Ventilator Weaning and Terminal Extubation: Withdrawal of Life-Sustaining Therapy in Children. Secondary Analysis of the Death One Hour After Terminal Extubation Study.

OBJECTIVE: Terminal extubation (TE) and terminal weaning (TW) during withdrawal of life-sustaining therapies (WLSTs) have been described and defined in adults. The recent Death One Hour After Terminal Extubation study aimed to validate a model developed to predict whether a child would die within 1 hour after discontinuation of mechanical ventilation for WLST. Although TW has not been described in children, pre-extubation weaning has been known to occur before WLST, though to what extent is unknown. In this preplanned secondary analysis, we aim to describe/define TE and pre-extubation weaning (PW) in children and compare characteristics of patients who had ventilatory support decreased before WLST with those who did not. DESIGN: Secondary analysis of multicenter retrospective cohort study. SETTING: Ten PICUs in the United States between 2009 and 2021. PATIENTS: Nine hundred thirteen patients 0-21 years old who died after WLST. INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: 71.4% ( n = 652) had TE without decrease in ventilatory support in the 6 hours prior. TE without decrease in ventilatory support in the 6 hours prior = 71.4% ( n = 652) of our sample. Clinically relevant decrease in ventilatory support before WLST = 11% ( n = 100), and 17.6% ( n = 161) had likely incidental decrease in ventilatory support before WLST. Relevant ventilator parameters decreased were F io2 and/or ventilator set rates. There were no significant differences in any of the other evaluated patient characteristics between groups (weight, body mass index, unit type, primary diagnostic category, presence of coma, time to death after WLST, analgosedative requirements, postextubation respiratory support modality). CONCLUSIONS: Decreasing ventilatory support before WLST with extubation in children does occur. This practice was not associated with significant differences in palliative analgosedation doses or time to death after extubation.

Cardiac resternotomy after cardiac surgery in kids: CRACK the chest.

OBJECTIVE: Emergent resuscitation of postoperative paediatric cardiac surgical patients requires specialised skills and multidisciplinary teamwork. Bedside resternotomy is a rare but life-saving procedure and few studies focus on ways to prepare providers and improve performance. We created a multidisciplinary educational intervention that addressed teamwork and technical skills. We aimed to evaluate the efficiency of the intervention to decrease time to perform critical tasks and improve caregiver comfort. METHODS: A simulation-based, in situ resternotomy educational intervention was implemented. Pre-intervention data were collected. Educational aids were used weekly during day and night nursing huddles over a three-month period. All ICU charge nurses had separate educational sessions with study personnel and were required to demonstrate competency in all the critical tasks. Post-intervention simulations were performed after intervention and at 6 months and post-intervention surveys were performed. RESULTS: A total of 186 providers participated in the intervention. There was a decrease in time to obtain defibrillator, setup resternotomy equipment and internal defibrillator paddles and deliver sedation and fluid (all p < 0.05). Time to escort family from the room and obtain blood was significantly decreased after intervention (p < 0.05). There was no difference in time to first dose of epinephrine, defibrillator pads on the patient, or time to call the cardiovascular surgeon or blood bank. Providers reported increased comfort in identifying equipment needed for resternotomy (p < 0.01) and setting up the internal defibrillator paddles (p < 0.01). CONCLUSIONS: Implementation of a novel educational intervention increased provider comfort and decreased time to perform critical tasks in an emergent resternotomy scenario.

Oral Nirmatrelvir and Ritonavir for Coronavirus Disease 2019 in Vaccinated, Nonhospitalized Adults Aged 18-50 Years.

BACKGROUND: The effects of nirmatrelvir/ritonavir (NMV/r [Paxlovid]) on coronavirus disease 2019 (COVID-19) outcomes in younger vaccinated adults are unclear. The objective of this study was to assess if NMV/r use in vaccinated adults aged ≤50 years is associated with improved outcomes and to identify beneficial and nonbeneficial subgroups. METHODS: In this cohort study, we generated 2 propensity-matched cohorts of 2547 patients from an 86 119-person cohort assembled from the TriNetX database. Patients in 1 cohort received NMV/r, and patients in the matched control cohort did not. The main outcome was composite of all-cause emergency department visits, hospitalization, and mortality. RESULTS: The composite outcome was detected in 4.9% of the NMV/r cohort and 7.0% of the non-NMV/r cohort (odds ratio, 0.683 [95% confidence interval, .540-.864]; P = .001), indicating a 30% relative risk reduction. The number needed to treat (NNT) for the primary outcome was 47. Subgroup analyses found significant associations for patients with cancer (NNT = 45), cardiovascular disease (NNT = 30), and both conditions (NNT = 16). No benefit was found for patients with only chronic lower respiratory disorders (asthma/chronic obstructive pulmonary disease [COPD]) or without serious comorbidities. Thirty-two percent of NMV/r prescriptions in the overall database were for 18- to 50-year-olds. CONCLUSIONS: NMV/r use in vaccinated adults aged 18-50 years, especially with serious comorbidities, was associated with reduced all-cause hospital visits, hospitalization, and mortality in the first 30 days of COVID-19 illness. However, NMV/r in patients without significant comorbidities or with only asthma/COPD had no association of benefit. Therefore, identifying high-risk patients should be a priority and overprescription should be avoided.

Oral Nirmatrelvir and Ritonavir in Nonhospitalized Vaccinated Patients With Coronavirus Disease 2019.

BACKGROUND: Treatment of coronavirus disease 2019 (COVID-19) with nirmatrelvir plus ritonavir (NMV-r) in high-risk nonhospitalized unvaccinated patients reduced the risk of progression to severe disease. However, the potential benefits of NMV-r among vaccinated patients are unclear. METHODS: We conducted a comparative retrospective cohort study using the TriNetX research network. Patients ≥18 years of age who were vaccinated and subsequently developed COVID-19 between 1 December 2021 and 18 April 2022 were included. Cohorts were developed based on the use of NMV-r within 5 days of diagnosis. The primary composite outcome was all-cause emergency room (ER) visit, hospitalization, or death at a 30-day follow-up. Secondary outcomes included individual components of primary outcomes, multisystem symptoms, COVID-19-associated complications, and diagnostic test utilization. RESULTS: After propensity score matching, 1130 patients remained in each cohort. A primary composite outcome of all-cause ER visits, hospitalization, or death in 30 days occurred in 89 (7.87%) patients in the NMV-r cohort compared with 163 (14.4%) patients in the non-NMV-r cohort (odds ratio: .5; 95% confidence interval: .39-.67; P < .005) consistent with 45% relative risk reduction. A significant reduction in multisystem symptom burden and subsequent complications, such as lower respiratory tract infection, cardiac arrhythmia, and diagnostic radiology testing, were noted in NMV-r-treated patients. There was no apparent increase in serious complications between days 10 and 30. CONCLUSIONS: Treatment with NMV-r in nonhospitalized vaccinated patients with COVID-19 was associated with a reduced likelihood of ER visits, hospitalization, or death. Complications and overall resource utilization were also decreased.

Analgesia and Sedation at Terminal Extubation: A Secondary Analysis From Death One Hour After Terminal Extubation Study Data.

OBJECTIVES: To describe the doses of opioids and benzodiazepines administered around the time of terminal extubation (TE) to children who died within 1 hour of TE and to identify their association with the time to death (TTD). DESIGN: Secondary analysis of data collected for the Death One Hour After Terminal Extubation study. SETTING: Nine U.S. hospitals. PATIENTS: Six hundred eighty patients between 0 and 21 years who died within 1 hour after TE (2010-2021). MEASUREMENTS AND MAIN RESULTS: Medications included total doses of opioids and benzodiazepines 24 hours before and 1 hour after TE. Correlations between drug doses and TTD in minutes were calculated, and multivariable linear regression performed to determine their association with TTD after adjusting for age, sex, last recorded oxygen saturation/F io2 ratio and Glasgow Coma Scale score, inotrope requirement in the last 24 hours, and use of muscle relaxants within 1 hour of TE. Median age of the study population was 2.1 years (interquartile range [IQR], 0.4-11.0 yr). The median TTD was 15 minutes (IQR, 8-23 min). Forty percent patients (278/680) received either opioids or benzodiazepines within 1 hour after TE, with the largest proportion receiving opioids only (23%, 159/680). Among patients who received medications, the median IV morphine equivalent within 1 hour after TE was 0.75 mg/kg/hr (IQR, 0.3-1.8 mg/kg/hr) ( n = 263), and median lorazepam equivalent was 0.22 mg/kg/hr (IQR, 0.11-0.44 mg/kg/hr) ( n = 118). The median morphine equivalent and lorazepam equivalent rates after TE were 7.5-fold and 22-fold greater than the median pre-extubation rates, respectively. No significant direct correlation was observed between either opioid or benzodiazepine doses before or after TE and TTD. After adjusting for confounding variables, regression analysis also failed to show any association between drug dose and TTD. CONCLUSIONS: Children after TE are often prescribed opioids and benzodiazepines. For patients dying within 1 hour of TE, TTD is not associated with the dose of medication administered as part of comfort care.

Assessing Thailand's 1-3-7 surveillance strategy in accelerating malaria elimination.

BACKGROUND: Thailand's strong malaria elimination programme relies on effective implementation of its 1-3-7 surveillance strategy, which was endorsed and implemented nationwide in 2016. For each confirmed malaria patient, the Ministry of Public Health's Division of Vector Borne Diseases (DVBD) ensures completion of case notification within 1 day, case investigation within 3 days, and foci investigation within 7 days. To date, there has not been a comprehensive assessment of the performance and achievements of the 1-3-7 surveillance strategy although such results could help Thailand's future malaria elimination strategic planning. METHODS: This study examined adherence to the 1-3-7 protocols, tracked progress against set targets, and examined geographic variations in implementation of the 1-3-7 strategy in the programme's initial 5 years. An auto-regressive integrated moving average (ARIMA) time series analysis with seasonal decomposition assessed the plausible implementation effect of the 1-3-7 strategy on malaria incidence in the programme's initial 5 years. The quantitative analysis included all confirmed malaria cases from public health and non-governmental community facilities from October 2014 to September 2021 (fiscal year [FY] 2015 to FY 2021) (n = 77,405). The spatial analysis included active foci with known geocoordinates that reported more than five cases from FY 2018 to FY 2021. RESULTS: From FY 2017 to FY 2021, on-time case notification improved from 24.4% to 89.3%, case investigations from 58.0% to 96.5%, and foci investigations from 37.9% to 87.2%. Adherence to timeliness protocols did not show statistically significant variation by area risk classification. However, adherence to 1-3-7 protocols showed a marked spatial heterogeneity among active foci, and the ARIMA model showed a statistically significant acceleration in the reduction of malaria incidence. The 1-3-7 strategy national indicators and targets in Thailand have shown progressive success, and most targets were achieved for FY 2021. CONCLUSION: The results of Thailand's 1-3-7 surveillance strategy are associated with a decreased incidence in the period following the adoption of the strategy although there is notable geographic variation. The DVBD will continue to implement and adapt the 1-3-7 strategy to accelerate progress toward malaria elimination. This assessment may be useful for domestic strategic planning and to other countries considering more intensive case and foci investigation and response strategies.

Outcomes of patients presenting with Guillain-Barre Syndrome at a tertiary care center in India.

BACKGROUND: The Guillain-Barre Syndrome (GBS), also known as acute idiopathic polyneuritis, is a critical acquired condition associated with preceding nonspecific infection or triggering factors like trauma, surgery, or vaccination. GBS is currently the most frequent cause of acute flaccid paralysis in India. This study evaluates the short-term and in-hospital outcomes in different subtypes of GBS. METHODS: A prospective observational study was conducted at V.S. Hospital, Ahmedabad, from September 2015 to December 2017. Patients above the age of 12 were included. Patients having other underlying neurological conditions, as well as immunodeficiency disorders, were excluded. The patients were classified into different subtypes of GBS, and functional outcomes were recorded on admission and discharge according to Hughes Scoring System. All statistical analyses were performed by using SPSS software. RESULTS: Out of 50 patients, 35 (70%) were males. The mean age was of 37.18 +/- 18.35 years. 25 (50%) patients had a preceding infection. 88% of patients presented with cranial nerve (CN) involvement had a Hughes Score of >/= 3 (p = 0.0087). They had less improvement of Hughes Score on discharge (0.13 +/- 0.04) as compared to the patients without cranial nerve involvement (0.38 +/- 0.08) (p = 0.008). Respiratory involvement was associated with a higher Hughes Score (p = 0.005) on admission. 85% of patients diagnosed with an axonal subtype of GBS had a Hughes Score of >/= 3 (p = 0.06) compared to 74% patients with demyelinating subtype. Axonal subtype required double period (11 +/- 2.34) to show improvement as compared to demyelinating subtype (6 +/- 1.2) (p = 0.020). Irrespective of the subtypes, in two different treatment cohorts (PLEX vs IVIG), there was no difference in short term functional outcomes measured by improvement in the Hughes scores (p = 0.89). CONCLUSIONS: Early cranial nerve and respiratory involvement in patients presenting with GBS are associated with poor outcomes warranting immediate critical care involvement. In our study, amongst all the subtypes, axonal had poor clinical outcomes. Further clinical trials on the Indian subpopulation will help us evaluate the impact of different treatment modalities on this disease.

A foci cohort analysis to monitor successful and persistent foci under Thailand's Malaria Elimination Strategy.

BACKGROUND: Thailand's success in reducing malaria burden is built on the efficient "1-3-7" strategy applied to the surveillance system. The strategy is based on rapid case notification within 1 day, case investigation within 3 days, and targeted foci response to reduce the spread of Plasmodium spp. within 7 days. Autochthonous transmission is still occurring in the country, threatening the goal of reaching malaria-free status by 2024. This study aimed to assess the effectiveness of the 1-3-7 strategy and identify factors associated with presence of active foci. METHODS: Data from the national malaria information system were extracted from fiscal years 2013 to 2019; after data cleaning, the final dataset included 81,012 foci. A Cox's proportional hazards model was built to investigate factors linked with the probability of becoming an active focus from 2015 to 2019 among foci that changed status from non-active to active focus during the study period. We performed a model selection technique based on the Akaike Information Criteria (AIC). RESULTS: The number of yearly active foci decreased from 2227 to 2013 to 700 in 2019 (68.5 %), and the number of autochthonous cases declined from 17,553 to 3,787 (78.4 %). The best Cox's hazard model showed that foci in which vector control interventions were required were 18 % more likely to become an active focus. Increasing compliance with the 1-3-7 strategy had a protective effect, with a 22 % risk reduction among foci with over 80 % adherence to 1-3-7 timeliness protocols. Other factors associated with likelihood to become or remain an active focus include previous classification as an active focus, presence of Plasmodium falciparum infections, level of forest disturbance, and location in border provinces. CONCLUSIONS: These results identified factors that favored regression of non-active foci to active foci during the study period. The model and relative risk map align with the national malaria program's district stratification and shows strong spatial heterogeneity, with high probability to record active foci in border provinces. The results of the study may be useful for honing Thailand's program to eliminate malaria and for other countries aiming to accelerate malaria elimination.

Progress and challenges of integrated drug efficacy surveillance for uncomplicated malaria in Thailand.

BACKGROUND: Integrated drug efficacy surveillance (iDES) was formally introduced nationally across Thailand in fiscal year 2018 (FY2018), building on a history of drug efficacy monitoring and interventions. According to the National Malaria Elimination Strategy for Thailand 2017-2026, diagnosis is microscopically confirmed, treatment is prescribed, and patients are followed up four times to ensure cure. METHODS: Routine patient data were extracted from the malaria information system for FY2018-FY2020. Treatment failure of first-line therapy was defined as confirmed parasite reappearance within 42 days for Plasmodium falciparum and 28 days for Plasmodium vivax. The primary outcome was the crude drug efficacy rate, estimated using Kaplan-Meier methods, at day 42 for P. falciparum treated with dihydroartemisinin-piperaquine plus primaquine, and day 28 for P. vivax treated with chloroquine plus primaquine; day 60 and day 90 efficacy were secondary outcomes for P. vivax. RESULTS: The proportion of patients with outcomes recorded at day 42 for P. falciparum malaria and at day 28 for P. vivax malaria has been increasing, with FY2020 follow-up rates of 61.5% and 57.2%, respectively. For P. falciparum malaria, day 42 efficacy in FY2018 was 92.4% (n = 249), in FY2019 93.3% (n = 379), and in FY2020 98.0% (n = 167). Plasmodium falciparum recurrences occurred disproportionally in Sisaket Province, with day 42 efficacy rates of 75.9% in FY2018 (n = 59) and 49.4% in FY2019 (n = 49), leading to an update in first-line therapy to pyronaridine-artesunate at the provincial level, rolled out in FY2020. For P. vivax malaria, day 28 efficacy (chloroquine efficacy) was 98.5% in FY2018 (n = 2048), 99.1% in FY2019 (n = 2206), and 99.9% in FY2020 (n = 2448), and day 90 efficacy (primaquine efficacy) was 94.8%, 96.3%, and 97.1%, respectively. CONCLUSIONS: In Thailand, iDES provided operationally relevant data on drug efficacy, enabling the rapid amendment of treatment guidelines to improve patient outcomes and reduce the potential for the spread of drug-resistant parasites. A strong case-based surveillance system, integration with other health system processes, supporting biomarker collection and molecular analyses, and cross-border collaboration may maximize the potential of iDES in countries moving towards elimination.

Implementation and success factors from Thailand's 1-3-7 surveillance strategy for malaria elimination.

Thailand's National Malaria Elimination Strategy 2017-2026 introduced the 1-3-7 strategy as a robust surveillance and response approach for elimination that would prioritize timely, evidence-based action. Under this strategy, cases are reported within 1 day, cases are investigated within 3 days, and foci are investigated and responded to within 7 days, building on Thailand's long history of conducting case investigation since the 1980s. However, the hallmark of the 1-3-7 strategy is timeliness, with strict deadlines for reporting and response to accelerate elimination. This paper outlines Thailand's experience adapting and implementing the 1-3-7 strategy, including success factors such as a cross-sectoral Steering Committee, participation in a collaborative regional partnership, and flexible local budgets. The programme continues to evolve to ensure prompt and high-quality case management, capacity maintenance, and adequate supply of lifesaving commodities based on surveillance data. Results from implementation suggest the 1-3-7 strategy has contributed to Thailand's decline in malaria burden; this experience may be useful for other countries aiming to eliminate malaria.

Prompt access to effective malaria treatment among children under five in sub-Saharan Africa: a multi-country analysis of national household survey data.

BACKGROUND: Scaling up diagnostic testing and treatment is a key strategy to reduce the burden of malaria. Delays in accessing treatment can have fatal consequences; however, few studies have systematically assessed these delays among children under five years of age in malaria-endemic countries of sub-Saharan Africa. This study identifies predictors of prompt treatment with first-line artemisinin combination therapy (ACT) and describes profiles of children who received this recommended treatment. METHODS: This study uses data from the most recent Demographic and Health Survey, Malaria Indicator Survey, or Anaemia and Parasite Prevalence Survey conducted in 13 countries. A Chi square automatic interaction detector (CHAID) model was used to identify factors associated with prompt and effective treatment among children under five years of age. RESULTS: The percentage of children with fever who received any anti-malarial treatment varies from 3.6 % (95 % CI 2.8-4.4 %) in Ethiopia to 64.5 % (95 % CI 62.7-66.2 %) in Uganda. Among those who received prompt treatment with any anti-malarial medicine, the percentage who received ACT ranged from 32.2 % (95 % CI 26.1-38.4 %) in Zambia to nearly 100 % in Tanzania mainland and Zanzibar. The CHAID analysis revealed that country of residence is the best predictor of prompt and effective treatment (p < 0.001). Depending on the country, the second best predictor was maternal education (p = 0.004), place of residence (p = 0.008), or household wealth index (p < 0.001). CONCLUSIONS: This study reveals that country of residence, maternal education, place of residence, and socio-economic status are key predictors of prompt access to malaria treatment. Achieving universal coverage and the elimination agenda will require effective monitoring to detect disparities early and sustained investments in routine data collection and policy formulation.

Malaria Stratification Mapping in Thailand to Support Prevention of Reestablishment.

Thailand aims to eliminate malaria by 2026, with 46 of the country's 77 provinces already verified as malaria free. However, these provinces remain susceptible to the reestablishment of indigenous transmission that would threaten the national goal. Thus, the country is prioritizing national and subnational prevention of reestablishment (POR) planning while considering the spatial heterogeneity of the remaining malaria caseload. To support POR efforts, a novel nonmodeling method produced a malaria stratification map at the tambon (subdistrict) level, incorporating malaria case data, demographic data, and environmental factors. The stratification analysis categorized 7,425 tambons into the following four risk strata: Local Transmission (2.9%), At Risk for Transmission (3.1%), High Risk for Reintroduction (2.9%), and Low Risk for Reintroduction (91.1%). The stratification map will support the national program to target malaria interventions in remaining hotspots and mitigate the risk of transmission in malaria-free areas.

A holistic approach to performance prediction in collegiate athletics: player, team, and conference perspectives.

Predictive sports data analytics can be revolutionary for sports performance. Existing literature discusses players' or teams' performance, independently or in tandem. Using Machine Learning (ML), this paper aims to holistically evaluate player-, team-, and conference (season)-level performances in Division-1 Women's basketball. The players were monitored and tested through a full competitive year. The performance was quantified at the player level using the reactive strength index modified (RSImod), at the team level by the game score (GS) metric, and finally at the conference level through Player Efficiency Rating (PER). The data includes parameters from training, subjective stress, sleep, and recovery (WHOOP straps), in-game statistics (Polar monitors), and countermovement jumps. We used data balancing techniques and an Extreme Gradient Boosting (XGB) classifier to predict RSI and GS with greater than 90% accuracy and a 0.9 F1 score. The XGB regressor predicted PER with an MSE of 0.026 and an R2 of 0.680. Ensemble of Random Forest, XGB, and correlation finds feature importance at all levels. We used Partial Dependence Plots to understand the impact of each feature on the target variable. Quantifying and predicting performance at all levels will allow coaches to monitor athlete readiness and help improve training.

Idiopathic pulmonary fibrosis: Diagnosis, biomarkers and newer treatment protocols.

Idiopathic pulmonary fibrosis (IPF) is a chronic, progressive lung condition marked by lung scarring that progresses over time and with usual interstitial pneumonia histology (UIP). It is linked to a worsening cough, dyspnea, and a worse quality of life. Around 3 million persons worldwide suffer from IPF, and the prevalence rises sharply with advancing age. The detection of the UIP pattern, generally using high-resolution CT; lung biopsy may be necessary in certain individuals; the diagnostic approach also includes the elimination of other interstitial lung illnesses or overlapping problems. The UIP pattern is mostly bilateral, peripheral, and basal, with clusters of subpleural cystic airspaces and reticular alterations linked to traction bronchiectasis. Although there are still many uncertainties about how to define susceptibility, it is believed that the molecular mechanisms causing IPF reflect an abnormal reparative response to repeated alveolar epithelial damage in an aging genetically sensitive individual. With the availability of two pharmacotherapeutic drugs, pirfenidone and nintedanib, that slow physiological advancement and potentially increase progression-free survival, significant progress has been made in our knowledge of the clinical treatment of IPF. The goal of current research is to develop early biomarkers for IPF that may include circulating variables, demographic information, and imaging data.

Environmental Factors Linked to Reporting of Active Malaria Foci in Thailand.

Thailand has made substantial progress towards malaria elimination, with 46 of the country's 77 provinces declared malaria-free as part of the subnational verification program. Nonetheless, these areas remain vulnerable to the reintroduction of malaria parasites and the reestablishment of indigenous transmission. As such, prevention of reestablishment (POR) planning is of increasing concern to ensure timely response to increasing cases. A thorough understanding of both the risk of parasite importation and receptivity for transmission is essential for successful POR planning. Routine geolocated case- and foci-level epidemiological and case-level demographic data were extracted from Thailand's national malaria information system for all active foci from October 2012 to September 2020. A spatial analysis examined environmental and climate factors associated with the remaining active foci. A logistic regression model collated surveillance data with remote sensing data to investigate associations with the probability of having reported an indigenous case within the previous year. Active foci are highly concentrated along international borders, particularly Thailand's western border with Myanmar. Although there is heterogeneity in the habitats surrounding active foci, land covered by tropical forest and plantation was significantly higher for active foci than other foci. The regression results showed that tropical forest, plantations, forest disturbance, distance from international borders, historical foci classification, percentage of males, and percentage of short-term residents were associated with the high probability of reporting indigenous cases. These results confirm that Thailand's emphasis on border areas and forest-going populations is well placed. The results suggest that environmental factors alone are not driving malaria transmission in Thailand; rather, other factors, including demographics and behaviors that intersect with exophagic vectors, may also be contributors. However, these factors are syndemic, so human activities in areas covered by tropical forests and plantations may result in malaria importation and, potentially, local transmission, in foci that had previously been cleared. These factors should be addressed in POR planning.

The contribution of active case detection to malaria elimination in Thailand.

INTRODUCTION: Thailand's malaria surveillance system complements passive case detection with active case detection (ACD), comprising proactive ACD (PACD) methods and reactive ACD (RACD) methods that target community members near index cases. However, it is unclear if these resource-intensive surveillance strategies continue to provide useful yield. This study aimed to document the evolution of the ACD programme and to assess the potential to optimise PACD and RACD. METHODS: This study used routine data from all 6 292 302 patients tested for malaria from fiscal year 2015 (FY15) to FY21. To assess trends over time and geography, ACD yield was defined as the proportion of cases detected among total screenings. To investigate geographical variation in yield from FY17 to FY21, we used intercept-only generalised linear regression models (binomial distribution), allowing random intercepts at different geographical levels. A costing analysis gathered the incremental financial costs for one instance of ACD per focus. RESULTS: Test positivity for ACD was low (0.08%) and declined over time (from 0.14% to 0.03%), compared with 3.81% for passive case detection (5.62%-1.93%). Whereas PACD and RACD contributed nearly equal proportions of confirmed cases in FY15, by FY21 PACD represented just 32.37% of ACD cases, with 0.01% test positivity. Each geography showed different yields. We provide a calculator for PACD costs, which vary widely. RACD costs an expected US$226 per case investigation survey (US$1.62 per person tested) or US$461 per mass blood survey (US$1.10 per person tested). CONCLUSION: ACD yield, particularly for PACD, is waning alongside incidence, offering an opportunity to optimise. PACD may remain useful only in specific microcontexts with sharper targeting and implementation. RACD could be narrowed by defining demographic-based screening criteria rather than geographical based. Ultimately, ACD can continue to contribute to Thailand's malaria elimination programme but with more deliberate targeting to balance operational costs.

Cardiovascular Drug Interactions With Nirmatrelvir/Ritonavir in Patients With COVID-19: JACC Review Topic of the Week.

Nirmatrelvir-ritonavir (NMVr) is used to treat symptomatic, nonhospitalized patients with coronavirus disease-2019 (COVID-19) who are at high risk of progression to severe disease. Patients with cardiovascular risk factors and cardiovascular disease are at a high risk of developing adverse events from COVID-19 and as a result have a higher likelihood of receiving NMVr. Ritonavir, the pharmaceutical enhancer used in NMVr, is an inhibitor of the enzymes of CYP450 pathway, particularly CYP3A4 and to a lesser degree CYP2D6, and affects the P-glycoprotein pump. Co-administration of NMVr with medications commonly used to manage cardiovascular conditions can potentially cause significant drug-drug interactions and may lead to severe adverse effects. It is crucial to be aware of such interactions and take appropriate measures to avoid them. In this review, we discuss potential drug-drug interactions between NMVr and commonly used cardiovascular medications based on their pharmacokinetics and pharmacodynamic properties.

Framework for Evaluating the Health Impact of the Scale-Up of Malaria Control Interventions on All-Cause Child Mortality in Sub-Saharan Africa.

Concerted efforts from national and international partners have scaled up malaria control interventions, including insecticide-treated nets, indoor residual spraying, diagnostics, prompt and effective treatment of malaria cases, and intermittent preventive treatment during pregnancy in sub-Saharan Africa (SSA). This scale-up warrants an assessment of its health impact to guide future efforts and investments; however, measuring malaria-specific mortality and the overall impact of malaria control interventions remains challenging. In 2007, Roll Back Malaria's Monitoring and Evaluation Reference Group proposed a theoretical framework for evaluating the impact of full-coverage malaria control interventions on morbidity and mortality in high-burden SSA countries. Recently, several evaluations have contributed new ideas and lessons to strengthen this plausibility design. This paper harnesses that new evaluation experience to expand the framework, with additional features, such as stratification, to examine subgroups most likely to experience improvement if control programs are working; the use of a national platform framework; and analysis of complete birth histories from national household surveys. The refined framework has shown that, despite persisting data challenges, combining multiple sources of data, considering potential contributions from both fundamental and proximate contextual factors, and conducting subnational analyses allows identification of the plausible contributions of malaria control interventions on malaria morbidity and mortality.