RESUMO
While the Plasmodium falciparum malaria parasite continues to cause severe disease globally, Mozambique is disproportionally represented in malaria case totals. Acquisition of copy number variations (CNVs) in the parasite genome contributes to antimalarial drug resistance through overexpression of drug targets. Of interest, piperaquine resistance is associated with plasmepsin 2 and 3 CNVs (pfpmp2 and pfpmp3, respectively), while CNVs in the multidrug efflux pump, multidrug resistance-1 (pfmdr1), increase resistance to amodiaquine and lumefantrine. These antimalarials are partner drugs in artemisinin combination therapies (ACTs) and therefore, CNV detection with accurate and efficient tools is necessary to track ACT resistance risk. Here, we evaluated ~300 clinically derived samples collected from three sites in Mozambique for resistance-associated CNVs. We developed a novel, medium-throughput, quadruplex droplet digital PCR (ddPCR) assay to simultaneously quantify the copy number of pfpmp3, pfpmp2, and pfmdr1 loci in these clinical samples. By using DNA from laboratory parasite lines, we show that this nanodroplet-based method is capable of detecting picogram levels of parasite DNA, which facilitates its application for low yield and human host-contaminated clinical surveillance samples. Following ddPCR and the application of quality control standards, we detected CNVs in 13 of 229 high-quality samples (prevalence of 5.7%). Overall, our study revealed a low number of resistance CNVs present in the parasite population across all three collection sites, including various combinations of pfmdr1, pfpmp2, and pfpmp3 CNVs. The potential for future ACT resistance across Mozambique emphasizes the need for continued molecular surveillance across the region.
Assuntos
Antimaláricos , Variações do Número de Cópias de DNA , Resistência a Medicamentos , Malária Falciparum , Plasmodium falciparum , Proteínas de Protozoários , Antimaláricos/farmacologia , Moçambique , Plasmodium falciparum/genética , Plasmodium falciparum/efeitos dos fármacos , Humanos , Resistência a Medicamentos/genética , Variações do Número de Cópias de DNA/genética , Malária Falciparum/parasitologia , Malária Falciparum/tratamento farmacológico , Proteínas de Protozoários/genética , Reação em Cadeia da Polimerase/métodos , Quinolinas/farmacologia , Amodiaquina/farmacologia , Proteínas Associadas à Resistência a Múltiplos Medicamentos/genética , Ácido Aspártico Endopeptidases/genética , Artemisininas/farmacologia , Lumefantrina/farmacologia , PiperazinasRESUMO
OBJECTIVE: Accumulating more steps/day is associated with a lower risk of cancer mortality and composite cancer outcomes. However, less is known about the relationship of steps/day with the risk of multiple site-specific cancers. METHODS: This study included >22,000 women from the Women's Health Accelerometry Collaboration Cohort (2011-2022), comprised of women from the Women's Health Study and Women's Health Initiative Objective Physical Activity and Cardiovascular Health Study. Steps/day and step intensity were collected with accelerometry. Incident cancer cases and deaths were adjudicated. Stratified Cox proportional hazards models were used to estimate hazard ratios (HRs) and 95% confidence intervals (CIs) of the associations of steps/day and step intensity with incident breast, colon, endometrial, lung, and ovarian cancers, a composite of 13 physical activity-related cancers, total invasive cancer, and fatal cancer. RESULTS: On average, women were 73.4 years old, accumulated 4993 steps/day, and had 7.9 years of follow-up. There were small nonsignificant inverse associations with the risks of colon cancer (HR = 0.94, 95% CI: 0.83, 1.05), endometrial cancer (HR = 0.91, 95% CI: 0.82, 1.01), and fatal cancer (HR = 0.95 95% CI: 0.90, 1.00) per 1000 steps/day. More minutes at ≥40 steps/min and a faster peak 10- and 30-min step cadence were associated with a lower risk of endometrial cancer, but findings were attenuated after adjustment for body mass index and steps/day. CONCLUSIONS: Among women 62-97 years, there were small nonsignificant inverse associations of colon, endometrial, and fatal cancer with more steps/day. Epidemiologic studies with longer follow-up and updated assessments are needed to further explore these associations.
Assuntos
Acelerometria , Neoplasias , Saúde da Mulher , Humanos , Feminino , Idoso , Neoplasias/epidemiologia , Neoplasias/mortalidade , Pessoa de Meia-Idade , Exercício Físico , Fatores de Risco , Estudos de Coortes , Caminhada , Modelos de Riscos Proporcionais , Estudos ProspectivosRESUMO
Importance: Current US physical activity (PA) guidelines prescribe moderate to vigorous PA (MVPA) time of at least 150 minutes per week for health. An analogous step-based recommendation has not been issued due to insufficient evidence. Objective: To examine the associations of MVPA time and step counts with all-cause mortality and cardiovascular disease (CVD). Design, Setting, and Participants: This cohort study analyzed data from an ongoing follow-up study of surviving participants of the Women's Health Study, a randomized clinical trial conducted from 1992 to 2004 in the US to evaluate use of low-dose aspirin and vitamin E for preventing cancer and CVD. Participants were 62 years or older who were free from CVD and cancer, completed annual questionnaires, and agreed to measure their PA with an accelerometer as part of a 2011-2015 ancillary study. Participants were followed up through December 31, 2022. Exposures: Time spent in MVPA and step counts, measured with an accelerometer for 7 consecutive days. Main Outcomes and Measures: The associations of MVPA time and step counts with all-cause mortality and CVD (composite of myocardial infarction, stroke, and CVD mortality) adjusted for confounders. Cox proportional hazards regression models, restricted mean survival time differences, and area under the receiver operating characteristic curve (AUC) were used to evaluate the associations. Results: A total of 14â¯399 women (mean [SD] age, 71.8 [5.6] years) were included. The median (IQR) MVPA time and step counts were 62 (20-149) minutes per week and 5183 (3691-7001) steps per day, respectively. During a median (IQR) follow-up of 9.0 (8.0-9.9) years, the hazard ratios (HR) per SD for all-cause mortality were 0.82 (95% CI, 0.75-0.90) for MVPA time and 0.74 (95% CI, 0.69-0.80) for step counts. Greater MVPA time and step counts (top 3 quartiles vs bottom quartile) were associated with a longer period free from death: 2.22 (95% CI, 1.58-2.85) months and 2.36 (95% CI, 1.73-2.99) months at 9 years follow-up, respectively. The AUCs for all-cause mortality from MVPA time and step counts were similar: 0.55 (95% CI, 0.52-0.57) for both metrics. Similar associations of these 2 metrics with CVD were observed. Conclusion and Relevance: Results of this study suggest that among females 62 years or older, MVPA time and step counts were qualitatively similar in their associations with all-cause mortality and CVD. Step count-based goals should be considered for future guidelines along with time-based goals, allowing for the accommodation of personal preferences.
Assuntos
Doenças Cardiovasculares , Exercício Físico , Humanos , Feminino , Doenças Cardiovasculares/mortalidade , Doenças Cardiovasculares/prevenção & controle , Pessoa de Meia-Idade , Idoso , Fatores de Tempo , Acelerometria , Seguimentos , Estados Unidos/epidemiologia , Estudos de Coortes , Saúde da Mulher , Causas de MorteRESUMO
Background: In sub-Saharan Africa, the provision of infection prevention and control (IPC) measures are often limited by resource constraints. Aim: To determine the association of supportive supervision activities with the availability of the WHO core components for IPC at health facilities in Southwestern Uganda. Methods: We employed a before and after quality improvement study design. We conducted a baseline assessment of the availability of the WHO IPC core components and provided supportive supervision activities, which was followed by a second IPC assessment. We included health centers II-IV, which have increasing clinical care capacity, and regional hospitals. Findings: Of 244 regional health facilities, baseline assessment occurred at 111 (45%) of which 23 (21%) were reassessed. The number of facilities in the Red (<70%) category for each core component stayed the same or decreased at each facility type, but there was an increase from five to six health center III facilities scoring Red (<70%) for PPE. The number of facilities in the Green (>85%) category for each core component stayed the same or was increased at each facility type, but there was a decrease from four to two health center III facilities scoring Green (>85%) for instrument processing. There was an increase in the median (interquartile range [IQR]) overall score for all facilities (65 [54-72] vs 75 [68-83], P=0.0001). Conclusion: Supportive supervision activities were associated with improved availability of the core components of IPC at health facilities in Southwestern Uganda. PPE should be prioritized in health care facilities in Southwestern Uganda.
RESUMO
BACKGROUND: Describing correlates of physical activity (PA) and sedentary behavior (SB) among postmenopausal cancer survivors can help identify risk profiles and can be used to support development of targeted interventions to improve PA and reduce SB in this population. OBJECTIVE: To describe PA/SB and identify correlates of PA/SB among cancer and cancer-free post-menopausal women. METHODS: Women from the Women's Health Study (N = 16,629) and Women's Health Initiative/Objective Physical Activity and Cardiovascular Health Study (N = 6,079) were asked to wear an accelerometer on the hip for 7 days. Multiple mixed-effects linear regression models were used to identify sociodemographic-, health-, and chronic condition-related correlates (independent variables) associated with PA and SB (dependent variables) among women with (n = 2,554) and without (n = 20,154) a history of cancer. All correlates were mutually adjusted for each other. RESULTS: In unadjusted analyses, women with a history of cancer took fewer mean daily steps (4,572 (standard deviation 2557) vs 5,029 (2679) steps/day) and had lower mean moderate-to-vigorous PA (74.9 (45.0) vs. 81.6 (46.7) minutes/day) than cancer-free women. In adjusted analyses, for cancer and cancer-free women, age, diabetes, overweight, and obesity were inversely associated with all metrics of PA (average vector magnitude, time in moderate-to-vigorous PA, step volume, time at ≥40 steps/minutes, and peak 30-minute step cadence). In unadjusted analyses, mean SB was similar for those with and without cancer (529.7 (98.1) vs. 521.7 (101.2) minutes/day). In adjusted analyses, for cancer and cancer-free women, age, diabetes, cardiovascular disease, current smoking, overweight, and obesity were positive correlates of SB, while Black or Hispanic race/ethnicity, weekly/daily alcohol intake, and excellent/very good/good self-rated health were inverse correlates of SB. CONCLUSION: Several sociodemographic, health, and chronic conditions were correlates of PA/SB for postmenopausal women with and without cancer. Future studies should examine longitudinal relationships to gain insight into potential determinants of PA/SB.