Determinants of cognitive performance and decline in 20 diverse ethno-regional groups: A COSMIC collaboration cohort study.

BACKGROUND: With no effective treatments for cognitive decline or dementia, improving the evidence base for modifiable risk factors is a research priority. This study investigated associations between risk factors and late-life cognitive decline on a global scale, including comparisons between ethno-regional groups. METHODS AND FINDINGS: We harmonized longitudinal data from 20 population-based cohorts from 15 countries over 5 continents, including 48,522 individuals (58.4% women) aged 54-105 (mean = 72.7) years and without dementia at baseline. Studies had 2-15 years of follow-up. The risk factors investigated were age, sex, education, alcohol consumption, anxiety, apolipoprotein E ε4 allele (APOE*4) status, atrial fibrillation, blood pressure and pulse pressure, body mass index, cardiovascular disease, depression, diabetes, self-rated health, high cholesterol, hypertension, peripheral vascular disease, physical activity, smoking, and history of stroke. Associations with risk factors were determined for a global cognitive composite outcome (memory, language, processing speed, and executive functioning tests) and Mini-Mental State Examination score. Individual participant data meta-analyses of multivariable linear mixed model results pooled across cohorts revealed that for at least 1 cognitive outcome, age (B = -0.1, SE = 0.01), APOE*4 carriage (B = -0.31, SE = 0.11), depression (B = -0.11, SE = 0.06), diabetes (B = -0.23, SE = 0.10), current smoking (B = -0.20, SE = 0.08), and history of stroke (B = -0.22, SE = 0.09) were independently associated with poorer cognitive performance (p < 0.05 for all), and higher levels of education (B = 0.12, SE = 0.02) and vigorous physical activity (B = 0.17, SE = 0.06) were associated with better performance (p < 0.01 for both). Age (B = -0.07, SE = 0.01), APOE*4 carriage (B = -0.41, SE = 0.18), and diabetes (B = -0.18, SE = 0.10) were independently associated with faster cognitive decline (p < 0.05 for all). Different effects between Asian people and white people included stronger associations for Asian people between ever smoking and poorer cognition (group by risk factor interaction: B = -0.24, SE = 0.12), and between diabetes and cognitive decline (B = -0.66, SE = 0.27; p < 0.05 for both). Limitations of our study include a loss or distortion of risk factor data with harmonization, and not investigating factors at midlife. CONCLUSIONS: These results suggest that education, smoking, physical activity, diabetes, and stroke are all modifiable factors associated with cognitive decline. If these factors are determined to be causal, controlling them could minimize worldwide levels of cognitive decline. However, any global prevention strategy may need to consider ethno-regional differences

Comparative Genomics of the Apicomplexan Parasites Toxoplasma gondii and Neospora caninum: Coccidia Differing in Host Range and Transmission Strategy

Toxoplasma gondii is a zoonotic protozoan parasite which infects nearly one third of the human population and is found in an extraordinary range of vertebrate hosts. Its epidemiology depends heavily on horizontal transmission, especially between rodents and its definitive host, the cat. Neospora caninum is a recently discovered close relative of Toxoplasma, whose definitive host is the dog. Both species are tissue-dwelling Coccidia and members of the phylum Apicomplexa; they share many common features, but Neospora neither infects humans nor shares the same wide host range as Toxoplasma, rather it shows a striking preference for highly efficient vertical transmission in cattle. These species therefore provide a remarkable opportunity to investigate mechanisms of host restriction, transmission strategies, virulence and zoonotic potential. We sequenced the genome of N. caninum and transcriptomes of the invasive stage of both species, undertaking an extensive comparative genomics and transcriptomics analysis. We estimate that these organisms diverged from their common ancestor around 28 million years ago and find that both genomes and gene expression are remarkably conserved. However, in N. caninum we identified an unexpected expansion of surface antigen gene families and the divergence of secreted virulence factors, including rhoptry kinases. Specifically we show that the rhoptry kinase ROP18 is pseudogenised in N. caninum and that, as a possible consequence, Neospora is unable to phosphorylate host immunity-related GTPases, as Toxoplasma does. This defense strategy is thought to be key to virulence in Toxoplasma. We conclude that the ecological niches occupied by these species are influenced by a relatively small number of gene products which operate at the host-parasite interface and that the dominance of vertical transmission in N. caninum may be associated with the evolution of reduced virulence in this species

May Measurement Month 2018: a pragmatic global screening campaign to raise awareness of blood pressure by the International Society of Hypertension

Aims Raised blood pressure (BP) is the biggest contributor to mortality and disease burden worldwide and fewer than half of those with hypertension are aware of it. May Measurement Month (MMM) is a global campaign set up in 2017, to raise awareness of high BP and as a pragmatic solution to a lack of formal screening worldwide. The 2018 campaign was expanded, aiming to include more participants and countries. Methods and results Eighty-nine countries participated in MMM 2018. Volunteers (≥18 years) were recruited through opportunistic sampling at a variety of screening sites. Each participant had three BP measurements and completed a questionnaire on demographic, lifestyle, and environmental factors. Hypertension was defined as a systolic BP ≥140 mmHg or diastolic BP ≥90 mmHg, or taking antihypertensive medication. In total, 74.9% of screenees provided three BP readings. Multiple imputation using chained equations was used to impute missing readings. 1 504 963 individuals (mean age 45.3 years; 52.4% female) were screened. After multiple imputation, 502 079 (33.4%) individuals had hypertension, of whom 59.5% were aware of their diagnosis and 55.3% were taking antihypertensive medication. Of those on medication, 60.0% were controlled and of all hypertensives, 33.2% were controlled. We detected 224 285 individuals with untreated hypertension and 111 214 individuals with inadequately treated (systolic BP ≥ 140 mmHg or diastolic BP ≥ 90 mmHg) hypertension. Conclusion May Measurement Month expanded significantly compared with 2017, including more participants in more countries. The campaign identified over 335 000 adults with untreated or inadequately treated hypertension. In the absence of systematic screening programmes, MMM was effective at raising awareness at least among these individuals at risk

Tracheostomy procedures in the intensive care unit: an international survey

Abstract Introduction Percutaneous dilatational tracheostomy (PDT) is one of the most frequent procedures performed in the intensive care unit (ICU). PDT may add potential benefit to clinical management of critically ill patients. Despite this, no clinical guidelines are available. We sought to characterize current practice in this international survey. Methods An international survey, endorsed and peer reviewed by European Society of Intensive Care Medicine (ESICM), was carried out from May to October 2013. The questionnaire was accessible from the ESICM website in the ‘survey of the month’ section. Results 429 physicians from 59 countries responded to this survey. Single step dilatational tracheostomy was the most used PDT in ICU. Almost 75 % of PDT’s were performed by intensive care physicians. The main indication for PDT was prolonged mechanical ventilation. Tracheostomies were most frequently performed between 7–15 days after ICU admission. Volume control mechanical ventilation, and a combination of sedation, analgesia, neuromuscular blocking agents and fiberoptic bronchoscopy were used. Surgical tracheostomy was mainly performed in ICU by ENT specialists, and was generally chosen when for patients at increased risk for difficult PDT insertion. Bleeding controlled by compression and stoma infection/inflammation were the most common intra-procedural and late complications, respectively. Informed consent for PDT was obtained in only 60 % of cases. Conclusions This first international picture of current practices in regard to tracheostomy insertion demonstrates considerable geographic variation in practice, suggesting a need for greater standardization of approaches to tracheostomy insertion

Gonorrhea in Indonesia: High Prevalence of Asymptomatic Urogenital Gonorrhea but No Circulating Extended Spectrum Cephalosporins-Resistant Neisseria gonorrhoeae Strains in Jakarta, Yogyakarta, and Denpasar, Indonesia

Little is known about the epidemiology of asymptomatic urogenital gonorrhea and antimicrobial susceptibility of Neisseria gonorrhoeae (NG) strains circulating in Indonesia. We studied these issues in 3 large Indonesian cities. In 2014, participants were recruited from sexually transmitted infection clinics and through outreach in Jakarta, Yogyakarta, and Denpasar. Neisseria gonorrhoeae detection in genital specimens was performed with NG-qPCR at the Public Health Service in Amsterdam. Antimicrobial susceptibility was investigated using the Etest. Among 992 participants, 781 were asymptomatic and included in the risk factors analysis: 439 (56.2%) men, 258 (33.0%) women, and 84 (10.8%) transwomen. They differed significantly in age and were mostly men who have sex with men (35.2%) and female sex workers (29.3%).Overall, 175 (22.4%) asymptomatic participants had a positive NG-qPCR result. Factors positively associated with asymptomatic urogenital gonorrhea were being recruited through outreach (vs clinic-based), inconsistent condom use, and being divorced/widowed (vs single).Among 79 urogenital cultured isolates derived from 27 symptomatic and 52 asymptomatic participants, all isolates were susceptible to ceftriaxone and cefixime, and 98.7% of isolates were susceptible to azithromycin. In contrast, resistance to doxycycline (98.7%) and ciprofloxacin (97.4%) was common. Prevalence of asymptomatic urogenital gonorrhea among Indonesian key populations is very high. Little to no resistance against extended spectrum cephalosporins and azithromycin was observed. However, almost all isolates were resistant to doxycycline and ciprofloxacin. Strengthening outreach sexually transmitted infections services, composing guidelines to screen asymptomatic individuals, and implementing periodical antimicrobial resistance surveillance are recommende

Value of light microscopy to diagnose urogenital gonorrhoea: a diagnostic test study in Indonesian clinic-based and outreach sexually transmitted infections services

Introduction Gonorrhoea is a common sexually transmitted disease caused by Neisseria gonorrhoeae (Ng) infection. Light microscopy of urogenital smears is used as a simple tool to diagnose urogenital gonorrhoea in many resource-limited settings. We aimed to evaluate the accuracy of light microscopy to diagnose urogenital gonorrhoea as compared with a PCR-based test. Methods In 2014, we examined 632 male urethral and 360 endocervical smears in clinic-based and outreach settings in Jakarta, Yogyakarta and Denpasar, Indonesia. Using the detection of Ng DNA by a validated PCR as reference test, we evaluated the accuracy of two light microscopic criteria to diagnose urogenital gonorrhoea in genital smears: (1) the presence of intracellular Gram-negative diplococci (IGND) and (2) >= 5 polymorphonuclear leucocytes (PMNL)/oil-immersion field (oif) in urethral or >= 20 PMNL/oif in endocervical smears. Results In male urethral smears, IGND testing had a sensitivity (95% CI), specificity (95% CI) and kappa +/- SE of 59.0% (50.1 to 67.4), 89.4% (86.3 to 91.9) and 0.49 +/- 0.04, respectively. For PMNL count, these were 59.0% (50.1 to 67.4), 83.7% (80.2 to 86.9) and 0.40 +/- 0.04, respectively. The accuracy of IGND in the clinic-based settings (72.0% (57.5 to 83.3), 95.2% (91.8 to 97.5) and 0.68 +/- 0.06, respectively) was better than in the outreach settings (51.2% (40.0 to 62.3), 83.4% (78.2 to 87.8) and 0.35 +/- 0.06, respectively). In endocervical smears, light microscopy performed poorly regardless of the setting or symptomatology, with kappas ranging from -0.09 to 0.24. Conclusion Light microscopy using IGND and PMNL criteria can be an option with moderate accuracy to diagnose urethral gonorrhoea among males in a clinic-based setting. The poor accuracy in detecting endocervical infections indicates an urgent need to implement advanced methods, such as PCR. Further investigations are needed to identify the poor diagnostic outcome in outreach service

Spontaneous Clearance of Pharyngeal Gonococcal Infections: A Retrospective Study in Patients of the Sexually Transmitted Infections Clinic; Amsterdam, the Netherlands; 2012 to 2015

Introduction Pharyngeal Neisseria gonorrhoeae infections are mostly asymptomatic, yet sustain ongoing gonococcal transmission. We assessed the proportion of pharyngeal gonorrhea that spontaneously clears and identified determinants of clearance. Methods At the sexually transmitted infections clinic Amsterdam, at-risk women and men who have sex with men were routinely screened for pharyngeal N. gonorrhoeae using an RNA-based nucleic acid amplification test (NAAT; Aptima Combo 2). We retrospectively examined medical records of pharyngeal gonorrhea patients (January 2012-August 2015). We included patients who returned for antibiotic treatment and had a new sample taken for NAAT before treatment. Spontaneous clearance was defined as a negative NAAT result at the follow-up visit. Results During the study period, 1266 cases with a pharyngeal gonorrhea were not treated at the first consultation and returned for a follow-up visit. Median (interquartile range) time between the first consultation and follow-up was 10 (7-14) days. Spontaneous clearance was found in 139 cases (11.0%) and was associated with age at least 45 years (vs. 16-24 years; adjusted odds ratio, 2.02 [95% confidence interval, 1.09-3.75]) and with time from the first consultation to follow-up (adjusted odds ratio, 1.08 [1.06-1.10], per extra day). Conclusions Eleven percent of pharyngeal gonorrhea cases cleared spontaneously. Spontaneous clearance of pharyngeal gonorrhea was more often seen among older patients