other ethnic groups, starting in childhood. The magnitude of BMI misclassifications is unknown. AIM: To compare the BMI distribution of contemporary South Asian 0-20 year olds in the Netherlands with: (1) The South Asian norm reference (secular trends); and (2) The WHO child growth standard and reference. SUBJECTS AND METHODS: The BMI-for-age distribution of 6677 routine measurements of 3322 South Asian children, aged 0-20 years, was described with the LMS method and BMI z-scores. RESULTS: The BMI distribution in South Asian 0-4 year olds was almost similar to the norm reference (mean BMI z-score = 0.11, skewness = 0.31, SD = 1.0), whereas in 5-19 year olds the distribution had shifted upwards (mean = 0.53) and widened (skewness = -0.12, SD = 1.08). Overweight (incl. obesity) and obesity peaked at 8-10 years, at 45-48% and 35-37%, respectively. Relative to the WHO references, the BMI distribution was left-shifted at ages 0-4 years (mean BMI z-score = -0.46, skewness = 0.23, SD = 0.98) and widened at ages 5-20 years (mean = 0.05; skewness = -0.02, SD = 1.40). At most ages, thinness rates were significantly higher and obesity rates lower than based on South Asian norms. CONCLUSIONS: A secular change of BMI-for-age in South Asian children mostly affected children >4 years. WHO references likely under-estimate overweight and obesity rates in South Asian children.

Cross-sex hormone therapy in transgender persons affects total body weight, body fat and lean body mass: a meta-analysis.

Weight gain and body fat increase the risk of cardiometabolic disease. Cross-sex hormone therapy in transgender persons leads to changes in body weight and body composition, but it is unclear to what extent. We performed a meta-analysis to investigate the changes in body weight, body fat and lean body mass during cross-sex hormone therapy in transgender persons. We searched the PubMed database for eligible studies until November 2015. Ten studies reporting changes in body weight, body fat or lean mass in hormone naive transgender persons were included, examining 171 male-to-female and 354 female-to-male transgender people. Pooled effect estimates in the male-to-female group were +1.8 kg (95% CI: 0.2;3.4) for body weight, +3.0 kg (2.0;3.9) for body fat and -2.4 kg (-2.8; -2.1) for lean body mass. In the female-to-male group, body weight changed with +1.7 kg (0.7;2.7), body fat with -2.6 kg (-3.9; -1.4) and lean body mass with +3.9 kg (3.2;4.5). Cross-sex hormone therapy increases body weight in both sexes. In the male-to-female group, a gain in body fat and a decline in lean body mass are observed, while the opposite effects are seen in the female-to-male group. Possibly, these changes increase the risk of cardiometabolic disease in the male-to-female group.

Prolactin levels during short- and long-term cross-sex hormone treatment: an observational study in transgender persons.

The cause of prolactin alterations in transgender persons is often assigned to oestrogens, but the precise cause and time course during different phases of cross-sex hormone treatment (CHT) remain unclear. In this study, we prospectively examined prolactin levels in 55 female-to-males (FtMs) and 61 male-to-females (MtFs) during the first year of CHT. Because long-term prolactin data were not available in this population, we studied these levels in a retrospective population of 25 FtMs and 38 MtFs who underwent gonadectomy. FtMs were treated with testosterone and MtFs with estradiol, with or without the anti-androgen cyproterone acetate (CPA) (after gonadectomy CPA is cessated). During the first year of CHT, prolactin decreased with 25% (95CI: -33%, -12%) in FtMs and increased with 193% (95CI: 156%, 219%) in MtFs. Eighteen MtFs developed hyperprolactinemia (≥0.6 IU L-1 ). In the retrospective population, post-gonadectomy levels in FtMs were lower than baseline levels (-39%; 95CI: -51%, -20%) while in MtFs post-gonadectomy levels and baseline levels were comparable (-6%; 95CI: -24%, 15%). No hyperprolactinemia was found after gonadectomy. In conclusion, in FtMs, prolactin decreased consistently during CHT and in MtFs, prolactin increased during pre-surgical CHT but normalised after gonadectomy. It is likely that CPA induces increasing prolactin levels in MtFs.

A European Network for the Investigation of Gender Incongruence: Endocrine Part.

INTRODUCTION: Cross-sex hormone therapy is an essential part of gender affirming treatment of transgender individuals. Studies systematically describing the physical and psychological effects of hormonal treatment of transgender persons are scarce. AIM: The aim of the current protocol is to evaluate clinical and side-effects of cross-sex hormonal treatment in trans persons. METHODS: The European Network for the Investigation of Gender Incongruence (ENIGI) is a multicenter prospective study. Because of the relatively low prevalence of the condition and small number of specialized centers, international collaboration is warranted. Four European treatment centers, Ghent, Oslo, Florence, and Amsterdam, developed a common study and treatment protocol. MAIN OUTCOME MEASURES: Outcome measures include hormonal and metabolic parameters, bone density, secondary sex and anthropometric characteristics, and physical and psychological well-being. RESULTS: Thus far, 333 trans women and 343 trans men have been included in the ENIGI Endocrine protocol. The study is still ongoing. CONCLUSION: In recent years, the number of trans persons seeking gender affirming treatment has increased. However, well-designed prospective studies evaluating safety and effectiveness of current hormonal treatment protocols are lacking. Therefore we started the ENIGI collaboration. In this article we give a detailed description of the study protocol, objectives, and design of the ENIGI Endocrine protocol.

The impact of behavioural executive functioning and intelligence on math abilities in children with intellectual disabilities.

BACKGROUND: Little is known about the role of behavioural executive functioning (EF) skills and level of intelligence (IQ) on math abilities in children with mild to borderline intellectual disabilities. METHOD: Teachers of 63 children attending a school for special education (age: 10 to 13 years; IQ: 50 to 85) filled out a Behaviour Rating Inventory for Executive Function for each student. Furthermore, students took a standardised national composite math test and a specific math test on measurement and time problems. Information on level of intelligence was gathered through school records. Multiple regression analyses were performed to test direct, moderating and mediating effects of EF and IQ on math performance. RESULTS: Behavioural problems with working memory and flexibility had a direct negative effect on math outcome, while concurrently, level of intelligence had a positive effect. The effect of IQ on math skills was moderated by problems with inhibition: in children with a clinical level of inhibition problems, there was no effect of level of intelligence on math performance. CONCLUSIONS: Findings suggest that in students with mild to borderline intellectual disabilities and math difficulties, it is important to address their strengths and weaknesses with respect to EF and adjust instruction and remedial intervention accordingly.

Consumer behaviour towards vegetables: a study on domestic processing of broccoli and carrots by Dutch households.

BACKGROUND: Preferences for sensory properties (e.g. taste and texture) are assumed to control cooking behaviour with respect to vegetables. Conditions such as the cooking method, amount of water used and the time-temperature profile determine the nutritional quality (e.g. vitamins and phytochemicals) of cooked vegetables. Information on domestic processing and any underlying motives can be used to inform consumers about cooking vegetables that are equally liked and are nutrient-rich. METHODS: Two online self-reporting questionnaires were used to identify domestic processing conditions of broccoli and carrots by Dutch households. Questions on various aspects of domestic processing and consumer motives were included. Descriptive data analysis and hierarchical cluster analysis were performed for both vegetables, separately, to group consumers with similar motives and behaviour towards vegetables. RESULTS: Approximately 70% of consumers boiled vegetables, 8-9% steamed vegetables, 10-15% stir fried raw vegetables and 8-10% stir fried boiled vegetables. Mainly texture was used as a way to decide the 'doneness' of the vegetables. For both vegetables, three clusters of consumers were identified: texture-orientated, health-orientated, or taste-orientated. The texture-orientated consumers are identified as the most prevalent (56-59%) group in the present study. Statistically significant associations are found between domestic processing conditions and clusters, whereas no such association are found between demographic details and clusters. CONCLUSIONS: A wide variation in domestic processing of broccoli and carrots is found in the present study. Mainly sensory properties (i.e. texture and taste) determined the domestic processing conditions. The findings of the present study can be used to optimise cooking to yield vegetables that meet consumer's specific sensory preference and are higher in nutrients, and as well as to communicate with target consumer groups.

Prevalence of severe subclinical coronary artery disease on cardiac CT and MRI in patients with extra-cardiac arterial disease.

OBJECTIVE: Patients with extra-cardiac arterial disease (ECAD) are at high risk of coronary artery disease (CAD). Prevalence of silent, significant CAD in patients with stenotic or aneurysmal ECAD was examined. Early detection and treatment may reduce CAD mortality in this high-risk group. MATERIALS AND METHODS: ECAD patients without cardiac complaints underwent computed tomography (CT) for calcium scoring, coronary CT angiography (cCTA) if calcium score was 1,000 or under, and adenosine perfusion magnetic resonance imaging (APMR) if there was no left main stenosis. Significant CAD was defined as calcium score over 1,000, cCTA-detected coronary stenosis of at least 50% lumen diameter, and/or APMR-detected inducible myocardial ischemia. In cases of left main stenosis (or equivalent) or myocardial ischemia, patients were referred to a cardiologist. RESULTS: The prevalence of significant CAD was 56.8% (95% CI 47.5 to 66.0). One-hundred and eleven patients were included. Eighty-four patients (76%) had stenotic ECAD, and 27 (24%) had aneurysmal disease. In patients with stenotic ECAD, significant coronary stenosis was present in 32 (38%) and inducible ischemia in eight (12%). Corresponding results in aneurysmal ECAD were eight (30%) and two (11%), respectively (p for difference >.05). Sixteen (19%) patients with stenotic and six (22%) with aneurysmal ECAD were referred to a cardiologist, with subsequent cardiac intervention in seven (44%) and three (50%), respectively (both p >.05). CONCLUSIONS: Patients with stenotic or aneurysmal ECAD have a high prevalence of silent, significant CAD.

HNPCC-like cancer predisposition in mice through simultaneous loss of Msh3 and Msh6 mismatch-repair protein functions.

Cancer predisposition in hereditary non-polyposis colon cancer (HNPCC) is caused by defects in DNA mismatch repair (MMR). Mismatch recognition is attributed to two heterodimeric protein complexes: MutSalpha (refs 2, 3, 4, 5), a dimer of MutS homologues MSH2 and MSH6; and MutSbeta (refs 2,7), a dimer of MSH2 and MSH3. These complexes have specific and redundant mismatch recognition capacity. Whereas MSH2 deficiency ablates the activity of both dimers, causing strong cancer predisposition in mice and men, loss of MSH3 or MSH6 (also known as GTBP) function causes a partial MMR defect. This may explain the rarity of MSH6 and absence of MSH3 germline mutations in HNPCC families. To test this, we have inactivated the mouse genes Msh3 (formerly Rep3 ) and Msh6 (formerly Gtmbp). Msh6-deficient mice were prone to cancer; most animals developed lymphomas or epithelial tumours originating from the skin and uterus but only rarely from the intestine. Msh3 deficiency did not cause cancer predisposition, but in an Msh6 -deficient background, loss of Msh3 accelerated intestinal tumorigenesis. Lymphomagenesis was not affected. Furthermore, mismatch-directed anti-recombination and sensitivity to methylating agents required Msh2 and Msh6, but not Msh3. Thus, loss of MMR functions specific to Msh2/Msh6 is sufficient for lymphoma development in mice, whereas predisposition to intestinal cancer requires loss of function of both Msh2/Msh6 and Msh2/Msh3.

Abnormal myotonic dystrophy protein kinase levels produce only mild myopathy in mice.

Myotonic dystrophy (DM) is commonly associated with CTG repeat expansions within the gene for DM-protein kinase (DMPK). The effect of altered expression levels of DMPK, which is ubiquitously expressed in all muscle cell lineages during development, was examined by disrupting the endogenous Dmpk gene and overexpressing a normal human DMPK transgene in mice. Nullizygous (-/-) mice showed only inconsistent and minor size changes in head and neck muscle fibres at older age, animals with the highest DMPK transgene expression showed hypertrophic cardiomyopathy and enhanced neonatal mortality. However, both models lack other frequent DM symptoms including the fibre-type dependent atrophy, myotonia, cataract and male-infertility. These results strengthen the contention that simple loss- or gain-of-expression of DMPK is not the only crucial requirement for development of the disease.

Case definitions for onchocerciasis-associated epilepsy and nodding syndrome: A focused review.

Onchocerciasis-associated epilepsy (OAE) is an important but neglected public health problem in onchocerciasis-endemic areas with insufficient or inadequate onchocerciasis control. Hence, there is a need for an internationally accepted, easy-to-use epidemiological case definition of OAE to identify areas of high Onchocerca volvulus transmission and disease burden requiring treatment and prevention interventions. By including OAE as a manifestation of onchocerciasis, we will considerably improve the accuracy of the overall onchocerciasis disease burden, which is currently underestimated. Hopefully, this will lead to increased interest and funding for onchocerciasis research and control interventions, notably the implementation of more effective elimination measures and treatment and support for affected individuals and their families.

Strategies to improve the implementation of infection control link nurse programmes in acute-care hospitals.

BACKGROUND: Infection control practitioners face several challenges when implementing infection control link nurse (ICLN) programmes. Identification of strategies to address these can improve the impact of current ICLN programmes and guide their future implementation. AIM: We aimed to identify implementation strategies for ICLN programmes in acute-care hospitals with the Consolidated Framework for Implementation Research (CFIR)-Expert Recommendations for Implementing Change (ERIC) Implementation Strategy Matching tool. METHODS: An expert panel matched 19 implementation and sustainment barriers, identified in our previous studies, to the most fitting CFIR constructs. Subsequently, we applied the CFIR-ERIC Matching Tool and generated a list of implementation strategies to address these barriers. FINDINGS: Barriers were predominantly found within the CFIR domains 'inner setting' (characteristics of the implementing organization) and 'process' (stages of implementation). With the ERIC Matching Tool, we identified the 10 most important strategies to address barriers of implementation of ICLN programmes: identify and prepare champions, conduct local consensus discussions, assess for readiness and identify barriers and facilitators, inform local opinion leaders, use facilitation, create a learning collaborative, conduct local needs assessments, develop a formal implementation blueprint, build a coalition, and identify early adopters. CONCLUSION: The CFIR domains 'inner setting' and 'process' appeared to be the most important to impede implementation of ICLN programmes in acute-care hospitals. Application of the CFIR-ERIC tool highlighted the identification and preparation of champions as the leading strategy for the successful implementation of these programmes. With this tool, strategies can be specifically tailored towards local implementation and sustainment barriers.

Lifetime risk of suicide among survivors of the atomic bombings of Japan.

AIMS: The long-term physical health effects of the atomic bombings of Hiroshima and Nagasaki are well characterised, but the psychological effects remain unclear. Therefore, we sought to determine whether measures of exposure severity, as indirect measures of psychological trauma arising from exposure to the atomic bombings, are associated with suicide mortality among atomic bomb survivors. METHODS: The Life Span Study is a prospective cohort study of 93 741 Japanese atomic bomb survivors who were located within 10 km of the hypocentre in Hiroshima or Nagasaki at the time of the bombings in 1945, and 26 579 residents of Hiroshima and Nagasaki who were not in either city at the time of the bombings, matched to survivors on city, sex and age. Measures of exposure severity included: proximity to the hypocentre, type of shielding between the survivor and the blast and self-reported occurrence of acute radiation and thermal injuries. Date of death was obtained from the Japanese National Family Registry system. Cause of death was obtained from death certificates. Adjusted hazard ratios (HRs) were estimated from Cox regression models overall and stratified by sex and age. RESULTS: During the 60-year follow-up period (1950-2009), 1150 suicide deaths were recorded among 120 231 participants (23.6 per 100 000 person-years): 510 among 70 092 women (17.2 per 100 000 person-years) and 640 among 50 139 men (33.6 per 100 000 person-years). Overall, there was no association of proximity, type of shielding or the occurrence of acute injuries with suicide mortality. Among those <25 years of age at the time of the bombings, increased suicide risk was observed for survivors outside v. shielded inside any structure (HR: 1.24; 95% confidence interval (CI): 1.03, 1.48; interaction p = 0.054) and for those who reported flash burns (HR: 1.32; 95% CI: 1.00, 1.73; interaction p = 0.025). Sex-stratified analyses indicated that these associations were limited to men. Among women, closer proximity to the hypocentre was associated with a non-significant increase in suicide risk, with a positive association between proximity and suicide risk observed among women <15 years of age (HR: 1.09 per km; 95% CI: 1.00, 1.18; interaction p = 0.067). CONCLUSIONS: Proximity to the hypocentre, shielding and acute injury presence do not generally appear to influence suicide mortality among atomic bomb survivors. However, heterogeneity may exist by age and sex, with younger survivors potentially more sensitive to psychological trauma. Coupled with other studies, our results suggest the importance of long-term monitoring of mental health among young populations exposed to catastrophic events or mass trauma.

Recognition of child maltreatment in emergency departments in Europe: Should we do better?

OBJECTIVES: To evaluate the different policies to recognize child maltreatment in emergency departments (EDs) in Europe in order to define areas of improvement. METHODS: A survey was conducted on the recognition of child maltreatment in EDs in European countries with a focus on screening methods, parental risk factors, training and hospital policies. The survey was distributed through different key members from the EUSEM, REPEM and the EuSEN. A summary score based on the NICE guideline (4 questions on child characteristics, 4 questions on parental characteristics and 5 questions on hospital policy) was calculated. RESULTS: We analysed 185 completed surveys, representing 148 hospitals from 29 European countries. Of the respondents, 28.6% used a screening tool, and 31.8% had guidelines on parental risk factors. A total of 42.2% did not follow training based on child characteristics, and 57.6% did not follow training on parental characteristics. A total of 71.9% indicated that there was a need for training. 50.8% of the respondents reported a standardized policy for the detection of child maltreatment. Translating the survey results to NICE summary scores of the EDs in Europe, we found that 25.6% (34/133) met most, 22.6% (30/133) met some and 51.9% (69/133) met few of the NICE guideline recommendations. More specifically, with respect to hospital policies, 33.8% (45/133) met most, 15.0% (20/133) met some and 51.1% (68/133) met few of the NICE guideline recommendations. CONCLUSION: There is high variability regarding policies for child maltreatment detection and only a quarter of the EDs met most of the NICE guideline recommendations for child maltreatment. There is a need for the use of screening tools, training of ED staff and implementation of local hospital policies.

Ability of cystatin C to detect acute changes in glomerular filtration rate provoked by hyperglycaemia in uncomplicated Type 1 diabetes.

AIMS: Systematic study of hyperfiltration in diabetic nephropathy has been hindered by the lack of a simple glomerular filtration rate (GFR) measure that is accurate in this range of renal function. Serum cystatin C (GFR(CYSTATIN C) ) reflects long-term trends in GFR in normal or elevated ranges. To test whether it can reflect acute changes, we examined the impact of clamped hyperglycaemia on GFR(CYSTATIN C) and GFR(INULIN) in subjects with Type 1 diabetes. METHODS: GFR(INULIN) and GFR(CYSTATIN C) were measured in 32 normotensive, normoalbuminuric subjects during clamped euglycaemia and hyperglycaemia. For comparison, GFR(MDRD) was estimated according to the four-variable equation. RESULTS: During clamped euglycaemia, agreement between GFR(CYSTATIN C) and GFR(INULIN) was excellent, with mean bias +1.9 (90% distribution -29 to +31) ml min(-1) 1.73 m(-2), while GFR(MDRD) had mean bias +11.4 (-45 to +51) ml min(-1) 1.73 m(-2). With exposure to clamped hyperglycaemia, the mean increase in GFR(CYSTATIN C) (+17.5 ± 13.5 ml min(-1) 1.73 m(-2) ) reflected that observed with GFR(INULIN) (+15.3 ± 28.1 ml min(-1) 1.73 m(-2), P = 0.74), while GFR(MDRD) demonstrated a mean decline of -4.4 ± 33.6 ml min(-1) 1.73 m(-2) (P = 0.01). In all 24 subjects in whom GFR(INULIN) increased in response to hyperglycaemia, GFR(CYSTATIN C) reflected a concordant change (sensitivity, 100%) while GFR(MDRD) increased in 10/24 (sensitivity, 42%). In the eight remaining subjects, specificity was 25 and 75% for GFR(CYSTATIN C) and GFR(MDRD), respectively. CONCLUSION: GFR(CYSTATIN C) reflects normal and elevated renal function better than GFR(MDRD) even under the acute influences of hyperglycaemia, suggesting a role for cystatin C in clinical practice and research for the study of early renal function changes in Type 1 diabetes.

Strong relationships between disease activity, foot-related impairments, activity limitations and participation restrictions in children with juvenile idiopathic arthritis.

OBJECTIVES: To assess possible relationships between disease activity, foot-related impairments, activity limitations and participation restrictions in children with juvenile idiopathic arthritis (JIA). METHODS: Thirty-four children were studied. Disease activity was assessed with the Juvenile Arthritis Disease Activity Score in 71 joints (JADAS-71). Foot-related impairments, activity limitations and participation restrictions were measured with the Juvenile Arthritis Foot Disability Index (JAFI), the Childhood Health Assessment Questionnaire (CHAQ), self-reported or parent-reported and doctor-reported VAS scales. Relationships were quantified with Spearman's correlation coefficient. RESULTS: The mean age was 12.4±3.7 years, the median disease duration 1.5 years (interquartile range (IQR) 1.0-4.0), 88% were girls, and 76% had polyarticular disease course. The median JADAS-71 score (range 0-101) was 6 (IQR 1-13). On the JAFI sub-scores (range 0-4) 88% of the children reported some foot-related impairments (median 1.1, IQR 0.4-2.0); 82% reported some foot-related activity limitations (median 0.9, IQR 0.3-2.0), and 65% reported some foot-related participation restrictions (median 0.6, IQR 0-2.1). The median CHAQ score was 0.9 (IQR 0.1-1.8). The JADAS-71 correlated with all impairment, activity limitation and participation restriction variables (r=0.48-0.81, p<0.01). Most of the impairment variables correlated with activity limitation (r=0.39, p<0.05 to r=0.92, p<0.01) and participation restriction variables (r=0.44, p<0.05 to r=0.81, p<0.01). All activity limitation variables correlated with participation restriction variables (r=0.62-0.84, p<0.01). CONCLUSIONS: We observed strong relationships between disease activity, foot-related impairments, activity limitations and participation restrictions in children with JIA, and therefore suggest that standard screening for foot problems should be included in follow-up care for JIA patients.

Changes in striatal dopamine D2 receptor binding in pre-clinical Huntington's disease.

BACKGROUND: Carriers of the Huntington disease (HD) mutation develop a progressive neurodegenerative disorder after a pre-clinical phase. We examined the value of (11)C-raclopride PET (RAC) as a biomarker for pre-clinical HD pathophysiology. METHODS: In a prospective cohort study with clinical and neuropsychological assessment we collected complete RAC data in 18 pre-clinical mutation carriers (HD-PMC) and 11 controls. Follow-up was 2 years. We calculated striatal RAC binding potential (BP) to measure dopamine D2 receptor availability. RESULTS: No HD-PMC had overt neuropsychological dysfunction. RAC-BP in putamen was abnormal in up to 44% of HD-PMC. The rate of RAC-BP decline (2.6% per year) was not significantly higher than in controls. Follow-up putaminal BP correlated weakly with predicted distance to onset of clinical HD (P = 0.034), but the rate of decline did not. Three HD-PMC developed motor abnormalities suspect for HD but did not show an increased rate of decline of putaminal BP. CONCLUSIONS: Many HD-PMC have striatal abnormalities but we found no clearly increased rate of D2 receptor changes around the onset of clinical HD. A longer follow-up of the present study cohort is needed to establish the value of RAC-BP in assessing the risk of clinical conversion from striatal D2 binding data.

First familial Becker muscular dystrophy in Tanzania: Clinical and genetic features.

In African neurological practice, muscle disorders are either underdiagnosed or underrepresented. This may in part be due to the large burden of other more common neurological disorders. In this report we describe the first Tanzanian patient with genetically confirmed Becker muscular dystrophy. His phenotype and genotype were compatible with elsewhere in the world. Remarkably, this patient reported his progressive weakness of the legs with difficulty in walking only after a fall. We demonstrate that muscular dystrophies occur in sub-Saharan Africa. Neurologists must however be aware that patients are likely to delay seeking medical care for muscle disorders.

A Tanzanian Boy with Molecularly Confirmed X-Linked Adrenoleukodystrophy.

Adrenoleukodystrophy (ALD) is an X-linked peroxisomal disorder with classical features, which can be also recognised in a low resource setting. It had been described in various populations across the globe, but very few cases have been reported from Africa. In a boy with features of a progressive central nervous system condition and adrenal failure, ABCD1 gene screening was performed based on a clinical history and basic radiological features which were compatible with ALD. A common ABCD1 mutation was identified in this patient, which is the first report of genetically confirmed ALD in Sub-Saharan Africa. ALD is likely under recognised in those areas where there is no neurologist. This genetic confirmation widens geographical distribution of ABCD1-associated disease, and illustrates recognisability of this disorder, even when encountered in a low-resource environment.