Transmission Dynamics of Visceral Leishmaniasis in the Indian Subcontinent – A Systematic Literature Review

BackgroundAs Bangladesh, India and Nepal progress towards visceral leishmaniasis (VL) elimination, it is important to understand the role of asymptomatic Leishmania infection (ALI), VL treatment relapse and post kala-azar dermal leishmaniasis (PKDL) in transmission.

Methodology/ Principal Finding

We reviewed evidence systematically on ALI, relapse and PKDL. We searched multiple databases to include studies on burden, risk factors, biomarkers, natural history, and infectiveness of ALI, PKDL and relapse. After screening 292 papers, 98 were included covering the years 1942 through 2016. ALI, PKDL and relapse studies lacked a reference standard and appropriate biomarker. The prevalence of ALI was 4–17-fold that of VL. The risk of ALI was higher in VL case contacts. Most infections remained asymptomatic or resolved spontaneously. The proportion of ALI that progressed to VL disease within a year was 1.5–23%, and was higher amongst those with high antibody titres. The natural history of PKDL showed variability; 3.8–28.6% had no past history of VL treatment. The infectiveness of PKDL was 32–53%. The risk of VL relapse was higher with HIV co-infection. Modelling studies predicted a range of scenarios. One model predicted VL elimination was unlikely in the long term with early diagnosis. Another model estimated that ALI contributed to 82% of the overall transmission, VL to 10% and PKDL to 8%. Another model predicted that VL cases were the main driver for transmission. Different models predicted VL elimination if the sandfly density was reduced by 67% by killing the sandfly or by 79% by reducing their breeding sites, or with 4–6y of optimal IRS or 10y of sub-optimal IRS and only in low endemic setting.

Conclusion/ Significance

There is a need for xenodiagnostic and longitudinal studies to understand the potential of ALI and PKDL as reservoirs of infection.     

Whither Latin America? Trends and challenges of science in Latin America

Science in Latin America has experienced vigorous growth in the past decade, as demonstrated by the fact that the Latin American share of the world's scientific publications increased from 1.8% in 1991-1995 to 3.4% in 1999-2003. Significant growth has also taken place in the numbers of PhDs in science and engineering (S&E) awarded in Latin American countries in recent years, including those in the natural sciences. Importantly, albeit at different rates, growth has been verified in almost all countries in the region, indicating a general effort to promote the development of S&E. In most research fields, however, the recognition or relative impact of Latin American science, as measured by the average number of citations received by published articles (CpP), is still below world averages and much lower than in developed nations. We show that average CpP values for a set of 34 representative developing and developed countries correlate significantly with gross expenditure in research and development (GERD), with gross domestic product (GDP) per capita and with the number of researchers per million inhabitants (RpM). Among those countries, Latin American nations present some of the lowest average values of CpP (<6), GERD (< or =1% of GDP) and RpM (<2,000). We also examined recent trends in scientific activity in Latin America, with focus on the natural sciences and on biochemistry and molecular biology (BMB). In terms of citation scores, publications in BMB compare favorably to those in other research fields within Latin America. At the same time, however, Latin American BMB is one of the areas for which relative impact--compared to developed nations or normalized to world averages--is lowest. These observations clearly indicate the need to establish effective policies to increase competitiveness in terms of the quality and international recognition of Latin American natural sciences in general, and BMB in particular, as opposed to merely increasing the absolute numbers of publications or the numbers of PhDs awarded in the region.     

Measurement of Physician-Patient Communication—A Systematic Review

Background

Effective communication with health care providers has been found as relevant for physical and psychological health outcomes as well as the patients'' adherence. However, the validity of the findings depends on the quality of the applied measures. This study aimed to provide an overview of measures of physician-patient communication and to evaluate the methodological quality of psychometric studies and the quality of psychometric properties of the identified measures.

Methods

A systematic review was performed to identify psychometrically tested instruments which measure physician-patient communication. The search strategy included three databases (EMBASE, PsycINFO, PubMed), reference and citation tracking and personal knowledge. Studies that report the psychometric properties of physician-patient communication measures were included. Two independent raters assessed the methodological quality of the selected studies with the COSMIN (COnsensus based Standards for the selection of health status Measurement INtruments) checklist. The quality of psychometric properties was evaluated with the quality criteria of Terwee and colleagues.

Results

Data of 25 studies on 20 measures of physician-patient communication were extracted, mainly from primary care samples in Europe and the USA. Included studies reported a median of 3 out of the nine COSMIN criteria. Scores for internal consistency and content validity were mainly fair or poor. Reliability and structural validity were rated mainly of fair quality. Hypothesis testing scored mostly poor. The quality of psychometric properties of measures evaluated with Terwee et al.''s criteria was rated mainly intermediate or positive.

Discussion

This systematic review identified a number of measures of physician-patient communication. However, further psychometric evaluation of the measures is strongly recommended. The application of quality criteria like the COSMIN checklist could improve the methodological quality of psychometric property studies as well as the comparability of the studies'' results.     

Pneumococcal Carriage in Sub-Saharan Africa—A Systematic Review

Background

Pneumococcal epidemiology varies geographically and few data are available from the African continent. We assess pneumococcal carriage from studies conducted in sub-Saharan Africa (sSA) before and after the pneumococcal conjugate vaccine (PCV) era.

Methods

A search for pneumococcal carriage studies published before 2012 was conducted to describe carriage in sSA. The review also describes pneumococcal serotypes and assesses the impact of vaccination on carriage in this region.

Results

Fifty-seven studies were included in this review with the majority (40.3%) from South Africa. There was considerable variability in the prevalence of carriage between studies (I-squared statistic = 99%). Carriage was higher in children and decreased with increasing age, 63.2% (95% CI: 55.6–70.8) in children less than 5 years, 42.6% (95% CI: 29.9–55.4) in children 5–15 years and 28.0% (95% CI: 19.0–37.0) in adults older than 15 years. There was no difference in the prevalence of carriage between males and females in 9/11 studies. Serotypes 19F, 6B, 6A, 14 and 23F were the five most common isolates. A meta-analysis of four randomized trials of PCV vaccination in children aged 9–24 months showed that carriage of vaccine type (VT) serotypes decreased with PCV vaccination; however, overall carriage remained the same because of a concomitant increase in non-vaccine type (NVT) serotypes.

Conclusion

Pneumococcal carriage is generally high in the African continent, particularly in young children. The five most common serotypes in sSA are among the top seven serotypes that cause invasive pneumococcal disease in children globally. These serotypes are covered by the two PCVs recommended for routine childhood immunization by the WHO. The distribution of serotypes found in the nasopharynx is altered by PCV vaccination.     

Methods Used in Economic Evaluations of Chronic Kidney Disease Testing — A Systematic Review

BackgroundThe prevalence of chronic kidney disease (CKD) is high in general populations around the world. Targeted testing and screening for CKD are often conducted to help identify individuals that may benefit from treatment to ameliorate or prevent their disease progression.AimsThis systematic review examines the methods used in economic evaluations of testing and screening in CKD, with a particular focus on whether test accuracy has been considered, and how analysis has incorporated issues that may be important to the patient, such as the impact of testing on quality of life and the costs they incur.MethodsArticles that described model-based economic evaluations of patient testing interventions focused on CKD were identified through the searching of electronic databases and the hand searching of the bibliographies of the included studies.ResultsThe initial electronic searches identified 2,671 papers of which 21 were included in the final review. Eighteen studies focused on proteinuria, three evaluated glomerular filtration rate testing and one included both tests. The full impact of inaccurate test results was frequently not considered in economic evaluations in this setting as a societal perspective was rarely adopted. The impact of false positive tests on patients in terms of the costs incurred in re-attending for repeat testing, and the anxiety associated with a positive test was almost always overlooked. In one study where the impact of a false positive test on patient quality of life was examined in sensitivity analysis, it had a significant impact on the conclusions drawn from the model.ConclusionFuture economic evaluations of kidney function testing should examine testing and monitoring pathways from the perspective of patients, to ensure that issues that are important to patients, such as the possibility of inaccurate test results, are properly considered in the analysis.     

Trace Element Concentration in Primary Liver Cancers—A Systematic Review

Background The incidence of primary liver cancer varies between countries. Many of the etiological factors contributing to the geographical variations in incidence are unknown. Development of hepatocellular carcinoma has been linked to levels of trace elements. This review summarizes the evidence associating HCC with trace elements. Methods MEDLINE, EMBASE, and CENTRAL databases were searched. Various inclusion and exclusion criteria were applied to select the articles for inclusion. Data extraction was performed using a custom designed data extraction form. Results A total of 12,344 references were identified. Duplicates, 1,597, were excluded. Clearly irrelevant references, 10,676, were excluded through reading titles and abstracts. Some references (59) were excluded by applying the exclusion criteria. Twelve studies including 646 patients and measuring iron content (8), copper content (11), zinc (9), and selenium (2) qualified for the review. Although a meta-analysis was not possible due to heterogeneity between the studies, a clear pattern of distribution of the trace elements was discernible. Conclusion Iron and zinc content are lower in HCC than in surrounding tissues or normal controls. Copper content is lower in HCC than in surrounding tissues and cirrhotic controls. Epidemiological and physiological reasons for the trace element alterations should be further investigated.     

The Immune System in Children with Malnutrition—A Systematic Review

Background

Malnourished children have increased risk of dying, with most deaths caused by infectious diseases. One mechanism behind this may be impaired immune function. However, this immune deficiency of malnutrition has not previously been systematically reviewed.

Objectives

To review the scientific literature about immune function in children with malnutrition.

Methods

A systematic literature search was done in PubMed, and additional articles identified in reference lists and by correspondence with experts in the field. The inclusion criteria were studies investigating immune parameters in children aged 1–60 months, in relation to malnutrition, defined as wasting, underweight, stunting, or oedematous malnutrition.

Results

The literature search yielded 3402 articles, of which 245 met the inclusion criteria. Most were published between 1970 and 1990, and only 33 after 2003. Malnutrition is associated with impaired gut-barrier function, reduced exocrine secretion of protective substances, and low levels of plasma complement. Lymphatic tissue, particularly the thymus, undergoes atrophy, and delayed-type hypersensitivity responses are reduced. Levels of antibodies produced after vaccination are reduced in severely malnourished children, but intact in moderate malnutrition. Cytokine patterns are skewed towards a Th2-response. Other immune parameters seem intact or elevated: leukocyte and lymphocyte counts are unaffected, and levels of immunoglobulins, particularly immunoglobulin A, are high. The acute phase response appears intact, and sometimes present in the absence of clinical infection. Limitations to the studies include their observational and often cross-sectional design and frequent confounding by infections in the children studied.

Conclusion

The immunological alterations associated with malnutrition in children may contribute to increased mortality. However, the underlying mechanisms are still inadequately understood, as well as why different types of malnutrition are associated with different immunological alterations. Better designed prospective studies are needed, based on current understanding of immunology and with state-of-the-art methods.     

Using Multiple Types of Studies in Systematic Reviews of Health Care Interventions – A Systematic Review

Background

A systematic review may evaluate different aspects of a health care intervention. To accommodate the evaluation of various research questions, the inclusion of more than one study design may be necessary. One aim of this study is to find and describe articles on methodological issues concerning the incorporation of multiple types of study designs in systematic reviews on health care interventions. Another aim is to evaluate methods studies that have assessed whether reported effects differ by study types.

Methods and Findings

We searched PubMed, the Cochrane Database of Systematic Reviews, and the Cochrane Methodology Register on 31 March 2012 and identified 42 articles that reported on the integration of single or multiple study designs in systematic reviews. We summarized the contents of the articles qualitatively and assessed theoretical and empirical evidence. We found that many examples of reviews incorporating multiple types of studies exist and that every study design can serve a specific purpose. The clinical questions of a systematic review determine the types of design that are necessary or sufficient to provide the best possible answers. In a second independent search, we identified 49 studies, 31 systematic reviews and 18 trials that compared the effect sizes between randomized and nonrandomized controlled trials, which were statistically different in 35%, and not different in 53%. Twelve percent of studies reported both, different and non-different effect sizes.

Conclusions

Different study designs addressing the same question yielded varying results, with differences in about half of all examples. The risk of presenting uncertain results without knowing for sure the direction and magnitude of the effect holds true for both nonrandomized and randomized controlled trials. The integration of multiple study designs in systematic reviews is required if patients should be informed on the many facets of patient relevant issues of health care interventions.     

Does Exercise Improve Glycaemic Control in Type 1 Diabetes? A Systematic Review and Meta-Analysis

Objective

Whilst regular exercise is advocated for people with type 1 diabetes, the benefits of this therapy are poorly delineated. Our objective was to review the evidence for a glycaemic benefit of exercise in type 1 diabetes.

Research Design and Methods

Electronic database searches were carried out in MEDLINE, Embase, Cochrane’s Controlled Trials Register and SPORTDiscus. In addition, we searched for as yet unpublished but completed trials. Glycaemic benefit was defined as an improvement in glycosylated haemoglobin (HbA1c). Both randomised and non-randomised controlled trials were included.

Results

Thirteen studies were identified in the systematic review. Meta-analysis of twelve of these (including 452 patients) demonstrated an HbA1c reduction but this was not statistically significant (standardised mean difference (SMD) −0.25; 95% CI, −0.59 to 0.09).

Conclusions

This meta-analysis does not reveal evidence for a glycaemic benefit of exercise as measured by HbA1c. Reasons for this finding could include increased calorie intake, insulin dose reductions around the time of exercise or lack of power. We also suggest that HbA1c may not be a sensitive indicator of glycaemic control, and that improvement in glycaemic variability may not be reflected in this measure. Exercise does however have other proven benefits in type 1 diabetes, and remains an important part of its management.     

Quality of Animal Experiments in Anti-Angiogenic Cancer Drug Development – A Systematic Review

Translation from preclinical animal research to clinical bedside has proven to be difficult to impossible in many fields of research (e.g. acute stroke, ALS and HIV vaccination development) with oncology showing particularly low translation rates (5% vs. 20% for cardiovascular diseases). Several investigations on published preclinical animal research have revealed that apart from plain species differences, translational problems can arise from low study quality (e.g. study design) or non-representative experimental conditions (e.g. treatment schedule).This review assessed the published experimental circumstances and quality of anti-angiogenic cancer drug development in 232 in vivo studies. The quality of study design was often insufficient; at least the information published about the experiments was not satisfactory in most cases. There was no quality improvement over time, with the exception of conflict of interest statements. This increase presumably arose mainly because journal guidelines request such statements more often recently.Visual inspection of data and a cluster analysis confirmed a trend described in literature that low study quality tends to overestimate study outcome. It was also found that experimental outcome was more favorable when a potential drug was investigated as the main focus of a study, compared to drugs that were used as comparison interventions. We assume that this effect arises from the frequent neglect of blinding investigators towards treatment arms and refer to it as hypothesis bias.In conclusion, the reporting and presumably also the experimental performance of animal studies in drug development for oncology suffer from similar shortcomings as other fields of research (such as stroke or ALS). We consider it necessary to enforce experimental quality and reporting that corresponds to the level of clinical studies. It seems that only clear journal guidelines or guidelines from licensing authorities, where failure to fulfill prevents publication or experimental license, can help to improve this situation.     

Economic Benefits of Investing in Women’s Health: A Systematic Review

Background

Globally, the status of women’s health falls short of its potential. In addition to the deleterious ethical and human rights implications of this deficit, the negative economic impact may also be consequential, but these mechanisms are poorly understood. Building on the literature that highlights health as a driver of economic growth and poverty alleviation, we aim to systematically investigate the broader economic benefits of investing in women’s health.

Methods

Using the Preferred Reporting Items for Systematic Reviews and Meta-Analysis (PRISMA) guidelines, we systematically reviewed health, gender, and economic literature to identify studies that investigate the impact of women’s health on micro- and macroeconomic outcomes. We developed an extensive search algorithm and conducted searches using 10 unique databases spanning the timeframe 01/01/1970 to 01/04/2013. Articles were included if they reported on economic impacts stemming from changes in women’s health (table of outcome measures included in full review,

Pediatric Visceral Leishmaniasis in Albania: A Retrospective Analysis of 1,210 Consecutive Hospitalized Patients (1995–2009)

Background

Little information is available about infantile visceral leishmaniasis (VL) in Albania as regards incidence, diagnosis and management of the disease.

Methodology/Principal Findings

Demographic data, clinical and laboratory features and therapeutic findings were considered in children admitted to University Hospital of Tirana from 1995 to 2009, and diagnosed as having VL. The diagnosis was based on bone-marrow microscopy/culture in 77.5% of patients, serology in 16.1%, and ex juvantibus in 6.4%. A total of 1,210 children were considered, of whom 74% came from urbanized areas. All patients were in the age range 0–14 years, with a median of 4 years. Hepatosplenomegaly was recorded in 100%, fever in 95.4% and moderate to severe anemia in 88% of cases. Concomitant conditions were frequent: 84% had bronchopneumonia; diarrhea was present in 27%, with acute manifestations in 5%; 3% had salmonellosis. First-line therapy was meglumine antimoniate for all patients, given at the standard Sb^v dosage of 20 mg/kg/day for 21 to 28 days. Two children died under treatment, one of sepsis, the other of acute renal impairment. There were no cases of primary unresponsiveness to treatment, and only 8 (0.67%) relapsed within 6–12 months after therapy. These patients have been re-treated with liposomal amphotericin B, with successful cure.

Conclusions

Visceral leishmaniasis in pediatric age is relatively frequent in Albania; therefore an improvement is warranted of a disease-specific surveillance system in this country, especially as regards diagnosis. Despite recent reports on decreased responses to antimonial drugs of patients with Mediterranean VL, meglumine antimoniate treatment appears to be still highly effective in Albania.     

The one‐person household in Latin America: A brief note

Abstract

This study provides a much‐needed exploration of the determinants of age‐discrepant unions in Canada. What little research has been conducted in this area of sociology of the family is now outdated. Further, the growing number of Canadians living in nonmarital cohabitation warrants their inclusion in any consideration of contemporary, heterosexual unions, and we have done so here. Utilizing multinomial Iogit modeling techniques, we analyze data drawn from the 1995 Canadian General Social Survey. We find that cohabitations and remarriages are more likely to be age‐discrepant than marriages, and that as age at union formation increases, so does the likelihood that the union will be age‐heterogamous. Although we hypothesized a positive relationship between education and the chances of age‐heterogamous unions because the availability of eligible mates may decrease with education, we actually find an inverse association for women: a one‐level increase in education decreases a woman's odds of entering an age‐discrepant union by about 4 percent. We speculate that for women, greater education (economic position) may increase age‐homogamy because they may be more economically attractive and thus more able to select a partner of their own age.     

Health Effects of Trace Metals in Electronic Cigarette Aerosols—a Systematic Review

Biological Trace Element Research - Electronic cigarettes (ECs) are essentially nicotine delivery devices that mimic the appearance of a conventional cigarette (CC). Lately, they have been marketed...     

Persistent Difficulties in Switching to Second-Line ART in Sub-Saharan Africa — A Systematic Review and Meta-Analysis

Objectives

Switching to second-line antiretroviral therapy (ART) largely depends on careful clinical assessment and access to biological measurements. We performed a systematic review and meta-analysis to estimate the incidence of switching to second-line ART in sub-Saharan Africa and its main programmatic determinants.

Methods

We searched 2 databases for studies reporting the incidence rate of switching to second-line ART in adults living in sub-Saharan Africa. Data on the incidence rate of switching were pooled, and random-effect models were used to evaluate the effect of factors measured at the programme level on this incidence rate.

Results

Nine studies (157,340 patients) in 21 countries were included in the meta-analysis. All studies considered patients under first-line ART and conditions to initiate ART were similar across studies. Overall, 3,736 (2.4%) patients switched to second-line ART. Incidence rate of switch was in mean 2.65 per 100 person-years (PY) (95% confidence interval: 2.01–3.30); it ranged from 0.42 to 4.88 per 100 PY and from 0 to 4.80 per 100 PY in programmes with and without viral load monitoring, respectively. No factors measured at the programme level were associated with the incidence rate of switching to second-line ART.

Conclusion

The low incidence rate of switching to second-line ART suggests that the monitoring of patients under ART is challenging and that access to second-line ART is ineffective; efforts should be made to increase access to second-line ART to those in need by providing monitoring tools, education and training, as well as a more convenient regimen.