Impact of cash transfer programs on healthcare utilization and catastrophic health expenditures in rural Zambia: a cluster randomized controlled trial.

Background: Nearly 100 million people are pushed into poverty every year due to catastrophic health expenditures (CHE). We evaluated the impact of cash support programs on healthcare utilization and CHE among households participating in a cluster-randomized controlled trial focusing on adolescent childbearing in rural Zambia. Methods and findings: The trial recruited adolescent girls from 157 rural schools in 12 districts enrolled in grade 7 in 2016 and consisted of control, economic support, and economic support plus community dialogue arms. Economic support included 3 USD/month for the girls, 35 USD/year for their guardians, and up to 150 USD/year for school fees. Interviews were conducted with 3,870 guardians representing 4,110 girls, 1.5-2 years after the intervention period started. Utilization was defined as visits to formal health facilities, and CHE was health payments exceeding 10% of total household expenditures. The degree of inequality was measured using the Concentration Index. In the control arm, 26.1% of the households utilized inpatient care in the previous year compared to 26.7% in the economic arm (RR = 1.0; 95% CI: 0.9-1.2, p = 0.815) and 27.7% in the combined arm (RR = 1.1; 95% CI: 0.9-1.3, p = 0.586). Utilization of outpatient care in the previous 4 weeks was 40.7% in the control arm, 41.3% in the economic support (RR = 1.0; 95% CI: 0.8-1.3, p = 0.805), and 42.9% in the combined arm (RR = 1.1; 95% CI: 0.8-1.3, p = 0.378). About 10.4% of the households in the control arm experienced CHE compared to 11.6% in the economic (RR = 1.1; 95% CI: 0.8-1.5, p = 0.468) and 12.1% in the combined arm (RR = 1.1; 95% CI: 0.8-1.5, p = 0.468). Utilization of outpatient care and the risk of CHE was relatively higher among the least poor than the poorest households, however, the degree of inequality was relatively smaller in the intervention arms than in the control arm. Conclusions: Economic support alone and in combination with community dialogue aiming to reduce early childbearing did not appear to have a substantial impact on healthcare utilization and CHE in rural Zambia. However, although cash transfer did not significantly improve healthcare utilization, it reduced the degree of inequality in outpatient healthcare utilization and CHE across wealth groups. Trial Registration: https://classic.clinicaltrials.gov/ct2/show/NCT02709967, ClinicalTrials.gov, identifier (NCT02709967).

Life Expectancy Gains from Dietary Modifications: A Comparative Modelling Study in Seven Countries.

BACKGROUND: Eating healthier is associated with a range of favorable health outcomes. Our previous model estimated the impact of dietary changes on life expectancy gains, but did not consider height, weight, or physical activity. OBJECTIVE: We estimate the increase in life expectancy resulting from the transition from typical national dietary patterns to longevity-optimizing dietary changes, more feasible dietary modifications, and optimized vegan dietary changes for China, France, Germany, Iran, Norway, the United Kingdom, and the United States. METHODS: Our modeling study uses data from meta-analyses presenting dose-response relationships between intake of fifteen food groups and mortality. Background mortality data are from the Global Burden of Disease study. We use national food intake data and adjust for height, weight, and physical activity level. RESULTS: For 40-year-olds, estimated life expectancy gains ranged from 6.2 years (with uncertainty intervals 5.7;7.5) for Chinese females to 9.7 years (8.1;11.3) for US males following sustained changes from typical country-specific dietary patterns to longevity-optimized dietary changes, and from 5.2 years (4.0;6.5) for Chinese females to 8.7 years (7.1;10.3) for US males following changes to an optimized vegan dietary changes. CONCLUSION: A sustained change from country-specific typical dietary pattern patterns to longevity-optimized dietary changes, more feasible dietary changes, or optimized vegan dietary changes, are all projected to result in substantial life expectancy gains across ages and countries. These changes included more whole grains, legumes, and nuts, and less red/processed meats and sugars and sugar-sweetened beverages. The largest gains from dietary changes would be in the United States.

Profiling amyloid-ß peptides as biomarkers for cerebral amyloid angiopathy.

Brain amyloid-ß (Aß) deposits are key pathological hallmarks of both cerebral amyloid angiopathy (CAA) and Alzheimer's disease (AD). Microvascular deposits in CAA mainly consist of the Aß40 peptide, whereas Aß42 is the predominant variant in parenchymal plaques in AD. The relevance in pathogenesis and diagnostic accuracy of various other Aß isoforms in CAA remain understudied. We aimed to investigate the biomarker potential of various Aß isoforms in cerebrospinal fluid (CSF) to differentiate CAA from AD pathology. We included 25 patients with probable CAA, 50 subjects with a CSF profile indicative of AD pathology (AD-like), and 23 age- and sex-matched controls. CSF levels of Aß1-34 , Aß1-37 , Aß1-38 , Aß1-39 , Aß1-40 , and Aß1-42 were quantified by liquid chromatography mass spectrometry. Lower CSF levels of all six Aß peptides were observed in CAA patients compared with controls (p = 0.0005-0.03). Except for Aß1-42 (p = 1.0), all peptides were decreased in CAA compared with AD-like subjects (p = 0.007-0.03). Besides Aß1-42 , none of the Aß peptides were decreased in AD-like subjects compared with controls. All Aß peptides combined differentiated CAA from AD-like subjects better (area under the curve [AUC] 0.84) than individual peptide levels (AUC 0.51-0.75). Without Aß1-42 in the model (since decreased Aß1-42 served as AD-like selection criterion), the AUC was 0.78 for distinguishing CAA from AD-like subjects. CAA patients and AD-like subjects showed distinct disease-specific CSF Aß profiles. Peptides shorter than Aß1-42 were decreased in CAA patients, but not AD-like subjects, which could suggest different pathological mechanisms between vascular and parenchymal Aß accumulation. This study supports the potential use of this panel of CSF Aß peptides to indicate presence of CAA pathology with high accuracy.

Effect of integrated hepatitis C virus treatment on psychological distress in people with substance use disorders.

People with substance use disorders (SUD) have a high prevalence of chronic hepatitis C virus (HCV) infection and mental health disorders. We aimed to assess the impact of integrated HCV treatment on psychological distress measured by Hopkins-symptom-checklist-10 (SCL-10). This multi-center randomized controlled trial evaluated psychological distress as a secondary outcome of integrated HCV treatment (INTRO-HCV trial). From 2017 to 2019, 289 participants were randomly assigned to receive either integrated or standard HCV treatment with direct-acting antiviral therapy. Integrated HCV treatment was delivered in eight decentralized outpatient opioid agonist therapy clinics and two community care centers; standard treatment was delivered in internal medicine outpatient clinics at centralized hospitals. Participants in the integrated treatment arm had a sustained virologic response of 93% compared to 73% for those in standard treatment arm. Psychological distress was assessed using SCL-10 prior to initiation of HCV treatment and 12 weeks after treatment completion. The mean SCL-10 score prior to HCV treatment was 2.2 (standard deviation [SD]: 0.7) for patients receiving integrated HCV treatment and 2.2 (SD: 0.8) for those receiving standard HCV treatment. Twelve weeks after the end of treatment, the mean SCL-10 score change was - 0.1 (- 0.3;0.0) in the integrated compared to the standard arm. Psychological distress did not substantially change during the treatment period and was not significantly different between the treatment arms.

Methadone pharmacokinetics in opioid agonist treatment: Influencing factors and clinical implications.

BACKGROUND: A considerable inter-individual variability has been reported in the relationship between methadone doses applied and serum concentrations achieved in methadone maintenance treatment. However, the underlying causes for this variability are not fully understood. OBJECTIVES: We investigated the influence of genetic, pathophysiological and pharmacological factors on serum methadone concentration-to-dose ratio (CDR) and discussed the clinical implications of the findings. METHODS: We used data from two retrospective laboratory databases and a prospective cohort study to investigate the impact on methadone CDR of hepatic cytochrome P450 enzyme system (CYP) genetic polymorphisms, age, sex, concomitant medication, liver fibrosis and body mass index through linear mixed model analyses. FINDINGS: A positive association was found between CDR and the homozygous CYP2B6*6 genotype, concurrent treatment with CYP3A4 inhibitors and body mass index. CDR was lower among women and during concomitant use of CYP inducers. CDR was not associated with age or the degree of liver fibrosis in our investigations. CONCLUSIONS: This research work supports the need for individually tailored dosage considering the various factors that influence methadone CDR. The gained knowledge can contribute to reducing the risks associated with the treatment and optimizing the desired outcomes.

Effectiveness of interventions for emergency care of hypoglycaemia and diabetic ketoacidosis: A systematic review.

AIM: This systematic review aims to provide evidence on effectiveness of interventions used in emergency care of hypoglycaemia and diabetic ketoacidosis (DKA). METHODOLOGY: This is a systematic review of randomized controlled trials and analytical studies. We selected studies based on eligibility criteria. The databases Medline, Cochrane library and Embase were searched from their inception till November 2, 2022, using search strategy. We used the term such as "diabetes mellitus", "treatment", "hypoglycaemia", "diabetic ketoacidosis", "low blood sugar", "high blood sugar" and Mesh terms like "disease management", "hypoglycaemia", "diabetic ketoacidosis", and "diabetes mellitus" to form search strategy. RESULTS: Hypoglycemia: Both 10 % dextrose (D10) and 50 % dextrose (D50) are effective options with similar hospital mortality D10 (4.7 %) and D50 (6.2 %). DKA: Low dose insulin is non-inferior to standard dose with time till resolution of DKA 16.5 (7.2) hours and 17.2 (7.7) hours (p value = 0.73) respectively. In children, subcutaneous insulin was associated with reduced ICU admissions and hospital readmissions (67.8 % to 27.9 %). Plasmalyte (PL) is noninferior to sodium chloride (SC), with ICU length of stay 49 h (IQR 23-72) and 55 h (IQR 41-80) respectively, hyperchloremia was associated with longer in-hospital length of stay and longer time to resolution of DKA. And potassium replacement at < 10 mmol/L was associated with higher mortality (n = 72). CONCLUSION: We conclude either of the 10 % or 50 % dextrose is effective for management of hypoglycaemia. For DKA subcutaneous insulin and intravenous insulin, chloride levels ≤ 109 mEq/L, potassium above 10 mmol/l, IV fluids like Plasmalyte and normal saline are effective.

Life expectancy can increase by up to 10 years following sustained shifts towards healthier diets in the United Kingdom.

Adherence to healthy dietary patterns can prevent the development of non-communicable diseases and affect life expectancy. Here, using a prospective population-based cohort data from the UK Biobank, we show that sustained dietary change from unhealthy dietary patterns to the Eatwell Guide dietary recommendations is associated with 8.9 and 8.6 years gain in life expectancy for 40-year-old males and females, respectively. In the same population, sustained dietary change from unhealthy to longevity-associated dietary patterns is associated with 10.8 and 10.4 years gain in life expectancy in males and females, respectively. The largest gains are obtained from consuming more whole grains, nuts and fruits and less sugar-sweetened beverages and processed meats. Understanding the contribution of sustained dietary changes to life expectancy can provide guidance for the development of health policies.

Financial hardship associated with catastrophic out-of-pocket spending tied to primary care services in low- and lower-middle-income countries: findings from a modeling study.

BACKGROUND: Financial risk protection (FRP) is a key component of universal health coverage (UHC): all individuals must be able to obtain the health services they need without experiencing financial hardship. In many low-income and lower-middle-income countries, however, the health system fails to provide sufficient protection against high out-of-pocket (OOP) spending on health services. In 2018, OOP health spending comprised approximately 40% of current health expenditures in low-income and lower-middle-income countries. METHODS: We model the household risk of catastrophic health expenditures (CHE), conditional on having a given disease or condition-defined as OOP health spending that exceeds a threshold percentage (10, 25, or 40%) of annual income-for 29 health services across 13 disease categories (e.g., diarrheal diseases, cardiovascular diseases) in 34 low-income and lower-middle-income countries. Health services were included in the analysis if delivered at the primary care level and part of the Disease Control Priorities, 3rd edition "highest priority package." Data were compiled from several publicly available sources, including national health accounts, household surveys, and the published literature. A risk of CHE, conditional on having disease, was modeled as depending on usage, captured through utilization indicators; affordability, captured via the level of public financing and OOP health service unit costs; and income. RESULTS: Across all countries, diseases, and health services, the risk of CHE (conditional on having a disease) would be concentrated among poorer quintiles (6.8% risk in quintile 1 vs. 1.3% in quintile 5 using a 10% CHE threshold). The risk of CHE would be higher for a few disease areas, including cardiovascular disease and mental/behavioral disorders (7.8% and 9.8% using a 10% CHE threshold), while lower risks of CHE were observed for lower cost services. CONCLUSIONS: Insufficient FRP stands as a major barrier to achieving UHC, and risk of CHE is a major problem for health systems in low-income and lower-middle-income countries. Beyond its threat to the financial stability of households, CHE may also lead to worse health outcomes, especially among the poorest for whom both ill health and financial risk are most severe. Modeling the risk of CHE associated with specific disease areas and services can help policymakers set progressive health sector priorities. Decision-makers could explicitly include FRP as a criterion for consideration when assessing the health interventions for inclusion in national essential benefit packages.

Cost-effectiveness of integrated treatment for hepatitis C virus (HCV) among people who inject drugs in Norway: An economic evaluation of the INTRO-HCV trial.

BACKGROUND AND AIMS: The INTRO-HCV randomized controlled trial conducted in Norway over 2017-2019 found that integrated treatment, compared with standard-of-care hospital treatment, for hepatitis C virus (HCV) with direct-acting antivirals (DAAs) improved treatment outcomes among people who inject drugs (PWID). We evaluated cost-effectiveness of the INTRO-HCV intervention. DESIGN: A Markov health state transition model of HCV disease progression and treatment with cost-effectiveness analysis from the health-provider perspective. Primary cost, utility, and health outcome data were derived from the trial. Costs and health benefits (quality-adjusted life-years, QALYs) were tracked over 50 years. Probabilistic and univariate sensitivity analyses investigated DAA price reductions and variations in HCV treatment and disease care cost assumptions, using costs from different countries (Norway, United Kingdom, United States, France, Australia). SETTING AND PARTICIPANTS: PWID attending community-based drug treatment centers for people with opioid dependence in Norway. MEASUREMENTS: Incremental cost-effectiveness ratio (ICER) in terms of cost per QALY gained, compared against a conventional (€70 000/QALY) willingness-to-pay threshold for Norway and lower (€20 000/QALY) threshold common among high-income countries. FINDINGS: Integrated treatment resulted in an ICER of €13 300/QALY gained, with 99% and 71% probability of being cost-effective against conventional and lower willingness-to-pay thresholds, respectively. A 30% lower DAA price reduced the ICER to €6 900/QALY gained, with 91% probability of being cost-effective at the lower willingness-to-pay threshold. A 60% and 90% lower DAA price had 36% and >99% probability of being cost-saving, respectively. Sensitivity analyses suggest integrated treatment was cost-effective at the lower willingness-to-pay threshold (>60% probability) across different assumptions on HCV treatment and disease care costs with 30% DAA price reduction, and became cost-saving with 60%-90% price reductions. CONCLUSIONS: Integrated hepatitis C virus treatment for people who inject drugs in community settings is likely cost-effective compared with standard-of-care referral pathways in Norway and may be cost-saving in settings with particular characteristics.

Attention-deficit/hyperactivity disorder (ADHD) symptoms and their relation to diagnosed ADHD, sociodemographic characteristics, and substance use among patients receiving opioid agonist therapy: a Norwegian cohort study.

BACKGROUND: Attention-deficit/hyperactivity disorder (ADHD) symptoms may challenge sufficient treatment of substance use and mental disorders. The literature on the extent of such symptoms among patients receiving opioid agonist therapy (OAT) is scarce. This study examined ADHD symptoms using the ADHD self-report scale (ASRS) and the association between the 'ASRS-memory' and 'ASRS-attention' scores and substance use and sociodemographic characteristics among patients receiving OAT. METHODS: We used data from assessment visits of a cohort of patients in Norway. In total, 701 patients were included from May 2017 to March 2022. All patients responded at least once to two ASRS questions assessing memory and attention, respectively. Ordinal regression analyses were performed to investigate whether the two obtained scores were associated with age, sex, frequent substance use, injecting use, housing status, and educational attainment at baseline, i.e., the first assessment, and over time. The results are presented as odds ratios (OR) with 95% confidence intervals (CI). Additionally, a subsample of 225 patients completed an extended interview, including the ASRS-screener and collection of registered mental disorder diagnoses from the medical records. Standard cutoffs were used to define the presence of each ASRS symptom or a positive ASRS-screener ('ASRS-positive'). RESULTS: At baseline, 428 (61%) and 307 (53%) patients scored over the cutoffs on the 'ASRS-memory' and 'ASRS-attention,' respectively. Frequent cannabis use was associated with higher 'ASRS-memory' (OR: 1.7, 95% CI: 1.1-2.6) and 'ASRS-attention' (1.7, 1.1-2.5) scores compared with less or no use at baseline, though reduced score on the 'ASRS-memory' over time (0.7, 0.6-1.0). At baseline, frequent stimulant use (1.8, 1.0-3.2) and low educational attainment (0.1, 0.0-0.8) were associated with higher 'ASRS-memory' scores. In the subsample fulfilling the ASRS-screener, 45% of the patients were 'ASRS-positive,' of whom 13% with a registered ADHD diagnosis. CONCLUSIONS: Our findings illustrate a relationship between the ASRS-memory and -attention scores and frequent cannabis and stimulant use. Furthermore, nearly half of the subsample was 'ASRS-positive.' Patients receiving OAT might benefit from being further assessed for ADHD, but improved diagnostic methods are required.

The efficacy of integrated hepatitis C virus treatment in relieving fatigue in people who inject drugs: a randomized controlled trial.

BACKGROUND: Most people who inject drugs (PWIDs) suffer from severe fatigue, and chronic hepatitis C virus (HCV) infection may play a role in this. However, there is scarce evidence about interventions that alleviate fatigue among PWIDs. The present study investigated the effect of integrated HCV treatment on fatigue in this population compared to the effect of standard HCV treatment, adjusted for sustained virological response of the HCV treatment. METHODS: This multi-center, randomized controlled trial evaluated fatigue as a secondary outcome of integrated HCV treatment (the INTRO-HCV trial). From May 2017 to June 2019, 276 participants in Bergen and Stavanger, Norway, were randomly assigned to receive integrated and standard HCV treatment. Integrated treatment was delivered in eight decentralized outpatient opioid agonist therapy clinics and two community care centers; standard treatment was delivered in specialized infectious disease outpatient clinics at referral hospitals. Fatigue was assessed prior to treatment and 12 weeks after treatment using the nine-item Fatigue Severity Scale (FSS-9). We applied a linear mixed model to evaluate the impact of integrated HCV treatment on changes in FSS-9 (ΔFSS-9) sum scores. RESULTS: At baseline, the mean FSS-9 sum score was 46 (standard deviation (SD): 15) for participants on integrated HCV treatment and 41 (SD: 16) for those on standard treatment. Twelve weeks after completed HCV treatment, the mean FSS-9 sum score for participants receiving integrated HCV treatment was 42 (SD: 15) and 40 (SD: 14) for those receiving standard HCV treatment. Integrated HCV treatment did not reduce the FSS-9 scores compared to standard HCV treatment (ΔFSS-9: -3.0, 95% confidence interval (CI): -6.4;0.4). CONCLUSIONS: Fatigue is a common symptom among PWIDs. Integrated HCV treatment is at least equal to standard HCV treatment in improving fatigue. TRIAL REGISTRATION: ClinicalTrials.gov.no NCT03155906, 16/05/2017.

Country readiness and prerequisites for successful design and transition to implementation of essential packages of health services: experience from six countries.

This paper reviews the experience of six low-income and lower middle-income countries in setting their own essential packages of health services (EPHS), with the purpose of identifying the key requirements for the successful design and transition to implementation of the packages in the context of accelerating progress towards universal health coverage (UHC). The analysis is based on input from three meetings of a knowledge network established by the Disease Control Priorities 3 Country Translation Project and working groups, supplemented by a survey of participating countries.All countries endorsed the Sustainable Development Goals target 3.8 on UHC for achievement by 2030. The assessment of country experiences found that health system strengthening and mobilising and sustaining health financing are major challenges. EPHS implementation is more likely when health system gaps are addressed and when there are realistic and sustainable financing prospects. However, health system assessments were inadequate and the government planning and finance sectors were not consistently engaged in setting the EPHS in most of the countries studied. There was also a need for greater engagement with community and civil society representatives, academia and the private sector in package design. Leadership and reinforcement of technical and managerial capacity are critical in the transition from EPHS design to sustained implementation, as are strong human resources and country ownership of the process. Political commitment beyond the health sector is key, particularly commitment from parliamentarians and policymakers in the planning and finance sectors. National ownership, institutionalisation of technical and managerial capacity and reinforcing human resources are critical for success.The review concludes that four prerequisites are crucial for a successful EPHS: (1) sustained high-level commitment, (2) sustainable financing, (3) health system readiness, and (4) institutionalisation.

Decision-making processes for essential packages of health services: experience from six countries.

Many countries around the world strive for universal health coverage, and an essential packages of health services (EPHS) is a central policy instrument for countries to achieve this. It defines the coverage of services that are made available, as well as the proportion of the costs that are covered from different financial schemes and who can receive these services. This paper reports on the development of an analytical framework on the decision-making process of EPHS revision, and the review of practices of six countries (Afghanistan, Ethiopia, Pakistan, Somalia, Sudan and Zanzibar-Tanzania).The analytical framework distinguishes the practical organisation, fairness and institutionalisation of decision-making processes. The review shows that countries: (1) largely follow a similar practical stepwise process but differ in their implementation of some steps, such as the choice of decision criteria; (2) promote fairness in their EPHS process by involving a range of stakeholders, which in the case of Zanzibar included patients and community members; (3) are transparent in terms of at least some of the steps of their decision-making process and (4) in terms of institutionalisation, express a high degree of political will for ongoing EPHS revision with almost all countries having a designated governing institute for EPHS revision.We advise countries to organise meaningful stakeholder involvement and foster the transparency of the decision-making process, as these are key to fairness in decision-making. We also recommend countries to take steps towards the institutionalisation of their EPHS revision process.

Microglia in Cultured Porcine Retina: Qualitative Immunohistochemical Analyses of Reactive Microglia in the Outer Retina.

A late stage of several retinal disorders is retinal detachment, a complication that results in rapid photoreceptor degeneration and synaptic damages. Experimental retinal detachment in vivo is an invasive and complicated method performed on anesthetized animals. As retinal detachment may result in visual impairment and blindness, research is of fundamental importance for understanding degenerative processes. Both morphological and ethical issues make the porcine retina a favorable organotypic model for studies of the degenerative processes that follow retinal detachment. In the cultured retina, photoreceptor degeneration and synaptic injuries develop rapidly and correlate with resident microglial cells' transition into a reactive phenotype. In this immunohistochemical study, we have begun to analyze the transition of subsets of reactive microglia which are known to localize close to the outer plexiform layer (OPL) in degenerating in vivo and in vitro retina. Biomarkers for reactive microglia included P2Ry12, CD63 and CD68 and the general microglial markers were CD11b, Iba1 and isolectin B4 (IB4). The reactive microglia markers labeled microglia subpopulations, suggesting that protective or harmful reactive microglia may be present simultaneously in the injured retina. Our findings support the usage of porcine retina cultures for studies of photoreceptor injuries related to retinal detachment.

Association between oral and general health related quality of life among Norwegian patients with substance use disorders in opioid agonist therapy.

OBJECTIVE: Assess the association between oral and general health related quality of life using oral impacts on daily performances (OIDP) and the quality of life tool EQ-5D-5L from EuroQoL among patients with substance use disorder (SUD) who receive opioid agonist therapy. METHOD: 609 patients with SUD completed the EQ-5D-5L. A dental sub-study of 167 patients completed OIDP and an oral examination when attending outpatient clinics in Western Norway for their opioid agonist therapy. The merged analytical sample consisted of 165 patients. The association between OIDP and EQ-5D-5L was assessed by Spearman's rho and a linear multiple variable regression analysis. A line graph and a Pen's parade displayed the distributions of OIDP sum scores and EQ-5D-5L index values. RESULTS: Overall mean summary- and index EQ-5D-5L scores were 9.97 (sd 3.25) and 0.69 (sd 0.22). Mean score for OIDP was 9.75 (sd 9.59). Spearman's rho was 0.34 (p < .01) between OIDP and EQ-5D-5L summary scores. Linear regression revealed an association adjusted for sex and age of 0.12 (95% CI 0.07-0.17) and a coefficient of determination of 0.1460. CONCLUSION: This study reveals a strong association between OIDP and EQ-5D-5L reflecting the importance of oral health to general health for patients with SUD. Health care professionals should pay attention to oral health. Effective interventions might improve patients' oral and health related quality of life.

Impact of liver fibrosis and clinical characteristics on dose-adjusted serum methadone concentrations.

BACKGROUND: There is limited knowledge on the causes of large variations in serum methadone concentrations and dose requirements. OBJECTIVES: We investigated the impact of the degree of liver fibrosis on dose-adjusted steady-state serum methadone concentrations. METHODS: We assessed the clinical and laboratory data of 155 Norwegian patients with opioid use disorder undergoing methadone maintenance treatment in outpatient clinics in the period 2016-2020. A possible association between the degree of liver fibrosis and dose-adjusted serum methadone concentration was explored using a linear mixed-model analysis. RESULTS: When adjusted for age, gender, body mass index, and genotypes of CYP2B6 and CYP3A5, the concentration-to-dose ratio of methadone did not increase among the participants with liver fibrosis (Coefficient: 0.70; 95% CI: -2.16, 3.57; P: 0.631), even among those with advanced cirrhosis (-0.50; -4.59, 3.59; 0.810). CONCLUSIONS: Although no correlation was found between the degree of liver stiffness and dose-adjusted serum methadone concentration, close clinical monitoring should be considered, especially among patients with advanced cirrhosis. Still, serum methadone measurements can be considered a supplement to clinical assessments, taking into account intra-individual variations.

Effect of kangaroo mother care initiated in community settings on financial risk protection of low-income households: a randomised controlled trial in Haryana, India.

INTRODUCTION: Many families in low-income and middle-income countries have high out-of-pocket expenditures (OOPE) for healthcare, and some face impoverishment. We aimed to assess the effect of Kangaroo Mother Care initiated in community setting (ciKMC) on financial risk protection estimated by healthcare OOPE, catastrophic healthcare expenditure (CHE) and impoverishment due to healthcare seeking for low birthweight infants, using a randomised controlled trial design. METHODS: We included 4475 low birthweight infants randomised to a ciKMC (2491 infants) and a control (1984 infants) arm, in a large trial conducted between 2017 and 2018 in Haryana, India. We used generalised linear models of the Gaussian family with an identity link to estimate the mean difference in healthcare OOPE, and Cox regression to estimate the HRs for CHE and impoverishment, between the trial arms. RESULTS: Overall, in the 8-week observation period, the mean healthcare OOPE per infant was lower (US$20.0) in the ciKMC arm compared with the control arm (US$25.6) that is, difference of -US$5.5, 95% CI -US$11.4 to US$0.3, p=0.06). Among infants who sought care it was US$8.5 (95% CI -US$17.0 to -US$0.03, p=0.03) lower in the ciKMC arm compared with the control arm. The HR for impoverishment due to healthcare seeking was 0.56 (95% CI 0.36 to 0.89, p=0.01) and it was 0.91 (95% CI 0.74 to 1.12, p=0.37) for CHE. CONCLUSION: ciKMC can substantially reduce the cost of care seeking and the risk of impoverishment for households. Our findings show that supporting mothers to provide KMC to low birthweight infants at home, in addition to reducing early infant mortality, may provide financial risk protection. TRIAL REGISTRATION NUMBER: CTRI/2017/10/010114.

Vitamin D status and associations with substance use patterns among people with severe substance use disorders in Western Norway.

Chronic and harmful substance use is associated with a cluster of harms to health, including micronutrient deficiencies. Maintaining adequate levels of vitamin D is important for musculoskeletal and other aspects of health. In this prospective longitudinal cohort study, 666 participants drawn from outpatient opioid agonist therapy (OAT) clinics and community care clinics for substance use disorder in Western Norway were assessed annually for determination of serum 25-hydroxyvitamin D [s-25(OH)D] levels. Fifty-seven percent were deficient at baseline (s-25(OH)D < 50 nmol/l), and 19% were severely deficient (s-25(OH)D < 25 nmol/l). Among those deficient/severely deficient at baseline, 70% remained deficient/severely deficient at the last measurement (mean duration 714 days). Substance use patterns and dosage of opioids for OAT were not associated with vitamin D levels. One exception was found for cannabis, where consumption on a minimum weekly basis was associated with lower levels at baseline (mean difference: -5.2 nmol/l, 95% confidence interval [CI]: -9.1, - 1.3), but without clear time trends (mean change per year: 1.4 nmol/l, CI: - 0.86, 3.7). The high prevalence of sustained vitamin D deficiency in this cohort highlights the need for targeted monitoring and supplementation for this and similar at-risk populations.

Folate Status as a Nutritional Indicator among People with Substance Use Disorder; A Prospective Cohort Study in Norway.

Substance use disorder (SUD) is associated with poor nutrition. Vitamin B9, or folate, is an important micronutrient for health. The aim of this prospective longitudinal cohort study was to assess serum folate levels among people with SUD and to investigate the impact of factors related to substance use severity on folate status. Participants were recruited from outpatient clinics for opioid agonist therapy (OAT) and municipal health-care clinics for SUD in Western Norway. They were assessed annually, including blood sampling for determination of micronutrient status. Overall, 663 participants with a total of 2236 serum folate measurements were included. A linear mixed model was applied, and measures are presented as ß-coefficients with 95% confidence interval (CI). Forty-eight percent (CI: 44−51) of the population had low serum folate levels (s-folate < 10 nmol/L), and 23% (CI: 20−26) were deficient (s-folate < 6.8 nmol/L) at baseline. Sixty percent (CI: 53−65) sustained their poor folate status in at least one subsequent assessment. Except for weekly use of cannabis (mean difference in serum folate [nmol/L]: −1.8, CI: −3.3, −0.25) and alcohol (1.9, CI: 0.15, 3.6), weekly use of no other substance class was associated with baseline differences in serum folate when compared to less frequent or no use. Injecting substances was associated with a reduction in serum folate over time (−1.2, CI: −2.3, −0.14), as was higher dosages of OAT medication (−1.1, CI: −2.2, −0.024). Our findings emphasize the need of addressing nutrition among people with severe SUD.

Vitamin B12 Levels, Substance Use Patterns and Clinical Characteristics among People with Severe Substance Use Disorders: A Cohort Study from Western Norway.

People with severe substance use disorder (SUD) have a higher burden of micronutrient deficiency compared with the general population. The aim of this study was to investigate vitamin B12 status and risk factors of deficiency related to substance use, opioid agonist therapy (OAT), as well as hepatitis C infection and liver fibrosis. In this prospective cohort study, participants were recruited from outpatient OAT and SUD clinics in western Norway, and assessed annually with a clinical interview and exam, including venous blood sampling. Data were collected between March 2016 and June 2020, and a total of 2451 serum vitamin B12 measurements from 672 participants were included. The median serum vitamin B12 concentration was 396 (standard deviation 198) pmol/L at baseline, 22% of the population had suboptimal levels (<300 pmol/L) and 1.2% were deficient at baseline (<175 pmol/L). No clear associations were seen with substance use patterns, but liver disease and younger age were associated with higher vitamin B12 levels. Although the majority of participants had satisfactory vitamin B12 levels, about a fifth had suboptimal levels that might or might not be adequate for metabolic needs. Future studies could investigate potential gains in interventions among patients with suboptimal but non-deficient levels.