Providing antiretroviral care in conflict settings.

There has been an historic expectation that delivering combination antiretroviral therapy (cART) to populations affected by violent conflict is untenable due to population movement and separation of drug supplies. There is now emerging evidence that cART provision can be successful in these populations. Using examples from Médecins Sans Frontières experience in a variety of African settings and also local nongovernmental organizations' experiences in northern Uganda, we examine novel approaches that have ensured retention in programs and adequate adherence. Emerging guidelines from United Nations bodies now support the expansion of cART in settings of conflict

Traditional Chinese medicines in the treatment of hepatocellular cancers: a systematic review and meta-analysis

<p>Abstract</p> <p>Background</p> <p>Liver cancer is a common malignancy with a high mortality rate. Given the poor prognosis associated with this cancer, many patients seek additional therapies that may improve quality of life or survival. Several Traditional Chinese Medicines (TCM) have been evaluated in clinical trials, but little is known about them outside of China.</p> <p>Methods</p> <p>We searched independently and in duplicate 8 electronic databases, including 2 Chinese language databases, until February 2009. We included any randomized clinical trials (RCT) evaluating a TCM oral preparation for the treatment of hepatocellular cancers. We abstracted data on survival, tumor response, and performance scores. We conducted a random-effects meta-analysis and applied a meta-regression analysis.</p> <p>Results</p> <p>We included 45 RCTs (n = 3,236). All studies employed an active control group. In general, the reporting of methodological issues was poor. We analyzed data from 37 trials reporting on complete response effects score (Relative Risk [RR] of 1.26 (95 CI, 1.04–1.52, P = 0.01, I²= 0%, P = 0.99). Products containing ginseng, astragalus and mylabris had a larger treatment effect (OR 1.34, 95% CI, 1.04–1.71, P = 0.01) than the pooled broad estimate, also the case for astragalus-based treatments (OR 1.35, 95% CI, 1.001–1.80. P = 0.048). We examined survival rates and pooled 15 studies reporting on 6 month outcomes (RR 1.10, 95% CI, 1.04–1.15, P = < 0.0001, I²= 0%, P = 0.60). This effect was consistent at other prospective dates, including 12 months (22 trials, RR 1.26, 95% CI, 1.17–1.36, P = < 0.0001, I²= 7%, P = 0.36), 24 months (15 trials, 1.72, 95% CI, 1.40–2.03, P = < 0.0001, I²= 0%, P = 0.75); and, at 36 months (8 trials, RR 2.40, 95% CI, 1.65–3.49, P = < 0.0001, I²= 0%, P = 0.62).</p> <p>Limitations</p> <p>All included trials were conducted in China where emerging evidence suggests many RCTs are not, in fact, randomized. Publication bias may exist, favouring positive reports.</p> <p>Conclusion</p> <p>Our meta-analysis displays compelling evidence of effectiveness for hepatocellular cancers that should be evaluated in high-quality and transparent clinical trials.</p

Reporting of noninferiority and equivalence randomized trials for major prostaglandins: A systematic survey of the ophthalmology literature

<p>Abstract</p> <p>Background</p> <p>Standards for reporting clinical trials have improved the transparency of patient-important research. The Consolidated Standards of Reporting Trials (CONSORT) published an extension to address noninferiority and equivalence trials. We aimed to determine the reporting quality of prostaglandin noninferiority and equivalence trials in the treatment of glaucoma.</p> <p>Methods</p> <p>We searched, independently and in duplicate, 6 electronic databases for eligible trials evaluating prostaglandins. We abstracted data on reporting of methodological criteria, including reporting of per-protocol [PP] and intention-to-treat [ITT] analysis, sample size estimation with margins, type of statistical analysis conducted, efficacy summaries, and use of hyperemia measures.</p> <p>Results</p> <p>Trials involving the four major prostaglandin groups (latanoprost, travoprost, bimatoprost, unoprostone) were analyzed. We included 36 noninferiority and 11 equivalence trials. Seventeen out of the included 47 trials (36%, 95% Confidence Intervals [CI]: 24–51) were crossover designs. Only 3 studies (6%, 95% CI: 2–17) reported a presented results of both ITT and PP populations. Twelve studies (26%, 95% CI: 15–39) presented only ITT results but mentioned that PP population had similar results. Thirteen trials (28%, 95% CI: 17–42) presented only PP results with no mention of ITT population results while 17 studies (36%, 95% CI: 24–51) presented only ITT results with no mention of PP population results. Thirty-four (72%, 95% CI: 58–83) of studies adequately described their margin of noninferiority/equivalence. Sequence generation was reported in 22/47 trials (47%, 95% CI: 33–61). Allocation concealment was reported in only 10/47 (21%, 95% CI: 12–35) of the trials. Thirty-five studies (74%, 95% CI: 60–85) employed masking of at least two groups, 4/47 (9%, 95% CI: 3–20) masked only patients and 8/47 (17%, 95% CI: 9–30) were open label studies. Eight (17%, 95% CI: 9–30) of the 47 trials employed a combined test of noninferiority and superiority. We also found 6 differing methods of evaluating hyperemia.</p> <p>Conclusion</p> <p>The quality of reporting noninferiority/equivalency trials in the field of glaucoma is markedly heterogeneous. The adoption of the extended CONSORT statement by journals will potentially improve the transparency of this field.</p

The Economic Burden of Prematurity in Canada

Background Preterm birth is a major risk factor for morbidity and mortality among infants worldwide, and imposes considerable burden on health, education and social services, as well as on families and caregivers. Morbidity and mortality resulting from preterm birth is highest among early (&lt; 28&nbsp;weeks gestational age) and moderate (28–32&nbsp;weeks) preterm infants, relative to late preterm infants (33–36&nbsp;weeks). However, substantial societal burden is associated with late prematurity due to the larger number of late preterm infants relative to early and moderate preterm infants. Methods The aim in this study was to characterize the burden of premature birth in Canada for early, moderate, and late premature infants, including resource utilization, direct medical costs, parental out-of-pocket costs, education costs, and mortality, using a validated and published decision model from the UK, and adapting it to a Canadian setting based on analysis of administrative, population-based data from Québec. Results Two-year survival was estimated at 56.0% for early preterm infants, 92.8% for moderate preterm infants, and 98.4% for late preterm infants. Per infant resource utilization consistently decreased with age. For moderately preterm infants, hospital days ranged from 1.6 at age two to 0.09 at age ten. Cost per infant over the first ten years of life was estimated to be $67,467 for early preterm infants,$52,796 for moderate preterm infants, and id="mce_marker"0,010 for late preterm infants. Based on population sizes this corresponds to total national costs of id="mce_marker"23.3 million for early preterm infants, $255.6 million for moderate preterm infants,$208.2 million for late preterm infants, and $587.1 million for all infants. Conclusion Premature birth results in significant infant morbidity, mortality, healthcare utilization and costs in Canada. A comprehensive decision-model based on analysis of a Canadian population-based administrative data source suggested that the greatest national-level burden is associated with moderate preterm infants due to both a large cost per infant and population size while the highest individual-level burden is in early preterm infants and the largest total population size is in late preterm infants. Although the highest medical costs are incurred during the neonatal period, greater resource utilization and costs extend into childhood

Intensive statin therapy compared with moderate dosing for prevention of cardiovascular events: a meta-analysis of >40 000 patients

Aims Statin therapy is associated with important benefits for patients at risk of, and with, established cardiovascular disease. There is widespread interest in whether intensive dosing of statins yields larger treatment effects. We aimed to determine if intensive dosing is clinically important using a meta-analysis of randomized clinical trials (RCTs). Methods We conducted comprehensive searches of electronic databases from inception to December 2010. We included any RCT evaluating a larger dose with a clinically common dose. Two reviewers independently extracted data, in duplicate. We performed random-effects meta-analysis and a trial sequential analysis. Results We identified 10 RCTs enrolling a total of 41 778 participants. Trials followed patients for a mean of 2.5 years. We did not find statistically significant effects on all-cause mortality [relative risk (RR) 0.92, 95% confidence interval (CI), 0.83-1.03, P = 0.14, I2 = 38%] or cardiovascular disease (CVD) deaths (RR 0.89, 95% CI, 0.78-1.01, P = 0.07, I2 = 34%). When we pooled the composite endpoint of coronary heart disease (CHD) death plus non-fatal myocardial infarction (MI), we found a significant protective effect of intensive statin dosing (RR 0.90, 95% CI, 0.84-0.96, P ≤ 0.0001, I2 = 0%). We also found a significant effect on non-fatal MIs (RR 0.82, 95% CI, 0.76-0.89, P ≤ 0.0001, I2 = 0%) and a significant reduction in the composite of fatal and non-fatal strokes (excluding transient ischaemic attacks) reported in 10 RCTs (RR 0.86, 95% CI, 0.77-0.96, P = 0.006, I2 = 0%). A subgroup analysis of three trials examining acute coronary syndrome patients found significant effects on all-cause (RR 0.75, 95% CI, 0.61-0.91, P = 0.005, I2 = 0%) and CVD mortality (RR 0.74, 95% CI, 0.59-0.94, P = 0.013, I2 = 0%) with intensive dosing. Applying an analysis of optimal information size on the primary analysis, we found that the evidence for CHD death plus non-fatal MIs is conclusive. The evidence for CVD deaths alone is not yet conclusive. Conclusions Available evidence suggests that intensive statin therapy reduces the risk of non-fatal events and may have a role in reducing mortalit

Risk of Myocardial Infarction among People Living With HIV: An Updated Systematic Review and Meta-Analysis

Objective Cardiovascular disease (CVD) is one of the leading non-AIDS-defining causes of death among HIV-positive (HIV+) individuals. However, the evidence surrounding specific components of CVD risk remains inconclusive. We conducted a systematic review and meta-analysis to synthesise the available evidence and establish the risk of myocardial infarction (MI) among HIV+ compared with uninfected individuals. We also examined MI risk within subgroups of HIV+ individuals according to exposure to combination antiretroviral therapy (ART), ART class/regimen, CD4 cell count and plasma viral load (pVL) levels. Design Systematic review and meta-analysis. Data sources We searched MEDLINE, EMBASE, Cochrane Central Register of Controlled Trials and Cochrane Database of Systematic Reviews until 18 July 2018. Furthermore, we scanned recent HIV conference abstracts (CROI, IAS/AIDS) and bibliographies of relevant articles. Eligibility criteria Original studies published after December 1999 and reporting comparative data relating to the rate of MI among HIV+ individuals were included. Data extraction and synthesis Two reviewers working in duplicate, independently extracted data. Data were pooled using random-effects meta-analysis and reported as relative risk (RR) with 95% CI. Results Thirty-two of the 8130 identified records were included in the review. The pooled RR suggests that HIV+ individuals have a greater risk of MI compared with uninfected individuals (RR: 1.73; 95%&thinsp;CI 1.44 to 2.08). Depending on risk stratification, there was moderate variation according to ART uptake (RR, ART-treated=1.80; 95%&thinsp;CI 1.17 to 2.77; ART-untreated HIV+ individuals: 1.25; 95%&thinsp;CI 0.93 to 1.67, both relative to uninfected individuals). We found low CD4 count, high pVL and certain ART characteristics including cumulative ART exposure, any/cumulative use of protease inhibitors as a class, and exposure to specific ART drugs (eg, abacavir) to be importantly associated with a greater MI risk. Conclusions Our results indicate that HIV infection, low CD4, high pVL, cumulative ART use in general including certain exposure to specific ART class/regimen are associated with increased risk of MI. The association with cumulative ART may be an index of the duration of HIV infection with its attendant inflammation, and not entirely the effect of cumulative exposure to ART per se. &nbsp

Subnational mapping of HIV incidence and mortality among individuals aged 15–49 years in sub-Saharan Africa, 2000–18 : a modelling study

Background: High-resolution estimates of HIV burden across space and time provide an important tool for tracking and monitoring the progress of prevention and control efforts and assist with improving the precision and efficiency of targeting efforts. We aimed to assess HIV incidence and HIV mortality for all second-level administrative units across sub-Saharan Africa. Methods: In this modelling study, we developed a framework that used the geographically specific HIV prevalence data collected in seroprevalence surveys and antenatal care clinics to train a model that estimates HIV incidence and mortality among individuals aged 15–49 years. We used a model-based geostatistical framework to estimate HIV prevalence at the second administrative level in 44 countries in sub-Saharan Africa for 2000–18 and sought data on the number of individuals on antiretroviral therapy (ART) by second-level administrative unit. We then modified the Estimation and Projection Package (EPP) to use these HIV prevalence and treatment estimates to estimate HIV incidence and mortality by second-level administrative unit. Findings: The estimates suggest substantial variation in HIV incidence and mortality rates both between and within countries in sub-Saharan Africa, with 15 countries having a ten-times or greater difference in estimated HIV incidence between the second-level administrative units with the lowest and highest estimated incidence levels. Across all 44 countries in 2018, HIV incidence ranged from 2 ·8 (95% uncertainty interval 2·1–3·8) in Mauritania to 1585·9 (1369·4–1824·8) cases per 100 000 people in Lesotho and HIV mortality ranged from 0·8 (0·7–0·9) in Mauritania to 676· 5 (513· 6–888·0) deaths per 100 000 people in Lesotho. Variation in both incidence and mortality was substantially greater at the subnational level than at the national level and the highest estimated rates were accordingly higher. Among second-level administrative units, Guijá District, Gaza Province, Mozambique, had the highest estimated HIV incidence (4661·7 [2544·8–8120·3]) cases per 100000 people in 2018 and Inhassunge District, Zambezia Province, Mozambique, had the highest estimated HIV mortality rate (1163·0 [679·0–1866·8]) deaths per 100 000 people. Further, the rate of reduction in HIV incidence and mortality from 2000 to 2018, as well as the ratio of new infections to the number of people living with HIV was highly variable. Although most second-level administrative units had declines in the number of new cases (3316 [81· 1%] of 4087 units) and number of deaths (3325 [81·4%]), nearly all appeared well short of the targeted 75% reduction in new cases and deaths between 2010 and 2020. Interpretation: Our estimates suggest that most second-level administrative units in sub-Saharan Africa are falling short of the targeted 75% reduction in new cases and deaths by 2020, which is further compounded by substantial within-country variability. These estimates will help decision makers and programme implementers expand access to ART and better target health resources to higher burden subnational areas

Mapping 123 million neonatal, infant and child deaths between 2000 and 2017

Since 2000, many countries have achieved considerable success in improving child survival, but localized progress remains unclear. To inform efforts towards United Nations Sustainable Development Goal 3.2—to end preventable child deaths by 2030—we need consistently estimated data at the subnational level regarding child mortality rates and trends. Here we quantified, for the period 2000–2017, the subnational variation in mortality rates and number of deaths of neonates, infants and children under 5 years of age within 99 low- and middle-income countries using a geostatistical survival model. We estimated that 32% of children under 5 in these countries lived in districts that had attained rates of 25 or fewer child deaths per 1,000 live births by 2017, and that 58% of child deaths between 2000 and 2017 in these countries could have been averted in the absence of geographical inequality. This study enables the identification of high-mortality clusters, patterns of progress and geographical inequalities to inform appropriate investments and implementations that will help to improve the health of all populations

Estimating global injuries morbidity and mortality : methods and data used in the Global Burden of Disease 2017 study

Background: While there is a long history of measuring death and disability from injuries, modern research methods must account for the wide spectrum of disability that can occur in an injury, and must provide estimates with sufficient demographic, geographical and temporal detail to be useful for policy makers. The Global Burden of Disease (GBD) 2017 study used methods to provide highly detailed estimates of global injury burden that meet these criteria. Methods: In this study, we report and discuss the methods used in GBD 2017 for injury morbidity and mortality burden estimation. In summary, these methods included estimating cause-specific mortality for every cause of injury, and then estimating incidence for every cause of injury. Non-fatal disability for each cause is then calculated based on the probabilities of suffering from different types of bodily injury experienced. Results: GBD 2017 produced morbidity and mortality estimates for 38 causes of injury. Estimates were produced in terms of incidence, prevalence, years lived with disability, cause-specific mortality, years of life lost and disability-adjusted life-years for a 28-year period for 22 age groups, 195 countries and both sexes. Conclusions: GBD 2017 demonstrated a complex and sophisticated series of analytical steps using the largest known database of morbidity and mortality data on injuries. GBD 2017 results should be used to help inform injury prevention policy making and resource allocation. We also identify important avenues for improving injury burden estimation in the future