Rural‒urban disparities in household catastrophic health expenditure in Bangladesh: a multivariate decomposition analysis.

BACKGROUND: Rural‒urban disparity in catastrophic healthcare expenditure (CHE) is a well-documented challenge in low- and middle-income countries, including Bangladesh, limiting financial protection and hindering the achievement of the Universal Health Coverage target of the United Nations Sustainable Development Goals. However, the factors driving this divide remain poorly understood. Therefore, this study aims to identify the key determinants of the rural‒urban disparity in CHE incidence in Bangladesh and their changes over time. METHODS: We used nationally representative data from the latest three rounds of the Bangladesh Household Income and Expenditure Survey (2005, 2010, and 2016). CHE incidence among households seeking healthcare was measured using the normative food, housing, and utilities method. To quantify covariate contributions to the rural‒urban CHE gap, we employed the Oaxaca-Blinder multivariate decomposition approach, adapted by Powers et al. for nonlinear response models. RESULTS: CHE incidence among rural households increased persistently during the study period (2005: 24.85%, 2010: 25.74%, 2016: 27.91%) along with a significant (p-value ≤ 0.01) rural‒urban gap (2005: 9.74%-points, 2010: 13.94%-points, 2016: 12.90%-points). Despite declining over time, substantial proportions of CHE disparities (2005: 87.93%, 2010: 60.44%, 2016: 61.33%) are significantly (p-value ≤ 0.01) attributable to endowment differences between rural and urban households. The leading (three) covariate categories consistently contributing significantly (p-value ≤ 0.01) to the CHE gaps were composition disparities in the lowest consumption quintile (2005: 49.82%, 2010: 36.16%, 2016: 33.61%), highest consumption quintile (2005: 32.35%, 2010: 15.32%, 2016: 18.39%), and exclusive reliance on informal healthcare sources (2005: -36.46%, 2010: -10.17%, 2016: -12.58%). Distinctively, the presence of chronic illnesses in households emerged as a significant factor in 2016 (9.14%, p-value ≤ 0.01), superseding the contributions of composition differences in household heads with no education (4.40%, p-value ≤ 0.01) and secondary or higher education (7.44%, p-value ≤ 0.01), which were the fourth and fifth significant contributors in 2005 and 2010. CONCLUSIONS: Rural‒urban differences in household economic status, educational attainment of household heads, and healthcare sources were the key contributors to the rural‒urban CHE disparity between 2005 and 2016 in Bangladesh, with chronic illness emerging as a significant factor in the latest period. Closing the rural‒urban CHE gap necessitates strategies that carefully address rural‒urban variations in the characteristics identified above.

Fabrication of Highly Sensitive and Selective Nitrite Colorimetric Sensor Based on the Enhanced Peroxidase Mimetic Activity of Using Acetic Acid Capped Zinc Oxide Nanosheets.

Nitrite ions (NO2-), as one of the leading type-A inorganic-anion, showing significant-effects in the aquatic environment and also to humans health. Whereas, the higher uptake causes detrimental threat to human health leading to various chronic diseases, thus demanding efficient, reliable and convenient method for its monitoring. For this purpose, in the present research study we have fabricated the mimetic nonozyme like catalyst based colorimetric nitrite sensor. The acetic acid capped Zinc Oxide (ZnO) nanosheets (NSs) were introduce as per-oxidase mimetic like catalyst which shows high efficiency towards the oxidative catalysis of colorless tetramethylbenzidine (TMB) to oxidized-TMB (blue color) in the presence of Hydrogen-peroxide (H2O2). The present nitrite ions will stimulate the as formed oxidized-TMB (TMBox), and will caused diazotization reaction (diazotized-TMBox), which will not only decreases the peak intensity of UV-visible peak of TMBox at 652 nm but will also produces another peak at 446 nm called as diazotized-TMBox peak, proving the catalytic reaction between the nitrite ions and TMBox. Further, the prepared colorimetric sensor exhibits better sensitivity with a wider range of concentration (1 × 10-3-4.50 × 10-1 µM), lowest limit of detection (LOD) of 0.22 ± 0.05 nM and small limit of quantification (LOQ) 0.78 ± 0.05 nM having R2 value of 0.998. Further, the colorimetric sensor also manifest strong selectivity towards NO2- as compared to other interference in drinking water system. Resultantly, the prepared sensor with outstanding repeatability, stability, reproducibility, re-usability and its practicability in real water samples also exploit its diverse applications in food safety supervision and environmental monitoring.

Patterns and determinants of healthcare utilization and medication use before and during the COVID-19 crisis in Afghanistan, Bangladesh, and India.

BACKGROUND: COVID-19 rapidly spread through South Asian countries and overwhelmed the health systems that were unprepared for such an outbreak. Evidence from high-income countries showed that COVID-19 impacted healthcare utilization, including medication use, but empirical evidence is lacking in South Asia. This study aimed to investigate the effect of COVID-19 on healthcare utilization and medication use in South Asia. METHOD: The current study used longitudinal data from the 'Premise Health Service Disruption Survey' 2020 and 2021. The countries of interest were limited to Afghanistan, Bangladesh, and India. In these surveys, data related to healthcare utilization and medication use were collected for three-time points; 'Pre-COVID phase', 'Initial phase of COVID-19 outbreak', and 'One year of COVID-19 outbreak'. Generalized estimating equation (GEE) along with McNemar's test, Kruskal-Wallis test and χ2 test were applied in this study following the conceptualization of Andersen's healthcare utilization model. RESULT: The use of healthcare and medication was unevenly impacted by the COVID-19 epidemic in Afghanistan, Bangladesh, and India. Immediately after the COVID-19 outbreak, respondents in Bangladesh reported around four times higher incomplete healthcare utilization compared to pre-COVID phase. In contrast, respondents in Afghanistan reported lower incomplete utilization of healthcare in a similar context. In the post COVID-19 outbreak, non-adherence to medication use was significantly higher in Afghanistan (OR:1.7; 95%CI:1.6,1.9) and India (OR:1.3; 95%CI:1.1,1.7) compared to pre-COVID phase. Respondents of all three countries who sought assistance to manage non-communicable diseases (NCDs) had higher odds (Afghanistan: OR:1.5; 95%CI:1.3,1.8; Bangladesh: OR: 3.7; 95%CI:1.9,7.3; India: OR: 2.3; 95% CI: 1.4,3.6) of non-adherence to medication use after the COVID-19 outbreak compared to pre-COVID phase. CONCLUSION: The present study documented important evidence of the influence of COVID-19 epidemic on healthcare utilization and medication use in three countries of South Asia. Lessons learned from this study can feed into policy responses to the crisis and preparedness for future pandemics.

A single-centre RetrospeCtive sTudy Investigating patient-reported outcomeS of extended dressing wear time for incisional healing following orthopaedic surgery: the ARCTIS study.

OBJECTIVE: Orthopaedic surgery is an effective intervention for treating the symptoms of degenerative joint disease or osteoarthritis (OA). Frequent wound dressing changes, unless clinically indicated, can disrupt the healing process and increase the occurrence of incision site contamination. Protection from contamination is critical for surgical incisions and, therefore, undisturbed wound healing (UWH) in surgical wound management is vital. This article describes a retrospective study reporting the clinical performance of a self-adherent, absorbent postoperative dressing, with a focus on dressing wear time. METHOD: A single-centre, retrospective electronic medical record review of a convenience sample of adult patients treated with a dressing (Mepilex Border Post Op; Mölnlycke, Sweden) following elective hip or knee replacement was undertaken. Data relating to dressing wear time, rationale for dressing changes and patient-reported outcomes were extracted from a mobile health application moveUP Therapy (moveUP NV, Belgium). Health-related quality of life assessment was conducted using the EQ-5D-5L questionnaire and orthopaedic-specific quality of life (QoL) indicator tools. RESULTS: Of the 558 records reviewed, 151 respondents (27.1%) reported outcomes relating to dressing wear time and frequency of dressing change. The average wear time of the first dressing was 13.6 days (second dressing: 5.3 days). The proportion of patients who wore the first dressing for 1-7 days, 8-13 days and for ≥14 days was 17.2%, 13.2% and 69.5%, respectively. Data from the completed questionnaires revealed improvement in QoL over time. CONCLUSION: The results of this study are a good indicator of the suitability of the postoperative dressing for a 14-day wear time, in line with the principles of UWH.

Comparison of inequality in utilization of postnatal care services between Bangladesh and Pakistan: Evidence from the Demographic and Health Survey 2017-2018.

BACKGROUND: Inequality in postnatal care (PNC) has remained a challenge in many low- and middle-income countries, like Bangladesh and Pakistan. The study examines within-country and between-country inequality in utilizing PNC services for Bangladesh and Pakistan. METHODS: The study used the latest Demographic and Health Survey (DHS, 2017-2018) datasets of Bangladesh and Pakistan for women aged 15-49 years who had given at least one live birth in the three years preceding the survey. As outcome variables, three PNC service indicators were considered: PNC check of women, PNC check of newborns, and adequate PNC content of newborns. Concentration curves and equiplots were constructed to visually demonstrate inequality in PNC services. For ordered equity strata with more than two categories, the relative concentration index (RCI), absolute concentration index (ACI), and slope index of inequality (SII) were calculated to measure inequalities in the utilization of PNC services. For two categories equity strata, rate ratio (RR) and rate difference (RD) were calculated. RESULTS: In Bangladesh, the level of inequality was high and almost the same for the PNC check of women and newborns based on women's education (PNC women- RCI: 0.404, ACI: 0.403, SII: 0.624; and PNC newborn- RCI: 0.402, ACI: 0.402, SII: 0.622), wealth (PNC women- RCI: 0.448, ACI: 0.448, SII: 0.643; and PNC newborn- 0.441, ACI: 0.441, SII: 0.633), and number of ANC visits (PNC women- RCI: 0.329, ACI: 0.329, SII: 0.595; and PNC newborn- RCI: 0.329, ACI: 0.329, SII: 0.594). In Pakistan, the level of inequality was higher for the PNC check of women among all PNC services based on women's education (ACI: 0.388 and SII: 0.676) and wealth (ACI: 0.397 and SII: 0.598). For Bangladesh and Pakistan, RR values (2.114 and 3.873, respectively) indicated greater media exposure-related inequality in adequate PNC content of newborns. Inequality in facility delivery was highest for PNC checks of women and newborns in Bangladesh (PNC women- RD: 0.905, PNC newborn- RD: 0.900) and Pakistan (PNC women- RD: 0.726, PNC newborn-RD: 0.743). CONCLUSION: Inequality was higher in Bangladesh than in Pakistan for PNC checks of women and newborns based on wealth, media exposure, and mode of delivery. For adequate PNC content of newborns, inequality was greater in Pakistan than in Bangladesh. Country-specific customized policies would better minimize the gap between the privileged and underprivileged groups and reduce inequality.

Economic burden of non-communicable diseases on households in Nigeria: evidence from the Nigeria living standard survey 2018-19.

BACKGROUND: The importance of non-communicable diseases (NCDs) in Nigeria is reflected in their growing burden that is fast overtaking that of infectious diseases. As most NCD care is paid for through out-of-pocket (OOP) expenses, and NCDs tend to cause substantial income losses through chronic disabilities, the rising NCD-related health burden may also be economically detrimental. Given the lack of updated national-level evidence on the economic burden of NCDs in Nigeria, this study aims to produce new evidence on the extent of financial hardship experienced by households with NCDs in Nigeria due to OOP expenditure and productivity loss. METHODS: This study analysed cross-sectional data from the most recent round (2018-19) of the Nigeria Living Standard Survey (NLSS). Household-level health and consumption data were used to estimate catastrophic health expenditure (CHE) and impoverishing effects due to OOP health spending, using a more equitable method recently developed by the World Health Organization European region in 2018. The productivity loss by individuals with NCDs was also estimated from income and work-time loss data, applying the input-based human capital approach. RESULTS: On average, a household with NCDs spent ₦ 122,313.60 or $ 398.52 per year on NCD care, representing 24% of household food expenditure. The study found that OOP on cancer treatment, mental problems, and renal diseases significantly contribute to the cost of NCD care. The OOP expenditure led to catastrophic and impoverishing outcomes for households. The estimations showed that about 30% of households with NCDs experienced CHE in 2018, using the WHO Europe method at the 40% threshold. The study also found that the cost of NCD medications was a significant driver of CHE among NCD-affected households. The results showed heterogeneity in CHE and impoverishment across states and geographical regions in Nigeria, with a higher concentration in rural and North East geopolitical locations. The study also found that 20% of NCD-affected households were impoverished or further impoverished by OOP payment, and another 10% were on the verge of impoverishment. The results showed a negligible rate of unmet needs among households with NCDs. CONCLUSIONS: The study highlights the significant effect of NCDs on Nigerian households and the need for effective policy interventions to address this challenge, particularly among the poor and vulnerable.

Inequity in psychiatric healthcare use in Australia.

BACKGROUND: Despite recent substantial mental healthcare reforms to increase the supply of healthcare, mental health inequality in Australia is rising. Understanding of the level of inequity (unmet need gap) in psychiatric service use in Australia's mixed public-private health care system is lacking. OBJECTIVE: To present a novel method to measure inequity in the delivery of psychiatric care. METHODS: Data came from wave 9 (year 2009, n = 11,563) and wave 17 (year 2017, n = 16,194) of the Household, Income and Labour Dynamics in Australia (HILDA) survey. Multiple logistic regression was employed to estimate the psychiatric care utilisation compared to its need and the Gini index was used to estimate the standardised distribution of utilisation to measure the extent of inequity. RESULTS: The results show the inequity indices (need-standardised Gini) in psychiatric care utilisation were significant and found to be 0.066 and 0.096 in 2009 and 2017, respectively, for all individuals. In 2009, the inequity indices were found to be 0.051 and 0.078 for males and females, respectively, and 0.045 and 0.068 for rural and urban residents, respectively. In 2017, the indices were calculated to be 0.081 and 0.109 for males and females, respectively, and 0.086 and 0.097 for rural and urban residents, respectively. CONCLUSIONS: This study showed a marked increase in unmet needs in psychiatric care utilisation since 2009. There is a greater need to develop policies to improve equity in psychiatric care utilisation in Australia.

Comparison of inequality in utilization of maternal healthcare services between Bangladesh and Pakistan: evidence from the demographic health survey 2017-2018.

BACKGROUND: Inequality in maternal health has remained a challenge in many low-income countries, like Bangladesh and Pakistan. The study examines within-country and between-country inequality in utilization of maternal healthcare services for Bangladesh and Pakistan. METHODS: The study used the latest Demographic Health Surveys (DHS, 2017-2018) datasets of Bangladesh and Pakistan for women aged 15-49 years who had given at least one live birth in three years preceding the survey. Equity strata were identified from the literature and conformed by binary logistic regressions. For ordered equity strata with more than two categories, the relative concentration index (RCI), absolute concentration index (ACI) and the slope index of inequality (SII) were calculated to measure inequalities in the utilization of four maternal healthcare services. For two-categories equity strata, rate ratio (RR), and rate difference (RD) were calculated. Concentration curves and equiplots were constructed to visually demonstrate inequality in maternal healthcare services. RESULTS: In Bangladesh, there was greater inequality in skilled birth attendance (SBA) based on wealth (RCI: 0.424, ACI: 0.423, and SII: 0.612), women's education (RCI: 0.380, ACI: 0.379 and SII: 0.591), husband's education (RCI: 0.375, ACI: 0.373 and SII: 0.554) and birth order (RCI: - 0.242, ACI: - 0.241, and SII: -0.393). According to RCI, ACI, and SII, there was inequality in Pakistan for at least four ANC visits by the skilled provider based on wealth (RCI: 0.516, ACI: 0.516 and SII: 0.738), women's education (RCI: 0.470, ACI: 0.470 and SII: 0.757), and husband's education (RCI: 0.380, ACI: 0.379 and SII: 0.572). For Bangladesh, the RR (1.422) and RD (0.201) imply more significant urban-rural inequality in SBA. In Pakistan, urban-rural inequality was greater for at least four ANC visits by the skilled provider (RR: 1.650 and RD 0.279). CONCLUSION: Inequality in maternal healthcare is greater among the underprivileged group in Pakistan than in Bangladesh. In Bangladesh, the SBA is the most inequitable maternal healthcare, while for Pakistan it is at least four ANC visits by the skilled provider. Customized policies based on country context would be more effective in bridging the gap between the privileged and underprivileged groups.

Identification of Four Novel Candidate Genes for Non-syndromic Intellectual Disability in Pakistani Families.

Intellectual disability, a genetically and clinically varied disorder and is a significant health problem, particularly in less developed countries due to larger family size and high ratio of consanguineous marriages. In the current genetic study, we investigate and find the novel disease causative factors in the four Pakistani families with severe type of non-syndromic intellectual disability. For genetic analysis whole-exome sequencing (WES) and Sanger sequencing was performed. I-TASSER and Cluspro tools were used for Protein modeling and Protein-protein docking. Sanger sequencing confirms the segregation of novel homozygous variants in all the families i.e., c.245 T > C; p.Leu82Pro in SLC50A1 gene in family 1, missense variant c.1037G > A; p.Arg346His in TARS2 gene in family 2, in family 3 and 4, nonsense mutation c.234G > A; p.Trp78Term and missense mutation c.2200G > A; p.Asp734Asn in TBC1D3 and ANAPC2 gene, respectively. In silico functional studies have found the drastic effect of these mutations on protein structure and its interaction properties. Substituted amino acids were highly conserved and present on highly conserved region throughout the species. The discovery of pathogenic variants in SLC50A1, TARS2, TBC1D1 and ANAPC2 shows that the specific pathways connected with these genes may be important in cognitive impairment. The decisive role of pathogenic variants in these genes cannot be determined with certainty due to lack of functional data. However, exome sequencing and segregation analysis of all filtered variants revealed that the currently reported variants were the only variations from the respective families that segregated with the phenotype in the family.

Financial risk protection against noncommunicable diseases: trends and patterns in Bangladesh.

BACKGROUND: Demographic and epidemiological transitions are changing the disease burden from infectious to noncommunicable diseases (NCDs) in low- and middle-income countries, including Bangladesh. Given the rising NCD-related health burdens and growing share of household out-of-pocket (OOP) spending in total health expenditure in Bangladesh, we compared the country's trends and socioeconomic disparities in financial risk protection (FRP) among households with and without NCDs. METHODS: We used data from three recent waves of the Bangladesh Household Income and Expenditure Survey (2005, 2010, and 2016) and employed the normative food, housing (rent), and utilities method to measure the levels and distributions of catastrophic health expenditure (CHE) and impoverishing effects of OOP health expenditure among households without NCDs (i.e. non-NCDs only) and with NCDs (i.e. NCDs only, and both NCDs and non-NCDs). Additionally, we examined the incidence of forgone care for financial reasons at the household and individual levels. RESULTS: Between 2005 and 2016, OOP expenses increased by more than 50% across all households (NCD-only: USD 95.6 to 149.3; NCD-and-non-NCD: USD 89.5 to 167.7; non-NCD-only: USD 45.3 to 73.0), with NCD-affected families consistently spending over double that of non-affected households. Concurrently, CHE incidence grew among NCD-only families (13.5% to 14.4%) while declining (with fluctuations) among non-NCD-only (14.4% to 11.6%) and NCD-and-non-NCD households (12.9% to 12.2%). Additionally, OOP-induced impoverishment increased among NCD-only and non-NCD-only households from 1.4 to 2.0% and 1.1 to 1.5%, respectively, affecting the former more. Also, despite falling over time, NCD-affected individuals more frequently mentioned prohibiting treatment costs as the reason for forgoing care than the non-affected (37.9% vs. 13.0% in 2016). The lowest quintile households, particularly those with NCDs, consistently experienced many-fold higher CHE and impoverishment than the highest quintile. Notably, CHE and impoverishment effects were more pronounced among NCD-affected families if NCD-afflicted household members were female rather than male, older people, or children instead of working-age adults. CONCLUSIONS: The lack of FRP is more pronounced among households with NCDs than those without NCDs. Concerted efforts are required to ensure FRP for all families, particularly those with NCDs.

Financial risk protection from out-of-pocket health spending in low- and middle-income countries: a scoping review of the literature.

BACKGROUND: Financial risk protection (FRP), defined as households' access to needed healthcare services without experiencing undue financial hardship, is a critical health systems target, particularly in low- and middle-income countries (LMICs). Given the remarkable growth in FRP literature in recent times, we conducted a scoping review of the literature on FRP from out-of-pocket (OOP) health spending in LMICs. The objective was to review current knowledge, identify evidence gaps and propose future research directions. METHODS: We followed the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) 2020 guidelines to conduct this scoping review. We systematically searched PubMed, Scopus, ProQuest and Web of Science in July 2021 for literature published since 1 January 2015. We included empirical studies that used nationally representative data from household surveys to measure the incidence of at least one of the following indicators: catastrophic health expenditure (CHE), impoverishment, adoption of strategies to cope with OOP expenses, and forgone care for financial reasons. Our review covered 155 studies and analysed the geographical focus, data sources, methods and analytical rigour of the studies. We also examined the level of FRP by disease categories (all diseases, chronic illnesses, communicable diseases) and the effect of health insurance on FRP. RESULTS: The extant literature primarily focused on India and China as research settings. Notably, no FRP study was available on chronic illness in any low-income country (LIC) or on communicable diseases in an upper-middle-income country (UMIC). Only one study comprehensively measured FRP by examining all four indicators. Most studies assessed (lack of) FRP as CHE incidence alone (37.4%) or as CHE and impoverishment incidence (39.4%). However, the LMIC literature did not incorporate the recent methodological advances to measure CHE and impoverishment that address the limitations of conventional methods. There were also gaps in utilizing available panel data to determine the length of the lack of FRP (e.g. duration of poverty caused by OOP expenses). The current estimates of FRP varied substantially among the LMICs, with some of the poorest countries in the world experiencing similar or even lower rates of CHE and impoverishment compared with the UMICs. Also, health insurance in LMICs did not consistently offer a higher degree of FRP. CONCLUSION: The literature to date is unable to provide a reliable representation of the actual level of protection enjoyed by the LMIC population because of the lack of comprehensive measurement of FRP indicators coupled with the use of dated methodologies. Future research in LMICs should address the shortcomings identified in this review.

Recycling of silicon-rich agro-wastes by their combined application with phosphate solubilizing microbe to solubilize the native soil phosphorus in a sub-tropical Alfisol.

It is imperative to find suitable strategies to utilize the native soil phosphorus (P), as natural rock phosphate deposits are at a verge of depletion. We explored two such cost-effective and eco-friendly strategies for native soil P solubilization: silicon (Si)-rich agro-wastes (as Si source) and phosphate solubilizing microorganism (PSM). An incubation study was conducted in a sub-tropical Alfisol for 90 days at 25 °C under field capacity moisture. A factorial completely randomized design with 3 factors, namely: Si sources (three levels: sugarcane bagasse ash, rice husk ash, and corn cob ash), PSM (two levels: without PSM, and with PSM); and Si doses [three levels: no Si (Si0), 125 (Si125) and 250 (Si250) mg Si kg-1 soil] was followed. The PSM increased solution P and soluble Si level by ∼22.2 and 1.88%, respectively, over no PSM; whereas, Si125 and Si250 increased solution P by ∼60.4 and 77.1%, as well as soluble Si by ∼41.5 and 55.5%, respectively, over Si0. Also, interaction of PSM × Si doses was found significant (P<0.05). Activities of soil enzymes (dehydrogenase, acid phosphatase) and microbial biomass P also increased significantly both with PSM and Si application. Overall, PSM solubilized ∼4.18 mg kg-1 of inorganic P and mineralized ∼5.92 mg kg-1 of organic P; whereas, Si125 and Si250 solubilized ∼3.85 and 5.72 mg kg-1 of inorganic P, and mineralized ∼4.15 and 5.37 mg kg-1 of organic P, respectively. Path analysis revealed that inorganic P majorly contributed to total P solubilization; whereas, soluble and loosely bound, iron bound and aluminium bound P significantly influenced the inorganic P solubilization. Thus, utilization of such wastes as Si sources will not only complement the costly P fertilizers, but also address the waste disposal issue in a sustainable manner.

Gelatin-methacryloyl hydrogel based in vitro blood-brain barrier model for studying breast cancer-associated brain metastasis.

Breast cancer is one of the leading causes of brain metastasis. Metastasis to the brain occurs if cancer cells manage to traverse the 'blood-brain barrier' (BBB), which is a barrier with a very tight junction (TJ) of endothelial cells between blood circulation and brain tissue. It is highly important to develop novel in vitro BBB models to investigate breast cancer metastasis to the brain to facilitate the screening of chemotherapeutic agents against it. We herein report the development of gelatin methacryloyl (GelMA) modified transwell insert based BBB model composed of endothelial and astrocyte cell layers for testing the efficacy of anti-metastatic agents against breast cancer metastasis to the brain. We characterized the developed model for the morphology and in vitro breast cancer cell migration. Furthermore, we investigated the effect of cisplatin, a widely used chemotherapeutic agent, on the migration of metastatic breast cancer cells using the model. Our results showed that breast cancer cells migrate across the developed BBB model. Cisplatin treatment inhibited the migration of cancer cells across the model. Findings of this study suggest that our BBB model can be used as a suitable tool to investigate breast cancer-associated brain metastasis and to identify suitable therapeutic agents against this.

Joint modeling of longitudinal continuous, longitudinal ordinal, and time-to-event outcomes.

In this paper, we propose an innovative method for jointly analyzing survival data and longitudinally measured continuous and ordinal data. We use a random effects accelerated failure time model for survival outcomes, a linear mixed model for continuous longitudinal outcomes and a proportional odds mixed model for ordinal longitudinal outcomes, where these outcome processes are linked through a set of association parameters. A primary objective of this study is to examine the effects of association parameters on the estimators of joint models. The model parameters are estimated by the method of maximum likelihood. The finite-sample properties of the estimators are studied using Monte Carlo simulations. The empirical study suggests that the degree of association among the outcome processes influences the bias, efficiency, and coverage probability of the estimators. Our proposed joint model estimators are approximately unbiased and produce smaller mean squared errors as compared to the estimators obtained from separate models. This work is motivated by a large multicenter study, referred to as the Genetic and Inflammatory Markers of Sepsis (GenIMS) study. We apply our proposed method to the GenIMS data analysis.

Secondary metabolites from acridocarpus orientalis inhibits 4T1 cells and promotes mesenchymal stem cells (MSCs) proliferation.

Among medicinal plants, Acridocarpus orientalis (AO) possesses a remarkable anti-cancer potential, possibly because of its anti-oxidant property. In this study, the leaf and stem extracts from AO were assessed to find the bioactive compound with selective anti-cancer properties. The MTT viability and live and dead assays revealed that around 80% and 98% of 4T1 cells survival were declined after 48 h incubation with leaf and stem extracts, respectively. The leaf extract increased stem cell proliferation by 20% whereas the stem extract inhibited around 22% of stem cells proliferation after 48 h treatment. The live and dead assay of MSCs confirmed that 40% of the MSCs died when treated with AO stem extract. On the other hand, there were no dead cells after two days of treatment with the leaf extract. Followed by the induction of cell cycle arrest in G0/G1-phase, the real-time PCR demonstrated apoptosis properties in 4T1 cells through overexpression of Bax and down-regulation of BCL2 genes. Interestingly, within the pure compounds isolated from AO leaf extract, Morin was responsible for the inhibition of 4T1 cells proliferation as well as MSCs expansion, predicting to play an essential role in the treatment of cancer. The promising in vitro anti-cancer and stem cell-inductive properties of morin isolated from AO extract may provide a great potential to produce selective herbal derived drugs.

Correction: Does genomic sequencing early in the diagnostic trajectory make a difference? A follow-up study of clinical outcomes and cost-effectiveness.

The original PDF version of this Article omitted to list Clara L Gaff as a corresponding author and the affiliations were incorrectly labelled as Present Addresses. Furthermore, Tables 1 and 2 have been updated to clarify that the Australian dollar is used for the values. These errors have now been corrected in the PDF and HTML versions of the Article.

Does genomic sequencing early in the diagnostic trajectory make a difference? A follow-up study of clinical outcomes and cost-effectiveness.

PURPOSE: To systematically investigate the longer-term clinical and health economic impacts of genomic sequencing for rare-disease diagnoses. METHODS: We collected information on continuing diagnostic investigation, changes in management, cascade testing, and parental reproductive outcomes in 80 infants who underwent singleton whole-exome sequencing (WES). RESULTS: The median duration of follow-up following result disclosure was 473 days. Changes in clinical management due to diagnostic WES results led to a cost saving of AU$1,578 per quality-adjusted life year gained, without increased hospital service use. Uninformative WES results contributed to the diagnosis of non-Mendelian conditions in seven infants. Further usual diagnostic investigations in those with ongoing suspicion of a genetic condition yielded no new diagnoses, while WES data reanalysis yielded four. Reanalysis at 18 months was more cost-effective than every 6 months. The parents of diagnosed children had eight more ongoing pregnancies than those without a diagnosis. Taking the costs and benefits of cascade testing and reproductive service use into account, there was an additional cost of AU$8,118 per quality-adjusted life year gained due to genomic sequencing. CONCLUSION: These data strengthen the case for the early use of genomic testing in the diagnostic trajectory, and can guide laboratory policy on periodic WES data reanalysis.

Type 2 diabetes mellitus in Bangladesh: a prevalence based cost-of-illness study.

BACKGROUND: The economic burden of type 2 diabetes has not been adequately investigated in many low- and lower middle-income countries, including Bangladesh. The aim of this study was to estimate the cost-of-illness of type 2 diabetes and to find its determinants in Bangladesh. METHODS: A cross-sectional study was conducted in 2017 to recruit 1253 participants with type 2 diabetes from six diabetes hospitals, providing primary to tertiary health care services, located in the northern and central regions of Bangladesh. A structured questionnaire was used for face-to-face interviewing to collect non-clinical data. Patients' medical records were reviewed for clinical data and hospital records were reviewed for hospitalisation data. Cost was calculated from the patient's perspective using a bottom-up methodology. The direct costs for each patient and indirect costs for each patient and their attendants were calculated. The micro-costing approach was used to calculate direct cost and the human capital approach was used to calculate indirect cost. Median regression analysis was performed to identify the determinants of average annual cost. RESULTS: Among the participants, 54% were male. The mean (±SD) age was 55.1 ± 12.5 years and duration of diabetes was 10.7 ± 7.7 years. The average annual cost was US$864.7 per patient. Medicine cost accounted for 60.7% of the direct cost followed by a hospitalisation cost of 27.7%. The average annual cost for patients with hospitalisation was 4.2 times higher compared to those without hospitalisation. Being females, use of insulin, longer duration of diabetes, and presence of diabetes complications were significantly related to the average annual cost per patient. CONCLUSIONS: The cost of diabetes care is considerably high in Bangladesh, and it is primarily driven by the medicine and hospitalisation costs. Optimisation of diabetes management by positive lifestyle changes is urgently required for prevention of comorbidities and complications, which in turn will reduce the cost.

Cost-of-illness of type 2 diabetes mellitus in low and lower-middle income countries: a systematic review.

BACKGROUND: Diabetes is one of the world's most prevalent and serious non-communicable diseases (NCDs). It is a leading cause of death, disability and financial loss; moreover, it is identified as a major threat to global development. The chronic nature of diabetes and its related complications make it a costly disease. Estimating the total cost of an illness is a useful aid to national and international health policy decision making. The aim of this systematic review is to summarise the impact of the cost-of-illness of type 2 diabetes mellitus in low and lower-middle income countries, and to identify methodological gaps in measuring the cost-of-illness of type 2 diabetes mellitus. METHODS: This systematic review considers studies that reported the cost-of-illness of type 2 diabetes in subjects aged 18 years and above in low and lower-middle income countries. The search engines MEDLINE, EMBASE, CINAHL, PSYCINFO and COCHRANE were used form date of their inception to September 2018. Two authors independently identified the eligible studies. Costs reported in the included studies were converted to US dollars in relation to the dates mentioned in the studies. RESULTS: The systematic search identified eight eligible studies conducted in low and lower-middle income countries. There was a considerable variation in the costs and method used in these studies. The annual average cost (both direct and indirect) per person for treating type 2 diabetes mellitus ranged from USD29.91 to USD237.38, direct costs ranged from USD106.53 to USD293.79, and indirect costs ranged from USD1.92 to USD73.4 per person per year. Hospitalization cost was the major contributor of direct costs followed by drug costs. CONCLUSION: Type 2 diabetes mellitus imposes a considerable economic burden which most directly affects the patients in low and lower-middle income countries. There is enormous scope for adding research-based evidence that is methodologically sound to gain a more accurate estimation of cost and to facilitate comparison between studies.

Global Mortality From Firearms, 1990-2016.

Importance: Understanding global variation in firearm mortality rates could guide prevention policies and interventions. Objective: To estimate mortality due to firearm injury deaths from 1990 to 2016 in 195 countries and territories. Design, Setting, and Participants: This study used deidentified aggregated data including 13 812 location-years of vital registration data to generate estimates of levels and rates of death by age-sex-year-location. The proportion of suicides in which a firearm was the lethal means was combined with an estimate of per capita gun ownership in a revised proxy measure used to evaluate the relationship between availability or access to firearms and firearm injury deaths. Exposures: Firearm ownership and access. Main Outcomes and Measures: Cause-specific deaths by age, sex, location, and year. Results: Worldwide, it was estimated that 251 000 (95% uncertainty interval [UI], 195 000-276 000) people died from firearm injuries in 2016, with 6 countries (Brazil, United States, Mexico, Colombia, Venezuela, and Guatemala) accounting for 50.5% (95% UI, 42.2%-54.8%) of those deaths. In 1990, there were an estimated 209 000 (95% UI, 172 000 to 235 000) deaths from firearm injuries. Globally, the majority of firearm injury deaths in 2016 were homicides (64.0% [95% UI, 54.2%-68.0%]; absolute value, 161 000 deaths [95% UI, 107 000-182 000]); additionally, 27% were firearm suicide deaths (67 500 [95% UI, 55 400-84 100]) and 9% were unintentional firearm deaths (23 000 [95% UI, 18 200-24 800]). From 1990 to 2016, there was no significant decrease in the estimated global age-standardized firearm homicide rate (-0.2% [95% UI, -0.8% to 0.2%]). Firearm suicide rates decreased globally at an annualized rate of 1.6% (95% UI, 1.1-2.0), but in 124 of 195 countries and territories included in this study, these levels were either constant or significant increases were estimated. There was an annualized decrease of 0.9% (95% UI, 0.5%-1.3%) in the global rate of age-standardized firearm deaths from 1990 to 2016. Aggregate firearm injury deaths in 2016 were highest among persons aged 20 to 24 years (for men, an estimated 34 700 deaths [95% UI, 24 900-39 700] and for women, an estimated 3580 deaths [95% UI, 2810-4210]). Estimates of the number of firearms by country were associated with higher rates of firearm suicide (P < .001; R2 = 0.21) and homicide (P < .001; R2 = 0.35). Conclusions and Relevance: This study estimated between 195 000 and 276 000 firearm injury deaths globally in 2016, the majority of which were firearm homicides. Despite an overall decrease in rates of firearm injury death since 1990, there was variation among countries and across demographic subgroups.