The impact of health insurance on maternal and reproductive health service utilization and financial protection in low- and lower middle-income countries: a systematic review of the evidence.

BACKGROUND: Low- and middle-income countries have committed to achieving universal health coverage (UHC) as a means to enhance access to services and improve financial protection. One of the key health financing reforms to achieve UHC is the introduction or expansion of health insurance to enhance access to basic health services, including maternal and reproductive health care. However, there is a paucity of evidence of the extent to which these reforms have had impact on the main policy objectives of enhancing service utilization and financial protection. The aim of this systematic review is to assess the existing evidence on the causal impact of health insurance on maternal and reproductive health service utilization and financial protection in low- and lower middle-income countries. METHODS: The review followed the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines. The search included six databases: Medline, Embase, Web of Science, Cochrane, CINAHL, and Scopus as of 23rd May 2023. The keywords included health insurance, impact, utilisation, financial protection, and maternal and reproductive health. The search was followed by independent title and abstract screening and full text review by two reviewers using the Covidence software. Studies published in English since 2010, which reported on the impact of health insurance on maternal and reproductive health utilisation and or financial protection were included in the review. The ROBINS-I tool was used to assess the quality of the included studies. RESULTS: A total of 17 studies fulfilled the inclusion criteria. The majority of the studies (82.4%, n = 14) were nationally representative. Most studies found that health insurance had a significant positive impact on having at least four antenatal care (ANC) visits, delivery at a health facility and having a delivery assisted by a skilled attendant with average treatment effects ranging from 0.02 to 0.11, 0.03 to 0.34 and 0.03 to 0.23 respectively. There was no evidence that health insurance had increased postnatal care, access to contraception and financial protection for maternal and reproductive health services. Various maternal and reproductive health indicators were reported in studies. ANC had the greatest number of reported indicators (n = 10), followed by financial protection (n = 6), postnatal care (n = 5), and delivery care (n = 4). The overall quality of the evidence was moderate based on the risk of bias assessment. CONCLUSION: The introduction or expansion of various types of health insurance can be a useful intervention to improve ANC (receiving at least four ANC visits) and delivery care (delivery at health facility and delivery assisted by skilled birth attendant) service utilization in low- and lower-middle-income countries. Implementation of health insurance could enable countries' progress towards UHC and reduce maternal mortality. However, more research using rigorous impact evaluation methods is needed to investigate the causal impact of health insurance coverage on postnatal care utilization, contraceptive use and financial protection both in the general population and by socioeconomic status. TRIAL REGISTRATION: This study was registered with Prospero (CRD42021285776).

Extending universal health coverage to informal workers: A systematic review of health financing schemes in low- and middle-income countries in Southeast Asia.

Achieving universal health coverage (UHC) is a priority of most low- and middle-income countries, reflecting governments' commitments to improved population health. However, high levels of informal employment in many countries create challenges to progress toward UHC, with governments struggling to extend access and financial protection to informal workers. One region characterized by a high prevalence of informal employment is Southeast Asia. Focusing on this region, we systematically reviewed and synthesized published evidence of health financing schemes implemented to extend UHC to informal workers. Following PRISMA guidelines, we systematically searched for both peer-reviewed articles and reports in the grey literature. We appraised study quality using the Joanna Briggs Institute checklists for systematic reviews. We synthesized extracted data using thematic analysis based on a common conceptual framework for analyzing health financing schemes, and we categorized the effect of these schemes on progress towards UHC along the dimensions of financial protection, population coverage, and service access. Findings suggest that countries have taken a variety of approaches to extend UHC to informal workers and implemented schemes with different revenue raising, pooling, and purchasing provisions. Population coverage rates differed across health financing schemes; those with explicit political commitments toward UHC that adopted universalist approaches reached the highest coverage of informal workers. Results for financial protection indicators were mixed, though indicated overall downward trends in out-of-pocket expenditures, catastrophic health expenditure, and impoverishment. Publications generally reported increased utilization rates through the introduced health financing schemes. Overall, this review supports the existing evidence base that predominant reliance on general revenues with full subsidies for and mandatory coverage of informal workers are promising directions for reform. Importantly, the paper extends existing research by offering countries committed to progressively realizing UHC around the world a relevant updated resource, mapping evidence-informed approaches toward accelerated progress on the UHC goals.

Assessing progress towards universal health coverage in Cambodia: Evidence using survey data from 2009 to 2019.

Over the past decades, many low- and middle-income countries have implemented health financing and system reforms to progress towards universal health coverage (UHC). In the case of Cambodia, out-of-pocket expenditure (OOPE) remains the main source of current health expenditure after several decades of reform, exposing households to financial risks when accessing healthcare and violating UHC's key tenet of financial protection. We use pre-pandemic data from the nationally representative Cambodia Socio-Economic Surveys of 2009 to 2019 to assess progress in financial protection to evaluate the reforms and obtain internationally comparable estimates. We find that following strong improvements in financial protection between 2009 and 2017, there was a reversal in the trend thereafter. The OOPE budget share rose, and the incidence of catastrophic spending and impoverishment increased in nearly all geographical and socioeconomic strata. For example, 17.7% of households experienced catastrophic health expenditure in 2019 at the threshold of 10% of total household consumption expenditure, and 3.9% of households were pushed into poverty by OOPE. The distribution of all financial protection indicators varied strongly across socioeconomic and geographical strata in all years. Fundamentally, the demonstrated trend reversal may jeopardize Cambodia's ability to progress towards UHC. To improve financial protection in the short term, there is a need to address the burden created by OOPE through targeted interventions to household groups that are most affected. In the medium term, our findings emphasize the importance of expanding health pre-payment schemes to currently uncovered vulnerable groups, specifically the near-poor. The government also needs to consider extending the scope of services covered and the range of providers to include the private sector under these schemes to reduce reliance on OOPE.

Mutation of the Drosophila melanogaster serotonin transporter dSERT impacts sleep, courtship, and feeding behaviors.

The Serotonin Transporter (SERT) regulates extracellular serotonin levels and is the target of most current drugs used to treat depression. The mechanisms by which inhibition of SERT activity influences behavior are poorly understood. To address this question in the model organism Drosophila melanogaster, we developed new loss of function mutations in Drosophila SERT (dSERT). Previous studies in both flies and mammals have implicated serotonin as an important neuromodulator of sleep, and our newly generated dSERT mutants show an increase in total sleep and altered sleep architecture that is mimicked by feeding the SSRI citalopram. Differences in daytime versus nighttime sleep architecture as well as genetic rescue experiments unexpectedly suggest that distinct serotonergic circuits may modulate daytime versus nighttime sleep. dSERT mutants also show defects in copulation and food intake, akin to the clinical side effects of SSRIs and consistent with the pleomorphic influence of serotonin on the behavior of D. melanogaster. Starvation did not overcome the sleep drive in the mutants and in male dSERT mutants, the drive to mate also failed to overcome sleep drive. dSERT may be used to further explore the mechanisms by which serotonin regulates sleep and its interplay with other complex behaviors.

The cost-effectiveness of sexual and reproductive health and rights interventions in low- and middle-income countries: a scoping review.

Sexual and reproductive health and rights (SRHR) are an essential component of universal health coverage (UHC). In determining which SRHR interventions to include in their UHC benefits package, countries are advised to evaluate each service based on robust and reliable data, including cost-effectiveness data. We conducted a scoping review of full economic evaluations of the essential SRHR interventions included in the comprehensive package presented by the Guttmacher-Lancet Commission on SRHR. Of the 462 economic evaluations that met the inclusion criteria, the quantity of publications varied across regions, countries, and the components of the SRHR package, with the majority of publications reporting on HIV/AIDS, reproductive cancer, as well as antenatal care, childbirth, and postnatal care. Systematic reviews are needed for these components in support of more conclusive findings and actionable recommendations for programmes and policy. Further evaluations for interventions included in the remaining components are needed to provide a stronger evidence base for decision-making. The economic evaluations reviewed for this article were inherently varied in their applied methodologies, SRHR interventions and comparators, cost and effectiveness data, and cost-effectiveness thresholds, among others. Despite these differences, the vast majority of publications reported the evaluated SRHR interventions to be cost-effective.

Availability, prices and affordability of essential medicines for treatment of diabetes and hypertension in private pharmacies in Zambia.

OBJECTIVES: To explore availability, prices and affordability of essential medicines for diabetes and hypertension treatment in private pharmacies in three provinces of Zambia. METHODS: A cross-sectional survey was conducted in 99 pharmacies across three Zambian provinces. Methods were based on a standardized methodology by the World Health Organization and Health Action International. Availability was analysed as mean availability per pharmacy and individual medicine. Median prices were compared to international reference prices and differences in price between medicine forms (original brand or generic product) were computed. Affordability was assessed as number of days' salaries required to purchase a standard treatment course using the absolute poverty line and mean per capita provincial household income as standard. An analysis identifying medicines considered both available and affordable was conducted. RESULTS: Two antidiabetics and nine antihypertensives had high-level availability (≥80%) in all provinces; availability levels for the remaining surveyed antidiabetics and antihypertensives were largely found below 50%. Availability further varied markedly across medicines and medicine forms. Prices for most medicines were higher than international reference prices and great price variations were found between pharmacies, medicines and medicine forms. Compared to original brand products, purchase of generics was associated with price savings for patients between 21.54% and 96.47%. No medicine was affordable against the absolute poverty line and only between four and eleven using mean per capita provincial incomes. Seven generics in Copperbelt/Lusaka and two in Central province were highly available and affordable. CONCLUSIONS: The study showed that the majority of surveyed antidiabetic and antihypertensive medicines was inadequately available (<80%). In addition, most prices were higher than their international reference prices and that treatment with these medicines was largely unaffordable against the set affordability thresholds. Underlying reasons for the findings should be explored as a basis for targeted policy initiatives.

Correction: A Single Pair of Serotonergic Neurons Counteracts Serotonergic Inhibition of Ethanol Attraction in Drosophila.

[This corrects the article DOI: 10.1371/journal.pone.0167518.].

A Single Pair of Serotonergic Neurons Counteracts Serotonergic Inhibition of Ethanol Attraction in Drosophila.

Attraction to ethanol is common in both flies and humans, but the neuromodulatory mechanisms underlying this innate attraction are not well understood. Here, we dissect the function of the key regulator of serotonin signaling-the serotonin transporter-in innate olfactory attraction to ethanol in Drosophila melanogaster. We generated a mutated version of the serotonin transporter that prolongs serotonin signaling in the synaptic cleft and is targeted via the Gal4 system to different sets of serotonergic neurons. We identified four serotonergic neurons that inhibit the olfactory attraction to ethanol and two additional neurons that counteract this inhibition by strengthening olfactory information. Our results reveal that compensation can occur on the circuit level and that serotonin has a bidirectional function in modulating the innate attraction to ethanol. Given the evolutionarily conserved nature of the serotonin transporter and serotonin, the bidirectional serotonergic mechanisms delineate a basic principle for how random behavior is switched into targeted approach behavior.

Differential retrotranslocation of mitochondrial Bax and Bak.

The Bcl-2 proteins Bax and Bak can permeabilize the outer mitochondrial membrane and commit cells to apoptosis. Pro-survival Bcl-2 proteins control Bax by constant retrotranslocation into the cytosol of healthy cells. The stabilization of cytosolic Bax raises the question whether the functionally redundant but largely mitochondrial Bak shares this level of regulation. Here we report that Bak is retrotranslocated from the mitochondria by pro-survival Bcl-2 proteins. Bak is present in the cytosol of human cells and tissues, but low shuttling rates cause predominant mitochondrial Bak localization. Interchanging the membrane anchors of Bax and Bak reverses their subcellular localization compared to the wild-type proteins. Strikingly, the reduction of Bax shuttling to the level of Bak retrotranslocation results in full Bax toxicity even in absence of apoptosis induction. Thus, fast Bax retrotranslocation is required to protect cells from commitment to programmed death.

Impact of blanching on polyphenol stability and antioxidant capacity of innovative coriander (Coriandrum sativum L.) pastes.

Fresh coriander leaves were steam- and water-blanched at 100 °C and at 90 and 100 °C, respectively, for 1-10 min, and subsequently comminuted to form a paste. Pasty products obtained from coriander fruits were processed after water-blanching applying the same time-temperature regimes. Among the 11 phenolics characterised in leaves by high-performance liquid chromatography coupled to mass spectrometric detection, several caffeic acid derivatives, 5-feruloylquinic and 5-p-coumaroylquinic acids were tentatively identified for the first time. In fruits, 10 phenolics were detected, whereas rutin, a dicaffeic acid derivative and two feruloylquinic and caffeoylquinic acid isomers were newly detected. Upon steam-blanching for 1 min, phenolic contents and antioxidant capacities remained virtually unchanged. In contrast, water-blanching and extended steam-blanching even yielded increased levels compared to the unheated control, whereas short-time water-blanching resulted in higher values than prolonged heat treatment. Thus, short-time water-blanching is recommended as the initial unit in the processing of coriander leaves and fruits into novel pasty products.

Effects of blanching on polyphenol stability of innovative paste-like parsley (Petroselinum crispum (Mill.) Nym ex A. W. Hill) and marjoram (Origanum majorana L.) products.

Fresh herbs were water- and steam-blanched at 90-100°C and 100°C, respectively, for 1-10 min and 30 s to 7 min for parsley and marjoram, respectively, and subsequently minced to obtain a paste. For the first time, phenolic compounds of unheated marjoram were characterised by high-performance liquid chromatography coupled to mass spectrometry (HPLC-MS). Hereby, 10 phenolics were detected. Among them, apigenin-glucuronide, lucenin-2 and lithospermic acid were tentatively identified for the first time. In unheated parsley, apart from the major compound apiin, 10 further phenolics were characterised including several p-coumaric acid derivatives which were newly detected. Except for apiin, short-time steam- and water-blanching (1 min), respectively, did not cause significant losses of phenolic compounds, and thus proved to be the most suitable measures to ensure polyphenol retention. Consequently, blanching is a recommendable initial operation in the processing of parsley and marjoram into novel paste-like products.

Influence of thermal treatment on color, enzyme activities, and antioxidant capacity of innovative pastelike parsley products.

Conventional spice powders are often characterized by low sensory quality and high microbial loads. Furthermore, genuine enzymes are only inhibited but not entirely inactivated upon drying, so that they may regain their activity upon rehydration of dried foods. To overcome these problems, initial heating was applied in the present study as the first process step for the production of innovative pastelike parsley products. For this purpose, fresh parsley was blanched (80, 90, and 100 °C for 1-10 min) and subsequently comminuted to form a paste. Alternatively, mincing was carried out prior to heat treatment. Regardless of temperature, the color of the latter product did not show any change after heating for 1 min. With progressing exposure time the green color turned to olive hues due to marked pheophytin formation. Inactivation of genuine peroxidase (POD) and polyphenol oxidase (PPO) was achieved at all temperature-time regimes applied. In contrast, the parsley products obtained after immediate water-blanching were characterized by brighter green colors and enhanced pigment retention. With the exception of the variants water-blanched at 80 °C, POD and PPO were completely inactivated at any of the thermal treatments. Furthermore, in water-blanched samples, antioxidant capacities as determined by the TEAC and FRAP assays were even enhanced compared to unheated parsley, whereas a decrease of phenolic contents could not be prevented. Consequently, the innovative process presented in this study allows the production of novel herb and spice products characterized by improved sensory quality as compared to conventional spice products.

The influence of peritoneal endometriotic lesions on the generation of endometriosis-related pain and pain reduction after surgical excision.

PURPOSE: To investigate the influence of different kinds of endometriotic lesions, especially peritoneal endometriotic implants in pain generation and the pain reduction after surgical excision in a prospective study. METHODS: Fifty-one pre-menopausal patients underwent surgical laparoscopy due to chronic pelvic pain, dysmenorrhoea and/or for ovarian cysts. In 44 patients, endometriosis was diagnosed. The pre- and post-operative pain score was determined using a standardized questionnaire with a visual analogue scale. Patients with peritoneal endometriosis were divided into two different groups depending on their pre-operative pain score: group A had a pain score of 3 or more, while group B a pain score of 2 or less. Patients without peritoneal endometriosis were classified as group C, and patients without endometriosis were classified as group D. The pre- and post-operative pelvic pain and/or dysmenorrhoea was analysed according to the different types of endometriotic lesions. RESULTS: In groups A and C, the post-operative pain score decreased by at least 2 grades or more (p < 0.0). In group D, the post-operative pain score showed no significant reduction. CONCLUSION: The present study suggests that the surgical excision of endometriotic lesions -- including peritoneal implants -- is an effective treatment of endometriosis-associated pelvic pain and/or dysmenorrhoea.

A pilot study to evaluate the clinical relevance of endometriosis-associated nerve fibers in peritoneal endometriotic lesions.

OBJECTIVE: To investigate the clinical relevance of endometriosis-associated nerve fibers in the development of endometriosis-associated symptoms. DESIGN: Prospective nonrandomized study. SETTING: University hospital endometriosis center. PATIENT(S): Fifty-one premenopausal patients underwent surgical laparoscopy because of chronic pelvic pain, dysmenorrhea, or for ovarian cysts. Endometriosis was diagnosed in 44 patients. INTERVENTION(S): The preoperative and postoperative pain scores were determined using a standardized questionnaire with a visual analogue scale from 1-10. Patients with peritoneal endometriosis were divided into two groups depending on their preoperative pain score: group A with a pain score of at least 3 or more and group B with a pain score of 2 or less. Patients without peritoneal endometriosis were classified as group C and patients without endometriosis were classified as group D. Immunohistochemical analysis of neurofilament and protein gene product 9.5 were used for nerve fiber detection. Occurrence of endometriosis-associated nerve fibers was correlated with the severity of pelvic pain and/or dysmenorrhea. RESULT(S): Peritoneal endometriosis-associated nerve fibers were found significantly more frequently in group A than in group B (82.6% vs. 33.3%). CONCLUSION(S): The present study suggests that the presence of endometriosis-associated nerve fibers in the peritoneum is important for the development of endometriosis-associated pelvic pain and dysmenorrhea.

Profiling of Alk(en)ylresorcinols in cereals by HPLC-DAD-APcI-MSn.

5-Alk(en)ylresorcinols in rye, wheat, spelt, and barley have been characterized by high-performance liquid chromatography coupled to atmospheric pressure chemical ionization multistage mass spectrometry (HPLC-APcI-MS(n)) for the first time. Among the 29 compounds analysed, several major and minor C(15), C(17), C(19), C(21), C(23), and C(25)-substituted resorcinols with saturated, monoenoic, dienoic, and/or oxygenated side-chains were characterized by their specific fragmentation patterns in collision-induced dissociation experiments. Additionally, a C(27:0) homologue, which has probably been overlooked in previous studies based on HPLC alone, was detected in all cereals analysed. Furthermore, we provide tentative evidence for the occurrence of alkylresorcinols with triolefinic side-chains, which have, to our knowledge, so far not been reported in any cereal species.