Temporal genomic analysis of Plasmodium falciparum reveals increased prevalence of mutations associated with delayed clearance following treatment with artemisinin-lumefantrine in Choma District, Southern Province, Zambia.

The emergence of antimalarial drug resistance is an impediment to malaria control and elimination in Africa. Analysis of temporal trends in molecular markers of resistance is critical to inform policy makers and guide malaria treatment guidelines. In a low and seasonal transmission region of southern Zambia, we successfully genotyped 85.5% (389/455) of Plasmodium falciparum samples collected between 2013-2018 from 8 spatially clustered health centres using molecular inversion probes (MIPs) targeting key drug resistance genes. Aside from one sample carrying K13 R622I, none of the isolates carried other World Health Organization-validated or candidate artemisinin partial resistance (ART-R) mutations in K13. However, 13% (CI, 9.6-17.2) of isolates had the AP2MU S160N mutation, which has been associated with delayed clearance following artemisinin combination therapy in Africa. This mutation increased in prevalence between 2015-2018 and bears a genomic signature of selection. During this time period, there was an increase in the MDR1 NFD haplotype that is associated with reduced susceptibility to lumefantrine. Sulfadoxine-pyrimethamine polymorphisms were near fixation. While validated ART-R mutations are rare, a mutation associated with slow parasite clearance in Africa appears to be under selection in southern Zambia.

Assessing the nutrient content of plant-based milk alternative products available in the U.S.

BACKGROUND: Consumption of plant-based milk alternatives is increasing. Current dietary guidance primarily relies on dairy milk as a source of key nutrients of public health concern including calcium and vitamin D. OBJECTIVE: To compare the nutritional content of plant-based milk alternatives between categories (e.g., soy, almond, and oat) and with dairy milk. DESIGN: This study presents an evaluation of the nutritional content of 219 plant-based milk alternatives from 21 brands available in the US marketplace using data from the University of Minnesota Nutrition Coordinating Center's (NCC) database. MAIN OUTCOME MEASURES: Nutrients of focus include those identified as nutrients of public health concern in the Dietary Guidelines for American's (DGA) or used by the United States Department of Agriculture (USDA) as criteria for determining whether a plant-based milk is a suitable substitute for dairy milk. STATISTICAL ANALYSES PERFORMED: Most data are presented as percent Daily Values (% DV). Nutrients and food components were compared using means, medians, interquartile ranges (IQR), and ranges. Statistical tests for significance were not used to evaluate between category differences because the plant-based milk alternatives included are a full census of the products from 21 brands available in the marketplace. Because data are a census, differences can be understood to be true differences. RESULTS: Fortified soy-based products most closely mimic the nutrient content of dairy milk. High variability was present in all the nutrients and food components. Plant-based milk alternatives were generally lower in protein and saturated fatty acids than dairy milk, with high variability in added sugars content. Approximately 70% were fortified with both calcium and vitamin D. CONCLUSIONS: These results indicate that most plant-based milk alternative products are not nutritionally equivalent to dairy milk, and there is high nutritional variability between and within product types. These findings highlight the importance of communicating the nutritional differences between plant-based milk alternatives and dairy milk to consumers.

The effectiveness of abstinence-based and harm reduction-based interventions in reducing problematic substance use in adults who are experiencing homelessness in high income countries: A systematic review and meta-analysis: A systematic review.

Background: Homelessness is a traumatic experience, and can have a devastating effect on those experiencing it. People who are homeless often face significant barriers when accessing public services, and have often experienced adverse childhood events, extreme social disadvantage, physical, emotional and sexual abuse, neglect, low self-esteem, poor physical and mental health, and much lower life expectancy compared to the general population. Rates of problematic substance use are disproportionately high, with many using drugs and alcohol to deal with the stress of living on the street, to keep warm, or to block out memories of previous abuse or trauma. Substance dependency can also create barriers to successful transition to stable housing. Objectives: To understand the effectiveness of different substance use interventions for adults experiencing homelessness. Search Methods: The primary source of studies for was the 4th edition of the Homelessness Effectiveness Studies Evidence and Gaps Maps (EGM). Searches for the EGM were completed in September 2021. Other potential studies were identified through a call for grey evidence, hand-searching key journals, and unpacking relevant systematic reviews. Selection Criteria: Eligible studies were impact evaluations that involved some comparison group. We included studies that tested the effectiveness of substance use interventions, and measured substance use outcomes, for adults experiencing homelessness in high income countries. Data Collection and Analysis: Descriptive characteristics and statistical information in included studies were coded and checked by at least two members of the review team. Studies selected for the review were assessed for confidence in the findings. Standardised effect sizes were calculated and, if a study did not provide sufficient raw data for the calculation of an effect size, author(s) were contacted to obtain these data. We used random-effects meta-analysis and robust-variance estimation procedures to synthesise effect sizes. If a study included multiple effects, we carried out a critical assessment to determine (even if only theoretically) whether the effects are likely to be dependent. Where dependent effects were identified, we used robust variance estimation to determine whether we can account for these. Where effect sizes were converted from a binary to continuous measure (or vice versa), we undertook a sensitivity analysis by running an additional analysis with these studies omitted. We also assessed the sensitivity of results to inclusion of non-randomised studies and studies classified as low confidence in findings. All included an assessment of statistical heterogeneity. Finally, we undertook analysis to assess whether publication bias was likely to be a factor in our findings. For those studies that we were unable to include in meta-analysis, we have provided a narrative synthesis of the study and its findings. Main Results: We included 48 individual papers covering 34 unique studies. The studies covered 15, 255 participants, with all but one of the studies being from the United States and Canada. Most papers were rated as low confidence (n = 25, or 52%). By far the most common reason for studies being rated as low confidence was high rates of attrition and/or differential attrition of study participants, that fell below the What Works Clearinghouse liberal attrition standard. Eleven of the included studies were rated as medium confidence and 12 studies as high confidence. The interventions included in our analysis were more effective in reducing substance use than treatment as usual, with an overall effect size of -0.11 SD (95% confidence interval [CI], -0.27, 0.05). There was substantial heterogeneity across studies, and the results were sensitive to the removal of low confidence studies (-0.21 SD, 95% CI [-0.59, 0.17] - 6 studies, 17 effect sizes), the removal of quasi-experimental studies (-0.14 SD, 95% CI [-0.30, 0.02] - 14 studies, 41 effect sizes) and the removal of studies where an effect size had been converted from a binary to a continuous outcome (-0.08 SD, 95% CI [-0.31, 0.15] - 10 studies, 31 effect sizes). This suggests that the findings are sensitive to the inclusion of lower quality studies, although unusually the average effect increases when we removed low confidence studies. The average effect for abstinence-based interventions compared to treatment-as-usual (TAU) service provision was -0.28 SD (95% CI, -0.65, 0.09) (6 studies, 15 effect sizes), and for harm reduction interventions compared to a TAU service provision is close to 0 at 0.03 SD (95% CI, -0.08, 0.14) (9 studies, 30 effect sizes). The confidence intervals for both estimates are wide and crossing zero. For both, the comparison groups are primarily abstinence-based, with the exception of two studies where the comparison group condition was unclear. We found that both Assertative Community Treatment and Intensive Case Management were no better than treatment as usual, with average effect on substance use of 0.03 SD, 95% CI [-0.07, 0.13] and -0.47 SD, 95% CI [-0.72, -0.21] 0.05 SD, 95% CI [-0.28, 0.39] respectively. These findings are consistent with wider research, and it is important to note that we only examined the effect on substance use outcomes (these interventions can be effective in terms of other outcomes). We found that CM interventions can be effective in reducing substance use compared to treatment as usual, with an average effect of -0.47 SD, 95% CI (-0.72, -0.21). All of these results need to be considered in light of the quality of the underlying evidence. There were six further interventions where we undertook narrative synthesis. These syntheses suggest that Group Work, Harm Reduction Psychotherapy, and Therapeutic Communities are effective in reducing substance use, with mixed results found for Motivational Interviewing and Talking Therapies (including Cognitive Behavioural Therapy). The narrative synthesis suggested that Residential Rehabilitation was no better than treatment as usual in terms of reducing substance use for our population of interest. Authors' Conclusions: Although our analysis of harm reduction versus treatment as usual, abstinence versus treatment as usual, and harm reduction versus abstinence suggests that these different approaches make little real difference to the outcomes achieved in comparison to treatment as usual. The findings suggest that some individual interventions are more effective than others. The overall low quality of the primary studies suggests that further primary impact research could be beneficial.

Pharmaceutical and biotech industry perspectives on optimizing patient experience and treatment adherence through subcutaneous drug delivery design.

Subcutaneous (SC) drug delivery can be a safe, effective alternative to the traditional intravenous route of administration, potentially offering notable advantages for both patients and healthcare providers. The SC Drug Development & Delivery Consortium convened in 2018 to raise awareness of industry challenges to advance the development of patient-centric SC drug delivery strategies. The SC Consortium identified better understanding of patient preferences and perspectives as necessary to optimize SC product design attributes and help guide design decisions during SC product development. This manuscript provides a comprehensive overview of patient-centric factors for consideration in the SC drug delivery design and development process with the aim of establishing a foundation of existing knowledge for patient experiences related to SC drug delivery. This overview is informed by the outcomes of a multi-step survey of Consortium members and key pharmaceutical stakeholders. Framed in the context of the patient's treatment journey, the survey findings offer future perspectives to fill data gaps to advance patient-centric SC drug delivery.

The association of degree of polypharmacy before and after among hospitalised internal medicine patients and clinical outcomes: a retrospective, population-based cohort study.

OBJECTIVES: To determine the prevalence and incidence of polypharmacy/hyperpolypharmacy and which medications are most prescribed to patients with varying burden of polypharmacy. DESIGN: Retrospective, population-based cohort study. SETTING: Iceland. PARTICIPANTS: Including patients (≥18 years) admitted to internal medicine services at Landspitali - The National University Hospital of Iceland, between 1 January 2010 with a follow-up of clinical outcomes through 17 March 2022. MAIN OUTCOMES MEASURES: Participants were categorised into medication use categories of non-polypharmacy (<5), polypharmacy (5-10) and hyperpolypharmacy (>10) based on the number of medications filled in the year predischarge and postdischarge. The primary outcome was prevalence and incidence of new polypharmacy. Secondary outcomes were mortality, length of hospital stay and re-admission. RESULTS: Among 85 942 admissions (51% male), the median (IQR) age was 73 (60-83) years. The prevalence of preadmission non-polypharmacy was 15.1% (95% CI 14.9 to 15.3), polypharmacy was 22.9% (95% CI 22.6 to 23.2) and hyperpolypharmacy was 62.5% (95% CI 62.2 to 62.9). The incidence of new postdischarge polypharmacy was 33.4% (95% CI 32.9 to 33.9), and for hyperpolypharmacy was 28.9% (95% CI 28.3 to 29.5) for patients with preadmission polypharmacy. Patients with a higher level of medication use were more likely to use multidose drug dispensing and have a diagnosis of adverse drug reaction. Other comorbidities, including responsible subspeciality and estimates of comorbidity and frailty burden, were identical between groups of varying polypharmacy. There was no difference in length of stay, re-admission rate and mortality. CONCLUSIONS: Preadmission polypharmacy/hyperpolypharmacy and postdischarge new polypharmacy/hyperpolypharmacy is common amongst patients admitted to internal medicine. A higher level of medication use category was not found to be associated with demographic, comorbidity and clinical outcomes. Medications that are frequently inappropriately prescribed were among the most prescribed medications in the group. An increased focus on optimising medication usage is needed after hospital admission. TRIAL REGISTRATION NUMBER: NCT05756400.

Spatial-temporal vector abundance and malaria transmission dynamics in Nchelenge and Lake Mweru islands, a region with a high burden of malaria in northern Zambia.

BACKGROUND: Over a decade of vector control by indoor residual spraying (IRS) and long-lasting insecticidal nets (LLINs) distribution on the mainland, and only LLINs on islands had a minimal impact on disease burden in Nchelenge district, northern Zambia. Anopheles funestus and Anopheles gambiae are vectors known only from the mainland. Understanding vector bionomics in the district is necessary for planning and targeting effective vector control. This study aimed to provide information on abundance, seasonality, and Plasmodium falciparum sporozoite infectivity of malaria vectors in Nchelenge, including islands. METHODS: Mosquitoes were collected in 192 CDC indoor light traps set in 56 households between January 2015 and January 2016. Morphological and molecular species identifications and P. falciparum circumsporoites by ELISA were performed. Mosquito counts and relative abundances from the islands and mainland were compared, and household factors associated with vector counts were determined. RESULTS: A total of 5888 anophelines were collected during the study. Of these, 5,704 were female Anopheles funestus sensu lato (s.l.) and 248 female An. gambiae s.l. The highest proportion of An. funestus (n = 4090) was from Chisenga Island and An. gambiae (n = 174) was from Kilwa Island. The highest estimated counts per trap for An. funestus s.l. were from Chisenga island, (89.9, p < 0.001) and from the dry season (78.6, p < 001). For An. gambiae the highest counts per trap were from Kilwa island (3.1, p < 0.001) and the rainy season (2.5, p = 0.007). The highest estimated annual entomological inoculation rate was from Chisenga Island with 91.62 ib/p/y followed by Kilwa Island with 29.77 ib/p/yr, and then Mainland with 19.97 ib/p/yr. CONCLUSIONS: There was varied species abundance and malaria transmission risk across sites and seasons. The risk of malaria transmission was perennial and higher on the islands. The minimal impact of vector control efforts on the mainland was evident, but limited overall. Vector control intervention coverage with effective tools needs to be extended to the islands to effectively control malaria transmission in Nchelenge district.

Temporal and spatial analysis of Plasmodium falciparum genomics reveals patterns of parasite connectivity in a low-transmission district in Southern Province, Zambia.

BACKGROUND: Understanding temporal and spatial dynamics of malaria transmission will help to inform effective interventions and strategies in regions approaching elimination. Parasite genomics are increasingly used to monitor epidemiologic trends, including assessing residual transmission across seasons and importation of malaria into these regions. METHODS: In a low and seasonal transmission setting of southern Zambia, a total of 441 Plasmodium falciparum samples collected from 8 neighbouring health centres between 2012 and 2018 were genotyped using molecular inversion probes (MIPs n = 1793) targeting a total of 1832 neutral and geographically informative SNPs distributed across the parasite genome. After filtering for quality and missingness, 302 samples and 1410 SNPs were retained and used for downstream population genomic analyses. RESULTS: The analyses revealed most (67%, n = 202) infections harboured one clone (monogenomic) with some variation at local level suggesting low, but heterogenous malaria transmission. Relatedness identity-by-descent (IBD) analysis revealed variable distribution of IBD segments across the genome and 6% of pairs were highly-related (IBD ≥ 0.25). Some of the highly-related parasite populations persisted across multiple seasons, suggesting that persistence of malaria in this low-transmission region is fueled by parasites "seeding" across the dry season. For recent years, clusters of clonal parasites were identified that were dissimilar to the general parasite population, suggesting parasite populations were increasingly fragmented at small spatial scales due to intensified control efforts. Clustering analysis using PCA and t-SNE showed a lack of substantial parasite population structure. CONCLUSION: Leveraging both genomic and epidemiological data provided comprehensive picture of fluctuations in parasite populations in this pre-elimination setting of southern Zambia over 7 years.

Residual insecticide surface treatment for preventing malaria: a systematic review protocol.

INTRODUCTION: Malaria presents a significant global public health burden, although substantial progress has been made, with vector control initiatives such as indoor residual surface spraying with insecticides and insecticide-treated nets. There now exists many different approaches to apply residual insecticide to indoor and outdoor surfaces in malaria-endemic settings, although no comprehensive systematic reviews exist evaluating these interventions. This manuscript outlines the protocol for a systematic review which aims to synthesise the best available evidence regarding full or partial indoor or outdoor residual insecticide surface treatment for preventing malaria. METHODS AND ANALYSIS: This review will comprehensively search the literature (both published and unpublished) for any studies investigating the effectiveness of residual insecticide surface treatment for malaria. Studies will be screened to meet the inclusion criteria by a minimum of two authors, followed by assessment of risk of bias (using appropriate risk-of-bias tools for randomised and non-randomised studies) and extraction of relevant information using structured forms by two independent authors. Meta-analysis will be carried out where possible for epidemiological outcomes such as malaria, anaemia, malaria-related mortality, all-cause mortality and adverse effects. Certainty in the evidence will be established with GRADE assessments. ETHICS AND DISSEMINATION: A full review report will be submitted to the Vector Control & Insecticide Resistance Unit, Global Malaria Program, WHO. A version of this report will be submitted for publication in an open access peer-reviewed journal. The report will inform the development of WHO recommendations regarding residual insecticide treatment for malaria. This systematic review does not require ethics approval as it is a review of primary studies. SYSTEMATIC REVIEW REGISTRATION: PROSPERO 293194.

Semi-field evaluation of a volatile transfluthrin-based intervention reveals efficacy as a spatial repellent and evidence of other modes of action.

Presently, the most common malaria control tools-i.e., long lasting insecticide-treated nets (LLINs) and indoor residual spraying (IRS)-are limited to targeting indoor biting and resting behaviors of Anopheles mosquito species. Few interventions are targeted towards malaria control in areas where transmission is driven or persists due to outdoor biting behaviors. This study investigated a volatile pyrethroid-based spatial repellent (VPSR) designed to bridge this gap and provide protection from mosquito bites in outdoor spaces. Southern Province, Zambia, is one such environment where outdoor biting is suspected to contribute to malaria transmission, where people are active in the evening in open-walled outdoor kitchens. This study assessed the VPSR in replica kitchens within a controlled semi-field environment. Endpoints included effects on mosquito host seeking, immediate and delayed mortality, deterrence, blood feeding inhibition, and fertility. Host-seeking was reduced by approximately 40% over the course of nightly releases in chambers containing VPSR devices. Mosquito behavior was not uniform throughout the night, and the modeled effect of the intervention was considerably higher when hourly catch rates were considered. These two observations highlight a limitation of this overnight semi-field design and consideration of mosquito circadian rhythms is recommended for future semi-field studies. Additionally, deterrence and immediate mortality were both observed in treatment chambers, with evidence of delayed mortality and a dose related response. These results demonstrate a primarily personal protective mode of action with possible positive and negative community effects. Further investigation into this primary mode of action will be conducted through a field trial of the same product in nearby communities.

Human scent guides mosquito thermotaxis and host selection under naturalistic conditions.

The African malaria mosquito Anopheles gambiae exhibits a strong innate drive to seek out humans in its sensory environment, classically entering homes to land on human skin in the hours flanking midnight. To gain insight into the role that olfactory cues emanating from the human body play in generating this epidemiologically important behavior, we developed a large-scale multi-choice preference assay in Zambia with infrared motion vision under semi-field conditions. We determined that An. gambiae prefers to land on arrayed visual targets warmed to human skin temperature during the nighttime when they are baited with carbon dioxide (CO2) emissions reflective of a large human over background air, body odor from one human over CO2, and the scent of one sleeping human over another. Applying integrative whole body volatilomics to multiple humans tested simultaneously in competition in a six-choice assay, we reveal high attractiveness is associated with whole body odor profiles from humans with increased relative abundances of the volatile carboxylic acids butyric acid, isobutryic acid, and isovaleric acid, and the skin microbe-generated methyl ketone acetoin. Conversely, those least preferred had whole body odor that was depleted of carboxylic acids among other compounds and enriched with the monoterpenoid eucalyptol. Across expansive spatial scales, heated targets without CO2 or whole body odor were minimally or not attractive at all to An. gambiae. These results indicate that human scent acts critically to guide thermotaxis and host selection by this prolific malaria vector as it navigates towards humans, yielding intrinsic heterogeneity in human biting risk.

Epidemiology and association with outcomes of polypharmacy in patients undergoing surgery: retrospective, population-based cohort study.

BACKGROUND: The aim of this study was to determine the prevalence of preoperative polypharmacy and the incidence of postoperative polypharmacy/hyper-polypharmacy in surgical patients and their association with adverse outcomes. METHODS: This was a retrospective, population-based cohort study among patients older than or equal to 18 years undergoing surgery at a university hospital between 2005 and 2018. Patients were categorized based on the number of medications: non-polypharmacy (fewer than 5); polypharmacy (5-9); and hyper-polypharmacy (greater than or equal to 10). The 30-day mortality, prolonged hospitalization (greater than or equal to 10 days), and incidence of readmission were compared between medication-use categories. RESULTS: Among 55 997 patients, the prevalence of preoperative polypharmacy was 32.3 per cent (95 per cent c.i. 33.5 to 34.3) and the prevalence of hyper-polypharmacy was 25.5 per cent (95 per cent c.i. 25.2 to 25.9). Thirty-day mortality was higher for patients exposed to preoperative hyper-polypharmacy (2.3 per cent) and preoperative polypharmacy (0.8 per cent) compared with those exposed to non-polypharmacy (0.6 per cent) (P < 0.001). The hazards ratio (HR) of long-term mortality was higher for patients exposed to hyper-polypharmacy (HR 1.32 (95 per cent c.i. 1.25 to 1.40)) and polypharmacy (HR 1.07 (95 per cent c.i. 1.01 to 1.14)) after adjustment for patient and procedural variables. The incidence of longer hospitalization (greater than or equal to 10 days) was higher for hyper-polypharmacy (11.3 per cent) and polypharmacy (6.3 per cent) compared with non-polypharmacy (4.1 per cent) (P < 0.001). The 30-day incidence of readmission was higher for patients exposed to hyper-polypharmacy (10.2 per cent) compared with polypharmacy (6.1 per cent) and non-polypharmacy (4.8 per cent) (P < 0.001). Among patients not exposed to polypharmacy, the incidence of new postoperative polypharmacy/hyper-polypharmacy was 33.4 per cent (95 per cent c.i. 32.8 to 34.1), and, for patients exposed to preoperative polypharmacy, the incidence of postoperative hyper-polypharmacy was 16.3 per cent (95 per cent c.i. 16.0 to 16.7). CONCLUSION: Preoperative polypharmacy and new postoperative polypharmacy/hyper-polypharmacy are common and associated with adverse outcomes. This highlights the need for increased emphasis on optimizing medication usage throughout the perioperative interval. REGISTRATION NUMBER: NCT04805151 (http://clinicaltrials.gov).

Safety and effectiveness of the sodium-glucose cotransporter inhibitor bexagliflozin in cats newly diagnosed with diabetes mellitus.

BACKGROUND: Bexagliflozin is a sodium-glucose cotransporter 2 (SGLT2) inhibitor. A pilot study has shown that bexagliflozin can decrease dependence on exogenous insulin in cats with diabetes mellitus (DM). OBJECTIVE: To evaluate the safety and effectiveness of bexagliflozin as a monotherapy for DM in previously untreated cats. ANIMALS: Eighty-four client-owned cats. METHODS: Historically controlled prospective open-label clinical trial. Cats were dosed PO with 15 mg bexagliflozin once daily for 56 days, with a 124-day extension to evaluate safety and treatment effect durability. The primary endpoint was the proportion of cats experiencing a decrease in hyperglycemia and improvement in clinical signs of hyperglycemia from baseline on day 56. RESULTS: Of 84 enrolled cats, 81 were evaluable on day 56, and 68 (84.0%) were treatment successes. Decreases in mean serum glucose, fructosamine, and ß-hydroxybutyrate (ß-OHB) concentrations were observed, and investigator assessments of cat neurological status, musculature, and hair coat quality improved. Owner evaluations of both cat and owner quality of life were favorable. The fructosamine half-life in diabetic cats was found to be 6.8 days. Commonly observed adverse events included emesis, diarrhea, anorexia, lethargy, and dehydration. Eight cats experienced serious adverse events, 3 of which led to death or euthanasia. The most important adverse event was euglycemic diabetic ketoacidosis, diagnosed in 3 cats and presumed present in a fourth. CONCLUSION AND CLINICAL IMPORTANCE: Bexagliflozin decreased hyperglycemia and observed clinical signs in cats newly diagnosed with DM. As a once-daily PO medication, bexagliflozin may simplify management of DM in cats.

Hospital pharmacists' opinions on a risk prediction tool for medication-related harm in older people.

AIM: Older adults are particularly affected by medication-related harm (MRH) during transitions of care. There are no clinical tools predicting those at highest risk of MRH post hospital discharge. The PRIME study (prospective study to develop a model to stratify the risk of MRH in hospitalized patients) developed and internally validated a risk-prediction tool (RPT) that provides a percentage score of MRH in adults over 65 in the 8 weeks following hospital discharge. This qualitative study aimed to explore the views of hospital pharmacists around enablers and barriers to clinical implementation of the PRIME-RPT. METHODS: Ten hospital pharmacists: (band 6, n = 3; band 7, n = 2; band 8, n = 5) participated in semistructured interviews at the Royal Sussex County Hospital (Brighton, UK). The pharmacists were presented with five case-vignettes each with a calculated PRIME-RPT score to help guide discussion. Case-vignettes were designed to be representative of common clinical encounters. Data were thematically analysed using a "framework" approach. RESULTS: Seven themes emerged in relation to the PRIME-RPT: (1) providing a medicine-prioritisation aide; (2) acting as a deprescribing alert; (3) facilitating a holistic review of patient medication management; (4) simplifying communication of MRH to patients and the multidisciplinary team; (5) streamlining community follow-up and integration of risk discussion into clinical practice; (6) identifying barriers for the RPTs integration in clinical practice; and (7) acknowledging its limitations. CONCLUSION: Hospital pharmacists found the PRIME-RPT beneficial in identifying older patients at high risk of MRH following hospital discharge, facilitating prioritising interventions to those at highest risk while still acknowledging its limitations.

Implementation of a medicine management plan (MMP) to reduce medication-related harm (MRH) in older people post-hospital discharge: a randomised controlled trial.

BACKGROUND: Medication-related harm (MRH) is an escalating global challenge especially among older adults. The period following hospital discharge carries high-risk for MRH due to medication discrepancies, limited patient/carer education and support, and poor communication between hospital and community professionals. Discharge Medical Service (DMS), a newly introduced NHS scheme, aims to reduce post-discharge MRH through an electronic communication between hospital and community pharmacists. Our study team has previously developed a risk-prediction tool (RPT) for MRH in the 8-weeks period post discharge from a UK hospital cohort of 1280 patients. In this study, we aim to find out if a Medicines Management Plan (MMP) linked to the DMS is more effective than the DMS alone in reducing rates of MRH. METHOD: Using a randomized control trial design, 682 older adults ≥ 65 years due to be discharged from hospital will be recruited from 4 sites. Participants will be randomized to an intervention arm (individualised medicine management plan (MMP) plus DMS) or a control arm (DMS only) using a 1:1 ratio stratification. Baseline data will include patients' clinical and social demographics, and admission and discharge medications. At 8-weeks post-discharge, a telephone interview and review of GP records by the study pharmacist will verify MRH in both arms. An economic and process evaluation will assess the cost and acceptability of the study methods. DATA ANALYSIS: Univariate analysis will be done for baseline variables comparing the intervention and control arms. A multivariate logistic regression will be done incorporating these variables. Economic evaluation will compare the cost-of-service use among the study arms and modelled to provide national estimates. Qualitative data from focus-group interviews will explore practitioners' understanding, and acceptance of the MMP, DMS and the RPT. CONCLUSION: This study will inform the use of an objective, validated RPT for MRH among older adults after hospital discharge, and provide a clinical, economic, and service evaluation of a specific medicines management plan alongside the DMS in the National Health Service (UK).

Impact of aerial humidity on seasonal malaria: an ecological study in Zambia.

BACKGROUND: Seasonal patterns of malaria cases in many parts of Africa are generally associated with rainfall, yet in the dry seasons, malaria transmission declines but does not always cease. It is important to understand what conditions support these periodic cases. Aerial moisture is thought to be important for mosquito survival and ability to forage, but its role during the dry seasons has not been well studied. During the dry season aerial moisture is minimal, but intermittent periods may arise from the transpiration of peri-domestic trees or from some other sources in the environment. These periods may provide conditions to sustain pockets of mosquitoes that become active and forage, thereby transmitting malaria. In this work, humidity along with other ecological variables that may impact malaria transmission have been examined. METHODS: Negative binomial regression models were used to explore the association between peri-domestic tree humidity and local malaria incidence. This was done using sensitive temperature and humidity loggers in the rural Southern Province of Zambia over three consecutive years. Additional variables including rainfall, temperature and elevation were also explored. RESULTS: A negative binomial model with no lag was found to best fit the malaria cases for the full year in the evaluated sites of the Southern Province of Zambia. Local tree and granary night-time humidity and temperature were found to be associated with local health centre-reported incidence of malaria, while rainfall and elevation did not significantly contribute to this model. A no lag and one week lag model for the dry season alone also showed a significant effect of humidity, but not temperature, elevation, or rainfall. CONCLUSION: The study has shown that throughout the dry season, periodic conditions of sustained humidity occur that may permit foraging by resting mosquitoes, and these periods are associated with increased incidence of malaria cases. These results shed a light on conditions that impact the survival of the common malaria vector species, Anopheles arabiensis, in arid seasons and suggests how they emerge to forage when conditions permit.

Scientific Findings of the Southern and Central Africa International Center of Excellence for Malaria Research: Ten Years of Malaria Control Impact Assessments in Hypo-, Meso-, and Holoendemic Transmission Zones in Zambia and Zimbabwe.

For a decade, the Southern and Central Africa International Center of Excellence for Malaria Research has operated with local partners across study sites in Zambia and Zimbabwe that range from hypo- to holoendemic and vary ecologically and entomologically. The burden of malaria and the impact of control measures were assessed in longitudinal cohorts, cross-sectional surveys, passive and reactive case detection, and other observational designs that incorporated multidisciplinary scientific approaches: classical epidemiology, geospatial science, serosurveillance, parasite and mosquito genetics, and vector bionomics. Findings to date have helped elaborate the patterns and possible causes of sustained low-to-moderate transmission in southern Zambia and eastern Zimbabwe and recalcitrant high transmission and fatality in northern Zambia. Cryptic and novel mosquito vectors, asymptomatic parasite reservoirs in older children, residual parasitemia and gametocytemia after treatment, indoor residual spraying timed dyssynchronously to vector abundance, and stockouts of essential malaria commodities, all in the context of intractable rural poverty, appear to explain the persistent malaria burden despite current interventions. Ongoing studies of high-resolution transmission chains, parasite population structures, long-term malaria periodicity, and molecular entomology are further helping to lay new avenues for malaria control in southern and central Africa and similar settings.

Policy Implications of the Southern and Central Africa International Center of Excellence for Malaria Research: Ten Years of Malaria Control Impact Assessments in Hypo-, Meso-, and Holoendemic Transmission Zones in Zambia and Zimbabwe.

The International Centers of Excellence for Malaria Research (ICEMR) were established by the National Institute of Allergy and Infectious Diseases more than a decade ago to provide multidisciplinary research support to malaria control programs worldwide, operating in endemic areas and contributing technology, expertise, and ultimately policy guidance for malaria control and elimination. The Southern and Central Africa ICEMR has conducted research across three main sites in Zambia and Zimbabwe that differ in ecology, entomology, transmission intensity, and control strategies. Scientific findings led to new policies and action by the national malaria control programs and their partners in the selection of methods, materials, timing, and locations of case management and vector control. Malaria risk maps and predictive models of case detection furnished by the ICEMR informed malaria elimination programming in southern Zambia, and time series analyses of entomological and parasitological data motivated several major changes to indoor residual spray campaigns in northern Zambia. Along the Zimbabwe-Mozambique border, temporal and geospatial data are currently informing investigations into a recent resurgence of malaria. Other ICEMR findings pertaining to parasite and mosquito genetics, human behavior, and clinical epidemiology have similarly yielded immediate and long-term policy implications at each of the sites, often with generalizable conclusions. The ICEMR programs thereby provide rigorous scientific investigations and analyses to national control and elimination programs, without which the impediments to malaria control and their potential solutions would remain understudied.

A Systematic Review of the Current Evidence from Randomised Controlled Trials on the Impact of Medication Optimisation or Pharmacological Interventions on Quantitative Measures of Cognitive Function in Geriatric Patients.

BACKGROUND: Cognitive decline is common in older people. Numerous studies point to the detrimental impact of polypharmacy and inappropriate medication on older people's cognitive function. Here we aim to systematically review evidence on the impact of medication optimisation and drug interventions on cognitive function in older adults. METHODS: A systematic review was performed using MEDLINE and Web of Science on May 2021. Only randomised controlled trials (RCTs) addressing the impact of medication optimisation or pharmacological interventions on quantitative measures of cognitive function in older adults (aged > 65 years) were included. Single-drug interventions (e.g., on drugs for dementia) were excluded. The quality of the studies was assessed by using the Jadad score. RESULTS: Thirteen studies met the inclusion criteria. In five studies a positive impact of the intervention on metric measures of cognitive function was observed. Only one study showed a significant improvement of cognitive function by medication optimisation. The remaining four positive studies tested methylphenidate, selective oestrogen receptor modulators, folic acid and antipsychotics. The mean Jadad score was low (2.7). CONCLUSION: This systematic review identified a small number of heterogenous RCTs investigating the impact of medication optimisation or pharmacological interventions on cognitive function. Five trials showed a positive impact on at least one aspect of cognitive function, with comprehensive medication optimisation not being more successful than focused drug interventions. More prospective trials are needed to specifically assess ways of limiting the negative impact of certain medication in particular and polypharmacy in general on cognitive function in older patients.

The Unmeasured Burden of Febrile, Respiratory, and Diarrheal Illnesses Identified Through Active Household Surveillance in a Low Malaria Transmission Setting in Southern Zambia.

Malaria incidence has declined in southern Zambia over recent decades, leading to efforts to achieve and sustain malaria elimination. Understanding the remaining disease burden is key to providing optimal health care. A longitudinal study conducted in a rural area of Choma District, Southern Province, Zambia, assessed the prevalence of and factors associated with symptoms of non-malarial illnesses and treatment-seeking behavior. We analyzed data collected monthly between October 2018 through September 2020 from 1,174 individuals from 189 households. No incident malaria cases were detected by rapid diagnostic tests among febrile participants. Mixed-effects logistic regression identified factors associated with cough, fever, diarrhea, and treatment-seeking. Incidence rates of cough (192 of 1,000 person-months), fever (87 of 1,000 person-months), and fever with cough (37 of 1,000 person-months) were highest among adults older than 65 years. Diarrhea incidence (37 of 1,000 person-months) was highest among children younger than 5 years. For every additional symptomatic household member, one's odds of experiencing symptoms increased: cough by 47% (95% CI, 40-55), fever by 31% (95% CI, 23-40), diarrhea by 31% (95% CI, 17-46), and fever with cough by 112% (95% CI, 90-137), consistent with household clustering of illnesses. However, between 35% and 75% of participants did not seek treatment for their symptoms. Treatment-seeking was most common for children 5 to 9 years old experiencing diarrhea (adjusted odds ratio, 3.61; 95% CI, 1.42-9.18). As malaria prevalence reduces, respiratory and diarrheal infections persist, particularly among young children but, notably, also among adults older than 65 years. Increasing awareness of the disease burden and treatment-seeking behavior are important for guiding resource re-allocation as malaria prevalence declines in this region.

Expanded geographic distribution and host preference of Anopheles gibbinsi (Anopheles species 6) in northern Zambia.

BACKGROUND: Nchelenge District in northern Zambia suffers from holoendemic malaria transmission despite a decade of yearly indoor residual spraying (IRS) and insecticide-treated net (ITN) distributions. One hypothesis for this lack of impact is that some vectors in the area may forage in the early evening or outdoors. Anopheles gibbinsi specimens were identified in early evening mosquito collections performed in this study area, and further insight was gleaned into this taxon, including characterizing its genetic identity, feeding preferences, and potential role as a malaria vector. METHODS: Mosquitoes were collected in July and August 2019 by CDC light traps in Nchelenge District in indoor sitting rooms, outdoor gathering spaces, and animal pens from 16:00-22:00. Host detection by PCR, COI and ITS2 PCR, and circumsporozoite (CSP) ELISA were performed on all samples morphologically identified as An. gibbinsi, and a subset of specimens were selected for COI and ITS2 sequencing. To determine risk factors for increased abundance of An. gibbinsi, a negative binomial generalized linear mixed-effects model was performed with household-level variables of interest. RESULTS: Comparison of COI and ITS2 An. gibbinsi reference sequences to the NCBI database revealed > 99% identity to "Anopheles sp. 6" from Kenya. More than 97% of specimens were morphologically and molecularly consistent with An. gibbinsi. Specimens were primarily collected in animal pen traps (59.2%), followed by traps outdoors near where humans gather (24.3%), and traps set indoors (16.5%). Host DNA detection revealed a high propensity for goats, but 5% of specimens with detected host DNA had fed on humans. No specimens were positive for Plasmodium falciparum sporozoites. Animal pens and inland households > 3 km from Lake Mweru were both associated with increased An. gibbinsi abundance. CONCLUSIONS: This is the first report of An. gibbinsi in Nchelenge District, Zambia. This study provided a species identity for unknown "An. sp. 6" in the NCBI database, which has been implicated in malaria transmission in Kenya. Composite data suggest that this species is largely zoophilic and exophilic, but comes into contact with humans and the malaria parasites they carry. This species should continue to be monitored in Zambia and neighbouring countries as a potential malaria vector.