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.

     

The Asn-291→Ser and Ser-477→Stop mutations of the lipoprotein lipase gene and their significance for lipid metabolism in patients with hypertriglyceridaemia

We examined 99 Finnish patients whose serum fasting triglycerides (TG) had exceeded 6.0 mmol L^?1, with special interest to their lipid, lipoprotein and post-heparin plasma lipase activities. The control group consisted of 75 healthy individuals. We also determined the frequency of the Asn-291→Ser and Ser-447→Stop mutations both in hypertriglyceridaemic (HTG) subjects and in control subjects. A total of 51 of the original 99 hypertriglyceridaemic patients still had TG > 6.0 mmol L^?1 when measured a second time. They are referred to as persistently hypertriglyceridaemic subjects (pHTG). The remaining 48 subjects had TG < 6.0 mmol L^?1 in the second measurement and are referred to as sporadically hypertriglyceridaemic subjects (sHTG). The allelic frequencies of the Ser-447→Stop mutation in the total HTG and sHTG groups were similar to the frequencies present in the control group, but lower in pHTG patients compared with the control group (0.049 vs. 0.153, χ² = 6.63, P < 0.05). The Asn-291→Ser mutation was more frequent in HTG group than in the control group (0.0606 vs. 0.013, χ² = 4.86, P < 0.05). This difference was due to the higher frequency of the minor allele of Asn-291→Ser in the cohort with persistent hypertriglyceridaemia compared with the control group (0.088 vs. 0.013, χ² = 8.00, P < 0.01 ). The highest frequency (0.114) of the minor allele of Asn-291→Ser was found in type 2 diabetic patients with persistent hypertriglyceridaemia. The carrier status of Asn-291→Ser or Ser-447→Stop did not predict either post-heparin plasma lipoprotein lipase (LPL) activities or lipid and lipoprotein levels in any of the groups studied. Our data suggest that overproduction of very low-density lipoproteins (VLDL) is a more important cause of hypertriglyceridaemia in the Finns than is the LPL deficiency.     

Frequency of truncating FLCN variants and Birt-Hogg-Dubé–associated phenotypes in a health care system population

PurposePenetrance estimates of Birt-Hogg-Dubé syndrome (BHD)-associated cutaneous, pulmonary, and kidney manifestations are based on clinically ascertained families. In a health care system population, we used a genetics-first approach to estimate the prevalence of pathogenic/likely pathogenic (P/LP) truncating variants in FLCN, which cause BHD, and the penetrance of BHD-related phenotypes.MethodsExomes from 135,990 patient-participants in Geisinger’s MyCode cohort were assessed for P/LP truncating FLCN variants. BHD-related phenotypes were evaluated from electronic health records. Association between P/LP FLCN variants and BHD-related phenotypes was assessed using Firth’s logistic regression.ResultsP/LP truncating FLCN variants were identified in 35 individuals (1 in 3234 unrelated individuals), 68.6% of whom had BHD-related phenotype(s), including cystic lung disease (65.7%), pneumothoraces (17.1%), cutaneous manifestations (8.6%), and kidney cancer (2.9%). A total of 4 (11.4%) individuals had prior clinical BHD diagnoses.ConclusionIn this health care population, the frequency of P/LP truncating FLCN variants is 60 times higher than the previously reported prevalence. Although most variant-positive individuals had BHD-related phenotypes, a minority were previously clinically diagnosed, likely because cutaneous manifestations, pneumothoraces, and kidney cancer were observed at lower frequencies than in clinical cohorts. Improved clinical recognition of cystic lung disease and education concerning its association with FLCN variants could prompt evaluation for BHD.     

Population Pharmacokinetics Study of Nemonoxacin Among Chinese Patients With Moderate Hepatic Impairment

Purpose

Nemonoxacin is a novel C-8-methoxy nonfluorinated quinolone that has been approved for the treatment of community-acquired pneumonia (CAP) in adults. The goals of this study were to evaluate the pharmacokinetic (PK) and population PK parameters of nemonoxacin and to provide the appropriate dose adjustment recommendations for patients with hepatic impairment.

LncRNA GAS5基因启动子区5 bp插入/缺失多态性在广西地区人群中的分布

目的探讨广西地区人群中LncRNA GAS5基因启动子区1个功能性插入/缺失位点(rs145204276I/D)多态性的分布特点,并分析广西地区人群与其他地区人群rs145204276I/D位点多态性的分布差异。方法采用SNPscan技术对289例广西地区人群GAS5基因rs145204276I/D位点进行基因分型检测,统计其基因型和等位基因在广西地区人群不同性别间的分布,并分析其多态性与国际千人基因组计划(1000 genome project)数据库公布的欧洲人群(European,EUR)、日本人群(Japanese in Tokyo;JPT,)、西亚人群(South Asian,SAS)、美国人群(Ad Mixed American,AMR)、非洲人群(African,AFR)、北京人群(Han Chinese in Beijing,CHB)以及文献报道的南京、吉林、重庆和昆明人群的分布差异。结果广西地区人群GAS5基因rs145204276I/D位点I/I、I/D和D/D基因型频率分别为48.4%、43.6%和8.0%,I和D等位基因频率分别为70.2%和29.8%。rs145204276I/D基因型和等位基因频率在广西地区人群不同性别间比较差异无统计学意义(P0.05)。广西地区人群GAS5基因rs145204276I/D位点的基因型和等位基因频率与EUR、AFR、AMR和JPT人群比较差异均有统计学意义(P均0.05),而与CHB、南京、吉林、重庆和昆明人群比较差异均无统计学意义(P0.05)。结论广西地区人群LncRNA GAS5基因rs145204276I/D位点基因多态性在男性和女性人群中分布无差异,而其多态性与其他地区人群间比较存在不同程度的差异。     

Morphometry of auditory ossicles in medieval human remains from Central Europe

Human auditory ossicles, the malleus, the incus, and the stapes, are located in the tympanic cavity in the temporal bone and through forming a chain for the sound transmission from the tympanic membrane to the cochlea, they play an important role in the hearing process. Despite their clinical, phylogenetic, and evolutionary significance, the morphometry of the human ear bones has not been examined systematically. The ear ossicles are the smallest bones of the human skeleton, attaining their final size and morphology already at birth. Initially, they have been found to exhibit minimal morphometric variation, but further studies brought the opposite results. The aim of this study was to examine the morphometric variation of human auditory ossicles recovered from medieval and postmedieval subadult skeletons from Poland, Central Europe. The analysis involved in a total of 166 ear bones. Their measurements were performed on microscopic images using CorelDraw x4, according to a protocol of Quam and Rak with modification of Flohr et al. and Wadhwa et al. Our study showed a significant metric variation in the measurements taken at areas of the greatest morphological variability of the ossicles. We found that greater linear dimensions were associated with lower values of angular measurements. These results reveal the inherent variation found in these supposed functionally constrained structures. Representation of even greater number of populations, time periods, and developmental stages are needed. Further study will expand our understanding of the global scope of variation found in ear ossicular morphology and its functional implications for paleoanthropology.     

Primary resistance in <Emphasis Type="Italic">Helicobacter pylori</Emphasis> isolated in children from Iran

Helicobacter pylori-associated infection is extre-mely common in Iran, as in other developing countries, but few data exist on the susceptibility of H. pylori to antimicrobials commonly used in the eradication schedules in this country. This study was performed to determine the resistance rate to six antimicrobial agents used in the treatment of H. pylori infection in dyspeptic Iranian children and to recommend an updated anti-H. pylori treatment regimen to use in children. All H. pylori isolated from children who were undergoing gastroscopy were prospectively collected and subcultured to yield their susceptibility to six antimicrobial agents, by E test and disk diffusion methods. Demographic data and presenting symptoms were also collected. A prospective study was carried out from January 2003 to January 2005 with 100 strains of H. pylori isolated from children (40 girls and 60 boys; age range, 1.5 to 16 years [mean, 9.22 ± 3.25 years]); the strains had been successfully subcultured to yield antimicrobial sensitivity. Overall the H. pylori resistance rate was 95% to metronidazole, 59% to amoxicillin, 16% to clarithromycin, 9% to furazolidone, 7% to ciprofloxacin, and 5% to tetracycline. The most common presenting symptom was abdominal pain. There were no statistically significant differences in antimicrobial resistance rates related to age, sex, or clinical presentation. In the Iranian children, the prevalence of H. pylori resistance was very high to metronidazole and amoxicillin, moderate to clarithromycin, and low to ciprofloxacin and tetracycline.     

Floating stones in a nonopacified gallbladder: Ultrasonographic sign of gas-containing gallstones

Floating stones were noted in the nonopacified gallbladder at ultrasound examination. Gas-containing fissures in these stones could be demonstrated pre- and postoperatively (Mercedes Benz sign).     

农村成年及老年人失牙情况的Logistic回归分析

目的调查我国农村成年和老年人群的失牙原因。方法对北京延庆县古城村20~80岁村民587人的口腔健康状况进行了十年的纵向调查。用Logistic回归分析法预测该组人群失牙的原因。结果年龄、高牙本质龋数、高龋齿数、牙齿附着丧失≥7 mm,牙齿存在动度和低龈下结石沉积位点百分率是有意义的失牙预测因子。龋齿和牙周病同是10年后人群失牙率的重要预测因子;龋齿是失牙的主要预测因子。结论龋齿和牙周病是导致该人群10年后失牙的主要原因。     

Population pharmacokinetics of theophylline in very premature Japanese infants with apnoea

OBJECTIVE: To estimate the population pharmacokinetics of theophylline in very premature infants using the non-linear mixed effects modelling. METHOD: A total of 167 serum concentration measurements obtained from routine theophylline monitoring of 107 very premature Japanese infants were collected. RESULTS: The final pharmacokinetic parameters were CL (mL/h) = [6.98 . body weight (BW) (kg)(2.17) + 0.244 . post-conceptional age (weeks)] . 1.24(oxygen support), Vd (L) = 0.492 . BW (kg) and F = 0.660, respectively. Clearance was increased by 24% for patients receiving oxygen support. The inter-individual variabilities in clearance and apparent volume of distribution were 15.6% and 80.4%, respectively, and the residual variability was 34.2% as a coefficient of variation. CONCLUSION: Application of the findings in this study to patient care may permit selection of an appropriate initial maintenance dosage to achieve target theophylline concentrations, thus enabling the clinician to achieve the desired therapeutic effect in very premature Japanese infants.