bluuebunny/crossref_metadata_2025 huggingface dataset:
HOXA7 promotes the metastasis of KRAS mutant colorectal cancer by regulating myeloid-derived suppressor cells
Authors: Dang Yunzhi , Yu Jiao , Zhao Shuhong , Cao Ximing , Wang Qing
Published: February 2022

Background

KRAS mutation accounts for 30–50% of human colorectal cancer (CRC) cases. Due to the scarcity of effective treatment options, KRAS mutant CRC is difficult to treat in the clinic. Metastasis is still the major cause of the high mortality associated with KRAS mutant CRC, but the exact mechanism remains unclear. Here, we report a unique function of Homeobox 7 (HOXA7) in driving KRAS mutant CRC metastasis and explore therapeutic strategies for subpopulations of patients with this disease.

Methods

The expression of HOXA7 in a human CRC cohort was measured by immunohistochemistry. The function of HOXA7 in KRAS mutant CRC metastasis was analyzed with the cecum orthotopic model.

Results

Elevated HOXA7 expression was positively correlated with lymph node metastasis, distant metastasis, poor tumor differentiation, high TNM stage, and poor prognosis in CRC patients. Furthermore, HOXA7 was an independent prognostic marker in KRAS mutant CRC patients (P < 0.001) but not in KRAS wild-type CRC patients (P = 0.575). Overexpression of HOXA7 improved the ability of KRAS mutant CT26 cells to metastasize and simultaneously promoted the infiltration of myeloid-derived suppressor cells (MDSCs). When MDSC infiltration was blocked by a CXCR2 inhibitor, the metastasis rate of CT26 cells was markedly suppressed. The combination of the CXCR2 inhibitor SB265610 and programmed death-ligand 1 antibody (anti-PD-L1) could largely inhibit the metastasis of KRAS mutant CRC.

Conclusions

HOXA7 overexpression upregulated CXCL1 expression, which promoted MDSC infiltration. Interruption of this loop might provide a promising treatment strategy for HOXA7-mediated KRAS mutant CRC metastasis.
Malaria prevalence and performance of diagnostic tests among patients hospitalized with acute undifferentiated fever in Zanzibar
Authors: Onken Annette , Haanshuus Christel Gill , Miraji Mohammed Khamis , Marijani Msafiri , Kibwana Kibwana Omar , Abeid Khamis Ali , Mørch Kristine , Reimers Marianne , Langeland Nina , Müller Fredrik , Jenum Pål A. , Blomberg Bjørn
Published: February 2022

Background

Control efforts in Zanzibar reduced the burden of malaria substantially from 2000 to 2015, but re-emergence of falciparum malaria has been observed lately. This study evaluated the prevalence of malaria and performance of routine diagnostic tests among hospitalized fever patients in a 1.5 years period in 2015 and 2016.

Methods

From March 2015 to October 2016, paediatric and adult patients hospitalized with acute undifferentiated fever at Mnazi Mmoja Hospital, Zanzibar were included. The malaria prevalence, and performance of rapid diagnostic test (RDT) and microscopy, were assessed using polymerase chain reaction (PCR) as gold standard.

Results

The malaria prevalence was 9% (63/731). Children under 5 years old had lower malaria prevalence (5%, 14/260) than older children (15%, 20/131, p = 0.001) and persons aged 16 to 30 years (13%, 15/119, p = 0.02), but not different from persons over 30 years old (6%, 14/217, p = 0.7). All cases had Plasmodium falciparum infection, except for one case of Plasmodium ovale. Ten malaria patients had no history of visiting mainland Tanzania. The RDT had a sensitivity of 64% (36/56) and a specificity of 98% (561/575), and microscopy had a sensitivity of 50% (18/36) and  a specificity of 99% (251/254), compared to PCR. The malaria parasitaemia was lower in patients with false negative results on RDT (median 7 × 103 copies/µL, interquartile range [IQR] 2 × 103 – 8 × 104, p = 0.002) and microscopy (median 9 × 103 copies/µL, IQR 8 × 102 – 7 × 104, p = 0.006) compared to those with true positive RDT (median 2 × 105 copies/µL, IQR 3 × 104 – 5 × 105) and microscopy (median 2 × 105 copies/µL, IQR 6 × 104 – 5 × 105).

Conclusions

The study emphasizes that malaria was a frequent cause of febrile illness in hospitalized patients in Zanzibar in the years 2015-2016, particularly among school age children and young adults. We found evidence of autochthonous malaria transmission in Zanzibar. Compared to PCR, both RDT and microscopy had low sensitivity, and false negative results were associated with low parasitaemia. While low parasitaemia identified only by PCR in a semi-immune individual could be coincidental and without clinical relevance, clinicians should be aware of the risk of false negative results on routine tests.
Detecting asymptomatic carriage of Plasmodium falciparum in southern Ghana: utility of molecular and serological diagnostic tools
Authors: Agbana Hamza B. , Rogier Eric , Lo Aminata , Abukari Zakaria , Jones Sophie , Gyan Ben , Aidoo Michael , Amoah Linda E.
Published: February 2022

Background

Asymptomatic malaria infections can serve as potential reservoirs for malaria transmission. The density of parasites contained in these infections range from microscopic to submicroscopic densities, making the accurate detection of asymptomatic parasite carriage highly dependent on the sensitivity of the tools used for the diagnosis. This study sought to evaluate the sensitivities of a variety of molecular and serological diagnostic tools at determining the prevalence of asymptomatic Plasmodium falciparum parasite infections in two communities with varying malaria parasite prevalence.

Methods

Whole blood was collected from 194 afebrile participants aged between 6 and 70 years old living in a high (Obom) and a low (Asutsuare) malaria transmission setting of Ghana. Thick and thin blood smears, HRP2 based malaria rapid diagnostic test (RDT) and filter paper dried blood spots (DBS) were prepared from each blood sample. Genomic DNA was extracted from the remaining blood and used in Plasmodium specific photo-induced electron transfer polymerase chain reaction (PET-PCR) and Nested PCR, whilst the HRP2 antigen content of the DBS was estimated using a bead immunoassay. A comparison of malaria parasite prevalence as determined by each method was performed.

Results

Parasite prevalence in the high transmission site of Obom was estimated at 71.4%, 61.9%, 60%, 37.8% and 19.1% by Nested PCR, the HRP2 bead assay, PET-PCR, HRP2-RDT and microscopy respectively. Parasite prevalence in the low transmission site of Asutsuare was estimated at 50.1%, 11.2%, 5.6%, 0% and 2.2% by Nested PCR, the HRP2 bead assay, PET-PCR, RDT and microscopy, respectively. The diagnostic performance of Nested PCR, PET-PCR and the HRP2 bead assay was similar in Obom but in Asutsuare, Nested PCR had a significantly higher sensitivity than PET-PCR and the HRP2 bead assay, which had similar sensitivity.

Conclusions

Nested PCR exhibited the highest sensitivity by identifying the highest prevalence of asymptomatic P. falciparum in both the high and low parasite prevalence settings. However, parasite prevalence estimated by the HRP2 bead assay and PET-PCR had the highest level of inter-rater agreement relative to all the other tools tested and have the advantage of requiring fewer processing steps relative to Nested PCR and producing quantitative results.
How equitable is health spending on curative services and institutional delivery in Malawi? Evidence from a quasi-longitudinal benefit incidence analysis
Authors: Rudasingwa Martin , Yeboah Edmund , Ridde Valéry , Bonnet Emmanuel , De Allegri Manuela , Muula Adamson Sinjani
Published: February 2022

Background

Malawi is one of a handful of countries that had resisted the implementation of user fees, showing a commitment to providing free healthcare to its population even before the concept of Universal Health Coverage (UHC) acquired global popularity. Several evaluations have investigated the effects of key policies, such as the essential health package or performance-based financing, in sustaining and expanding access to quality health services in the country. Understanding the distributional impact of health spending over time due to these policies has received limited attention. Our study fills this knowledge gap by assessing the distributional incidence of public and overall health spending between 2004 and 2016.

Methods

We relied on a Benefit Incidence Analysis (BIA) to measure the socioeconomic inequality of public and overall health spending on curative services and institutional delivery across different health facility typologies. We used data from household surveys and National Health Accounts. We used a concentration index (CI) to determine the health benefits accrued by each socioeconomic group.

Results

Socioeconomic inequality in both public and overall health spending substantially decreased over time, with higher inequality observed in overall spending, non-public health facilities, curative health services, and at higher levels of care. Between 2004 and 2016, the inequality in public spending on curative services decreased from a CI of 0.037 (SE 0.013) to a CI of 0.004 (SE 0.011). Whiles, it decreased from a CI of 0.084 (SE 0.014) to a CI of 0.068 (SE 0.015) for overall spending in the same period. For institutional delivery, inequality in public and overall spending decreased between 2004 and 2016 from a CI of 0.032 (SE 0.028) to a CI of -0.057 (SE 0.014) and from a CI of 0.036 (SE 0.022) to a CI of 0.028 (SE 0.018), respectively.

Conclusions

Through its free healthcare policy, Malawi has reduced socioeconomic inequality in health spending over time, but some challenges still need to be addressed to achieve a truly egalitarian health system. Our findings indicate a need to increase public funding for the health sector to ensure access to care and financial protection.
Gender equity in vision care seeking behavior among caregivers: evidence from a randomized controlled trial in rural China
Authors: Wang Huan , Cousineau Claire , Fan Yingjie , Dill Sarah-Eve , Boswell Matthew , Rozelle Scott , Ma Xiaochen
Published: February 2022

Background

Despite rising incomes and rapid economic growth, there remains a significant gender gap in health outcomes among rural children in China. This study examines whether the gender gap in child health is related to the behavior of caregivers when seeking healthcare, and whether healthcare subsidies help to bridge the gender gap in rural health outcomes.

Methods

Focusing on vision care specifically, we draw on data from a randomized controlled trial of 13,100 children in Gansu and Shaanxi provinces in China that provided subsidized eyeglasses to myopic children in one set of schools (henceforth, referred to as the treatment schools) and provided prescription information but not subsidized eyeglasses to myopic children in another set of schools (control schools).

Results

The baseline results reveal that while female students generally have worse vision than male students, they are significantly less likely than male students to be taken by their caregivers to a vision exam. The experimental results indicate, however, that caregivers respond positively to both health information and subsidized healthcare, regardless of the gender of their children. When prescription information is paired with a subsidy voucher for healthcare (a free pair of eyeglasses), the uptake rate rises dramatically.

Conclusions

The gender gap in healthcare can be minimized by implementing subsidized healthcare policies.

Trial registration

The protocol for this study was approved in full by Institutional Review Boards at Stanford University (Palo Alto, California, USA) and the Zhongshan Ophthalmic Center of Sun Yat-sen University (ZOC, Guangzhou, China). Permission was received from local Boards of Education in each region and from the principals of all schools. The principles of the Declaration of Helsinki were followed throughout. The original trial (Registration site: http://isrctn.org. Registration number: ISRCTN03252665) was designed to study the effect of providing free spectacles on children’s educational performance. The original trial was retrospectively registered on 09/25/2012.
Social and geographic inequalities in water, sanitation and hygiene access in 21 refugee camps and settlements in Bangladesh, Kenya, Uganda, South Sudan, and Zimbabwe
Authors: Calderón-Villarreal Alhelí , Schweitzer Ryan , Kayser Georgia
Published: February 2022

Introduction

Many refugees face challenges accessing water, sanitation, and hygiene (WASH) services. However, there is limited literature on WASH access for refugee populations, including for menstrual health services. Unmet WASH access needs may therefore be hidden, amplifying morbidity and mortality risks for already vulnerable refugee populations. The aim of this study was therefore to quantitatively analyze WASH access among refugee camps, with a focus on households with women of reproductive age.

Methods

This was a cross-sectional study that utilized the Standardized WASH Knowledge, Attitude and Practice (KAP) Survey. A total of 5632 household questionnaires were completed by the United Nations Refugee Agency in 2019 in 21 refugee camps and settlements in Bangladesh, Kenya, South Sudan, Uganda, and Zimbabwe. WASH access (14 items) and social and geographic stratifiers were analyzed at the household-level including the refugee camp, country of the settlement, having women of reproductive age, members with disability/elderly status, and household size. We calculated frequencies, odds ratios, and performed bivariate and multivariate analyses to measure inequalities. We developed a Female WASH Access Index to characterize WASH access for households with women of reproductive age.

Results

Most refugee households had high levels of access to improved water (95%), low levels of access to waste disposal facility (64%) and sanitation privacy (63%), and very low access to basic sanitation (30%) and hand hygiene facility (24%). 76% of households with women of reproductive age had access to menstrual health materials. WASH access indicators and the Female WASH Access Index showed large inequalities across social and geographic stratifiers. Households with disabled or elderly members, and fewer members had poorer WASH access. Households with women of reproductive age had lower access to basic sanitation.

Conclusions

Large inequalities in WASH access indicators were identified between refugee sites and across countries, in all metrics. We found high levels of access to improved water across most of the refugee camps and settlements studied. Access to basic hygiene and sanitation, sanitation privacy, waste disposal, and menstrual health materials, could be improved across refugee sites. Households with women of reproductive age, with 4+ members, and without members with disability/elderly status were associated with higher WASH access. The female WASH access index piloted here could be a useful tool to quickly summarize WASH access in households with women of reproductive age.
Multi-level policy responses to tackle socioeconomic inequalities in the incidence of COVID-19 in a European urban area
Authors: Malmusi Davide , Pasarín M. Isabel , Marí-Dell’Olmo Marc , Artazcoz Lucía , Diez Elia , Tolosa Sara , Rodríguez-Sanz Maica , Pérez Glòria , Peña-Gallardo Conchita , Borrell Carme
Published: February 2022

Background

Spain has been hit hard by COVID-19 since March 2020, especially in its metropolitan areas. We share experiences from Barcelona in measuring socioeconomic inequalities in the incidence of COVID-19 in the different waves, and in implementing coordinated and equity-oriented public health policy responses.

Methods

We collected daily data on confirmed COVID-19 cases, geocoded the address of residence to assign each case to one of the 73 neighborhoods and 1068 census tracts, and calculated the cumulative incidence of COVID-19 by neighborhood and five income groups (quintiles of census tracts) by sex across four waves of the pandemic. We adjusted hierarchical Bayesian spatial models to obtain the relative risk (RR) of cumulative incidences in each quintile compared with the richest areas. A variety of public health policies implemented to tackle the pandemic and especially these inequalities in COVID-19 incidence and vaccination are selected and described.

Results

Area-level income inequalities in the incidence of COVID-19 were present at different degree in all four waves. In the second wave (10/1/2020 to 12/6/2020), RR for the poorest income quintile census tracts compared with the richest was 1.43 (95% credible interval-CI-: 1.22–1.67) for men and 1.58 (95% CI: 1.35–1.83) for women. Later, inequalities in vaccination coverage also arose. Equity-oriented policy responses included: “health hotels” or home delivery of basic products for individuals with COVID-19 and without adequate conditions for isolation; new emergency facilities for homeless people, including those with active drug use; mass screening in high incidence areas; contingency plans for nursing homes and schools; adapting community health programs for their early reactivation; digital self-appointment support points and community vaccination days.

Conclusion

COVID-19 hit Barcelona neighborhoods unequally, with variations between waves. The rapid availability of geolocalized data and by socioeconomic level helped public authorities to implement targeted policies and collaborative interventions for the most vulnerable populations. Further studies would be needed to evaluate their impact.
Measurement properties of the Swedish clinical outcomes in routine evaluation outcome measures (CORE-OM): Rasch analysis and short version for depressed and anxious out-patients in a multicultural area
Authors: Danielsson Louise , Elfström Magnus L. , Galan Henche Javier , Melin Jeanette
Published: February 2022

Introduction

The Swedish version of the patient-reported Clinical Outcomes in Routine Evaluation Outcome Measures (CORE-OM) has demonstrated high reliability and acceptable convergent validity in explanatory factor analyses. However, the fundamental scale properties have not yet been validated according to item response theory. The aim of this study was to analyze the measurement properties of the Swedish CORE-OM in a cohort of psychiatric out-patients with depression and anxiety in a multicultural area and to explore combinations of items based on shorter versions of the scale (CORE-10, CORE-6D) to improve measurement properties.

Methods

Data from CORE-OM assessments of 337 patients were analyzed using Rasch analysis. The patients had a mean age of 30 ± 14 years, the majority were women (72%). Requirements for measurement properties were checked: overall model fit, item fit residuals, targeting, internal consistency, differential item functioning and thresholds. Sensitivity to change was also analyzed.

Results

The CORE-OM showed high internal consistency (person separation index = 0.947) and adequate targeting, but there was overall model misfit (item trait interaction χ2 = 917.53,p < 0.001), indication of local dependency, and differential item functioning in 9 items. The risk items showed problems with disordered thresholds. The emotional component of the shorter CORE-6D showed the best fit for our sample. Adding 3 items to include depressive and trauma-related content resulted in a unidimensional 8-item set with acceptable reliability, model fit, targeting and sensitivity to change.

Conclusion

For out-patients with diagnosed depression or anxiety in a multicultural area, the Swedish CORE-OM showed high internal consistency, but also validity problems. Based on the shorter CORE-6D version, a unidimensional 8-item set could be an alternative brief measure of psychological distress for this population, but further validity studies are required. Qualitative studies exploring the CORE-OM items in non-native speakers are also warranted.
Nomogram for predicting occurrence of synchronous liver metastasis in colorectal cancer: a single-center retrospective study based on pathological factors
Authors: Liu Yunxiao , Wang Yuliuming , Zhang Hao , Zheng Mingyu , Wang Chunlin , Hu Zhiqiao , Wang Yang , Xiong Huan , Hu Hanqing , Tang Qingchao , Wang Guiyu
Published: February 2022

Purpose

The purpose of this study was to explore the risk factors for synchronous liver metastasis (LM) of colorectal cancer (CRC) and to construct a nomogram for predicting the occurrence of synchronous LM based on baseline and pathological information.

Methods

The baseline and pathological information of 3190 CRC patients were enrolled in the study from the Department of Colorectal Surgery, the Second Affiliated Hospital of Harbin Medical University between 2012 and 2020. All patients were divided into development and validation cohorts with the 1:1 ratio. The characters of LM and none-LM patients in newly diagnosed colorectal cancer were utilized to explore the risk factors for synchronous LM with the univariate and multivariate logistic regression analyses. A predictive nomogram was constructed by using an R tool. In addition, receiver operating characteristic (ROC) curves was calculated to describe the discriminability of the nomogram. A calibration curve was plotted to compare the predicted and observed results of the nomogram. Decision-making curve analysis (DCA) was used to evaluate the clinical effect of nomogram.

Results

The nomogram consisted of six features including tumor site, vascular invasion (VI), T stage, N stage, preoperative CEA, and CA-199 level. ROC curves for the LM nomogram indicated good discrimination in the development (AUC = 0.885, 95% CI 0.854–0.916) and validation cohort (AUC = 0.857, 95% CI 0.821–0.893). The calibration curve showed that the prediction results of the nomogram were in good agreement with the actual observation results. Moreover, the DCA curves determined the clinical application value of predictive nomogram.

Conclusions

The pathologic-based nomogram could help clinicians to predict the occurrence of synchronous LM in postoperative CRC patients and provide a reference to perform appropriate metastatic screening plans and rational therapeutic options for the special population.
Dietary patterns are associated with improved ovarian reserve in overweight and obese women: a cross-sectional study of the Lifestyle and Ovarian Reserve (LORe) cohort
Authors: Eskew Ashley M. , Bedrick Bronwyn S. , Chavarro Jorge E. , Riley Joan K. , Jungheim Emily S.
Published: February 2022

Background

Growing evidence suggests that adherence to certain dietary patterns is associated with improved fecundity and reproductive outcomes in the general population and infertile couples assisted reproductive treatments. The objective of this study was to assess if dietary patterns are associated with ovarian reserve in reproductive age women without a history of infertility.

Methods

This was a cross-sectional study of 185 women in the Lifestyle and Ovarian Reserve (LORe) cohort. Women aged 18–44 without a history of infertility were recruited from the local community at an academic medical center. Subjects completed validated food frequency and physical activity questionnaires to assess patterns over the year prior to presentation. Dietary patterns including a Western (including meat, refined carbohydrates, high-calorie drinks), prudent (including fruits, vegetables, olive oil and nuts), fertility (lower intake of trans fat with higher intake of monounsaturated fatty acids, increased intake of plant based protein, high-fat dairy, lower glycemic load carbohydrates and supplemental iron) and profertility diet (PFD) (characterize by whole grains, soy and seafood, low pesticide residue produce, supplemental folic acid, B12 and vitamin D) were identified through principal component analysis. Main outcome measures were serum antimullerian hormone concentration (AMH) (ng/mL) and antral follicle count (AFC) obtained by transvaginal ultrasound.

Results

After stratifying by BMI, adjusting for age, smoking and physical activity, dietary patterns were not associated with ovarian reserve in normal weight women. Increased adherence to a profertility diet in overweight and obese women (BMI ≥ 25 kg/m2) was associated with a significantly higher AMH. Women in the third and fourth quartiles of PFD adherence had a mean AMH concentration of 1.45 ng/mL (95%CI 0.33–2.56, p = 0.01) and 1.67 ng/mL (95%CI 0.60–2.74, p = 0.003) higher than women in the lowest quartile respectively. The highest adherence to PFD was also associated with a higher AFC in women with a BMI ≥ 25 kg/m2 (β = 7.8, 95%CI 0.003–15.34, p < 0.05). Other common dietary patterns were not significantly associated with ovarian reserve.

Conclusions

Increased adherence to a profertility diet is associated with improved markers of ovarian reserve in overweight and obese women. These findings provide novel insight on potential modifiable lifestyle factors associated with ovarian reserve.
Growth differentiation factor-11 downregulates steroidogenic acute regulatory protein expression through ALK5-mediated SMAD3 signaling pathway in human granulosa-lutein cells
Authors: Jia Qiongqiong , Liu Boqun , Dang Xuan , Guo Yanjie , Han Xiaoyu , Song Tinglin , Cheng Jung-Chien , Fang Lanlan
Published: February 2022

Background

Growth differentiation factor-11 (GDF-11) belongs to the transforming growth factor-β (TGF-β) superfamily. To date, the expression of GDF-11 in the ovary and its role in regulating ovarian function are completely unknown. Ovarian granulosa cell-mediated steroidogenesis plays a pivotal role in maintaining normal female reproductive function. GDF-11 and GDF-8 share high sequence similarity and exhibit many similar features and functions. Steroidogenic acute regulatory protein (StAR) regulates the rate-limiting step in steroidogenesis and its expression can be downregulated by GDF-8. Polycystic ovary syndrome (PCOS) is the most common cause of female infertility. The expression levels of GDF-8 are upregulated in the human follicular fluid and granulosa-lutein (hGL) cells of PCOS patients. However, whether similar results can be observed for the GDF-11 needs to be determined.

Methods

The effect of GDF-11 on StAR expression and the underlying molecular mechanisms were explored by a series of in vitro experiments in a primary culture of hGL cells obtained from patients undergoing in vitro fertilization (IVF) treatment. Human follicular fluid samples were obtained from 36 non-PCOS patients and 36 PCOS patients. GDF-11 levels in follicular fluid were measured by ELISA.

Results

GDF-11 downregulates StAR expression, whereas the expression levels of the P450 side-chain cleavage enzyme (P450scc) and 3β-hydroxysteroid dehydrogenase (3β-HSD) are not affected by GDF-11 in hGL cells. Using pharmacological inhibitors and a siRNA-mediated approach, we reveal that ALK5 but not ALK4 mediates the suppressive effect of GDF-11 on StAR expression. Although GDF-11 activates both SMAD2 and SMAD3 signaling pathways, only SMAD3 is involved in the GDF-11-induced downregulation of StAR expression. In addition, we show that SMAD1/5/8, ERK1/2, and PI3K/AKT signaling pathways are not activated by GDF-11 in hGL cells. RT-qPCR and ELISA detect GDF-11 mRNA expression in hGL cells and GDF-11 protein expression in human follicular fluid, respectively. Interestingly, unlike GDF-8, the expression levels of GDF-11 are not varied in hGL cells and follicular fluid between non-PCOS and PCOS patients.

Conclusions

This study increases the understanding of the biological function of GDF-11 and provides important insights into the regulation of ovarian steroidogenesis.
Strengthening institutions for public health education: results of an SWOT analysis from India to inform global best practices
Authors: Miller Emily , Reddy Megha , Banerjee Preetika , Brahmbhatt Haley , Majumdar Piyusha , Mangal D. K. , Gupta Shiv Dutt , Zodpey Sanjay , Shet Anita , Schleiff Meike
Published: February 2022

Background

Developing public health educational programs that provide workers prepared to adequately respond to health system challenges is an historical dilemma. In India, the focus on public health education has been mounting in recent years. The COVID-19 pandemic is a harbinger of the increasing complexities surrounding public health challenges and the overdue need to progress public health education around the world. This paper aims to explore strengths and challenges of public health educational institutions in India, and elucidate unique opportunities to emerge as a global leader in reform.

Methods

To capture the landscape of public health training in India, we initiated a web-based desk review of available offerings and categorized by key descriptors and program qualities. We then undertook a series of in-depth interviews with representatives from a purposively sample of institutions and performed a qualitative SWOT analysis.

Results

We found that public health education exists in many formats in India. Although Master of Public Health (MPH) and similar programs are still the most common type of public health training outside of community medicine programs, other postgraduate pathways exist including diplomas, PhDs, certificates and executive trainings. The strengths of public health education institutions include research capacities, financial accessibility, and innovation, yet there is a need to improve collaborations and harmonize training with well-defined career pathways. Growing attention to the sector, improved technologies and community engagement all hold exciting potential for public health education, while externally held misconceptions can threaten institutional efficacy and potential.

Conclusions

The timely need for and attention to public health education in India present a critical juncture for meaningful reform. India may also be well-situated to contextualize and scale the types of trainings needed to address complex challenges and serve as a model for other countries and the world.
The association between health workforce availability and HIV-program outcomes in Côte d’Ivoire
Authors: Akoku Derick Akompab , Tickell Kirkby D. , Niamien Kouadio R. , Kemper Kathryn E. , Yacouba Doumbia , Kouyate Seydou , Kouassi Daniel A. , Balachandra Shirish , Swor Meghan , Luxenberg Audrey Knutson , Gloyd Steve , Kone Ahoua
Published: February 2022

Objective

The purpose of this study was to assess the distribution of HIV-program staff and the extent to which their availability influences HIV programmatic and patient outcomes.

Methods

The study was a facility level cross-sectional survey. Data from October 2018 to September 2019 were abstracted from HIV program reports conducted in 18 districts of Côte d’Ivoire. The distribution of staff in clinical, laboratory, pharmacy, management, lay, and support cadres were described across high and low antiretroviral therapy (ART) volume facilities. Non-parametric regression was used to estimate the effects of cadre categories on the number of new HIV cases identified, the number of cases initiated on ART, and the proportion of patients achieving viral load suppression.

Results

Data from 49,871 patients treated at 216 health facilities were included. Low ART volume facilities had a median of 8.1 staff-per-100 ART patients, significantly higher than the 4.4 staff-per-100 ART patients at high-ART volume facilities. One additional laboratory staff member was associated with 4.30 (IQR: 2.00–7.48,p < 0.001) more HIV cases identified and 3.81 (interquartile range [IQR]: 1.44–6.94,p < 0.001) additional cases initiated on ART. Similarly, one additional lay worker was associated with 2.33 (IQR: 1.00–3.43,p < 0.001) new cases identified and 2.24 (IQR: 1.00–3.31,p < 0.001) new cases initiated on ART. No cadres were associated with viral suppression.

Conclusions

HCWs in the laboratory and lay cadre categories were associated with an increase in HIV-positive case identification and initiation on ART. Our findings suggest that allocation of HCWs across health facilities should take into consideration the ART patient volume. Overall, increasing investment in health workforce is critical to achieve national HIV goals and reaching HIV epidemic control.
Understanding the factors affecting attrition and intention to leave of health extension workers: a mixed methods study in Ethiopia
Authors: Tekle Merhawi Gebremedhin , Wolde Habtamu Milkias , Medhin Girmay , Teklu Alula M. , Alemayehu Yibeltal Kiflie , Gebre Esie Gebrewahd , Bekele Frehiwot , Arora Nikita
Published: February 2022

Background

The Health Extension Program (HEP) is Ethiopia’s flagship community health program, launched in 2003. Health Extension Workers (HEWs) are key vehicles for the delivery of the HEP. While it is believed that there is high attrition among HEWs, the magnitude of or reasons for attrition is unknown. Their intention to leave their jobs in the next 5 years has also never been investigated on a national scale. This study aimed to assess the magnitude of, and factors affecting HEWs’ attrition and intention to leave in Ethiopia.

Methods

The study used mixed methods to address the research objectives. Using stratified random sampling and regions as strata, 85 districts from nine regions were randomly selected in Ethiopia. Within each study district, six kebeles (village clusters) were randomly selected, and all HEWs working in these kebeles were interviewed to capture their 5-year intention to leave. The study team developed a data-extraction tool for a rapid review of district-level documents covering the period June 30, 2004 through June 30, 2019 to gather their attrition figures. We used survival analysis to model attrition data and checked model goodness-of-fit using the Cox–Snell residual test. We additionally collected qualitative data from HEWs who had left their positions.

Results

The attrition of HEWS over the lifespan of the HEP was 21.1% (95% CI 17.5–25.3%), and the median time to exit from HEWs workforce was 5.8 years. The incidence rate was 3.1% [95% CI 2.8–3.4]. The risk of attrition was lower amongst HEWs with level four certifications, with children, and among those working in urban settings. By contrast, HEWs who were not certified with a certificate of competency (COC), who were deployed after 2008, and those who were diploma/degree holders were more likely to exit the HEWs workforce. The magnitude of intention to leave was 39.5% (95% CI 32.5–47%) and the primary reasons to leave were low incentives, dearth of career development opportunities (50.8%), high workload (24.2%), and other psychosocial factors (25%).

Conclusion

Although the magnitude of attrition is not worryingly high, we see high magnitude in HEWs’ intention to leave, indicating a dissatisfied workforce. Multiple factors have contributed to attrition and intention to leave, the prevalence of many of which can be reduced to fit the needs of this workforce and to retain them for the sustained delivery of primary healthcare in the country. Ensuring HEWs’ job satisfaction is important and linked with their career development and potentially higher rates of retention.
Future health spending forecast in leading emerging BRICS markets in 2030: health policy implications
Authors: Jakovljevic Mihajlo , Lamnisos Demetrios , Westerman Ronny , Chattu Vijay Kumar , Cerda Arcadio
Published: February 2022

Background

The leading emerging markets of Brazil, Russia, India, China and South Africa (BRICS) are increasingly shaping the landscape of the global health sector demand and supply for medical goods and services. BRICS’ share of global health spending and future projections will play a prominent role during the 2020s. The purpose of the current research was to examine the decades-long underlying historical trends in BRICS countries’ health spending and explore these data as the grounds for reliable forecasting of their health expenditures up to 2030.

Methods

BRICS’ health spending data spanning 1995–2017 were extracted from the Institute for Health Metrics and Evaluation (IHME) Financing Global Health 2019 database. Total health expenditure, government, prepaid private and out-of-pocket spending per capita and gross domestic product (GDP) share of total health spending were forecasted for 2018–2030. Autoregressive integrated moving average (ARIMA) models were used to obtain future projections based on time series analysis.

Results

Per capita health spending in 2030 is projected to be as follows: Brazil, $1767 (95% prediction interval [PI] 1615, 1977); Russia, $1933 (95% PI 1549, 2317); India, $468 (95% PI 400.4, 535); China, $1707 (95% PI 1079, 2334); South Africa, $1379 (95% PI 755, 2004). Health spending as a percentage of GDP in 2030 is projected as follows: Brazil, 8.4% (95% PI 7.5, 9.4); Russia, 5.2% (95% PI 4.5, 5.9); India, 3.5% (95% PI 2.9%, 4.1%); China, 5.9% (95% PI 4.9, 7.0); South Africa, 10.4% (95% PI 5.5, 15.3).

Conclusions

All BRICS countries show a long-term trend towards increasing their per capita spending in terms of purchasing power parity (PPP). India and Russia are highly likely to maintain stable total health spending as a percentage of GDP until 2030. China, as a major driver of global economic growth, will be able to significantly expand its investment in the health sector across an array of indicators. Brazil is the only large nation whose health expenditure as a percentage of GDP is about to contract substantially during the third decade of the twenty-first century. The steepest curve of increased per capita spending until 2030 seems to be attributable to India, while Russia should achieve the highest values in absolute terms. Health policy implications of long-term trends in health spending indicate the need for health technology assessment dissemination among the BRICS ministries of health and national health insurance funds. Matters of cost-effective allocation of limited resources will remain a core challenge in 2030 as well.
Rapid research response to the COVID-19 pandemic: perspectives from a National Institute for Health Biomedical Research Centre
Authors: Henderson Lorna R. , McShane Helen , Kiparoglou Vasiliki
Published: February 2022

With over 5 million COVID-19 deaths at the time of writing, the response of research leaders was and is critical to developing treatments to control the global pandemic. As clinical research leaders urgently repurposed existing research programmes and resources towards the COVID-19 pandemic, there is an opportunity to reflect on practices observed in Biomedical Research Centre (BRC) settings. BRCs are partnerships between leading National Health Service organizations and universities in England conducting translational research for patient benefit funded by the National Institute for Health Research (NIHR). Oxford BRC-supported researchers have led the rapid set-up of numerous COVID-19 research studies at record speed with global impact. However, the specific contribution of BRCs to the COVID-19 pandemic in the literature is sparse. Firstly, we reflect on the strategic work of clinical research leaders, creating resilient NIHR research infrastructure to facilitate rapid COVID-19 research. Secondly, we discuss how COVID-19 rapid research exemplars supported by Oxford BRC illustrate “capacity”, “readiness” and “capability” at an organizational and individual level to respond to the global pandemic. Rapid response research in turbulent environments requires strategic organizational leadership to create resilient infrastructure and resources. The rapid research exemplars from the Oxford BRC illustrate capability and capacity at an organizational and individual level in a dynamic environment to respond during the COVID-19 public health challenge. This response was underpinned by swift adaptation and repurposing of existing research resources and expertise by the Oxford BRC to deliver rapid research to address different aspects of COVID-19.
Estimating district HIV prevalence in Zambia using small-area estimation methods (SAE)
Authors: Mweemba Chris , Hangoma Peter , Fwemba Isaac , Mutale Wilbroad , Masiye Felix
Published: February 2022

Background

The HIV/AIDS pandemic has had a very devastating impact at a global level, with the Eastern and Southern African region being the hardest hit. The considerable geographical variation in the pandemic means varying impact of the disease in different settings, requiring differentiated interventions. While information on the prevalence of HIV at regional and national levels is readily available, the burden of the disease at smaller area levels, where health services are organized and delivered, is not well documented. This affects the targeting of HIV resources. There is need, therefore, for studies to estimate HIV prevalence at appropriate levels to improve HIV-related planning and resource allocation.

Methods

We estimated the district-level prevalence of HIV using Small-Area Estimation (SAE) technique by utilizing the 2016 Zambia Population-Based HIV Impact Assessment Survey (ZAMPHIA) data and auxiliary data from the 2010 Zambian Census of Population and Housing and the HIV sentinel surveillance data from selected antenatal care clinics (ANC). SAE models were fitted in R Programming to ascertain the best HIV predicting model. We then used the Fay–Herriot (FH) model to obtain weighted, more precise and reliable HIV prevalence for all the districts.

Results

The results revealed variations in the district HIV prevalence in Zambia, with the prevalence ranging from as low as 4.2% to as high as 23.5%. Approximately 32% of the districts (n = 24) had HIV prevalence above the national average, with one district having almost twice as much prevalence as the national level. Some rural districts have very high HIV prevalence rates.

Conclusions

HIV prevalence in Zambian is highest in districts located near international borders, along the main transit routes and adjacent to other districts with very high prevalence. The variations in the burden of HIV across districts in Zambia point to the need for a differentiated approach in HIV programming within the country. HIV resources need to be prioritized toward districts with high population mobility.
CRISPR screening of E3 ubiquitin ligases reveals Ring Finger Protein 185 as a novel tumor suppressor in glioblastoma repressed by promoter hypermethylation and miR-587
Authors: Lin Kun , Shen Shang-Hang , Lu Feng , Zheng Pengfeng , Wu Shizhong , Liao Jingwei , Jiang Xiaohang , Zeng Guangming , Wei De
Published: February 2022

Glioblastoma (GBM) is the most common and aggressive malignant primary brain tumor. E3 ligases play important functions in glioma pathogenesis. CRISPR system offers a powerful platform for genome manipulation, while the screen of E3 ligases in GBM still remains to be explored. Here, we first constructed an E3 ligase small guide RNA (sgRNAs) library for glioma cells growth screening. After four passages, 299 significantly enriched or lost genes (SELGs) were compared with the initial state. Then the clinical significance of SELGs were validated and analyzed with TCGA glioblastoma and CGGA datasets. As RNF185 showed lost signal, decreased expression and favorable prognostic significance, we chose RNF185 for functional analysis. In vitro overexpressed cellular phenotype showed that RNF185 was a tumor suppressor in two glioma cell lines. Finally, the molecular mechanism of decreased RNF185 expression was investigated and increased miR-587 expression and DNA hypermethylation was evaluated. This study would provide a link between the molecular basis and glioblastoma pathogenesis, and a novel perspective for glioblastoma treatment.
Influence of education on sexual and reproductive health service utilization for persons with disabilities in nationwide Bangladesh: an explanatory sequential mixed-methods study
Authors: Du Katherine Coral , Mohosin Arifa Bente , Amin Amina , Hasan Md Tanvir
Published: February 2022

Background

Persons with disabilities comprise more than one billion people in the world, yet they are one of the most discriminated groups and face significant health disparities. Particularly in developing countries, which contain 80% of the entire population with disabilities, these individuals experience major barriers in accessing sexual and reproductive health (SRH) services. Education is an important factor that greatly affects individuals’ SRH service utilization. Hence, we sought to investigate the relationship between education and SRH service utilization for persons with disabilities in Bangladesh.

Methods

Using an explanatory sequential mixed-methods design, a total of 5000 persons with disabilities were surveyed for the quantitative component and 15 mini-ethnographic case studies were conducted with persons with disabilities for the qualitative component. Chi-squared tests and logistic regression analyses were performed on the survey data, while the qualitative interviews were coded and their SRH themes synthesized accordingly.

Results

Our quantitative findings show that education statistically significantly increases persons with disabilities’ SRH service utilization of antenatal care, delivery care, postnatal care, and family planning (P < 0.05). Interestingly, for persons with disabilities, primary education shows increased adjusted odds of family planning use but is likely not enough to increase antenatal care, delivery care, or postnatal care use; secondary or post-secondary education may be required to improve utilization of these latter services. Qualitative findings support the association between higher education levels and greater SRH service use. Persons with disabilities of lower educational attainment held misinformation and distrust in SRH services and experienced mistreatment by SRH healthcare providers, discouraging them from seeking future SRH services.

Conclusions

We report that higher formal education level is associated with greater SRH service use for persons with disabilities in Bangladesh. Formally educating persons with disabilities expands their SRH knowledge and familiarity with SRH services, as well as leads to more economic opportunities so they can afford SRH services. Increasing formal education levels for persons with disabilities, paired with integrating comprehensive sexuality education (CSE) in their schools, will likely help close the gap in SRH health disparities for this vulnerable population.