Myopathy associated with homozygous PYROXD1 pathogenic variants detected by genome sequencing

Biallelic pathogenic variants in the gene PYROXD1 have recently been described to cause early-onset autosomal recessive myopathy. Myopathy associated with PYROXD1 pathogenic variants is rare and reported in only 17 individuals. Known pathogenic variants in PYROXD1 include missense, insertion and essential splice-site variants. Here we describe a consanguineous family of individuals affected with late-onset myopathy and homozygous PYROXD1 missense variants (NM_024854.5:c.464A>G [p.Asn155Ser]) expanding our understanding of the possible disease phenotypes of PYROXD1-associated myopathy.     

Declining prevalence of undiagnosed HIV in Melbourne: results from community‐based bio‐behavioural studies of gay and bisexual men

Objective: To measure changes in undiagnosed HIV among gay and bisexual men (GBM) in Melbourne. Methods: Undiagnosed HIV was compared between GBM recruited anonymously in 2008 in gay venues only and GBM anonymously or confidentially (results delivery) recruited in 2014 at gay venues and a community festival. Surveys were completed and oral fluid specimens collected for HIV testing; positive tests among GBM reporting being HIV‐negative or unknown/untested were classified as undiagnosed. Tests of proportions compared serological prevalence, undiagnosed prevalence and participant characteristics. Results: HIV prevalence was 9.5% and 7.1% among 639 and 993 GBM recruited in 2008 and 2014, respectively; undiagnosed prevalence declined significantly from 31.1% to 7.1% (p<0.001). Sexual risk and undiagnosed HIV was highest among venue‐recruited participants in 2014 (17.6%). Fewer diagnosed GBM participated confidentially in 2014, but this did not meaningfully influence comparative undiagnosed HIV prevalence. Conclusion: We provide the first estimates of changes in undiagnosed HIV in Australia, demonstrating a marked decline in undiagnosed HIV among GBM. Implications for public health: Our findings are consistent with reports of increases in HIV testing among GBM. Given sustained high HIV diagnosis rates, new testing models that encourage high frequency testing are needed to control the local HIV epidemic.     

Undiagnosed Acute Viral Febrile Illnesses,Sierra Leone

Sierra Leone in West Africa is in a Lassa fever–hyperendemic region that also includes Guinea and Liberia. Each year, suspected Lassa fever cases result in submission of ≈500–700 samples to the Kenema Government Hospital Lassa Diagnostic Laboratory in eastern Sierra Leone. Generally only 30%–40% of samples tested are positive for Lassa virus (LASV) antigen and/or LASV-specific IgM; thus, 60%–70% of these patients have acute diseases of unknown origin. To investigate what other arthropod-borne and hemorrhagic fever viral diseases might cause serious illness in this region and mimic Lassa fever, we tested patient serum samples that were negative for malaria parasites and LASV. Using IgM-capture ELISAs, we evaluated samples for antibodies to arthropod-borne and other hemorrhagic fever viruses. Approximately 25% of LASV-negative patients had IgM to dengue, West Nile, yellow fever, Rift Valley fever, chikungunya, Ebola, and Marburg viruses but not to Crimean-Congo hemorrhagic fever virus.     

Revealing geographical and population heterogeneity in HIV incidence,undiagnosed HIV prevalence and time to diagnosis to improve prevention and care: estimates for France

Introduction

To close gaps in HIV prevention and care, knowledge about locations and populations most affected by HIV is essential. Here, we provide subnational and sub‐population estimates of three key HIV epidemiological indicators, which have been unavailable for most settings.

Methods

We used surveillance data on newly diagnosed HIV cases from 2004 to 2014 and back‐calculation modelling to estimate in France, at national and subnational levels, by exposure group and country of birth: the numbers of new HIV infections, the times to diagnosis, the numbers of undiagnosed HIV infections. The denominators used for rate calculations at national and subnational levels were based on population size (aged 18 to 64) estimates produced by the French National Institute of Statistics and Economic Studies and the latest national surveys on sexual behaviour and drug use.

Results

We estimated that, in 2014, national HIV incidence was 0.17‰ (95% confidence intervals (CI): 0.16 to 0.18) or 6607 (95% CI: 6057 to 7196) adults, undiagnosed HIV prevalence was 0.64‰ (95% CI: 0.57 to 0.70) or 24,197 (95% CI: 22,296 to 25,944) adults and median time to diagnosis over the 2011 to 2014 period was 3.3 years (interquartile range: 1.2 to 5.7). Three mainland regions, including the Paris region, out of the 27 French regions accounted for 56% of the total number of new and undiagnosed infections. Incidence and undiagnosed prevalence rates were 2‐ to 10‐fold higher than the national rates in three overseas regions and in the Paris region (p‐values < 0.001). Rates of incidence and undiagnosed prevalence were higher than the national rates for the following populations (p‐values < 0.001): born‐abroad men who have sex with men (MSM) (respectively, 108‐ and 78‐fold), French‐born MSM (62‐ and 44‐fold), born‐abroad persons who inject drugs (14‐ and 18‐fold), sub‐Saharan African‐born heterosexuals (women 15‐ and 15‐fold, men 11‐ and 13‐fold). Importantly, affected populations varied from one region to another, and in regions apparently less impacted by HIV, some populations could be as impacted as those living in most impacted regions.

Conclusions

In France, some regions and populations have been most impacted by HIV. Subnational and sub‐population estimates of key indicators are not only essential to adapt, design implement and evaluate tailored HIV interventions in France, but also elsewhere where similar heterogeneity is likely to exist.

     

A multivariate logistic regression equation to screen for dysglycaemia: development and validation.

AIMS: To develop and validate an empirical equation to screen for dysglycaemia [impaired fasting glucose (IFG), impaired glucose tolerance (IGT) and undiagnosed diabetes]. METHODS: A predictive equation was developed using multiple logistic regression analysis and data collected from 1032 Egyptian subjects with no history of diabetes. The equation incorporated age, sex, body mass index (BMI), post-prandial time (self-reported number of hours since last food or drink other than water), systolic blood pressure, high-density lipoprotein (HDL) cholesterol and random capillary plasma glucose as independent covariates for prediction of dysglycaemia based on fasting plasma glucose (FPG)>or=6.1 mmol/l and/or plasma glucose 2 h after a 75-g oral glucose load (2-h PG)>or=7.8 mmol/l. The equation was validated using a cross-validation procedure. Its performance was also compared with static plasma glucose cut-points for dysglycaemia screening. RESULTS: The predictive equation was calculated with the following logistic regression parameters: P=1+1/(1+e-X)=where X=-8.3390+0.0214 (age in years)+0.6764 (if female)+0.0335 (BMI in kg/m2)+0.0934 (post-prandial time in hours)+0.0141 (systolic blood pressure in mmHg)-0.0110 (HDL in mmol/l)+0.0243 (random capillary plasma glucose in mmol/l). The cut-point for the prediction of dysglycaemia was defined as a probability>or=0.38. The equation's sensitivity was 55%, specificity 90% and positive predictive value (PPV) 65%. When applied to a new sample, the equation's sensitivity was 53%, specificity 89% and PPV 63%. CONCLUSIONS: This multivariate logistic equation improves on currently recommended methods of screening for dysglycaemia and can be easily implemented in a clinical setting using readily available clinical and non-fasting laboratory data and an inexpensive hand-held programmable calculator.     

Screening for Type 2 diabetes in the accident and emergency department.

AIM: To assess the proportion of patients, aged 40 years and over, attending an inner city accident and emergency department that have Type 2 diabetes, and the proportion previously undiagnosed, and to assess whether the identification of undiagnosed Type 2 diabetes is feasible in this setting. METHODS: Five hundred unselected people participated. All completed a demographic questionnaire regarding risk factors for diabetes. In those without known diabetes, random capillary blood glucose (CBG) was measured. If this was greater than 7.0 mmol/l, patients were asked to return for two fasting blood glucose tests. Diagnosis of diabetes was based on World Health Organization criteria. RESULTS: Of the 500 participating subjects, 73 were already known to have Type 2 diabetes. Of the remaining 427 subjects, 36 had CBG>7.0 mmol/l. All 36 returned for fasting blood tests: 13 fulfilled the diagnostic criteria for Type 2 diabetes, eight for impaired fasting glucose (IFG), and 15 had normal fasting glucose values. The prevalence of Type 2 diabetes was therefore 17.2%, including 2.6% with a new diagnosis, and 14.6% with pre-existing disease; 1.6% were found to have IFG. Body mass index was greater in those with Type 2 diabetes (previously and newly diagnosed) [27.1 (5.15) (mean+/-standard deviation)] vs. 25.8 (4.70) kg/m2; unpaired t-test P=0.0213), and those with Type 2 diabetes were more likely to be of black and minority ethnic origin (57 vs. 28%; chi2 P<0.001) and to have a first-degree family history of diabetes (45 vs. 23%; chi2 P<0.001). CONCLUSIONS: It can be estimated from this survey that, annually, this case-finding methodology could identify 539 (95% CI 249-828) people aged 40 years and over attending our accident and emergency department with previously undiagnosed Type 2 diabetes.