A Systematic Review of the Role of Proprietary and Patent Medicine Vendors in Healthcare Provision in Nigeria

Background

Interventions to reduce the burden of disease and mortality in sub-Saharan Africa increasingly recognize the important role that drug retailers play in delivering basic healthcare services. In Nigeria, owner-operated drug retail outlets, known as patent and proprietary medicine vendors (PPMVs), are a main source of medicines for acute conditions, but their practices are not well understood. Greater understanding of the role of PPMVs and the quality of care they provide is needed in order to inform ongoing national health initiatives that aim to incorporate PPMVs as a delivery mechanism.

Objective and Methods

This paper reviews and synthesizes the existing published and grey literature on the characteristics, knowledge and practices of PPMVs in Nigeria. We searched published and grey literature using a number of electronic databases, supplemented with website searches of relevant international agencies. We included all studies providing outcome data on PPMVs in Nigeria, including non-experimental studies, and assessed the rigor of each study using the WHO-Johns Hopkins Rigor scale. We used narrative synthesis to evaluate the findings.

Results

We identified 50 articles for inclusion. These studies provided data on a wide range of PPMV outcomes: training; health knowledge; health practices, including drug stocking and dispensing, client interaction, and referral; compliance with regulatory guidelines; and the effects of interventions targeting PPMVs. In general, PPMVs have low health knowledge and poor health treatment practices. However, the literature focuses largely on services for adult malaria, and little is known about other health areas or services for children.

Conclusions

This review highlights several concerns with the quality of the private drug retail sector in Nigeria, as well as gaps in the existing evidence base. Future research should adopt a more holistic view of the services provided by PPMV shops, and evaluate intervention strategies that may improve the services provided in this sector.     

A Systematic Review on Health Resilience to Economic Crises

Background

The health effects of recent economic crises differ markedly by population group. The objective of this systematic review is to examine evidence from longitudinal studies on factors influencing resilience for any health outcome or health behaviour among the general population living in countries exposed to financial crises.

Methods

We systematically reviewed studies from six electronic databases (EMBASE, Global Health, MEDLINE, PsycINFO, Scopus, Web of Science) which used quantitative longitudinal study designs and included: (i) exposure to an economic crisis; (ii) changes in health outcomes/behaviours over time; (iii) statistical tests of associations of health risk and/or protective factors with health outcomes/behaviours. The quality of the selected studies was appraised using the Quality Assessment Tool for Quantitative Studies. PRISMA reporting guidelines were followed.

Results

From 14,584 retrieved records, 22 studies met the eligibility criteria. These studies were conducted across 10 countries in Asia, Europe and North America over the past two decades. Ten socio-demographic factors that increased or protected against health risk were identified: gender, age, education, marital status, household size, employment/occupation, income/ financial constraints, personal beliefs, health status, area of residence, and social relations. These studies addressed physical health, mortality, suicide and suicide attempts, mental health, and health behaviours. Women’s mental health appeared more susceptible to crises than men’s. Lower income levels were associated with greater increases in cardiovascular disease, mortality and worse mental health. Employment status was associated with changes in mental health. Associations with age, marital status, and education were less consistent, although higher education was associated with healthier behaviours.

Conclusions

Despite widespread rhetoric about the importance of resilience, there was a dearth of studies which operationalised resilience factors. Future conceptual and empirical research is needed to develop the epidemiology of resilience.     

Rural-to-Urban Migrants' Experiences with Primary Care under Different Types of Medical Institutions in Guangzhou,China

Objectives

China is facing the unprecedented challenge of rapidly increasing rural-to-urban migration. Migrants are in a vulnerable state when they attempt to access to primary care services. This study was designed to explore rural-to-urban migrants’ experiences in primary care, comparing their quality of primary care experiences under different types of medical institutions in Guangzhou, China.

Methods

The study employed a cross-sectional survey of 736 rural-to-urban migrants in Guangzhou, China in 2014. A validated Chinese version of Primary Care Assessment Tool—Adult Short Version (PCAT-AS), representing 10 primary care domains was used to collect information on migrants’ quality of primary care experiences. These domains include first contact (utilization), first contact (accessibility), ongoing care, coordination (referrals), coordination (information systems), comprehensiveness (services available), comprehensiveness (services provided), family-centeredness, community orientation and culturally competent. These measures were used to assess the quality of primary care performance as reported from patients’ perspective. Analysis of covariance was conducted for comparison on PCAT scores among migrants accessing primary care in tertiary hospitals, municipal hospitals, community health centers/community health stations, and township health centers/rural health stations. Multiple linear regression models were used to explore factors associated with PCAT total scores.

Results

After adjustments were made, migrants accessing primary care in tertiary hospitals (25.49) reported the highest PCAT total scores, followed by municipal hospitals (25.02), community health centers/community health stations (24.24), and township health centers/rural health stations (24.18). Tertiary hospital users reported significantly better performance in first contact (utilization), first contact (accessibility), coordination (information system), comprehensiveness (service available), and cultural competence. Community health center/community health station users reported significantly better experience in the community orientation domain. Township health center/rural health station users expressed significantly better experience in the ongoing care domain. There were no statistically significant differences across settings in the ongoing care, comprehensiveness (services provided), and family-centeredness domains. Multiple linear regression models showed that factors positively associated with higher PCAT total scores also included insurance covering parts of healthcare payment (P<0.001).

Conclusions

This study highlights the need for improvement in primary care provided by primary care institutions for rural-to-urban migrants. Relevant policies related to medical insurance should be implemented for providing affordable healthcare services for migrants accessing primary care.     

A Comparison of Technique Modifications in Laparoscopic Donor Nephrectomy: A Systematic Review and Meta-Analysis

Objective

To compare the effectiveness of different technique modifications in laparoscopic donor nephrectomy.

Design

Systematic review and meta-analyses.

Data Sources

Searches of PubMed, EMBASE, Web of Science and Central from January 1st 1997 until April 1st 2014.

Study Design

All cohort studies and randomized clinical trials comparing fully laparoscopic donor nephrectomy with modifications of the standard technique including hand-assisted, retroperitoneoscopic and single port techniques, were included.

Data-Extraction and Analysis

The primary outcome measure was the number of complications. Secondary outcome measures included: conversion to open surgery, first warm ischemia time, estimated blood loss, graft function, operation time and length of hospital stay. Each technique modification was compared with standard laparoscopic donor nephrectomy. Data was pooled with a random effects meta-analysis using odds ratios, weighted mean differences and their corresponding 95% confidence intervals. To assess heterogeneity, the I2 statistic was used. First, randomized clinical trials and cohort studies were analyzed separately, when data was comparable, pooled analysis were performed.

Results

31 studies comparing laparoscopic donor nephrectomy with other technique modifications were identified, including 5 randomized clinical trials and 26 cohort studies. Since data of randomized clinical trials and cohort studies were comparable, these data were pooled. There were significantly less complications in the retroperitoneoscopic group as compared to transperitoneal group (OR 0.52, 95%CI 0.33–0.83, I2 = 0%). Hand-assisted techniques showed shorter first warm ischemia and operation times.

Conclusions

Hand-assistance reduces the operation and first warm ischemia times and may improve safety for surgeons with less experience in laparoscopic donor nephrectomy. The retroperitoneoscopic approach was significantly associated with less complications. However, given the, in general, poor to intermediate quality and considerable heterogeneity in the included studies, further high-quality studies are required.

Trial Registration

The review protocol was registered in the PROSPERO database before the start of the review process (CRD number 42013006565).     

Social Support and Health in Diabetes Patients: An Observational Study in Six European Countries in an Era of Austerity

Introduction

Support from individual social networks, community organizations and neighborhoods is associated with better self-management and health outcomes. This international study examined the relative impact of different types of support on health and health-related behaviors in patients with type 2 diabetes.

Methods

Observational study (using interviews and questionnaires) in a sample of 1,692 type 2 diabetes patients with 5,433 connections from Bulgaria, Greece, Netherlands, Norway, Spain, and the United Kingdom. Outcomes were patient-reported health status (SF-12), physical exercise (RAPA), diet and smoking (SDCSCA). Random coefficient regression models were used to examine linkages with individual networks, community organizations, and neighborhood type (deprived rural, deprived urban, or affluent urban).

Results

Patients had a median of 3 support connections and 34.6% participated in community organizations. Controlled for patients’ age, sex, education, income and comorbidities, large emotional support networks were associated with decrease of non-smoking (OR = 0.87). Large practical support networks were associated with worse physical and mental health (B = -0.46 and -0.27 respectively) and less physical activity (OR = 0.90). Participation in community organizations was associated with better physical and mental health (B = 1.39 and 1.22, respectively) and, in patients with low income, with more physical activity (OR = 1.53).

Discussion

Participation in community organizations was most consistently related to better health status. Many diabetes patients have individual support networks, but this study did not provide evidence to increase their size as a public health strategy. The consistent association between participation in community organizations and health status provides a clear target for interventions and policies.     

Barriers in the Delivery of Emergency Obstetric and Neonatal Care in Post-Conflict Africa: Qualitative Case Studies of Burundi and Northern Uganda

Objectives

Maternal and neonatal mortality and morbidity rates are particularly grim in conflict, post-conflict and other crisis settings, a situation partly blamed on non-availability and/or poor quality of emergency obstetric and neonatal care (EmONC) services. The aim of this study was to explore the barriers to effective delivery of EmONC services in post-conflict Burundi and Northern Uganda, in order to provide policy makers and other relevant stakeholders context-relevant data on improving the delivery of these lifesaving services.

Methods

This was a qualitative comparative case study that used 42 face-to-face semi-structured in-depth interviews and 4 focus group discussions for data collection. Participants were 32 local health providers and 37 staff of NGOs working in the area of maternal health. Data was analysed using the framework approach.

Results

The availability, quality and distribution of EmONC services were major challenges across the sites. The barriers in the delivery of quality EmONC services were categorised into two major themes; human resources-related challenges, and systemic and institutional failures. While some of the barriers were similar, others were unique to specific sites. The common barriers included shortage of qualified staff; lack of essential installations, supplies and medications; increasing workload, burn-out and turnover; and poor data collection and monitoring systems. Barriers unique to Northern Uganda were demoralised personnel and lack of recognition; poor referral system; inefficient drug supply system; staff absenteeism in rural areas; and poor coordination among key personnel. In Burundi, weak curriculum; poor harmonisation and coordination of training; and inefficient allocation of resources were the unique challenges. To improve the situation across the sites, efforts are ongoing to improve the training and recruitment of more staff; harmonise and strengthen the curriculum and training; increase the number of EmONC facilities; and improve staff supervision, monitoring and support.

Conclusions

Post-conflict health systems face different challenges in the delivery of EmONC services and as such require context-specific interventions to improve the delivery of these services.     

Flooding and Mental Health: A Systematic Mapping Review

Background

Floods are the most common type of global natural disaster. Floods have a negative impact on mental health. Comprehensive evaluation and review of the literature are lacking.

Objective

To systematically map and review available scientific evidence on mental health impacts of floods caused by extended periods of heavy rain in river catchments.

Methods

We performed a systematic mapping review of published scientific literature in five languages for mixed studies on floods and mental health. PUBMED and Web of Science were searched to identify all relevant articles from 1994 to May 2014 (no restrictions).

Results

The electronic search strategy identified 1331 potentially relevant papers. Finally, 83 papers met the inclusion criteria. Four broad areas are identified: i) the main mental health disorders—post-traumatic stress disorder, depression and anxiety; ii] the factors associated with mental health among those affected by floods; iii) the narratives associated with flooding, which focuses on the long-term impacts of flooding on mental health as a consequence of the secondary stressors; and iv) the management actions identified. The quantitative and qualitative studies have consistent findings. However, very few studies have used mixed methods to quantify the size of the mental health burden as well as exploration of in-depth narratives. Methodological limitations include control of potential confounders and short-term follow up.

Limitations

Floods following extreme events were excluded from our review.

Conclusions

Although the level of exposure to floods has been systematically associated with mental health problems, the paucity of longitudinal studies and lack of confounding controls precludes strong conclusions.

Implications

We recommend that future research in this area include mixed-method studies that are purposefully designed, using more rigorous methods. Studies should also focus on vulnerable groups and include analyses of policy and practical responses.     

Adolescent Sexual and Reproductive Health Services and Implications for the Provision of Voluntary Medical Male Circumcision: Results of a Systematic Literature Review

Background

Voluntary medical male circumcision (VMMC) is a critical HIV prevention tool. Since 2007, sub-Saharan African countries with the highest prevalence of HIV have been mobilizing resources to make VMMC available. While implementers initially targeted adult men, demand has been highest for boys under age 18. It is important to understand how male adolescents can best be served by quality VMMC services.

Methods and Findings

A systematic literature review was performed to synthesize the evidence on best practices in adolescent health service delivery specific to males in sub-Saharan Africa. PubMed, Scopus, and JSTOR databases were searched for literature published between January 1990 and March 2014. The review revealed a general absence of health services addressing the specific needs of male adolescents, resulting in knowledge gaps that could diminish the benefits of VMMC programming for this population. Articles focused specifically on VMMC contained little information on the adolescent subgroup. The review revealed barriers to and gaps in sexual and reproductive health and VMMC service provision to adolescents, including structural factors, imposed feelings of shame, endorsement of traditional gender roles, negative interactions with providers, violations of privacy, fear of pain associated with the VMMC procedure, and a desire for elements of traditional non-medical circumcision methods to be integrated into medical procedures. Factors linked to effective adolescent-focused services included the engagement of parents and the community, an adolescent-friendly service environment, and VMMC counseling messages sufficiently understood by young males.

Conclusions

VMMC presents an opportune time for early involvement of male adolescents in HIV prevention and sexual and reproductive health programming. However, more research is needed to determine how to align VMMC services with the unique needs of this population.     

Re-Infection Outcomes following One- and Two-Stage Surgical Revision of Infected Hip Prosthesis: A Systematic Review and Meta-Analysis

Background

The two-stage revision strategy has been claimed as being the “gold standard” for treating prosthetic joint infection. The one-stage revision strategy remains an attractive alternative option; however, its effectiveness in comparison to the two-stage strategy remains uncertain.

Objective

To compare the effectiveness of one- and two-stage revision strategies in treating prosthetic hip infection, using re-infection as an outcome.

Design

Systematic review and meta-analysis.

Data Sources

MEDLINE, EMBASE, Web of Science, Cochrane Library, manual search of bibliographies to March 2015, and email contact with investigators.

Study Selection

Cohort studies (prospective or retrospective) conducted in generally unselected patients with prosthetic hip infection treated exclusively by one- or two-stage revision and with re-infection outcomes reported within two years of revision. No clinical trials were identified.

Review Methods

Data were extracted by two independent investigators and a consensus was reached with involvement of a third. Rates of re-infection from 38 one-stage studies (2,536 participants) and 60 two-stage studies (3,288 participants) were aggregated using random-effect models after arcsine transformation, and were grouped by study and population level characteristics.

Results

In one-stage studies, the rate (95% confidence intervals) of re-infection was 8.2% (6.0–10.8). The corresponding re-infection rate after two-stage revision was 7.9% (6.2–9.7). Re-infection rates remained generally similar when grouped by several study and population level characteristics. There was no strong evidence of publication bias among contributing studies.

Conclusion

Evidence from aggregate published data suggest similar re-infection rates after one- or two-stage revision among unselected patients. More detailed analyses under a broader range of circumstances and exploration of other sources of heterogeneity will require collaborative pooling of individual participant data.

Systematic Review Registration

PROSPERO 2015: CRD42015016559     

Re-Infection Outcomes Following One- And Two-Stage Surgical Revision of Infected Knee Prosthesis: A Systematic Review and Meta-Analysis

Background

Periprosthetic joint infection (PJI) is a serious complication of total knee arthroplasty. Two-stage revision is the most widely used technique and considered as the most effective for treating periprosthetic knee infection. The one-stage revision strategy is an emerging alternative option, however, its performance in comparison to the two-stage strategy is unclear. We therefore sought to ask if there was a difference in re-infection rates and other clinical outcomes when comparing the one-stage to the two-stage revision strategy.

Objective

Our first objective was to compare re-infection (new and recurrent infections) rates for one- and two-stage revision surgery for periprosthetic knee infection. Our second objective was to compare between the two revision strategies, clinical outcomes as measured by postoperative Knee Society Knee score, Knee Society Function score, Hospital for Special Surgery knee score, WOMAC score, and range of motion.

Design

Systematic review and meta-analysis.

Data sources

MEDLINE, EMBASE, Web of Science, Cochrane Library, reference lists of relevant studies to August 2015, and correspondence with investigators.

Study selection

Longitudinal (prospective or retrospective cohort) studies conducted in generally unselected patients with periprosthetic knee infection treated exclusively by one- or two-stage revision and with re-infection outcomes reported within two years of revision surgery. No clinical trials comparing both revision strategies were identified.

Review methods

Two independent investigators extracted data and discrepancies were resolved by consensus with a third investigator. Re-infection rates from 10 one-stage studies (423 participants) and 108 two-stage studies (5,129 participants) were meta-analysed using random-effect models after arcsine transformation.

Results

The rate (95% confidence intervals) of re-infection was 7.6% (3.4–13.1) in one-stage studies. The corresponding re-infection rate for two-stage revision was 8.8% (7.2–10.6). In subgroup analyses, re-infection rates remained generally similar for several study-level and clinically relevant characteristics. Postoperative clinical outcomes of knee scores and range of motion were similar for both revision strategies.

Limitations

Potential bias owing to the limited number of one-stage revision studies and inability to explore heterogeneity in greater detail.

Conclusions

Available evidence from aggregate published data suggest the one-stage revision strategy may be as effective as the two-stage revision strategy in treating infected knee prostheses in generally unselected patients. Further investigation is warranted.

Systematic review registration

PROSPERO 2015: CRD42015017327     

Lowering Cardiovascular Disease Risk for People with Severe Mental Illnesses in Primary Care: A Focus Group Study

Background

People with severe mental illnesses die early from cardiovascular disease. Evidence is lacking regarding effective primary care based interventions to tackle this problem.

Aim

To identify current procedures for, barriers to, and facilitators of the delivery of primary care based interventions for lowering cardiovascular risk for people with severe mental illnesses.

Method

75 GPs, practice nurses, service users, community mental health staff and carers in UK GP practice or community mental health settings were interviewed in 14 focus groups which were audio-recorded, transcribed and analysed using Framework Analysis.

Results

Five barriers to delivering primary care based interventions for lowering cardiovascular risk in people with severe mental illnesses were identified by the groups: negative perceptions of people with severe mental illnesses amongst some health professionals, difficulties accessing GP and community-based services, difficulties in managing a healthy lifestyle, not attending appointments, and a lack of awareness of increased cardiovascular risk in people with severe mental illnesses by some health professionals. Identified facilitators included involving supportive others, improving patient engagement with services, continuity of care, providing positive feedback in consultations and goal setting.

Conclusion

We identified a range of factors which can be incorporated in to the design, delivery and evaluation of services to reduce cardiovascular risk for people with severe mental illnesses in primary care. The next step is determining the clinical and cost effectiveness of primary care based interventions for lowering cardiovascular risk in people with severe mental illnesses, and evaluating the most important components of such interventions.     

Level of Young People Sexual and Reproductive Health Service Utilization and Its Associated Factors among Young People in Awabel District,Northwest Ethiopia

Background

Currently in Ethiopia, young people’s sexual and reproductive health services are limited and there is a growing issue of confidentiality and affordability of these health services. Moreover, the available services provided are not sensitive to the special needs of young people. Therefore, this study was aimed to assess young people’s sexual and reproductive health service utilization and its associated factors in Awabel district, Northwest Ethiopia.

Methods

A community based cross-sectional study was conducted among 781 randomly selected young people using a pre-tested structured questionnaires in Awabel district, Northwest Ethiopia. Data were entered into Epi data version 3.1 and analyzed using SPSS version 16.0 software.

Results

The mean age of respondents were 17.80 (+ 2.65) years. About 41% of young people had utilized sexual and reproductive health services. Young people from families of higher family expenditure, lived with mothers, participated in peer education and lived near to a Health Center were more likely to utilize sexual and reproductive health services. Furthermore, those who had a parental discussion on sexual and reproductive health (AOR (95% C.I): 2.23 (1.43, 3.46)) and ever had sexual intercourse (AOR (95% C.I): 1.88 (1.30, 2.71)) were more likely to utilize the service than their counterparts. On the other hand, those young people lived with their father and had a primary level of educational attainment was less likely to utilize the service.

Conclusion

Utilization of sexual and reproductive health services is low which needs a great attention where; if not intervened, young people might engage in risky sexual activities. Therefore, it needs a concerted effort from all the concerned bodies to improve their service utilization and thereby reduce the burden of young people’s disease and disabilities associated with sexual and reproductive health.     

Mental Health Help-Seeking Intentions and Preferences of Rural Chinese Adults

Purpose

We aimed to investigate mental health help-seeking intentions and preferences of rural Chinese adults and determine predictors of the intentions.

Methods

A total of 2052 representative rural residents aged 18–60 completed a cross-sectional survey by face-to-face interviews. The survey included seven questions asking about respondents’ help-seeking intentions and preferences, and a series of internationally validated instruments to assess self-perceived health status, depression, anxiety, alcohol abuse, mental health literacy, and attitudes towards mental illness.

Results

Nearly 80% of respondents were willing to seek psychological help if needed, and 72.4% preferred to get help from medical organizations, yet only 12% knew of any hospitals or clinics providing such help. A multivariate analysis of help-seeking intention revealed that being female, having lower education, higher social health, higher mental health knowledge, and physical causal attribution for depression were positive predictors of help-seeking intention.

Conclusion

A huge gap exists between the relatively higher intention for help-seeking and significantly lower knowledge of helpful resources. Predictors of help-seeking intention for mental problems in the current study are consistent with previous studies. Interventions to increase help-seeking for mental problems by Chinese rural adults may be best served by focusing on increasing public awareness of help sources, as well as improving residents’ mental health literacy and social health, with special focus on males and those more educated.     

Factors Associated with Bacterial Vaginosis among Women Who Have Sex with Women: A Systematic Review

Background

Women who have sex with women (WSW) have a higher burden of bacterial vaginosis (BV) than heterosexual women; studies of risk factors specific to this population are limited. We summarised current knowledge regarding risk factors for BV among WSW by systematic review.

Methods

This systematic review was conducted according to the PRISMA statement. PUBMED, EMBASE, Web of Science and The Cochrane Library were searched to 31^st December, 2014. Inclusion criteria: 1) WSW included in the study population; 2) accepted BV diagnostic method; 3) investigated or could extrapolate factors(s) associated with BV acquisition, persistence or transmission in WSW specifically by comparing BV positive to BV negative women. Search was limited to English-language publications.

Results

A limited number of studies have investigated BV in WSW. Of 71 unique references, 18 full-text articles were assessed and 14 studies fulfilled inclusion criteria. BV was positively associated with higher numbers of female partners, both lifetime and in the three months prior to diagnosis, and confirmed BV in a female partner, but inconsistently associated with partners’ BV history or symptoms. BV was not associated with ethnicity, vaginal douching or hormonal contraception. The impact of specific sexual activities, male sexual contact, smoking and the menstrual cycle varied considerably between study populations.

Conclusion

BV in WSW is associated with increased numbers of recent and past female partners and confirmed BV in a female partner. There are limited studies of BV in WSW populations, and research is needed to further elucidate risk factors for BV among WSW. However these data provide epidemiological evidence that BV risk in women is directly related to exposure to other female partners and a partner with BV, providing support for the concept that BV is likely to be transmitted between women.

Systematic Review Registration Number

CRD42014009536 (PROSPERO)     

The Costs of Delivering Integrated HIV and Sexual Reproductive Health Services in Limited Resource Settings

Objective

To present evidence on the total costs and unit costs of delivering six integrated sexual reproductive health and HIV services in a high and medium HIV prevalence setting, in order to support policy makers and planners scaling up these essential services.

Design

A retrospective facility based costing study conducted in 40 non-government organization and public health facilities in Kenya and Swaziland.

Methods

Economic and financial costs were collected retrospectively for the year 2010/11, from each study site with an aim to estimate the cost per visit of six integrated HIV and SRH services. A full cost analysis using a combination of bottom-up and step-down costing methods was conducted from the health provider’s perspective. The main unit of analysis is the economic unit cost per visit for each service. Costs are converted to 2013 International dollars.

Results

The mean cost per visit for the HIV/SRH services ranged from $Int 14.23 (PNC visit) to $Int 74.21 (HIV treatment visit). We found considerable variation in the unit costs per visit across settings with family planning services exhibiting the least variation ($Int 6.71-52.24) and STI treatment and HIV treatment visits exhibiting the highest variation in unit cost ranging from ($Int 5.44-281.85) and ($Int 0.83-314.95), respectively. Unit costs of visits were driven by fixed costs while variability in visit costs across facilities was explained mainly by technology used and service maturity.

Conclusion

For all services, variability in unit costs and cost components suggest that potential exists to reduce costs through better use of both human and capital resources, despite the high proportion of expenditure on drugs and medical supplies. Further work is required to explore the key drivers of efficiency and interventions that may facilitate efficiency improvements.     

Risk of Fatal Bleeding in Episodes of Major Bleeding with New Oral Anticoagulants and Vitamin K Antagonists: A Systematic Review and Meta-Analysis

Background

The reversibility of new/novel oral anticoagulants (NOAC) is not well understood, whereas the reversal strategies for bleeding associated with vitamin k antagonists (VKA), such as warfarin, is well established. It is unknown whether outcomes are different between bleeds occurring with NOAC compared to VKA use.

Objectives

This systematic review and meta-analysis of randomized controlled trials determines the relative odds of fatal bleeding given that a patient suffered a major bleed while on NOAC versus VKA therapy.

Search Methods

Data on major and fatal bleeding events was sought from randomized controlled trials of NOAC agents compared to VKAs.

Main Results

20 trials were included in the meta-analysis. From which, 4056 first-time, major bleeding events were reported and included in the primary analysis. The summary odds ratio for the conditional odds of fatal bleeding given that a major bleeding event occurred was 0.65 [0.52, 0.81] favoring the NOAC agents (p = 0.0001). The reduced odds of fatal bleeding with NOACs was not demonstrated after controlling for bleeding location. Given that an intracranial bleeding event occurred, the summary odds ratio for the conditional odds of fatal bleeding was 0.96 [0.70, 1.32]. For extracranial bleeding events, the summary odds ratio was also statistically insignificant at 0.945 [0.66, 1.35].

Author’s Conclusions

The odds ratio calculated in this meta-analysis showed a reduced odds of death in major bleeding associated with NOAC use. This risk reduction was due to a disproportionate amount of intracranial bleeding in the VKA arms. For any given bleeding site, there was no evidence of a significant difference in fatal outcomes from bleeds associated with NOAC versus VKA use.

Protocol Registration

Protocol registered on PROSPERO under CRD42014013294.     

The Effects of Angiotensin Converting Enzyme Inhibitors (ACE-I) on Human N-Acetyl-Seryl-Aspartyl-Lysyl-Proline (Ac-SDKP) Levels: A Systematic Review and Meta-Analysis

Background

Tuberculous pericardial effusion is a pro-fibrotic condition that is complicated by constrictive pericarditis in 4% to 8% of cases. N-acetyl-seryl-aspartyl-lysyl-proline (Ac-SDKP) is a ubiquitous tetrapeptide with anti-fibrotic properties that is low in tuberculous pericardial effusion, thus providing a potential mechanism for the heightened fibrotic state. Angiotensin-converting enzyme inhibitors (ACE-I), which increase Ac-SDKP levels with anti-fibrotic effects in animal models, are candidate drugs for preventing constrictive pericarditis if they can be shown to have similar effects on Ac-SDKP and fibrosis in human tissues.

Objective

To systematically review the effects of ACE-Is on Ac-SDKP levels in human tissues.

Methods

We searched five electronic databases (1996 to 2014) and conference abstracts with no language restrictions. Two reviewers independently selected studies, extracted data and assessed methodological quality. The protocol was registered in PROSPERO.

Results

Four studies with a total of 206 participants met the inclusion criteria. Three studies (106 participants) assessed the change in plasma levels of Ac-SDKP following ACE-I administration in healthy humans. The administration of an ACE-I was associated with an increase in Ac-SDKP levels (mean difference (MD) 5.07 pmol/ml (95% confidence intervals (CI) 0.64 pmol/ml to 9.51 pmol/ml)). Two studies with 100 participants further assessed the change in Ac-SDKP level in humans with renal failure using ACE-I. The administration of an ACE-I was associated with a significant increase in Ac-SDKP levels (MD 8.94 pmol/ml; 95% CI 2.55 to 15.33; I² = 44%).

Conclusion

ACE-I increased Ac-SDKP levels in human plasma. These findings provide the rationale for testing the impact of ACE-I on Ac-SDKP levels and fibrosis in tuberculous pericarditis.