Variations in common diseases, hospital admissions, and deaths in middle-aged adults in 21 countries from five continents (PURE): a prospective cohort study

BACKGROUND: To our knowledge, no previous study has prospectively documented the incidence of common diseases and related mortality in high-income countries (HICs), middle-income countries (MICs), and low-income countries (LICs) with standardised approaches. Such information is key to developing global and context-specific health strategies. In our analysis of the Prospective Urban Rural Epidemiology (PURE) study, we aimed to evaluate differences in the incidence of common diseases, related hospital admissions, and related mortality in a large contemporary cohort of adults from 21 HICs, MICs, and LICs across five continents by use of standardised approaches. METHODS: The PURE study is a prospective, population-based cohort study of individuals aged 35-70 years who have been enrolled from 21 countries across five continents. The key outcomes were the incidence of fatal and non-fatal cardiovascular diseases, cancers, injuries, respiratory diseases, and hospital admissions, and we calculated the age-standardised and sex-standardised incidence of these events per 1000 person-years. FINDINGS: This analysis assesses the incidence of events in 162 534 participants who were enrolled in the first two phases of the PURE core study, between Jan 6, 2005, and Dec 4, 2016, and who were assessed for a median of 9·5 years (IQR 8·5-10·9). During follow-up, 11 307 (7·0%) participants died, 9329 (5·7%) participants had cardiovascular disease, 5151 (3·2%) participants had a cancer, 4386 (2·7%) participants had injuries requiring hospital admission, 2911 (1·8%) participants had pneumonia, and 1830 (1·1%) participants had chronic obstructive pulmonary disease (COPD). Cardiovascular disease occurred more often in LICs (7·1 cases per 1000 person-years) and in MICs (6·8 cases per 1000 person-years) than in HICs (4·3 cases per 1000 person-years). However, incident cancers, injuries, COPD, and pneumonia were most common in HICs and least common in LICs. Overall mortality rates in LICs (13·3 deaths per 1000 person-years) were double those in MICs (6·9 deaths per 1000 person-years) and four times higher than in HICs (3·4 deaths per 1000 person-years). This pattern of the highest mortality in LICs and the lowest in HICs was observed for all causes of death except cancer, where mortality was similar across country income levels. Cardiovascular disease was the most common cause of deaths overall (40%) but accounted for only 23% of deaths in HICs (vs 41% in MICs and 43% in LICs), despite more cardiovascular disease risk factors (as judged by INTERHEART risk scores) in HICs and the fewest such risk factors in LICs. The ratio of deaths from cardiovascular disease to those from cancer was 0·4 in HICs, 1·3 in MICs, and 3·0 in LICs, and four upper-MICs (Argentina, Chile, Turkey, and Poland) showed ratios similar to the HICs. Rates of first hospital admission and cardiovascular disease medication use were lowest in LICs and highest in HICs. INTERPRETATION: Among adults aged 35-70 years, cardiovascular disease is the major cause of mortality globally. However, in HICs and some upper-MICs, deaths from cancer are now more common than those from cardiovascular disease, indicating a transition in the predominant causes of deaths in middle-age. As cardiovascular disease decreases in many countries, mortality from cancer will probably become the leading cause of death. The high mortality in poorer countries is not related to risk factors, but it might be related to poorer access to health care. (AU)

The household economic burden of non-communicable diseases in 18 countries

BACKGROUND: Non-communicable diseases (NCDs) are the leading cause of death globally. In 2014, the United Nations committed to reducing premature mortality from NCDs, including by reducing the burden of healthcare costs. Since 2014, the Prospective Urban and Rural Epidemiology (PURE) Study has been collecting health expenditure data from households with NCDs in 18 countries. METHODS: Using data from the PURE Study, we estimated risk of catastrophic health spending and impoverishment among households with at least one person with NCDs (cardiovascular disease, diabetes, kidney disease, cancer and respiratory diseases; n=17 435), with hypertension only (a leading risk factor for NCDs; n=11 831) or with neither (n=22 654) by country income group: high-income countries (Canada and Sweden), upper middle income countries (UMICs: Brazil, Chile, Malaysia, Poland, South Africa and Turkey), lower middle income countries (LMICs: the Philippines, Colombia, India, Iran and the Occupied Palestinian Territory) and low-income countries (LICs: Bangladesh, Pakistan, Zimbabwe and Tanzania) and China. RESULTS: The prevalence of catastrophic spending and impoverishment is highest among households with NCDs in LMICs and China. After adjusting for covariates that might drive health expenditure, the absolute risk of catastrophic spending is higher in households with NCDs compared with no NCDs in LMICs (risk difference=1.71%; 95% CI 0.75 to 2.67), UMICs (0.82%; 95% CI 0.37 to 1.27) and China (7.52%; 95% CI 5.88 to 9.16). A similar pattern is observed in UMICs and China for impoverishment. A high proportion of those with NCDs in LICs, especially women (38.7% compared with 12.6% in men), reported not taking medication due to costs. CONCLUSIONS: Our findings show that financial protection from healthcare costs for people with NCDs is inadequate, particularly in LMICs and China. While the burden of NCD care may appear greatest in LMICs and China, the burden in LICs may be masked by care foregone due to costs. The high proportion of women reporting foregone care due to cost may in part explain gender inequality in treatment of NCDs. (AU)

Supplemental oxygen and surgical-site infections: an alternating intervention controlled trial.

BACKGROUND: The main defence against bacterial infection is oxidative killing by neutrophils, which requires molecular oxygen in wounded tissues. High inspired-oxygen fractions increase tissue oxygenation. But, whether improving tissue oxygenation actually reduces surgical-site infection (SSI) remains controversial. We therefore tested the primary hypothesis that supplemental oxygen (80% vs 30%) reduces the risk of a 30-day composite of deep tissue or organ-space SSI, healing-related wound complications, and mortality. METHODS: In an isolated suite of operating rooms, the inspired-oxygen concentration was alternated between 30% and 80% at 2-week intervals for 39 months. The analysis was restricted to patients who had major intestinal surgery lasting at least 2 h. Qualifying operations (5749) were analysed, including 2843 (49%) colorectal resections, 1866 (32%) lower gastrointestinal therapeutic procedures, 373 (6%) small-bowel resections, and 667 (13%) other colorectal procedures. RESULTS: The 80% and 30% oxygen groups were well balanced on all of the demographic, baseline, and procedural variables. The oxygen intervention had no effect on the composite primary outcome or any of its components. The overall observed incidence of the composite outcome was 10.8% (314/2896) in the 80% oxygen group and 11.0% (314/2853) in the 30% group. The estimated relative risk was 0.99 (95% CI: 0.85, 1.14) for 80% vs 30%, P=0.85. CONCLUSIONS: Supplemental oxygen does not prevent major infection and healing-related complications after major intestinal surgery. CLINICAL TRIAL REGISTRATION: NCT01777568.

Enterococcus spp. in a single blood culture: bacteremia or contamination?

We retrospectively evaluated adult cases with Enterococcus spp. in 1 blood culture (BC) (1/1/2010-12/31/2015; n=294) and stratified them into bacteremia or contamination. Contamination frequency was similar in community versus hospital-onset, E. faecalis versus E. faecium, and number of BC drawn per day. Contamination predictors were vancomycin-resistance, ampicillin-resistance, commensal organism copresence, and nonurinary/abdominal sources.

Evaluation of the Methods and Management of Acute Coronary Events (EMMACE)-3: protocol for a longitudinal study.

INTRODUCTION: Patients with cardiovascular disease are living longer and are more frequently accessing healthcare resources. The Evaluation of the Methods and Management of Acute Coronary Events (EMMACE)-3 national study is designed to improve understanding of the effect of quality of care on health-related outcomes for patients hospitalised with acute coronary syndrome (ACS). METHODS AND ANALYSIS: EMMACE-3 is a longitudinal study of 5556 patients hospitalised with an ACS in England. The study collects repeated measures of health-related quality of life, information about medications and patient adherence profiles, a survey of hospital facilities, and morbidity and mortality data from linkages to multiple electronic health records. Together with EMMACE-3X and EMMACE-4, EMMACE-3 will assimilate detailed information for about 13 000 patients across more than 60 hospitals in England. ETHICS AND DISSEMINATION: EMMACE-3 was given a favourable ethical opinion by Leeds (West) Research Ethics committee (REC reference: 10/H131374). On successful application, study data will be shared with academic collaborators. The findings from EMMACE-3 will be disseminated through peer-reviewed publications, at scientific conferences, the media, and through patient and public involvement. STUDY REGISTRATION NUMBER: ClinicalTrials.gov Identifier: NCT01808027. Information about the study is also available at EMMACE.org.

Blood culture series benefit may be limited to selected clinical conditions: time to reassess.

Blood cultures are often submitted as series (two to three sets per 24 hours) to maximize sample recovery. We assessed the actual benefit of additional sets. Blood cultures submitted from adults (≥ 18 years old) over 1 year (1 February 2012 to 31 January 2013) were examined. The medical records of patients with positive cultures were reviewed. Cultures with commensal organisms were considered contamination in the absence of a source and clinical findings. The impact of additional sets on antibiotic therapy was estimated. We evaluated 15,394 blood cultures. They were submitted as two to five sets per 24 hours in 12,236 (79.5%) instances. Pathogens were detected in 1227 sets, representing 741 bacteremias, of which 618 (83.4%) were detected in the first set and 123 (16.6%) in the additional sets. Pathogens missed in the first set were recovered from patients receiving antibiotics (n = 72; 58.5%) and after undergoing a procedure (n = 54; 43.9%). The additional sets' results could have influenced antibiotic therapy in 76/6235 (1.2%) instances, including 40 (0.6%) antibiotic switches and 36 (0.6%) possible extensions of therapy. The potential impact of the detection of missed pathogens on antibiotic therapy was not apparent in patients who had an endovascular infection (26/27, 96.3%) and those who lacked an obvious source of pathogens (10/10, 100%). These findings suggest that one blood culture is probably adequate in patients with an obvious source of pathogens. Blood culture series are beneficial in patients without an obvious source of pathogens and in those with endovascular infections. It is time to reassess the benefit of blood culture series, perhaps limiting them to selected conditions.

Is Early Treatment with a Cervical Pessary an Option in Patients with a History of Surgical Conisation and a Short Cervix?

Objective: Patients with a history of one or more conizations have an increased risk of spontaneous preterm birth (SPTB). The aim of this study was to investigate the outcome of pregnancies in patients with a history of conization and early treatment with a cervical pessary. Methods: In this pilot observational study we included 21 patients and evaluated the obstetric history, the interval between pessary placement and delivery, gestational age at delivery, the neonatal outcome and the number of days of maternal and neonatal admission. Results: Among the study group of 21 patients, 20 patients had a singleton and one had a dichorionic/diamniotic twin pregnancy. At insertion, the mean gestational age was 17 + 2 (10 + 5-24 + 0) weeks and the mean cervical length was 19 (4-36) mm. Six patients presented with funneling at insertion with a mean funneling width of 19.7 (10-38) mm and funneling length of 19.9 (10-37) mm. Five patients had already lost at least one child due to early spontaneous preterm birth and another five had at least one previous abortion, who have now delivered beyond 34 weeks. The mean gestational age at delivery was 38 (31 + 1-41 + 0) gestational weeks and the mean interval between insertion and delivery was 145 (87-182) days. Conclusion: Our findings suggest a beneficial effect of an early pessary placement for patients at high-risk for preterm birth due to conization.

Correlation of methicillin-resistant Staphylococcus aureus vancomycin minimal inhibitory concentration results by Etest and broth microdilution methods with population analysis profile: lack of Etest overestimation of the MIC.

Methicillin-resistant Staphylococcus aureus (MRSA) vancomycin minimum inhibitory concentrations (V-MICs) are sometimes reported to be higher according to Etest versus broth microdilution (BMD). These observations are often interpreted as an Etest overestimation of the actual MIC. We measured V-MIC of 484 MRSA blood isolates using Etest, BMD, and a modified BMD (M-BMD) with incremental dilutions parallel to the Etest scale, correlated the results with population analysis profile-area under the curve (PAP-AUC). All MIC tests were done in parallel. The mean V-MIC was comparable (1.83 ± 0.44 [Etest], 1.88 ± 0.67 [BMD] and 1.75 ± 0.57 mg/L [M-BMD]; p = 0.9 [ANOVA]). The V-MICs/PAP-AUC correlation coefficient was 0.555 (Etest), 0.513 (BMD), and 0.586 (M-BMD). Etest MICs were equal (44.2 %), one dilution higher (21.9 %), two dilutions higher (2.5 %), one dilution lower (29.8 %), and two dilutions lower (1.6 %) than BMD MICs and were equal (61.5 %), one dilution higher (28.3 %), two dilutions higher (0.4 %), one dilution lower (9.5 %), and two dilutions lower (0.2 %) than M-BMD MICs. The mean PAP-AUC for Etest vs M-BMD among isolates with similar Etest/M-BMD MIC values was 0.25 ± 0.15 vs 0.35 ± 0.13 (p = 0.8), 0.46 ± 0.16 vs 0.50 ± 0.17 (p = 0.8), 0.64 ± 0.19 vs 0.67 ± 0.21 (p = 0.9), and 0.90 ± 0.31 vs 0.88 ± 0.25 (p = 1.0) for isolates with V-MIC of ≤ 1, 1.5, 2, and ≥ 3 mg/L respectively. These results suggest that Etest might not overestimate V-MIC in comparison to M-BMD or BMD; Etest and M-BMD tests depict comparable PAP-AUC and have a higher correlation with PAP-AUC than the conventional BMD, probably because of the more detailed results. Etest may be more suitable than conventional BMD for MIC outcome assessment because of the more detailed MICs.

Detection of intermediately vancomycin-susceptible and heterogeneous Staphylococcus aureus isolates: comparison of Etest and Agar screening methods.

Detection of Staphylococcus aureus isolates with intermediate vancomycin susceptibility (VISA) and heteroresistance (hVISA) remains problematic. The population analysis profile/area under the curve (PAP/AUC) is the gold standard but is cumbersome. We compared the performance of two Etest screening methods (macromethod [MAC] and glycopeptide resistance detection [GRD]) plus brain heart infusion (BHI) agars supplemented with 3 (BHI-V3) or 4 (BHI-V4) mg/liter vancomycin in detecting hVISA and/or VISA phenotypes. Etest hVISA screenings were done in parallel for 485 saved methicillin-resistant S. aureus (MRSA) blood isolates according to the manufacturer's instructions. The PAP/AUC was measured for all isolates according to the modified method. PAP/AUC test isolate/Mu3 ratios of <0.9, 0.9 to 1.3, and >1.3 were considered positive for susceptible MRSA (S-MRSA), hVISA, and VISA, respectively. PAP/AUC revealed seven VISA and 33 hVISA phenotypes. MAC screening was positive for 30 (75.0%) hVISA/VISA and 49 (11.0%) S-MRSA isolates. GRD screening was positive for 28 (70.0%) hVISA/VISA and 63 (14.2%) S-MRSA isolates. Growth on BHI-V3 was noted in all hVISA/VISA and 24 (5.4%) S-MRSA isolates. Growth on BHI-V4 was noted in all VISA and four (12.1%) hVISA isolates. None of the S-MRSA isolates grew on BHI-V4 agar. The sensitivity, specificity, and positive (PPV) and negative (NPV) predictive values were 75.0%, 89.0%, 38.0%, and 97.5% for MAC; 70.0%, 85.8%, 30.8%, and 97.0% for GRD; 100%, 94.6%, 62.5%, and 100% for BHI-V3; and 100, 99.2%, 63.6%, and 100% for BHI-V4 (for detecting VISA). These findings suggest that both Etest screening methods have excellent NPV, but positive results require confirmation. BHI-V3 and BHI-V4 agars provide more precise identification of hVISA and VISA, respectively; they may be reasonable alternatives to PAP/AUC.

Short communication: Validation of in vitro fertility genes in a Holstein bull population.

Previously, we constructed an in vitro fertilization system for the identification of genes affecting fertility traits in dairy cattle. The efficiency of this system has been demonstrated by the identification of several genes affecting fertilization rate and early embryonic survival. However, to employ these genetic markers in marker- and gene-assisted selection programs, there is a need to validate in vitro results in phenotypic data sets collected in vivo. Thus, the objective of this study was to validate, in a population of Holstein bulls, the fertility trait genes we previously identified in an in vitro system. Estimated relative conception rate (ERCR) data from 222 Holstein bulls were obtained from 5 different artificial insemination companies in the United States. Bulls were genotyped for the genes FGF2, POU1F1, PRL, PRLR, GH, GHR, STAT5A, OPN, and UTMP, and the data were analyzed for association with ERCR using a mixed effects sire model. A stepwise model selection procedure revealed evidence of association with ERCR for FGF2 and STAT5A polymorphisms. The in vivo validation suggests that these genes can be used in gene-assisted selection programs for reproductive performance in dairy cattle. The genotypes found to be associated with low bull fertility in this study have been reported to be associated with high milk composition in previous studies. These findings provide molecular evidence for the antagonistic relationship between milk production and fertility observed for many years in different breeds of dairy cattle.

Medicine utilisation review in selected non-governmental organisations primary healthcare clinics in the West Bank in Palestine.

BACKGROUND: Information on prescribing practices in Palestine is lacking, however, still essential for strategic planning. PURPOSE: To characterise prescribing patterns and specific medicine use indicators in selected non-governmental organisations' (NGO) primary healthcare clinics/centres (PHC) in the West Bank (WB) in Palestine. METHODOLOGY: A prospective cross-sectional survey of prescribing practices based on medical records of 6032 patients with acute symptoms frequenting 41 NGO PHCs in the WB, between July and September 2004. A systematic random sample of every 10th patient appearing on the patient registration list was selected. Direct observation of consultation and dispensing practices and times in a sub-group of patients was completed utilising special forms. RESULTS: Respiratory tract infections were the most commonly occurring conditions. On average, 1.9 drugs were prescribed per encounter and antibiotics were the most commonly prescribed medications, followed by Analgesics and NSAIDs accounting for 46 and 20% of the total medications expenditures, respectively. Injections and combined medications use per encounter was 16 and 8%, respectively. Most commonly prescribed medications were of local production. Consultation (6.4 +/- 4.6 minutes) and dispensing times (1.6 +/- 1.5 minutes) were short with inadequate labelling. Provision of reference sources and treatment guidelines implementation were also inadequate. CONCLUSION: The results suggest that prescribing practices could be improved through wider implementation of treatment guidelines, a review of antibiotic prescribing, and increased time spent with patients to promote concordance. Strategies aimed at improving prescribing and dispensing practices should be addressed through new innovative capacity building models based on problem solving and feedback mechanisms.

High rate of decreasing daptomycin susceptibility during the treatment of persistent Staphylococcus aureus bacteremia.

Daptomycin is bactericidal against Staphylococcus aureus, with susceptibility defined as a minimal inhibitory concentration (MIC) < or =1 microg/ml. Higher MIC developed in a few cases during therapy. The frequency of MIC rise in persistent bacteremia is unknown. We evaluated all patients with S. aureus bacteremia (SAB) treated with daptomycin (> or =2 days) from 1 April 2004 to 30 October 2006. All patients with post-daptomycin-exposure saved isolates were studied. Daptomycin susceptibility was determined (in duplicate) on all pre- and post-daptomycin-exposure isolates by the broth (Mueller-Hinton) microdilution method. Among 74 treatment courses in 67 patients, 18 were for SAB. Ten had persistent bacteremia (median = 11 days; range = 1-21) and post-daptomycin-exposure saved isolates. The patient age was 29-84 years (median = 57.5 years). Intravascular catheter was the most common source (50%). Most patients (90%) failed therapy prior to starting daptomycin. The initial daptomycin dose was 4 mg/kg in four (40%) cases. The pre-exposure MIC was 0.125-0.5 microg/ml. The post-exposure MIC increased in four cases and was elevated in two cases (60%), to 2 microg/ml in five and 4 microg/ml in one. MIC rise was noted within 5-15 days of exposure and persisted up to 247 days after stopping daptomycin. Pulse-field gel electrophoresis (PFGE) band pattern of isolates with increased MIC revealed 1-3-band differences, implying genetic relatedness. All patients with non-susceptible isolates relapsed or failed therapy. These findings illustrate that daptomycin susceptibility often decreases during the treatment of persistent SAB. Therefore, susceptibility should be closely monitored during therapy.

[Assessment of medical waste management in a Palestinian hospital].

We studied medical waste management in a Palestinian hospital in the West Bank and the role of municipality in this management. In general, "good management practices" were inadequate; there was insufficient separation between hazardous and non-hazardous wastes, an absence of necessary rules and regulations for the collection of wastes from the hospital wards and the on-site transport to a temporary storage location inside and outside the hospital and inadequate waste treatment and disposal of hospital wastes along with municipal garbage. Moreover, training of personnel was lacking and protective equipment and measures for staff were not available. No special landfills for hazardous wastes were found within the municipality.

Interinstitutional and intrainstitutional transmission of a strain of Acinetobacter baumannii detected by molecular analysis: comparison of pulsed-field gel electrophoresis and repetitive sequence-based polymerase chain reaction.

Pulsed-field gel electrophoresis and repetitive sequence-based polymerase chain reaction provided comparable strain discrimination with minor discordance in typing Acinetobacter baumannii clinical isolates from patients at our hospital and affiliated institutions. Typing revealed a cluster strain with intrainstitutional and interinstitutional spread during the study period. A long-term acute care facility may have been the reservoir.

Fever treatment and household wealth: the challenge posed for rolling out combination therapy for malaria.

OBJECTIVE: To investigate the variation in malaria parasitaemia, reported fever, care seeking, antimalarials obtained and household expenditure by socio-economic status (SES), and to assess the implications for ensuring equitable and appropriate use of antimalarial combination therapy. METHODS: A total of 2,500 households were surveyed in three rural districts in southern Tanzania in mid-2001. Blood samples and data on SES were collected from all households. Half the households completed a detailed questionnaire on care seeking and treatment costs. Households were categorised into SES thirds based on an index of household wealth derived using principal components analysis. RESULTS: Of individuals completing the detailed survey, 16% reported a fever episode in the previous 2 weeks. People from the better-off stratum were significantly less likely to be parasitaemic, and significantly more likely to obtain antimalarials than those in the middle or poor stratum. The better treatment obtained by the better off led them to spend two to three times more than the middle and poor third spent. This reflected greater use of non-governmental organisation (NGO) facilities, which were the most expensive source of care, and higher expenditure at NGO facilities and drug stores. CONCLUSION: The coverage of appropriate malaria treatment was low in all SES groups, but the two poorer groups were particularly disadvantaged. As countries switch to antimalarial combination therapy, distribution must be targeted to ensure that the poorest groups fully benefit from these new and highly effective medicines.