Genotype by environment interaction effect and fresh root yield stability of cassava genotypes under contrasting nitrogen regimes.

Nitrogen (N) is an important nutrient element needed by cassava for optimum yield and it is a vital component of nucleotides (nucleic acids), enzymes, amino acids (proteins), chlorophyll molecules and hormones, among other essential compounds required for growth and development of cassava. Nitrogen stress is a major cassava production constraint, the study aimed to examine genotype by environment interaction (GEI) effects and fresh root yield stability of 203 diverse cassava clones to identify genotypes with stable performance under low and optimum nitrogen regimes across environments using AMMI and GGE biplot analysis. Experiments were conducted using an augmented block design with three replications for two years in three locations in Nigeria. There were significant differences (p < 0.001) in the genotype's mean performances as well as significant differences (p < 0.001) in the environment's mean performances for all the traits measured in both nitrogen regimes. The AMMI analysis of variance showed significant effects (p < 0.001) for genotypes, environments and the interactions for fresh root yield in both nitrogen regimes. The biplot analysis showed that for fresh root yield in the optimum nitrogen regime, the principal component accounted for 81.54% of the G + GE (Genotype plus and Genotype by Environment) variation. The G + GE for fresh root yield in the low nitrogen regime accounted for a total of 71.64% of the variation. Ten genotypes were identified as the best genotypes under the optimum nitrogen regime, while eleven genotypes were the best under the low nitrogen regime. Three genotypes under optimum nitrogen regimes were high-yielding. Still, they were unstable in their fresh root yield performance across the environments and can be recommended as specifically adapted to the environments they performed best. Three other genotypes were high-yielding genotypes under low nitrogen but were highly unstable in their fresh root yield mean performance across the environments. The environments Otobi_YR1, Igbariam_YR2, and Umudike_YR1 were identified as the most discriminatory among the test environments. The environments Umudike_YR2 and Igbariam_YR1 were identified as the most representative of the test environments and can represent a mega-environment. The best 21 genotypes that performed above the grand mean for fresh root yield in both nitrogen regimes can be further evaluated on the farmer's field for possible advancement.

Impact of COVID-19 Response Strategies on Frontline Health Workers' Motivation: A Case Study in Two Regional Referral Hospitals in Ghana and Uganda.

Background: Several health systems developed interventions and strategies in response to the COVID-19 pandemic, some of which were broad-based, some of which focused on service delivery, and others on frontline health workers. The goal of this study was to see how COVID-19 interventions affected the motivation of frontline health workers in Ghana and Uganda. Methods: The research was undertaken during the period of May to July 2020, coinciding with the initial three months of the global response to the COVID-19 pandemic. This was a critical juncture when the majority of the proposed strategies were in the nascent stages of execution. The research methodology employed was cross-sectional study design, utilizing a qualitative phenomenological approach. The study was conducted across two regional referral hospitals located in Ghana and Uganda. Sixteen frontline healthcare workers from both Uganda and Ghana were selected for interviews, which were conducted both in-person and telephonically. Additionally, one managerial staff member from each hospital was also interviewed. The collected data were subsequently subjected to a deductive thematic analysis. Results: The three themes that emerged from the study include the interventions mentioned by the healthcare workers, the interventions that serve as motivators, and those interventions that act as demotivators. The conceptualization and implementation of the COVID-19 response interventions resulted in differential perceptions regarding their impact on the motivation of healthcare workers in the two hospitals under study. The primary catalysts for healthcare professionals' motivation were the leadership exhibited by their respective governments and supervisors, coupled with certain promises made. These included financial incentives that initially appeared to be motivational, as well as proposals to offer complimentary services. However, the failure to fulfill some of these commitments, along with the unequal distribution of the financial incentives, led to a decrease in motivation among the healthcare workers. Certain human resources for health strategies were perceived as poorly planned and impracticable, resulting in a demotivation among COVID-19 frontline healthcare providers. Conclusion: The COVID-19 response interventions' implementation yielded varied perceptions on healthcare workers' motivation both positive and negative. These were attributed to leadership quality, promises like financial incentives and complementary services, and unmet commitments. The COVID-19 pandemic response strategies in both countries underscore the need for preparedness in the face of unforeseen outbreaks. Failure to sustain healthcare worker motivation may compromise future response effectiveness. Governments must learn from this and come up with well sought of response strategies incorporating health workers' input for comprehensive crisis management. They should establish well-resourced, multisectoral units with specific incentives to handle the response.

Coverage of Child Disability Detection, Management, and Rehabilitation Health Services in Central Uganda.

Background: Child disability is a significant public health concern which impacts 1 in 20 children. Children with disabilities (CwDs) encounter deprivation of rights, biases in society, and a lack of access to necessary services, all of which are exacerbated by structural obstacles. This study assessed the coverage of child disability prevention, management and rehabilitation services in four districts of Central Uganda after two years of interventions to improve these services. Methods: The Lot Quality Assurance Sampling (LQAS) rapid health facility assessment method was employed to assess coverage of services based on sixteen indicators. The indicators were set based on constructs of: provision of disability-related services to CwDs; use of rehabilitation services; readiness of the health facilities (HFs) to provide basic disability management and rehabilitation services; community structures for linkage to disability management and rehabilitation services; psychosocial support provision; and upholding and protecting the rights of CwDs. A district-level decision rule was set based on 80% coverage target. Results: Despite the interventions, the services have yet to provide the desired level of benefit to CwDs and their caregivers. Out of the sixteen indicators for healthcare service coverage for CwDs, only three attained the 80% coverage target. Conclusion: The findings suggest that greater focus by health service planners and project implementers is still needed, especially at the community and health facility levels to enhance the prevention, management and rehabilitation of CwDs. Psychosocial health services for caregivers of CwDs need special attention in order to achieve better service approaches.

Evaluating Antiretroviral Therapy Service Delivery Models Through Lot Quality Assurance Sampling in Central Uganda.

Background: This study evaluated the effectiveness and responsiveness of differentiated Human Immunodeficiency Virus (HIV)/Acquired Immuno-Deficiency Syndrome (AIDS) service delivery models (DSDMs) implemented to enhance antiretroviral therapy (ART) access and outcomes for patients while addressing Tuberculosis (TB)-HIV integration, focusing on four of the five DSDMs currently implemented in Uganda. Methodology: A descriptive cross-sectional survey was conducted in eight districts of central Uganda using Lot Quality Assurance Sampling approach from 7th to 23rd March 2023. We randomly sampled 2668 patients who have been on ART for at least 1 year in a Facility-Based Individual Management (FBIM) model or in a non-FBIM DSDM for at least one year. Data were collected through patient interviews and review of records in ART and DSDM registers as well as ART cards. We analyzed the data in proportions, comparing the selected ART outcome and responsiveness indicators between Community Client Led ART Distribution (CCLAD), Community Drugs Distribution Point (CDDP) and Fast-Track Drug Refill (FTDR) DSDMs with the standard care (FBIM) model. The ART outcome variables include patients retained in the 1st line of the ART regimen, patients in World Health Organization clinical stage 1 during the last facility visit, patients who had no CD4 request during the past 12 months, viral load suppression, ART adherence, and patients who reported that they did not experience HIV/AIDS-related symptoms in the past 6 months. The variables on TB care include screening for TB using the intensified case finding form and patients tested positive for TB. Responsiveness variables include the perceived; travel time for ART refill, travel distance for ART refill, convenience and flexibility during ART refill, cost of travel for ART refill, fear of being seen at ART refill point, waiting time before service, adequacy of service time, crowding and risk of infections, social support, ability to address ART treatment challenges, HIV status disclosure and barriers to access. Non-overlap in 95% confidence interval in indicator proportion between non-FBIM DSDM and FBIM means a statistically significant difference in proportion, or otherwise non-significant. Results: Higher proportions of ART patients in the CCLAD and CDDP DSDMs adhered to ART, had suppressed viral load, and a lower TB prevalence than those in FBIM model. Additionally, more CCLAD and CDDP clients reported shorter travel time and distance to access ART than their counterparts in the FBIM model. Compared to FBIM model, higher proportions of those in CCLAD and CDDP also reported flexibility in ART refill scheduling, reduced transport costs, fewer privacy concerns, less HIV/AIDS-related stigma, shorter waiting times, more efficient services, decreased congestion at ART pickup sites, enhanced peer support, improved problem-solving assistance, and increased HIV status disclosure. The FTDR model outperformed FBIM in proportions with fewer requests for CD4 testing, viral load suppression, as well as proportions of clients who reported; shorter travel time, lower transportation cost, decreased privacy concerns, shorter waiting time, and efficient service provision. Compared to both CDDP and FTDR, the FBIM had a higher proportion of clients remain on the first-line ART regimen. Conclusion: Community-based DSDMs show responsiveness to clients' needs without compromising the effectiveness of ART care for patients. Although FTDR also demonstrates high effectiveness and responsiveness for clients on ART, there is potential for further improvement. Planners and implementers of ART programs should consider both demand- and supply-side innovations to sustain the continuation of DSDMs.

Electrochemical based quantification of bacterial growth in media using square wave voltammetry and low cost screen printed electrodes.

A novel method for determining the yield of bacterial growth using square wave voltammetry and screen printed electrodes is described here. This procedure was shown to be a reliable and accurate way to quickly determine the level of bacterial growth within culturing media and these results suggest that the combination of such sensors and the application of square wave voltammetry is suitable for applications such as within a bioreactor where the rapid determination of bacterial growth may be necessary.

Enhancing HIV treatment and support: a qualitative inquiry into client and healthcare provider perspectives on differential service delivery models in Uganda.

BACKGROUND: HIV/AIDS continues to be a significant contributor to illness and death, particularly in sub-Saharan Africa. In this study, we conducted a qualitative assessment to understand Client and Healthcare Provider Perspectives on Differential Service Delivery Models in Uganda. The purpose was to establish strengths and weaknesses within the services delivery models, inform policy and decision-making, and to facilitate context specific solutions. METHODS: Between February and April 2023, a qualitative cross-sectional study was utilised to gather insights from a targeted selection of individuals, including People Living with HIV (PLHIV), healthcare workers, HIV focal persons, community retail pharmacists, and various stakeholders. The data collection process included eleven in-depth interviews, nine key informant interviews, and eight focus group discussions carried out across eight districts in Central Uganda. The collected data was analyzed through inductive thematic analysis with the aid of Excel. RESULTS: The various Differentiated Service Delivery Models (DSDMs), notably Community-Client-Led Drug Distribution (CCLAD), Community Drug Distribution Point (CDDP), Community Retail Pharmacy Drug Distribution Point (CRPDDP), and the facility-based Facility Based Individual Model (FBIM), were reported to have several positive impacts. These included improved treatment adherence, efficient management of antiretroviral (ARV) supplies, reduced exposure to infectious diseases, enhanced healthcare worker hospitality, minimized travel time for ART refills, stigma reduction, and decreased waiting times. Concern was raised about the lack of improvement in HIV status disclosure, opportunistic infection treatment, adherence to seasonal appointments, and sustainability due to the overreliance of the DSDMs on donor funding, suggesting potential discontinuation without funding. Doubts about health workers' commitment surfaced. Notably, the CCLAD model displayed self-sustainability, with clients financially supporting group members to collect medicines. CONCLUSION: Community-based DSDMs, such as CCLAD and CDDP, improve ART refill convenience, social support, and client experiences. These models reduce travel and waiting times, lowering infection risks. Addressing challenges and enhancing facility-based models is vital. In order to maintain funding after donor funding ends, sustainability measures like cross-subsidization can be used. If well implemented, the DSDMs have the potential to produce better or comparable ART outcomes compared to the FBIM model.

A systematic review of allometric scaling exponents for IgG mAbs.

Increasing complexity of mAbs in development creates challenges in predicting human pharmacokinetic (PK) parameters from preclinical data. The aim of this analysis was to identify optimal allometric scaling exponents.Data were extracted from literature to create a central database (currently the largest available published database) of two-compartment model parameters for mAbs (n = 59) in cynomolgus monkey (CM) and human.Global allometric exponents were calculated and drug-dependent factors were investigated as potential variables in determining the optimal scaling factor.The global exponents for scaling CM mAb PK data were 0.74 (CL), 0.80 (CL with Fc-modified mAbs excluded), 0.44 (CL with Fc-modified mAbs only), 0.71 (Q), 1.12 (V1), and 0.99 (V2). These values are in line with previously published literature values.

Determination of genomic regions associated with early storage root formation and bulking in cassava.

Early cassava storage root formation and bulking is a medium of escape that farmers and processors tend to adopt in cases of abiotic and biotic stresses like drought, flood, and destruction by domestic animals. In this study, 220 cassava genotypes from the International Institute of Tropical Agriculture (IITA), National Root Crops Research Institute (NRCRI), International Center for Tropical Agriculture (CIAT), local farmers (from farmer's field), and NextGen project were evaluated in three locations (Umudike, Benue, and Ikenne). The trials were laid out using a split plot in a randomized incomplete block design (alpha lattice) with two replications in 2 years. The storage roots for each plant genotype were sampled or harvested at 3, 6, 9, and 12 month after planting (MAP). All data collected were analyzed using the R-statistical package. The result showed moderate to high heritability among the traits, and there were significant differences (p< 0.05) among the performances of the genotypes. The genome-wide association mapping using the BLINK model detected 45 single-nucleotide polymorphism (SNP) markers significantly associated with the four early storage root bulking and formation traits on Chromosomes 1, 2, 3, 4, 5, 6, 8, 9, 10, 13, 14, 17, and 18. A total of 199 putative candidate genes were found to be directly linked to early storage root bulking and formation. The functions of these candidate genes were further characterized to regulate i) phytohormone biosynthesis, ii) cellular growth and development, and iii) biosynthesis of secondary metabolites for accumulation of starch and defense. Genome-wide association study (GWAS) also revealed the presence of four pleiotropic SNPs, which control starch content, dry matter content, dry yield, and bulking and formation index. The information on the GWAS could be used to develop improved cassava cultivars by breeders. Five genotypes (W940006, NR090146, TMS982123, TMS13F1060P0014, and NR010161) were selected as the best early storage root bulking and formation genotypes across the plant age. These selected cultivars should be used as sources of early storage root bulking and formation in future breeding programs.

Risk of Periprosthetic Joint Infection in Patients With Ipsilateral Infected Arthroplasties.

Background: The risk of periprosthetic joint infection (PJI) subsequently developing at a second site after an initial PJI has been documented to be approximately 18%-20%. To the best of our knowledge, only a single study has evaluated the incidence in ipsilateral joints and if the risk of infection would be different. While this was the only other study to evaluate this specific subfield, we set to re-evaluate and confirm the incidence of developing a second PJI in the setting of an ipsilateral prosthesis and possible associated risk factors. Methods: We retrospectively reviewed all patients treated surgically for lower-extremity PJI at our institution by 5 surgeons from 2015 to 2021. Patients with multiple arthroplasties on the ipsilateral extremity were included. Time between initial and subsequent infection, risk factors for infection, bacterial source, and bacteremia were identified. Results: Of 392 patients treated for PJI, 179 (45.6%) had multiple prosthetic joints. Forty-seven of those 179 patients had ipsilateral extremity prosthesis, which made up our study population. Three patients (6.4%) developed a separate infection at an ipsilateral TJA. In total, 10 patients (21.3%) developed a separate PJI. Patients on immunosuppressants had a higher likelihood of developing second PJI on the ipsilateral extremity (P = .02). Conclusions: Our study identified the risk of developing an ipsilateral PJI to not be any greater than that in patients with contralateral TJAs. It appears that sharing an extremity with an infected TJA does not pose substantially increased risk of subsequent infection of the un-involved prosthesis. Furthermore, immunosuppressant use may increase the risk of a separate ipsilateral PJI.

Alkoxyalkylation of Electron-Rich Aromatic Compounds.

Alkoxyalkylation and hydroxyalkylation methods utilizing oxo-compound derivatives such as aldehydes, acetals or acetylenes and various alcohols or water are widely used tools in preparative organic chemistry to synthesize bioactive compounds, biosensors, supramolecular compounds and petrochemicals. The syntheses of such molecules of broad relevance are facilitated by acid, base or heterogenous catalysis. However, degradation of the N-analogous Mannich bases are reported to yield alkoxyalkyl derivatives via the retro-Mannich reaction. The mutual derivative of all mentioned species are quinone methides, which are reported to form under both alkoxy- and aminoalkylative conditions and via the degradation of the Mannich-products. The aim of this review is to summarize the alkoxyalkylation (most commonly alkoxymethylation) of electron-rich arenes sorted by the methods of alkoxyalkylation (direct or via retro-Mannich reaction) and the substrate arenes, such as phenolic and derived carbocycles, heterocycles and the widely examined indole derivatives.

Atrial fibrillation inpatient management patterns and clinical outcomes during the conflict in Syria: An observational cohort study.

BACKGROUND: Atrial fibrillation (AF) is the most common sustained arrhythmia worldwide. However, there is no data on AF inpatient management strategies and clinical outcomes in Syria. OBJECTIVES: The study aims were to review the inpatient management of patients with AF and assess cardiovascular (CV) mortality in a tertiary cardiology centre in Latakia, Syria. METHODS: A single-centre retrospective observational cohort study was conducted at Tishreen's University Hospital, Latakia, Syria, from June 2021 to June 2023. Patients ≥16 years of age presenting and being treated for AF as the primary diagnosis with or without a thromboembolic event were included. Medical records were examined for patients' demographics, laboratory results, treatment plans and inpatient details. Studied outcomes include inpatient all-cause and CV mortality, ischemic and bleeding events, and conversion to sinus rhythm (SR). RESULTS: The study included 596 patients. The median age was 58, and 61% were males. 121 patients (20.3%) were known to have AF. A rhythm control strategy was pursued in 39% of patients. Ischemic and bleeding events occurred in 62 (11%) and 12 (2%), respectively. CV and all-cause mortality occurred in 28 (4.7%) and 31 patients (5%), respectively. The presence of valvular heart disease (VHD) (adjusted odds ratio (aOR) = 9.1, 95% confidence interval (CI): 1.7 to 55.1, p < .001), thyroid disease (aOR: 9.7, 95% CI = 1.2 to 91.6, p < .001) and chronic obstructive pulmonary disease (COPD) (aOR: 82, 95% CI: 12.7 to 71, p < .001) were independent risk factors of increased CV inpatient mortality. CONCLUSION: Syrian inpatients admitted with AF in Latakia are relatively younger than those in other countries. Active thyroid disease, COPD and VHD were independent risk factors of inpatient CV mortality with AF.

Dendritic cell subsets and implications for cancer immunotherapy.

Dendritic cells (DCs) play a central role in the orchestration of effective T cell responses against tumors. However, their functional behavior is context-dependent. DC type, transcriptional program, location, intratumoral factors, and inflammatory milieu all impact DCs with regard to promoting or inhibiting tumor immunity. The following review introduces important facets of DC function, and how subset and phenotype can affect the interplay of DCs with other factors in the tumor microenvironment. It will also discuss how current cancer treatment relies on DC function, and survey the myriad ways with which immune therapy can more directly harness DCs to enact antitumor cytotoxicity.

Attaining Equity of Access to Research: Perspective on Research in Pregnancy and Breastfeeding Following Dolores Shockley Lecture at ASCPT2024.

Everybody deserves access to evidence-based information to make decisions about their health. However, in many situations, clinical trial eligibility criteria mean that specific data do not exist for certain groups of individuals. These include pregnant and breastfeeding women, children, older people, those with hepatic and renal dysfunction, those with acute severe illness, and those with multiple co-morbidities and interacting medications. Resultantly, there may not be specific drug-dosing information for many patients who are treated in a clinical setting. The ASCPT2024 Dolores Shockley Lecture focused on the equitable access to research with a specific focus on clinical pharmacology studies in pregnancy and breastfeeding. To ensure the safe, effective use of medication in pregnancy and breastfeeding, women should be included in clinical trials and pharmacokinetic studies when a medication is anticipated to be used in women of childbearing potential. Community groups should be involved at all stages of research to maintain transparency and trust. This ensures that local priorities are investigated, that communities understand the findings and are empowered to make evidence-based decisions about their own medication use. Principles informing the design of such studies in pregnancy and lactation are in existence. Mathematical techniques such as physiologically-based pharmacokinetic modeling and stochastic simulation and estimation can enhance study design, and population pharmacokinetic modeling be used to understand variability within and between individuals. Data should be made findable, accessible, interoperable, and reusable (FAIR). Information (and where necessary, training) regarding the use of these approaches should be provided to decision-making stakeholders such as ethics committees and regulatory bodies.

Round and flat zygomatic implants: effectiveness after a 3­year follow­up non­interventional study.

PURPOSE: This non-interventional study investigates variations in the type and frequency of late complications linked to novel zygomatic implant designs, installed adhering to the Zygoma Anatomy-Guided Approach (ZAGA) concept, over an extended follow-up period of at least 3 years. METHODS: Consecutive patients presenting indications for treatment with ZIs were treated according to ZAGA recommendations. Implants were immediately loaded. The ORIS success criteria for prosthetic offset, stability, sinus changes and soft-tissue status were used to evaluate the outcome. RESULTS: Twenty patients were treated. Ten patients received two ZIs and regular implants; one received three ZIs plus regular implants, and nine received four ZIs. Fifty-nine ZIs were placed: thirty-six (61%) Straumann ZAGA-Flat implants and twenty-three (39%) Straumann ZAGA-Round implants. Four patients (20%) presented earlier sinus floor discontinuities. Fifteen patients (75%) had prior sinus opacities. Nineteen patients were followed for between 38 and 53 months (mean 46.5 months). One patient dropped out after 20 months. When comparing pre-surgical CBCT with post-surgical CBCT, 84.7% of the sites presented identical or less sinus opacity; nine locations (15%) showed decreased, and another nine increased (15%) post-surgical sinus opacity. Fifty-three ZIs (89.8%) maintained stable soft tissue. Six ZIs had recessions with no signs of infection. ZIs and prosthesis survival rate was 100%. CONCLUSIONS: The study highlights the effectiveness of ZAGA-based zygomatic implant rehabilitations using Round and Flat designs. Despite patient number constraints, minimal changes in the frequency of late complications from the 1-year follow-up were observed. 100% implant and prosthesis survival rate over a mean follow-up of 46.5 months is reported.

C-3 alkoxymethylation of 4-oxo-1,4-dihydroquinoline 2-carboxylic acid esters via organic additives.

Esters of kynurenic acid, a known neuroprotective agent were reacted with cyclic amino acids to yield novel alkoxymethylated products under optimized reaction conditions. The importance of amino acid based (primary, secondary, biogenic and synthetic) organic additives was proven by the conduction of numerous test reactions. Thoroughly extended investigations, directly focusing on amino acid catalysis, which is an emerging and up-to-date field of catalysis and green chemical processes, have been conducted. The mechanism of the alkoxymethylation reaction was proposed and later the findings supported the hypothesis of the first retro-Mannich step (formation of the ortho-quinone methide intermediate) and subsequent formation of the alkoxymethylated derivatives. As a preparative result, two novel kynurenic acid derivatives bearing an alkoxymethyl moiety and two additional derivatives having amino acid residues at the site C-3 were synthesized, thus setting the scope and limitations of the modified Mannich reaction of kynurenic acid derivatives using amino acid nucleophiles. The mechanistic investigations highlighted the significant physicochemical effects of used nucleophiles on the amino-acid driven one-pot retro-Mannich initiated alkoxylation of kynurenic acid.

Dose-Response Effects of MittEcho, a Measurement Feedback System, in an Indicated Mental Health Intervention for Children in Municipal and School Services in Norway.

Including routine client feedback can increase the effectiveness of mental health interventions for children, especially when implemented as intended. Rate of implementation, or dose, of such feedback interventions has been shown to moderate results in some studies. Variation in implementation and use of client feedback may also contribute to the mixed results observed within the feedback literature. This study evaluates dose-response associations of client feedback using a novel Measurement Feedback System (MFS) within an indicated group intervention. The primary aim was to determine whether the rate of MFS implementation predicts symptom reduction in anxiety and depression among school-aged children. The secondary aim was to assess whether the rate of MFS implementation influences children's satisfaction with the group intervention or their dropout rates. Data were collected via a randomized factorial study (clinicaltrials.gov NCT04263558) across 58 primary schools in Norway. Children aged 8 to 12 years (N = 701) participated in a group-based, transdiagnostic intervention targeting elevated symptoms of anxiety or depression. Half of the child groups also received the feedback intervention using the MittEcho MFS. Group leaders (N = 83), recruited locally, facilitated the interventions. The MFS dose was measured using the Implementation Index, which combines the use of MFS by both children and providers (group leaders) into a single dose variable. Results showed no significant additional effect of dose of MFS on change in depression or anxiety scores, on user satisfaction with the intervention or on intervention dropout. The discussion addresses potential reasons for these non-significant findings and implications for MFS implementation in preventive, group-based interventions in school settings.

Effectiveness, Safety and Patients' Satisfaction of Nabiximols (Sativex®) on Multiple Sclerosis Spasticity and Related Symptoms in a Swiss Multicenter Study.

Background: Cannabinoid oro-mucosal spray nabiximols is approved for patients with moderate to severe multiple sclerosis spasticity (MSS) resistant to other antispastic medications. Few real-world data are available on the effectiveness, safety and patients' satisfaction in MS patients treated with nabiximols as monotherapy. Methods: To investigate the effectiveness, tolerability and satisfaction of nabiximols in a real-life multicentric Swiss cohort as monotherapy or with stable doses of other antispastic medications, and explore clinical features which may predict treatment response. The following data were collected at treatment start (baseline) and 12 weeks thereafter: Modified Ashworth scale (MAS), scores at numerical rating scales ranging from 0 (absent) to 10 (considerable) for effect on spasticity (sNRS), pain (pNRS), gait (gNRS), urinary symptoms (uNRS), tolerability (tNRS) as assessed by the treating neurologist, and overall treatment satisfaction (TsNRS) and tolerability (tNRS) as assessed by the patient. Results: Ninety-five patients (44 relapsing remitting, 37 secondary progressive and 14 primary progressive MS; median age = 53 (IQR 45-62); female 70%; median EDSS 6 (IQR 4-6), concomitant antispastic treatments in 54% of patients) were included. From baseline to week 12, median MAS score decreased from 3.0 to 2.0 (p < 0.001). Median scores of the each NRS also significantly decreased (p < 0.001 for all comparisons). At week 12, the median TsNRS and tTS scores were 8/10 (IQR: 6-9) and 9/10 (IQR: 7-10), respectively, and 93.7% of patients continued to use nabiximols at the average dose of six sprays/day. No clinical factors, including use of nabiximols as add on vs. monotherapy, were associated with responder status. Conclusions: Our first Swiss, multicentric, observational, real-life study supports and enhances previous finding of nabiximols as monotherapy and as add-on therapy, being an effective, safe and well-tolerated treatment option for resistant MS spasticity and spasticity-related symptoms (pain, bladder dysfunction and gait).

Global Health Commodities Supply Chain in the Era of COVID-19 Pandemic: Challenges, Impacts, and Prospects: A Systematic Review.

Background: The COVID-19 pandemic led to the most substantial health crisis in the 21st Century. This pandemic interrupted the supply of essential commodities for human beings. Among the essential commodities for human survival, disruption of the supply of essential health commodities has become a global concern. Objective: The study aimed to systematically analyze published articles on the challenges, impacts, and prospects of the global health commodities' supply chain in the era of the COVID-19 pandemic. Methods: A standard searching strategy was conducted in seven research databases to retrieve pertinent articles. Finally, 459 articles were retrieved for further screening, and only 13 articles were selected for final synthesis. Results: Almost 38.5% of the studies targeted the supply chain of health commodities used to treat HIV, TB, and malaria. Lockdown policies, travel restrictions, lack of transportation, low manufacturing capacity, and rising costs were the significant challenges indicated for the supply interruption of essential health commodities and COVID-19 vaccines. Findings indicated that the supply interruption of essential health commodities leads to a devastating impact on global health. Conclusion: Global medicine shortages due to the pandemic crisis can have a devastatingly harmful impact on patient outcomes and might result in a devastatingly long-lasting effect on the health of the world community. Supply-related challenges of the COVID-19 vaccine affect countries' ambitions for achieving herd immunity quickly. Monitoring the pandemic's effect on the health commodities' supply system and designing a short-term and long-term resilient health supply chain system that can cope with current and future health catastrophes is pivotal.

Efficacy of a high-intensity home stretching device and traditional physical therapy in non-operative management of adhesive capsulitis - a prospective, randomized control trial.

BACKGROUND: Historically, in-person physical therapy serves as a foundational component of nonoperative treatment of adhesive capsulitis (AC). This study compares the effectiveness of an at-home high-intensity stretch (HIS) device to traditional physical therapy (PT) and to PT in combination with the HIS device. We hypothesize that the HIS device will be as effective as PT alone or as combination therapy in the first-line treatment of AC and use of the HIS device will exhibit improvement at higher rate. METHODS: Thirty-four patients with idiopathic adhesive capsulitis and a minimum of 12 months follow-up were included in this study. Patients were randomized into one of the three groups: HIS device, PT alone, or HIS device + PT. Passive range of motion (ROM), American Shoulder and Elbow Surgeons (ASES), and Simple Shoulder Test (SST) scores were measured. Additionally, patient satisfaction, compliance and complications were recorded. Paired t-test, ANOVA and Chi-squared tests were used in analysis. RESULTS: Final ROM in all planes improved for all groups compared to baseline (p < 0.001), with only HIS device group able to restore > 95% of contralateral ROM in all planes at final follow-up. Patients with PT alone were on average slowest to improve ROM from baseline, at 3 months, 6 months, and 1 year in all planes except internal rotation. ASES and SST scores improved for all groups when compared to baseline (p < 0.001). Use of HIS-device resulted in greater improvement in SST and ASES Total scores compared to PT alone (p = 0.045, and p = 0.048, respectively). CONCLUSIONS: Use of an at-home high-intensity stretching device for conservative treatment of idiopathic adhesive capsulitis improves outcomes in ROM and in ASES and SST scores both when used as an adjunct to physical therapy and when used alone. TRIAL REGISTRATION: The study protocol was registered at www. CLINICALTRIALS: gov (20/05/2022, NCT05384093).

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

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