Progress in prevention of mother-to-child transmission of HIV infection in Ukraine: results from a birth cohort study

Background: Ukraine was the epicentre of the HIV epidemic in Eastern Europe, which has the most rapidly accelerating HIV epidemic world-wide today; national HIV prevalence is currently estimated at 1.6%. Our objective was to evaluate the uptake and effectiveness of interventions for prevention of mother-to-child transmission (PMTCT) over an eight year period within operational settings in Ukraine, within the context of an ongoing birth cohort study.Methods: The European Collaborative Study (ECS) is an ongoing birth cohort study in which HIV-infected pregnant women identified before or during pregnancy or at delivery were enrolled and their infants prospectively followed. Three centres in Ukraine started enrolling in 2000, with a further three joining in September 2006.Results: Of the 3356 women enrolled, 21% (689) reported current or past injecting drug use (IDU). Most women were diagnosed antenatally and of those, the proportion diagnosed in the first/second trimester increased from 47% in 2000/01 (83/178) to 73% (776/1060) in 2006/07 (p < 0.001); intrapartum diagnosis was associated with IDU (Adjusted odds ratio 4.38; 95% CI 3.19-6.02). The percentage of women not receiving any antiretroviral prophylaxis declined from 18% (36/205) in 2001 to 7% in 2007 (61/843) p < 0.001). Use of sdNVP alone substantially declined after 2003, with a concomitant increase in zidovudine prophylaxis. Median antenatal zidovudine prophylaxis duration increased from 24 to 72 days between 2000 and 2007. Elective caesarean section (CS) rates were relatively stable over time and 34% overall. Mother-to-child transmission (MTCT) rates decreased from 15.2% in 2001 (95% CI 10.2-21.4) to 7.0% in 2006 (95% CI 2.6-14.6). In adjusted analysis, MTCT risk was reduced by 43% with elective CS versus vaginal delivery and by 75% with zidovudine versus no prophylaxis.Conclusion: There have been substantial improvements in use of PMTCT interventions in Ukraine, including earlier diagnosis of HIV-infected pregnant women and increasing coverage with antiretroviral prophylaxis and the initial MTCT rate has more than halved. Future research should focus on hard-to-reach populations such as IDU and on missed opportunities for further reducing the MTCT rate

Evaluation of appendicitis risk prediction models in adults with suspected appendicitis

Background: Appendicitis is the most common general surgical emergency worldwide, but its diagnosis remains challenging. The aim of this study was to determine whether existing risk prediction models can reliably identify patients presenting to hospital in the UK with acute right iliac fossa (RIF) pain who are at low risk of appendicitis.Methods: A systematic search was completed to identify all existing appendicitis risk prediction models. Models were validated using UK data from an international prospective cohort study that captured consecutive patients aged 16-45 years presenting to hospital with acute RIF in March to June 2017. The main outcome was best achievable model specificity (proportion of patients who did not have appendicitis correctly classified as low risk) whilst maintaining a failure rate below 5 per cent (proportion of patients identified as low risk who actually had appendicitis).Results: Some 5345 patients across 154 UK hospitals were identified, of which two-thirds (3613 of 5345, 67.6 per cent) were women. Women were more than twice as likely to undergo surgery with removal of a histologically normal appendix (272 of 964, 28.2 per cent) than men (120 of 993, 12.1 per cent) (relative risk 2.33, 95 per cent c.i. 1.92 to 2.84; P <0.001). Of 15 validated risk prediction models, the Adult Appendicitis Score performed best (cut-off score 8 or less, specificity 63.1 per cent, failure rate 3.7 per cent). The Appendicitis Inflammatory Response Score performed best for men (cut-off score 2 or less, specificity 24.7 per cent, failure rate 2.4 per cent).Conclusion: Women in the UK had a disproportionate risk of admission without surgical intervention and had high rates of normal appendicectomy. Risk prediction models to support shared decision-making by identifying adults in the UK at low risk of appendicitis were identified

Effect of Routine Low-Dose Oxygen Supplementation on Death and Disability in Adults With Acute Stroke: The Stroke Oxygen Study Randomized Clinical Trial.

Importance: Hypoxia is common in the first few days after acute stroke, is frequently intermittent, and is often undetected. Oxygen supplementation could prevent hypoxia and secondary neurological deterioration and thus has the potential to improve recovery. Objective: To assess whether routine prophylactic low-dose oxygen therapy was more effective than control oxygen administration in reducing death and disability at 90 days, and if so, whether oxygen given at night only, when hypoxia is most frequent, and oxygen administration is least likely to interfere with rehabilitation, was more effective than continuous supplementation. Design, Setting, and Participants: In this single-blind randomized clinical trial, 8003 adults with acute stroke were enrolled from 136 participating centers in the United Kingdom within 24 hours of hospital admission if they had no clear indications for or contraindications to oxygen treatment (first patient enrolled April 24, 2008; last follow-up January 27, 2015). Interventions: Participants were randomized 1:1:1 to continuous oxygen for 72 hours (n = 2668), nocturnal oxygen (21:00 to 07:00 hours) for 3 nights (n = 2667), or control (oxygen only if clinically indicated; n = 2668). Oxygen was given via nasal tubes at 3 L/min if baseline oxygen saturation was 93% or less and at 2 L/min if oxygen saturation was greater than 93%. Main Outcomes and Measures: The primary outcome was reported using the modified Rankin Scale score (disability range, 0 [no symptoms] to 6 [death]; minimum clinically important difference, 1 point), assessed at 90 days by postal questionnaire (participant aware, assessor blinded). The modified Rankin Scale score was analyzed by ordinal logistic regression, which yields a common odds ratio (OR) for a change from one disability level to the next better (lower) level; OR greater than 1.00 indicates improvement. Results: A total of 8003 patients (4398 (55%) men; mean [SD] age, 72 [13] years; median National Institutes of Health Stroke Scale score, 5; mean baseline oxygen saturation, 96.6%) were enrolled. The primary outcome was available for 7677 (96%) participants. The unadjusted OR for a better outcome (calculated via ordinal logistic regression) was 0.97 (95% CI, 0.89 to 1.05; P = .47) for oxygen vs control, and the OR was 1.03 (95% CI, 0.93 to 1.13; P = .61) for continuous vs nocturnal oxygen. No subgroup could be identified that benefited from oxygen. At least 1 serious adverse event occurred in 348 (13.0%) participants in the continuous oxygen group, 294 (11.0%) in the nocturnal group, and 322 (12.1%) in the control group. No significant harms were identified. Conclusions and Relevance: Among nonhypoxic patients with acute stroke, the prophylactic use of low-dose oxygen supplementation did not reduce death or disability at 3 months. These findings do not support low-dose oxygen in this setting. Trial Registration: ISRCTN Identifier: ISRCTN52416964

Rosuvastatin for primary prevention in patients with European systematic coronary risk evaluation risk ≥5% or Framingham risk >20%: post hoc analyses of the JUPITER trial requested by European health authorities

Aims: On the basis of the JUPITER trial, European health authorities recently approved the use of rosuvastatin to reduce first major cardiovascular events among ‘high' global risk primary prevention patients defined either by Framingham risk score >20% or European systematic coronary risk evaluation (SCORE) ≥5%. However, as these are post hoc analyses, data describing these subgroups have not previously been available to the clinical community. Methods and results: We randomized 17 802 apparently healthy men aged ≥50 and women ≥60 with low-density lipoprotein cholesterol (LDL-C) 20% or SCORE risk ≥5%. During 1.8-year median follow-up (maximum 5 years) of patients with Framingham risk >20%, the rate of myocardial infarction/stroke/cardiovascular death was 9.4 and 18.2 per 1000 person-years in rosuvastatin and placebo-allocated patients, respectively [hazard ratio (HR): 0.50, 95% confidence interval (CI): 0.27–0.93, P = 0.028]. Among patients with SCORE risk ≥5%, the corresponding rates were 6.9 and 12.0 using a model extrapolating risk for age ≥65 years (HR: 0.57, 95% CI: 0.43–0.78, P = 0.0003) and rates were 5.9 and 12.7 when risk for age was capped at 65 years (HR: 0.47, 95% CI: 0.32–0.68, P 20% or SCORE risk ≥5%), but LDL-C levels not requiring pharmacologic treatment, rosuvastatin 20 mg significantly reduced major cardiovascular events. ClinicalTrial.gov Identifier: NCT0023968

Exenatide compared with long-acting insulin to achieve glycaemic control with minimal weight gain in patients with type 2 diabetes: results of the Helping Evaluate Exenatide in patients with diabetes compared with Long-Acting insulin (HEELA) study

Aim: The Helping Evaluate Exenatide in overweight patients with diabetes compared with Long-Acting insulin (HEELA) study was designed to examine whether the glucagon-like peptide-1 (GLP-1) receptor agonist, exenatide, could improve HbA1c (≤7.4%) with minimal weight gain (≤1 kg) compared with insulin glargine

Planned Cesarean or planned vaginal delivery for twins : secondary analysis of randomized controlled trial

ACKNOWLEDGMENTS We thank all the participants in the Twin Birth Study and the staff at the Centre for Mother, Infant, and Child Research for their hard work and dedication. The Twin Birth Study was supported by a grant (63164) from the Canadian Institute of Health Research. P.T. and M.H.Z. were supported by a grant from The Netherlands Organization for Scientific Research (NWO ‐ grant number 401.16.080). The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.Peer reviewedPublisher PD

An observational study of patient characteristics and mortality following hypoglycemia in the community

Objectives: Characterize diabetes patients with severe hypoglycemia requiring emergency services intervention at home and investigate 12 month mortality. Research design and methods: Emergency services call-outs for hypoglycemia were recorded between 2005 and 2013 in an area covering 34000 patients with diabetes. Patient characteristics were documented together with capillary blood glucose (CBG), HbA1c and treatment for hypoglycemia. 12 month mortality and variables influencing survival were analysed. Results: In 1835 episodes amongst 1156 patients, 45% had type 1 diabetes (68.2% males), 44% had type 2 diabetes (49.4% males) with a minority unclassified. CBG at presentation (mean±SD) was 1.76±0.72 mmol/L in type 1 diabetes and 1.96±0.68 mmol/L in type 2 diabetes patients (p<0·0001), with higher HbA1c in the former group (8.3±1.52% (67.5±16.4 mmol/mol) and 7.8±1.74% (61.6±19.0 mmol/mol), respectively; p<0·0001). A third of type 2 diabetes patients were not on insulin therapy and displayed lower HbA1c compared with insulin users. Glucagon was used in 37% of type 1 diabetes and 28% of type 2 diabetes patients (p<0.0001). One year mortality was 4.45% in type 1 diabetes and 22.1% in type 2 diabetes. Age and type of diabetes were predictive of mortality in multivariable analysis, whereas CBG levels/frequency of hypoglycemia had no effect. Conclusions: Severe hypoglycemia in the community is common with a male predominance in type 1 diabetes. Severe hypoglycemia in non-insulin treated type 2 diabetes patients is associated with lower HbA1c compared with insulin users. Severe hypoglycemia appears to be associated with increased mortality at 12 months, particularly in type 2 diabetes. KEY MESSAGES Severe hypoglycemia in the community is common, and presents a large burden on both patients and healthcare workers. Using a large database of ambulance call-outs for hypoglycemia this study aimed to characterise those requiring the emergency services for an episode of hypoglycemia, and to investigate factors that may be associated with an increased risk of mortality. We found that a third of type 2 diabetes patients having severe hypoglycemic episodes were not using any insulin, these individuals had a lower HbA1c than those with type 2 diabetes requiring insulin treatment. 12 month mortality following an episode of severe hypoglycemia was high, especially in individuals with type 2 diabetes. More research is required to investigate the cause of death in these patient

Caracterización molecular de cepas invasivas de Streptococcus dysgalactiae subsp. equisimilis. Estudio multicéntrico Argentina 2011-2012

[EN] Streptococcus dysgalactiae subsp. equisimilis (SDSE) has virulence factors similar to those of Streptococcus pyogenes. Therefore, it causes pharyngitis and severe infections indistinguishable from those caused by the classic pathogen. The objectives of this study were: to know the prevalence of SDSE invasive infections in Argentina, to study the genetic diversity, to determine the presence of virulence genes, to study antibiotic susceptibility and to detect antibiotic resistance genes. Conventional methods of identification were used. Antibiotic susceptibility was determined by the disk diffusion and the agar dilution methods and the E-test. Twenty eight centers from 16 Argentinean cities participated in the study. Twenty three isolates (16 group G and 7 group C) were obtained between July 1 2011 and June 30 2012. Two adult patients died (8.7%). Most of the isolates were recovered from blood (60.9%). All isolates carried speJ and ssa genes. stG62647, stG653 and stG840 were the most frequent emm types. Nineteen different PFGE patterns were detected. All isolates were susceptible to penicillin and levofloxacin, 6 (26.1%) showed resistance or reduced susceptibility to erythromycin [1 mef(A), 3 erm(TR), 1 mef(A)+erm(TR) and 1 erm(TR)+erm(B)] and 7 (30.4%) were resistant or exhibited reduced susceptibility to tetracycline [2 tet(M), 5 tet(M)+tet(O)]. The prevalence in Argentina was of at least 23 invasive infections by SDSE. A wide genetic diversity was observed. All isolates carried speJ and ssa genes. Similarly to other studies, macrolide resistance (26.1%) was mainly associated to the MLSB phenotype. [ES] Streptococcus dysgalactiae subsp. equisimilis (SDSE) posee factores de virulencia similares a Streptococcus pyogenes y, en consecuencia, produce faringitis e infecciones graves indistinguibles de las generadas por este patógeno clásico. Los objetivos del estudio fueron conocer la prevalencia de SDSE en infecciones invasivas en Argentina, estudiar su diversidad genética, determinar la presencia de genes de virulencia, ensayar su sensibilidad a los antibióticos y conocer los genes de resistencia. Se emplearon métodos convencionales de identificación. La sensibilidad se determinó por difusión, Etest y dilución en agar. Participaron 28 centros de 16 ciudades argentinas. Se obtuvieron 23 aislamientos (16 del grupo G y 7 del grupo C) desde el 1-7-2011 hasta el 30-6-2012. Se registraron 2 muertes en adultos (8,7%). La mayoría de los aislamientos fueron obtenidos de sangre (60,9%). Todos eran portadores de los genes speJ y ssa. Los genotipos más frecuentes fueron stG62647, stG653 y stG840. Se detectaron 19 pulsotipos distintos. Todos los aislamientos fueron sensibles a penicilina y levofloxacina, 6 (26,1%) presentaron resistencia o sensibilidad disminuida a eritromicina (1 mef[A], 3 erm[TR], 1 mef[A] + erm[TR] y 1 erm[TR] + erm[B]) y 7 (30,4%) fueron resistentes o tuvieron sensibilidad disminuida a tetraciclina (2 tet[M], 5 tet[M] + tet[O]). La prevalencia anual en la Argentina fue de al menos 23 infecciones invasivas por SDSE y se observó una amplia diversidad genética. Todos los aislamientos presentaron los genes ssa y speJ. Como en otros estudios, la resistencia a macrólidos (26,1%) estuvo asociada, principalmente, al fenotipo MLSB.S

Lymphotoxin-α Gene and Risk of Myocardial Infarction in 6,928 Cases and 2,712 Controls in the ISIS Case-Control Study

Lymphotoxin-α (LTA) is a pro-inflammatory cytokine that plays an important role in the immune system and local inflammatory response. LTA is expressed in atherosclerotic plaques and has been implicated in the pathogenesis of atherosclerosis and coronary heart disease (CHD). Polymorphisms in the gene encoding lymphotoxin-α (LTA) on Chromosome 6p21 have been associated with susceptibility to CHD, but results in different studies appear to be conflicting. We examined the association of seven single nucleotide polymorphisms (SNPs) across the LTA gene, and their related haplotypes, with risk of myocardial infarction (MI) in the International Study of Infarct Survival (ISIS) case-control study involving 6,928 non-fatal MI cases and 2,712 unrelated controls. The seven SNPs (including the rs909253 and rs1041981 SNPs previously implicated in the risk of CHD) were in strong linkage disequilibrium with each other and contributed to six common haplotypes. Some of the haplotypes for LTA were associated with higher plasma concentrations of C-reactive protein (p = 0.004) and lower concentrations of albumin (p = 0.023). However, none of the SNPs or related haplotypes were significantly associated with risk of MI. The results of the ISIS study were considered in the context of six previously published studies that had assessed this association, and this meta-analysis found no significant association with CHD risk using a recessive model and only a modest association using a dominant model (with narrow confidence intervals around these risk estimates). Overall, these studies provide reliable evidence that these common polymorphisms for the LTA gene are not strongly associated with susceptibility to coronary disease