Targeted hepatitis C antibody testing interventions: a systematic review and meta-analysis

Testing for hepatitis C virus (HCV) infection may reduce the risk of liver-related morbidity, by facilitating earlier access to treatment and care. This review investigated the effectiveness of targeted testing interventions on HCV case detection, treatment uptake, and prevention of liver-related morbidity. A literature search identified studies published up to 2013 that compared a targeted HCV testing intervention (targeting individuals or groups at increased risk of HCV) with no targeted intervention, and results were synthesised using meta-analysis. Exposure to a targeted testing intervention, compared to no targeted intervention, was associated with increased cases detected [number of studies (n) = 14; pooled relative risk (RR) 1.7, 95 % CI 1.3, 2.2] and patients commencing therapy (n = 4; RR 3.3, 95 % CI 1.1, 10.0). Practitioner-based interventions increased test uptake and cases detected (n = 12; RR 3.5, 95 % CI 2.5, 4.8; and n = 10; RR 2.2, 95 % CI 1.4, 3.5, respectively), whereas media/information-based interventions were less effective (n = 4; RR 1.5, 95 % CI 0.7, 3.0; and n = 4; RR 1.3, 95 % CI 1.0, 1.6, respectively). This meta-analysis provides for the first time a quantitative assessment of targeted HCV testing interventions, demonstrating that these strategies were effective in diagnosing cases and increasing treatment uptake. Strategies involving practitioner-based interventions yielded the most favourable outcomes. It is recommended that testing should be targeted at and offered to individuals who are part of a population with high HCV prevalence, or who have a history of HCV risk behaviour

Zinc adjunct therapy reduces case fatality in severe childhood pneumonia: a randomized double blind placebo-controlled trial

<p>Abstract</p> <p>Background</p> <p>Pneumonia is a leading cause of children's deaths in developing countries and hinders achievement of the fourth Millennium Development Goal. This goal aims to reduce the under-five mortality rate, by two thirds, between 1990 and 2015.</p> <p>Few studies have examined the impact of zinc adjunct therapy on the outcome of childhood pneumonia. We determined the effect of zinc as adjunct therapy on time to normalization of respiratory rate, temperature and oxygen saturation. We also studied the effect of zinc adjunct therapy on case fatality of severe childhood pneumonia (as a secondary outcome) in Mulago Hospital, Uganda.</p> <p>Methods</p> <p>In this double blind, randomized, placebo-controlled clinical trial, 352 children aged 6 to 59 months, with severe pneumonia were randomized to zinc (20 mg for children ≥12 months, and 10 mg for those < 12 months) or a placebo once daily for seven days, in addition to standard antibiotics for severe pneumonia. Children were assessed every six hours. Oxygen saturation was normal if it was above 92% (breathing room air) for more than 15 minutes. The respiratory rate was normal if it was consistently (more than 24 hours) below 50 breaths per minute in infants and 40 breaths per minute in children above 12 months of age. Temperature was normal if consistently below 37.5°C. The difference in case fatality was expressed by the risk ratio between the two groups.</p> <p>Results</p> <p>Time to normalization of the respiratory rate, temperature and oxygen saturation was not significantly different between the two arms.</p> <p>Case fatality was 7/176 (4.0%) in the zinc group and 21/176 (11.9%) in the placebo group: Relative Risk 0.33 (95% CI 0.15 to 0.76). Relative Risk Reduction was 0.67 (95% CI 0.24 to 0.85), while the number needed to treat was 13. Among HIV infected children, case fatality was higher in the placebo (7/27) than in the zinc (0/28) group; RR 0.1 (95% CI 0.0, 1.0).</p> <p>Among 127 HIV uninfected children receiving the placebo, case fatality was 7/127 (5.5%); versus 5/129 (3.9%) among HIV uninfected group receiving zinc: RR 0.7 (95% CI 0.2, 2.2). The excess risk of death attributable to the placebo arm (Absolute Risk Reduction or ARR) was 8/100 (95% CI: 2/100, 14/100) children. This excess risk was substantially greater among HIV positive children than in HIV negative children (ARR: 26 (95% CI: 9, 42) per 100 versus 2 (95% CI: -4, 7) per 100); <it>P</it>-value for homogeneity of risk differences = 0.006.</p> <p>Conclusion</p> <p>Zinc adjunct therapy for severe pneumonia had no significant effect on time to normalization of the respiratory rate, temperature and oxygen saturation. However, zinc supplementation in these children significantly decreased case fatality.</p> <p>The difference in case fatality attributable to the protective effect of zinc therapy was greater among HIV infected than HIV uninfected children. Given these results, zinc could be considered for use as adjunct therapy for severe pneumonia, especially among Highly Active Antiretroviral Therapy</p> <p>naïve HIV infected children in our environment.</p> <p>Clinical trials registration number</p> <p>clinicaltrials.gov <a href="http://www.clinicaltrials.gov/ct2/show/NCT00373100">NCT00373100</a></p

Survival of neonates in rural Southern Tanzania: does place of delivery or continuum of care matter?

\ud The concept of continuum of care has recently been highlighted as a core principle of maternal, newborn and child health initiatives, and as a means to save lives. However, evidence has consistently revealed that access to care during and post delivery (intra and postpartum) remains a challenge in the continuum of care framework. In places where skilled delivery assistance is exclusively available in health facilities, access to health facilities is critical to the survival of the mother and her newborn. However, little is known about the association of place of delivery and survival of neonates. This paper uses longitudinal data generated in a Health and Demographic Surveillance System in rural Southern Tanzania to assess associations of neonatal mortality and place of delivery. Three cohorts of singleton births (born 2005, 2006 and 2007) were each followed up from birth to 28 days. Place of birth was classified as either "health facility" or "community". Neonatal mortality rates were produced for each year and by place of birth. Poisson regression was used to estimate crude relative risks of neonatal death by place of birth. Adjusted ratios were derived by controlling for maternal age, birth order, maternal schooling, sex of the child and wealth status of the maternal household. Neonatal mortality for health facility singleton deliveries in 2005 was 32.3 per 1000 live births while for those born in the community it was 29.7 per 1000 live births. In 2006, neonatal mortality rates were 28.9 and 26.9 per 1,000 live births for deliveries in health facilities and in the community respectively. In 2007 neonatal mortality rates were 33.2 and 27.0 per 1,000 live births for those born in health facilities and in the community respectively. Neonates born in a health facility had similar chances of dying as those born in the community in all the three years of study. Adjusted relative risks (ARR) for neonatal death born in a health facility in 2005, 2006 and 2007 were 0.99 (95% CI: 0.58 - 1.70), 0.98 (95% CI: 0.62 - 1.54) and 1.18 (95% CI: 0.76 - 1.85) respectively. We found no evidence to suggest that delivery in health facilities was associated with better survival chances of the neonates.\u

Poor newborn care practices - a population based survey in eastern Uganda

BACKGROUND: Four million neonatal deaths are estimated to occur each year and almost all in low income countries, especially among the poorest. There is a paucity of data on newborn health from sub-Saharan Africa and few studies have assessed inequity in uptake of newborn care practices. We assessed socioeconomic differences in use of newborn care practices in order to inform policy and programming in Uganda. METHODS: All mothers with infants aged 1-4 months (n = 414) in a Demographic Surveillance Site were interviewed. Households were stratified into quintiles of socioeconomic status (SES). Three composite outcomes (good neonatal feeding, good cord care, and optimal thermal care) were created by combining related individual practices from a list of twelve antenatal/essential newborn care practices. Multiple logistic regression analysis was used to identify determinants of each dichotomised composite outcome. RESULTS: There were low levels of coverage of newborn care practices among both the poorest and the least poor. SES and place of birth were not associated with any of the composite newborn care practices. Of newborns, 46% had a facility delivery and only 38% were judged to have had good cord care, 42% optimal thermal care, and 57% were considered to have had adequate neonatal feeding. Mothers were putting powder on the cord; using a bottle to feed the baby; and mixing/replacing breast milk with various substitutes. Multiparous mothers were less likely to have safe cord practices (OR 0.5, CI 0.3 - 0.9) as were mothers whose labour began at night (OR 0.6, CI 0.4 - 0.9). CONCLUSION: Newborn care practices in this setting are low and do not differ much by socioeconomic group. Despite being established policy, most neonatal interventions are not reaching newborns, suggesting a "policy-to-practice gap". To improve newborn survival, newborn care should be integrated into the current maternal and child interventions, and should be implemented at both community and health facility level as part of a universal coverage strategy

Trends in causes of death among children under 5 in Bangladesh, 1993-2004: an exercise applying a standardized computer algorithm to assign causes of death using verbal autopsy data

<p>Abstract</p> <p>Background</p> <p>Trends in the causes of child mortality serve as important global health information to guide efforts to improve child survival. With child mortality declining in Bangladesh, the distribution of causes of death also changes. The three verbal autopsy (VA) studies conducted with the Bangladesh Demographic and Health Surveys provide a unique opportunity to study these changes in child causes of death.</p> <p>Methods</p> <p>To ensure comparability of these trends, we developed a standardized algorithm to assign causes of death using symptoms collected through the VA studies. The original algorithms applied were systematically reviewed and key differences in cause categorization, hierarchy, case definition, and the amount of data collected were compared to inform the development of the standardized algorithm. Based primarily on the 2004 cause categorization and hierarchy, the standardized algorithm guarantees comparability of the trends by only including symptom data commonly available across all three studies.</p> <p>Results</p> <p>Between 1993 and 2004, pneumonia remained the leading cause of death in Bangladesh, contributing to 24% to 33% of deaths among children under 5. The proportion of neonatal mortality increased significantly from 36% (uncertainty range [UR]: 31%-41%) to 56% (49%-62%) during the same period. The cause-specific mortality fractions due to birth asphyxia/birth injury and prematurity/low birth weight (LBW) increased steadily, with both rising from 3% (2%-5%) to 13% (10%-17%) and 10% (7%-15%), respectively. The cause-specific mortality rates decreased significantly due to neonatal tetanus and several postneonatal causes (tetanus: from 7 [4-11] to 2 [0.4-4] per 1,000 live births (LB); pneumonia: from 26 [20-33] to 15 [11-20] per 1,000 LB; diarrhea: from 12 [8-17] to 4 [2-7] per 1,000 LB; measles: from 5 [2-8] to 0.2 [0-0.7] per 1,000 LB; injury: from 11 [7-17] to 3 [1-5] per 1,000 LB; and malnutrition: from 9 [6-13] to 5 [2-7]).</p> <p>Conclusions</p> <p>Pneumonia remained the top killer of children under 5 in Bangladesh between 1993 and 2004. The increasing importance of neonatal survival is highlighted by the growing contribution of neonatal deaths and several neonatal causes. Notwithstanding the limitations, standardized computer-based algorithms remain a promising tool to generate comparable causes of child death using VA data.</p

Ontogeny of Toll-Like and NOD-Like Receptor-Mediated Innate Immune Responses in Papua New Guinean Infants

Studies addressing the ontogeny of the innate immune system in early life have reported mainly on Toll-like receptor (TLR) responses in infants living in high-income countries, with little or even no information on other pattern recognition receptors or on early life innate immune responses in children living under very different environmental conditions in less-developed parts of the world. In this study, we describe whole blood innate immune responses to both Toll-like and nucleotide-binding oligomerization domain (NOD)-like receptor agonists including the widely used vaccine adjuvant ‘alum’ in a group of Papua New Guinean infants aged 1–3 (n = 18), 4–6 (n = 18), 7–12 (n = 21) and 13–18 (n = 10) months old. Depending on the ligands and cytokines studied, different age-related patterns were found: alum-induced IL-1β and CXCL8 responses were found to significantly decline with increasing age; inflammatory (IL-6, IL-1β, IFN-γ) responses to TLR2 and TLR3 agonists increased; and IL-10 responses remained constant or increased during infancy, while TNF-α responses either declined or remained the same. We report for the first time that whole blood innate immune responses to the vaccine adjuvant alum decrease with age in infancy; a finding that may imply that the adjuvant effect of alum in pediatric vaccines could be age-related. Our findings further suggest that patterns of innate immune development may vary between geographically diverse populations, which in line with the ‘hygiene hypothesis’ particularly involves persistence of innate IL-10 responses in populations experiencing higher infectious pressure

Radiographic progression with nonrising PSA in metastatic castration-resistant prostate cancer: post hoc analysis of PREVAIL.

Background Advanced prostate cancer is a phenotypically diverse disease that evolves through multiple clinical courses. PSA level is the most widely used parameter for disease monitoring, but it has well-recognized limitations. Unlike in clinical trials, in practice, clinicians may rely on PSA monitoring alone to determine disease status on therapy. This approach has not been adequately tested.Methods Chemotherapy-naive asymptomatic or mildly symptomatic men (n=872) with metastatic castration-resistant prostate cancer (mCRPC) who were treated with the androgen receptor inhibitor enzalutamide in the PREVAIL study were analyzed post hoc for rising versus nonrising PSA (empirically defined as >1.05 vs ⩽1.05 times the PSA level from 3 months earlier) at the time of radiographic progression. Clinical characteristics and disease outcomes were compared between the rising and nonrising PSA groups.Results Of 265 PREVAIL patients with radiographic progression and evaluable PSA levels on the enzalutamide arm, nearly one-quarter had a nonrising PSA. Median progression-free survival in this cohort was 8.3 months versus 11.1 months in the rising PSA cohort (hazard ratio 1.68; 95% confidence interval 1.26-2.23); overall survival was similar between the two groups, although less than half of patients in either group were still at risk at 24 months. Baseline clinical characteristics of the two groups were similar.Conclusions Non-rising PSA at radiographic progression is a common phenomenon in mCRPC patients treated with enzalutamide. As restaging in advanced prostate cancer patients is often guided by increases in PSA levels, our results demonstrate that disease progression on enzalutamide can occur without rising PSA levels. Therefore, a disease monitoring strategy that includes imaging not entirely reliant on serial serum PSA measurement may more accurately identify disease progression