Last data update: Dec 02, 2024. (Total: 48272 publications since 2009)
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Genomic cluster formation among invasive group A streptococcal infections in the USA: a whole-genome sequencing and population-based surveillance study
Li Y , Rivers J , Mathis S , Li Z , Chochua S , Metcalf BJ , Beall B , McGee L . Lancet Microbe 2024 100927 BACKGROUND: Clusters of invasive group A streptococcal (iGAS) infection, linked to genomically closely related group A streptococcal (GAS) isolates (referred to as genomic clusters), pose public health threats, and are increasingly identified through whole-genome sequencing (WGS) analysis. In this study, we aimed to assess the risk of genomic cluster formation among iGAS cases not already part of existing genomic clusters. METHODS: In this WGS and population-based surveillance study, we analysed iGAS case isolates from the Active Bacterial Core surveillance (ABCs), which is part of the US Centers for Disease Control and Prevention's Emerging Infections Program, in ten US states from Jan 1, 2015, to Dec 31, 2019. We included all residents in ABCs sites with iGAS infections meeting the case definition and excluded non-conforming GAS infections and cases with whole-genome assemblies of the isolate containing fewer than 1·5 million total bases or more than 150 contigs. For iGAS cases we collected basic demographics, underlying conditions, and risk factors for infection from medical records, and for isolates we included emm types, antimicrobial resistance, and presence of virulence-related genes. Two iGAS cases were defined as genomically clustered if their isolates differed by three or less single-nucleotide variants. An iGAS case not clustered with any previous cases at the time of detection, with a minimum trace-back time of 1 year, was defined as being at risk of cluster formation. We monitored each iGAS case at risk for a minimum of 1 year to identify any cluster formation event, defined as the detection of a subsequent iGAS case clustered with the case at risk. We used the Kaplan-Meier method to estimate the cumulative incidence of cluster formation events over time. We used Cox regression to assess associations between features of cases at risk upon detection and subsequent cluster formation. We developed a random survival forest machine-learning model based on a derivation cohort (random selection of 50% of cases at risk) to predict cluster formation risk. This model was validated using a validation cohort consisting of the remaining 50% of cases at risk. FINDINGS: We identified 2764 iGAS cases at risk from 2016 to 2018, of which 656 (24%) formed genomic clusters by the end of 2019. Overall, the cumulative incidence of cluster formation was 0·057 (95% CI 0·048-0·066) at 30 days after detection, 0·12 (0·11-0·13) at 90 days after detection, and 0·16 (0·15-0·18) at 180 days after detection. A higher risk of cluster formation was associated with emm type (adjusted hazard ratio as compared with emm89 was 2·37 [95% CI 1·71-3·30] for emm1, 2·72 [1·82-4·06] for emm3, 2·28 [1·49-3·51] for emm6, 1·47 [1·05-2·06] for emm12, and 2·21 [1·38-3·56] for emm92), homelessness (1·42 [1·01-1·99]), injection drug use (2·08 [1·59-2·72]), residence in a long-term care facility (1·78 [1·29-2·45]), and the autumn-winter season (1·34 [1·14-1·57]) in multivariable Cox regression analysis. The machine-learning model stratified the validation cohort (n=1382) into groups at low (n=370), moderate (n=738), and high (n=274) risk. The 90-day risk of cluster formation was 0·03 (95% CI 0·01-0·05) for the group at low risk, 0·10 (0·08-0·13) for the group at moderate risk, and 0·21 (0·17-0·25) for the group at high risk. These results were consistent with the cross-validation outcomes in the derivation cohort. INTERPRETATION: Using population-based surveillance data, we found that pathogen, host, and environment factors of iGAS cases were associated with increased likelihood of subsequent genomic cluster formation. Groups at high risk were consistently identified by a predictive model which could inform prevention strategies, although future work to refine the model, incorporating other potential risk factors such as host contact patterns and immunity to GAS, is needed to improve its predictive performance. FUNDING: Centers for Disease Control and Prevention. |
Survival of children with critical congenital heart defects in the National Birth Defects Prevention Study
Forestieri NE , Olshan AF , Oster ME , Ailes EC , Fundora MP , Fisher SC , Shumate C , Romitti PA , FLiberman R , Nembhard WN , Carmichael SL , Desrosiers TA . Birth Defects Res 2024 116 (9) e2394 BACKGROUND: Critical congenital heart defects (CCHDs) are associated with considerable morbidity and mortality. This study estimated survival of children with nonsyndromic CCHDs and evaluated relationships between exposures of interest and survival by CCHD severity (univentricular or biventricular function). METHODS: This analysis included 4380 infants with CCHDs (cases) born during 1999-2011 and enrolled in the National Birth Defects Prevention Study, a multisite, population-based case-control study of major birth defects. Cases were linked to state death files. Nonparametric Kaplan-Meier survival functions were used to estimate 1- and 5-year survival probabilities overall and by severity group (univentricular/biventricular) stratified by demographic and clinical exposure variables of interest. The log-rank test was used to determine whether stratified survival curves were equivalent. Survival and 95% confidence intervals (CIs) were also estimated using Cox proportional hazards modeling adjusted for maternal age, education, race/ethnicity, study site, and birth year. RESULTS: One- and five-year survival rates were 85.8% (CI 84.7-86.8) and 83.7% (CI 82.5-84.9), respectively. Univentricular 5-year survival was lower than biventricular case survival [65.3% (CI 61.7-68.5) vs. 89.0% (CI 87.8-90.1; p < 0.001)]. Clinical factors (e.g. preterm birth, low birthweight, and complex/multiple defects) were associated with lower survival in each severity group. Sociodemographic factors (non-Hispanic Black race/ethnicity, <high school education, smoking, and lower household income) were only associated with survival among biventricular cases. CONCLUSIONS: Mortality among children with CCHDs occurred primarily in the first year of life. Survival was lower for those with univentricular defects, and social determinants of health were most important in predicting survival for those with biventricular defects. |
Efficacy and safety of artemether-lumefantrine against uncomplicated falciparum malaria infection in Tanzania, 2022, a single arm clinical trial
Laury JE , Mugittu K , Kajeguka DC , Kamugisha E , Ishengoma DS , Mandara CI , Ngasala B , Chiduo MG , Mahende MK , Kitau J , Ahmed MM , Mkumbaye SI , Francis F , Chacky F , Warsame M , Serbantez N , Kitojo C , Reaves EJ , Bishanga DR , Bajic M , Kabula BI , Muro F , Kavishe RA . J Infect Dis 2024 BACKGROUND: Artemether-lumefantrine (AL) is the first line anti-malarial drug for the treatment of uncomplicated malaria in Tanzania. The World Health Organization (WHO) recommends regular efficacy monitoring of anti-malarial drugs to inform case management policy decisions. This study assessed the safety and efficacy of AL for treating uncomplicated P. falciparum malaria in Tanzania in 2022. METHODS: Children 6 months to 10 years with uncomplicated P. falciparum malaria were recruited from four sentinel sites and treated with the standard 6 dose, 3-day regimen for AL. Clinical and parasitological responses were monitored for 28 days using the WHO standard protocol. Genotyping based on msp1, msp2 and glurp was used to distinguish recrudescence from reinfection. SANGER sequencing was used to detect K13 mutations. RESULTS: 352 participants, 88 per site, were enrolled. Four withdrew and 55 experienced parasite recurrence. The PCR corrected Kaplan-Meier efficacies were, 89.9% in Pwani, 95.0% in Kigoma, 94.4% in Tanga, and 98.9% in Morogoro. No K13 mutations were found. CONCLUSIONS: Artemether-lumefantrine remains highly efficacious in three regions of Tanzania but the PCR-corrected efficacy in Pwani fell below the WHO-defined 90% threshold at which policy change is recommended. Implementing strategies to diversify ACTs to ensure effective case management in Tanzania is critical. |
Incidence and predictors of attrition from HIV treatment among adults living with HIV in high-caseload facilities following implementation of universal test and treat strategy in Ethiopia: A prospective cohort study
Bekele A , Ahmed I , Tefera F , Yimam JA , Woldeselassie FT , Abera G , Ahmed J , Mekonnen A , Haile A , Yohannes F , Getachew M , Abdella S , Shah M . HIV Med 2024 BACKGROUND: The introduction of universal test and treat (UTT) strategy has demonstrated a reduction in attrition in some low-resource settings. UTT was introduced in Ethiopia in 2016. However, there is a paucity of information regarding the magnitude and predictors of attrition from HIV treatment in Ethiopia. This study aims to assess the incidence and predictors of attrition from HIV treatment among adults living with HIV (PLHIV) in high-caseload facilities following the implementation of universal test and treat strategy in Ethiopia from March 2019 to June 2020. METHODS: A prospective cohort of individuals in HIV care from 39 high-caseload facilities in Oromia, Amhara, Tigray, Addis Ababa and Dire Dawa regions of Ethiopia was conducted for 12 months. Participants were adults aged 15 year and older who were first testers recruited for 3 months from March to June 2019. Subsequent follow-up was for 12 months, with data collected on sociodemographic and clinical conditions at baseline, 6 and 12 months and attrition at 6 and 12 months. We defined attrition as discontinuation from follow-up care due to loss to follow-up, dropout or death. Data were collected using Open Data Kit at field level and aggregated centrally. Kaplan-Meier survival analysis was employed to assess survival probability to the time of attrition from treatment. The Cox proportional hazards regression model was used to measure association of baseline predictor variables with the proportion of antiretroviral therapy (ART) patients retained in ART during the follow up period. RESULTS: The overall incidence rate for attrition from HIV treatment among the study participants during 12 months of follow-up was 5.02 cases per 1000 person-weeks [95% confidence interval (CI): 4.44-5.68 per 1000 person-weeks]. Study participants from health facilities in Oromia and Addis Ababa/Dire Dawa had 68% and 51% higher risk of attrition from HIV treatment compared with participants from the Amhara region, respectively [adjusted hazard ratio (AHR) = 1.68, 95% CI: 1.22-2.32 and AHR = 1.51, 95% CI: 1.05-2.17, respectively]. Participants who did not have a child had a 44% higher risk of attrition compared with those who had a child (AHR = 1.44, 95% CI: 1.12-1.85). Individuals who did not own mobile phone had a 37% higher risk of attrition than those who owned a mobile phone (AHR = 1.37, 95% CI: 1.02-1.83). Ambulatory/bedridden functional status at the time of diagnosis had a 44% higher risk of attrition compared with participants with a working functional status (AHR = 1.44, 95% CI: 1.08-1.92) at any time during the follow-up period. CONCLUSION: The overall incidence of attrition among people living with HIV enrolled into HIV treatment was not as high as what was reported by other studies. Independent predictors of attrition were administrative regions in Ethiopia where health facilities are located, not having a child, not owning a mobile phone and being ambulatory/bedridden functional status at the time of diagnosis. Concerted efforts should be taken to reduce the magnitude of attrition from HIV treatment and address its drivers. |
Retention of people who inject drugs enrolled in a 'medications for opioid use disorder' (MOUD) programme in Uganda
Mudiope P , Mutamba BB , Komuhangi L , Nangendo J , Alamo S , Mathers B , Makumbi F , Wanyenze R . Addict Sci Clin Pract 2024 19 (1) 39 BACKGROUND: Injection Drug use is associated with increased HIV risk behaviour that may result in the transmission of HIV and poor access to HIV prevention and treatment. In 2020, Uganda introduced the 'medication for opioid use disorder (MOUD) treatment' for People who inject drugs (PWID). We analysed the 12-month retention and associated factors among PWID enrolled on MOUD treatment in Kampala, Uganda. METHODS: We conducted a retrospective analysis of 343 PWID with OUD who completed 14 days of methadone induction from September 2020 to July 2022. Retention was defined as the number of individuals still in the programme divided by the total number enrolled, computed at 3-, 6-, 9-, and 12 months using lifetable and Kaplan-Meier survival analyses. Cox proportional regression analyses were conducted to assess factors associated with retention in the programme in the first 12 months. RESULTS: Overall, 243 (71%) of 343 participants stabilized at a methadone dose of 60 mg or more. The majority of participants were males (n = 284, 82.8%), and the median (interquartile range, IQR) age was 31 (26-38) years. Most participants (n = 276, 80.5%) lived 5 km or more away from the MOUD clinic. Thirty (8.8%) were HIV-positive, 52 (15.7%) had a major mental illness and 96 (27.9%) had a history of taking alcohol three months before enrollment. The cumulative retention significantly declined from 83.4% (95%CI = 79.0-87.0) at 3months to 71.9% (95%CI = 67.2-76.6) at 6months, 64% 95%CI = 58.7-68.9) at 9months, and 55.2%; 95% CI (49.8-60.3% at 12months. The 12-month retention was significantly higher for participants on methadone doses of 60 mg or more (adj.HR = 2.1, 95%CI = 1.41-3.22), while participants resident within 5 km of the MOUD clinic were 4.9 times more likely to be retained at 12 months, compared to those residing 5 km or more, (adj. HR = 4.81, 95%CI = 1.54-15). Other factors, including predisposing, need, and enabling factors, were not associated with retention. CONCLUSION: Our study demonstrates acceptable 12-month retention rates for people who inject drugs, comparable to previous studies done in both developing and developed countries. Sustaining and improving retention may require enhanced scaling up of MOUD dose to an optimal level in the first 14 days and reducing the distance between participant locale and MOUD clinics. |
Lessons learned from COVID-19 response in correctional and detention facilities
Waddell C , Meehan A , Schoonveld M , Kaplan Z , Bien M , Bailey C , Mosites E , Hagan LM . Emerg Infect Dis 2024 30 (13) S5-s12 The COVID-19 pandemic disproportionately affected persons held in and working in correctional and detention facilities, causing facilities' traditional priorities to shift when healthcare and public health needs temporarily drove many aspects of operations. During July-August 2022, we interviewed members of health departments and criminal justice organizations to document lessons learned from the COVID-19 response in correctional settings. Participants valued enhanced partnerships, flexibility, and innovation, as well as real-time data and corrections-specific public health guidance. Challenges included cross-sector collaborations, population density, scarcity of equipment and supplies, and mental health. Most participants reported improved relationships between criminal justice and public health organizations during the pandemic. Lessons from COVID-19 can be applied to everyday public health preparedness and emergency response in correctional facilities by ensuring representation of correctional health in public health strategy and practice and providing timely, data-driven, and partner-informed guidance tailored to correctional environments when public health needs arise. |
Efficacy and safety of artemether-lumefantrine for the treatment of uncomplicated falciparum malaria in mainland Tanzania, 2018
Ngasala B , Chiduo MG , Bushukatale S , Mmbando BP , Makene T , Kamugisha E , Ahmed M , Mandara CI , Francis F , Mahende MK , Kavishe RA , Muro F , Ishengoma DS , Mandike R , Molteni F , Chacky F , Kitojo C , Greer G , Bishanga D , Chadewa J , Njau R , Warsame M , Kabula B , Nyinondi SS , Reaves E , Mohamed A . Malar J 2024 23 (1) 95 BACKGROUND: The use of artemisinin-based combination therapy (ACT) is recommended by the World Health Organization for the treatment of uncomplicated falciparum malaria. Artemether-lumefantrine (AL) is the most widely adopted first-line ACT for uncomplicated malaria in sub-Saharan Africa (SSA), including mainland Tanzania, where it was introduced in December 2006. The WHO recommends regular assessment to monitor the efficacy of the first-line treatment specifically considering that artemisinin partial resistance was reported in Greater Mekong sub-region and has been confirmed in East Africa (Rwanda and Uganda). The main aim of this study was to assess the efficacy and safety of AL for the treatment of uncomplicated falciparum malaria in mainland Tanzania. METHODS: A single-arm prospective anti-malarial drug efficacy trial was conducted in Kibaha, Mlimba, Mkuzi, and Ujiji (in Pwani, Morogoro, Tanga, and Kigoma regions, respectively) in 2018. The sample size of 88 patients per site was determined based on WHO 2009 standard protocol. Participants were febrile patients (documented axillary temperature ≥ 37.5 °C and/or history of fever during the past 24 h) aged 6 months to 10 years. Patients received a 6-dose AL regimen by weight twice a day for 3 days. Clinical and parasitological parameters were monitored during 28 days of follow-up to evaluate the drug efficacy and safety. RESULTS: A total of 653 children were screened for uncomplicated malaria and 349 (53.7%) were enrolled between April and August 2018. Of the enrolled children, 345 (98.9%) completed the 28 days of follow-up or attained the treatment outcomes. There were no early treatment failures, but recurrent infections were higher in Mkuzi (35.2%) and Ujiji (23%). By Kaplan-Meier analysis of polymerase chain reaction (PCR) uncorrected adequate clinical and parasitological response (ACPR) ranged from 63.4% in Mkuzi to 85.9% in Mlimba, while PCR-corrected ACPR on day 28 varied from 97.6% in Ujiji to 100% in Mlimba. The drug was well tolerated; the commonly reported adverse events were cough, runny nose, and abdominal pain. No serious adverse event was reported. CONCLUSION: This study showed that AL had adequate efficacy and safety for the treatment of uncomplicated falciparum malaria. The high number of recurrent infections were mainly due to new infections, indicating the necessity of utilizing alternative artemisinin-based combinations, such as artesunate amodiaquine, which provide a significantly longer post-treatment prophylactic effect. |
Therapeutic response to four artemisinin-based combination therapies in Angola, 2021
Dimbu PR , Labuda S , Ferreira CM , Caquece F , André K , Pembele G , Pode D , João MF , Pelenda VM , Nieto Andrade B , Horton B , Kennedy C , Svigel SS , Zhou Z , Morais JFM , Rosário Jd , Fortes F , Martins JF , Plucinski MM . Antimicrob Agents Chemother 2024 e0152523 Monitoring antimalarial efficacy is important to detect the emergence of parasite drug resistance. Angola conducts in vivo therapeutic efficacy studies (TESs) every 2 years in its fixed sentinel sites in Benguela, Lunda Sul, and Zaire provinces. Children with uncomplicated Plasmodium falciparum malaria were treated with artemether-lumefantrine (AL), artesunate-amodiaquine (ASAQ), dihydroartemisinin-piperaquine (DP), or artesunate-pyronaridine (ASPY) and followed for 28 (AL and ASAQ) or 42 days (DP and ASPY) to assess clinical and parasitological response to treatment. Two drugs were sequentially assessed in each site in February-July 2021. The primary indicator was the Kaplan-Meier estimate of the PCR-corrected efficacy at the end of the follow-up period. A total of 622 patients were enrolled in the study and 590 (95%) participants reached a study endpoint. By day 3, ≥98% of participants were slide-negative in all study sites and arms. After PCR correction, day 28 AL efficacy was 88.0% (95% CI: 82%-95%) in Zaire and 94.7% (95% CI: 90%-99%) in Lunda Sul. For ASAQ, day 28 efficacy was 92.0% (95% CI: 87%-98%) in Zaire and 100% in Lunda Sul. Corrected day 42 efficacy was 99.6% (95% CI: 99%-100%) for ASPY and 98.3% (95% CI: 96%-100%) for DP in Benguela. High day 3 clearance rates suggest no clinical evidence of artemisinin resistance. This was the fourth of five rounds of TES in Angola showing a corrected AL efficacy <90% in a site. For Zaire, AL has had an efficacy <90% in 2013, 2015, and 2021. ASAQ, DP, and ASPY are appropriate choices as artemisinin-based combination therapies in Angola. |
Racial and ethnic differences in infant survival for hydrocephaly-Texas, 1999-2017
Ahmed M , Shumate C , Bojes H , Patel K , Agopian AJ , Canfield M . Birth Defects Res 2023 BACKGROUND: Congenital hydrocephaly, an abnormal accumulation of fluid within the ventricular spaces at birth, can cause disability or death if untreated. Limited information is available about survival of infants born with hydrocephaly in Texas. Therefore, the purpose of the study was to calculate survival estimates among infants born with hydrocephaly without spina bifida in Texas. METHODS: A cohort of live-born infants delivered during 1999-2017 with congenital hydrocephaly without spina bifida was identified from the Texas Birth Defects Registry. Deaths within 1 year of delivery were identified using vital and medical records. One-year infant survival estimates were generated for multiple descriptive characteristics using the Kaplan-Meier method. Crude hazard ratios (HRs) for one-year survival among infants with congenital hydrocephaly by maternal and infant characteristics and adjusted HRs for maternal race and ethnicity were estimated using Cox proportional hazard models. RESULTS: Among 5709 infants born with congenital hydrocephaly without spina bifida, 4681 (82%) survived the first year. The following characteristics were associated with infant survival: maternal race and ethnicity, clinical classification (e.g., chromosomal or syndromic), preterm birth, birth weight, birth year, and maternal education. In the multivariable Cox proportional hazards model, differences in survival were observed by maternal race and ethnicity after adjustment for other maternal and infant characteristics. Infants of non-Hispanic Black (HR: 1.28, 95% CI: 1.04-1.58) and Hispanic (HR: 1.31, 95% CI: 1.12-1.54) women had increased risk for mortality, compared with infants of non-Hispanic White women. CONCLUSIONS: This study showed infant survival among a Texas cohort differed by maternal race and ethnicity, clinical classification, gestational age, birth weight, birth year, and maternal education in infants with congenital hydrocephaly without spina bifida. Findings confirm that mortality continues to be common among infants with hydrocephaly without spina bifida. Additional research is needed to identify other risk factors of mortality risk. |
Rapid antiretroviral therapy initiation in patients with advanced HIV disease: 6-month outcomes of an observational cohort evaluation in Lesotho
Tiam A , Paulin H , Machekano R , Oboho I , Agyemang E , Mugyenyi FA , Maama-Maime L , Mengistu Y , Chatora T , Mungati M , Mokone M , Mots'oane T , Masheane A , Tukei V . PLoS One 2023 18 (10) e0292660 For adults and adolescents, the World Health Organization defines advanced HIV disease (AHD) as a CD4 (cluster of differentiation 4) count of <200 cells/mm3 or a clinical stage 3 or 4 event. We describe clinical outcomes in a cohort of AHD patients at two regional hospitals in Lesotho. From November 2018-June 2019, we prospectively enrolled eligible patients (≥15 years) not on antiretroviral therapy (ART) presenting with WHO-defined AHD into a differentiated model of care for AHD (including rapid ART initiation) and followed them for six months. All patients received Tuberculosis (TB) symptom screening with further diagnostic testing; serum cryptococcal antigen (CrAg) screening was done for CD4 <100 cells/mm3 or WHO clinical stage 3 or 4. Medical record data were abstracted using visit checklist forms. Categorical and continuous variables were summarized using frequencies, percentages, and means, respectively. Kaplan-Meier was used to estimate survival. Of 537 HIV-positive patients screened, 150 (27.9%) had AHD of which 109 were enrolled. Mean age was 38 years and 62 (56.9%) were men. At initial clinic visit, 8 (7.3%) were already on treatment and 33% (36/109) had presumptive TB per symptom screening. Among 39/109 (40.2%) patients screened for CrAg at initial visit, five (12.8%) were CrAg-positive. Among 109 enrolled, 77 (70.6%) initiated ART at their initial clinic visit, while 32 delayed ART initiation (median delay: 14 days). Of the 109 participants enrolled, 76 (69.7%) completed the 6-month follow-up, 17 (15.6%) were lost to follow-up, 5 (4.6%) transferred to other health facilities and 11 (10.1%) died. The 6-month survival was 87.4%; among 74 patients with a viral load result, 6-month viral suppression (<1,000 copies/ml) was 85.1%. Our study found that even after the implementation of Test and Treat of ART in 2016 in Lesotho, over 25% of patients screened had AHD. Patients with AHD had a high prevalence of TB and CrAg positivity, underscoring the need to assess for AHD and rapidly initiate ART within a package of AHD care for optimal patient outcomes. |
Analysis of interview breakoff in the Behavioral Risk Factor Surveillance System, 2018 and 2019
Hsia J , Gilbert M , Zhao G , Town M , Inusah S , Garvin W . AJPM Focus 2023 2 (2) 100076 INTRODUCTION: Survey breakoff is an important source of total survey error. Most studies of breakoff have been of web surveys-less is known about telephone surveys. In the past decade, the breakoff rate has increased in the Behavioral Risk Factor Surveillance System, the world's largest annual telephone survey. Analysis of breakoff in Behavioral Risk Factor Surveillance System can improve the quality of Behavioral Risk Factor Surveillance System. It will also provide evidence in research of total survey error on telephone surveys. METHODS: We used data recorded as breakoff in the 2018 and 2019 Behavioral Risk Factor Surveillance System. We converted questions and modules to a time variable and applied Kaplan-Meier method and a proportional hazard model to estimate the conditional and cumulative probabilities of breakoff and study the potential risk factors associated with breakoff. RESULTS: Cumulative probability of breakoffs up to the end of the core questionnaire was 7.03% in 2018 and 9.56% in 2019. The highest conditional probability of breakoffs in the core was 2.85% for the physical activity section. Cumulative probability of breakoffs up to the end of the core was higher among those states that inserted their own questions or optional modules than among those that did not in both years. The median risk ratio of breakoff among all states was 5.70 in 2018 and 3.01 in 2019. Survey breakoff was associated with the length of the questionnaire, the extent of expected recollection, and the location of questions. CONCLUSIONS: Breakoff is not an ignorable component of total survey error and should be considered in Behavioral Risk Factor Surveillance System data analyses when variables have higher breakoff rates. |
Prevalence and incidence of tuberculosis infection among healthcare workers in chest diseases hospitals, Bangladesh: Putting infection control into context
Islam MS , Gurley ES , Banu S , Hossain K , Heffelfinger JD , Amin Chowdhury KI , Ahmed S , Afreen S , Islam MT , Rahman SMM , Rahman A , Pearson ML , Chai SJ . PLoS One 2023 18 (9) e0291484 BACKGROUND: Healthcare workers (HCWs) are at increased risk of tuberculosis infection (TBI). We estimated the prevalence and incidence of TBI and risk factors among HCWs in Bangladeshi hospitals to target TB infection prevention and control (IPC) interventions. METHODS: During 2013-2016, we conducted a longitudinal study among HCWs in four chest disease hospitals. At baseline, we administered a questionnaire on sociodemographic and occupational factors for TB, tuberculin skin tests (TST) in all hospitals, and QuantiFERON ®-TB Gold in-Tube (QFT-GIT) tests in one hospital. We assessed factors associated with baseline TST positivity (induration ≥10mm), TST conversion (induration increase ≥10mm from baseline), baseline QFT-GIT positivity (interferon-gamma ≥0.35 IU/mL), and QFT-GIT conversion (interferon-gamma <0.35 IU/mL to ≥0.35 IU/mL). We included factors with a biologically plausible relationship with TBI identified in prior studies or having an association (p = <0.20) in the bivariate analyses with TST positivity or QFT-GIT positivity in multivariable generalized linear models. The Kaplan-Meier was used to estimate the cumulative TBI incidence rate per 100 person-years. RESULTS: Of the 758 HCWs invited, 732 (97%) consented to participate and 731 completed the one-step TST, 40% had a positive TST result, and 48% had a positive QFT-GIT result. In multivariable models, HCWs years of service 11-20 years had 2.1 (95% CI: 1.5-3.0) times higher odds of being TST-positive and 1.6 (95% CI 1.1-2.5) times higher odds of QFT-GIT-positivity at baseline compared with those working ≤10 years. HCWs working 11-20 years in pulmonary TB ward had 2.0 (95% CI: 1.4-2.9) times higher odds of TST positivity, and those >20 years had 2.5 (95% CI: 1.3-4.9) times higher odds of QFT-GIT-positivity at baseline compared with those working <10 years. TBI incidence was 4.8/100 person-years by TST and 4.2/100 person-years by QFT-GIT. Females had 8.5 (95% CI: 1.5-49.5) times higher odds of TST conversion than males. CONCLUSIONS: Prevalent TST and QFT-GIT positivity was associated with an increased number of years working as a healthcare worker and in pulmonary TB wards. The incidence of TBI among HCWs suggests ongoing TB exposure in these facilities and an urgent need for improved TB IPC in chest disease hospitals in Bangladesh. |
Medicaid coverage of guidelines-based asthma care across 50 states, the District of Columbia, and Puerto Rico, 2021-2022
Link J , Green H , Kaplan B , Collins P , Welch P , Johnson C . Prev Chronic Dis 2023 20 E79 INTRODUCTION: Asthma affects more than 25 million Americans, including 4.2 million children. The burden of asthma disproportionately affects people enrolled in Medicaid, among other disparate groups. Improved availability and accessibility of guidelines-based treatments and services may ensure positive health outcomes for people with asthma. In this article, we provide an update to the American Lung Association's Asthma Guidelines-Based Care Coverage Project (the Project) to determine the extent of asthma care coverage and associated barriers in Medicaid programs for all 50 states, the District of Columbia, and Puerto Rico, and examine improvements in coverage since 2017. METHODS: Findings from the Project, representing coverage from 2016-2017, were first published in Preventing Chronic Disease in 2018. The Project was updated in 2021 to reflect the National Asthma Education and Prevention Program guidelines 2020 Expert Panel Report-3 updates, which were finalized in December 2020. It now tracks coverage for 8 areas of guidelines-based care and 7 barriers to care in Medicaid programs by reviewing publicly available plan documents and engaging with Medicaid programs to review and confirm findings. RESULTS: Results from the Project, which reflect coverage in 2021-2022, show an increase in comprehensive coverage in Medicaid programs over the last 5 years. However, coverage remains inconsistent across programs, and barriers to accessing asthma care still exist. CONCLUSION: Although substantial improvement has been made to coverage, certain gaps and barriers to care must be addressed for patients to fully benefit from guidelines-based care to manage their asthma and improve health outcomes. |
Predicting daily COVID-19 case rates from SARS-CoV-2 RNA concentrations across a diversity of wastewater catchments (preprint)
Zulli A , Pan A , Bart SM , Crawford FW , Kaplan EH , Cartter M , Ko AI , Cozens D , Sanchez M , Brackney DE , Peccia J . medRxiv 2021 2021.04.27.21256140 We assessed the relationship between municipality COVID-19 case rates and SARS-CoV-2 concentrations in the primary sludge of corresponding wastewater treatment facilities. Over 1,000 daily primary sludge samples were collected from six wastewater treatment facilities with catchments serving 18 cities and towns in the State of Connecticut, USA. Samples were analyzed for SARS-CoV-2 RNA concentrations during a six-month time period that overlapped with fall 2020 and winter 2021 COVID-19 outbreaks in each municipality. We fit a single regression model to estimate reported case rates in the six municipalities from SARS-CoV-2 RNA concentrations collected daily from corresponding wastewater treatment facilities. Results demonstrate the ability of SARS-CoV-2 RNA concentrations in primary sludge to estimate COVID-19 reported case rates across treatment facilities and wastewater catchments, with coverage probabilities ranging from 0.94 to 0.96. Leave-one-out cross validation suggests that the model can be broadly applied to wastewater catchments that range in more than one order of magnitude in population served. Estimation of case rates from wastewater data can be useful in locations with limited testing availability or testing disparities, or delays in individual COVID-19 testing programs.Competing Interest StatementThe authors have declared no competing interest.Clinical TrialThis work did not result from a clinical trial. It is a comparison of wastewater concentrations with COVID-19 cases. The COVID-19 cases were obtained from publically available data. No human subjects were involved and all data is de-identified before being publically reported.Funding StatementThis project was supported by Cooperative Agreement no. 6NU50CK000524-01 from the Centers for Disease Control and Prevention using funds from the COVID-19 Paycheck Protection Program and Health Care Enhancement Act Response Activities. This activity was reviewed by CDC and was conducted consistent with applicable federal law and CDC policy. See e.g., 45 C.F.R. part 46.102(l)(2), 21 C.F.R. part 56; 42 U.S.C. 241(d); 5 U.S.C. 552a; 44 U.S.C. 3501 et seq. The findings and conclusions of this report are those of the author(s) and do not necessarily represent the official position of the Centers for Disease Control and Prevention.Author DeclarationsI confirm all relevant ethical guidelines have been followed, and any necessary IRB and/or ethics committee approvals have been obtained.YesThe details of the IRB/oversight body that provided approval or exemption for the research described are given below:No IRB is required. The study used publically available COVID-19 cased data. All data is de-identified.All necessary patient/participant consent has been obtained and the appropriate institutional forms have been archived.YesI understand that all clinical trials and any other prospective interventional studies must be registered with an ICMJE-approved registry, such as ClinicalTrials.gov. I confirm that any such study reported in the manuscript has been registered and the trial registration ID is provided (note: if posting a prospective study registered retrospectively, please provide a statement in the trial ID field explaining why the study was not registered in advance).YesI have followed all appropriate research reporting guidelines and uploaded the relevant EQUATOR Network research reporting checklist(s) and other pertinent material as supplementary files, if applicable.YesCOVID-19 case rate data was obtained from the CT department of health. Plots containing the case rate data and SARS-CoV-2 wastewater concentrations are available at: https://yalecovidwastewater.com/https://yalecovidwastewater.com/ |
Benefits of frequent HIV testing in the THRIVE demonstration project: United States, 2015-2020
Kimball AA , Zhu W , Yu L , Tanner MR , Iqbal K , Dominguez KL , Shankar A , Drezner K , Musgrove K , Mayes E , Robinson WT , Schumacher C , Delaney KP , Hoover KW . Am J Public Health 2023 113 (9) e1-e9 Objectives. To describe HIV testing among clients in the Targeted Highly Effective Interventions to Reverse the HIV Epidemic (THRIVE) demonstration project and evaluate testing frequency. Methods. We identified factors associated with an average testing frequency of 180 days or less compared with more than 180 days using adjusted Poisson regression models. We performed the Kaplan-Meier survival analysis to compare time to diagnosis by testing frequency. Results. Among 5710 clients with 2 or more tests and no preexposure prophylaxis (PrEP) prescription, 42.4% were tested frequently. Black/African American clients were 21% less likely and Hispanic/Latino clients were 18% less likely to be tested frequently than were White clients. Among 71 Black/African American and Hispanic/Latino cisgender men who have sex with men and transgender women with HIV diagnoses, those with frequent testing had a median time to diagnosis of 137 days, with a diagnostic testing yield of 1.5% compared with those tested less frequently, with 559 days and 0.8% yield. Conclusions. HIV testing at least every 6 months resulted in earlier HIV diagnosis and was efficient. Persons in communities with high rates of HIV who are not on PrEP can benefit from frequent testing, and collaborative community approaches may help reduce disparities. (Am J Public Health. Published online ahead of print July 6, 2023:e1-e9. https://doi.org/10.2105/AJPH.2023.307341). |
Survival from birth until young adulthood among individuals with congenital heart defects: CH STRONG
Downing KF , Nembhard WN , Rose CE , Andrews JG , Goudie A , Klewer SE , Oster ME , Farr SL . Circulation 2023 148 (7) 575-588 BACKGROUND: Limited population-based information is available on long-term survival of US individuals with congenital heart defects (CHDs). Therefore, we assessed patterns in survival from birth until young adulthood (ie, 35 years of age) and associated factors among a population-based sample of US individuals with CHDs. METHODS: Individuals born between 1980 and 1997 with CHDs identified in 3 US birth defect surveillance systems were linked to death records through 2015 to identify those deceased and the year of their death. Kaplan-Meier survival curves, adjusted risk ratios (aRRs) for infant mortality (ie, death during the first year of life), and Cox proportional hazard ratios for survival after the first year of life (aHRs) were used to estimate the probability of survival and associated factors. Standardized mortality ratios compared infant mortality, >1-year mortality, >10-year mortality, and >20-year mortality among individuals with CHDs with general population estimates. RESULTS: Among 11 695 individuals with CHDs, the probability of survival to 35 years of age was 81.4% overall, 86.5% among those without co-occurring noncardiac anomalies, and 92.8% among those who survived the first year of life. Characteristics associated with both infant mortality and reduced survival after the first year of life, respectively, included severe CHDs (aRR=4.08; aHR=3.18), genetic syndromes (aRR=1.83; aHR=3.06) or other noncardiac anomalies (aRR=1.54; aHR=2.53), low birth weight (aRR=1.70; aHR=1.29), and Hispanic (aRR=1.27; aHR=1.42) or non-Hispanic Black (aRR=1.43; aHR=1.80) maternal race and ethnicity. Individuals with CHDs had higher infant mortality (standardized mortality ratio=10.17), >1-year mortality (standardized mortality ratio=3.29), and >10-year and >20-year mortality (both standardized mortality ratios ≈1.5) than the general population; however, after excluding those with noncardiac anomalies, >1-year mortality for those with nonsevere CHDs and >10-year and >20-year mortality for those with any CHD were similar to the general population. CONCLUSIONS: Eight in 10 individuals with CHDs born between1980 and 1997 survived to 35 years of age, with disparities by CHD severity, noncardiac anomalies, birth weight, and maternal race and ethnicity. Among individuals without noncardiac anomalies, those with nonsevere CHDs experienced mortality between 1 and 35 years of age, similar to the general population, and those with any CHD experienced mortality between 10 and 35 years of age, similar to the general population. |
Timing of outpatient postpartum care utilization among women with chronic hypertension and hypertensive disorders of pregnancy
Aqua JK , Ford ND , Pollack LM , Lee JS , Kuklina EV , Hayes DK , Vaughan AS , Coronado F . Am J Obstet Gynecol MFM 2023 5 (9) 101051 BACKGROUND: The postpartum period represents an opportunity to assess the cardiovascular health of women who experience chronic hypertension or hypertensive disorders of pregnancy. OBJECTIVES: To determine whether women with chronic hypertension or hypertensive disorders of pregnancy access outpatient postpartum care more quickly compared to women with no hypertension. STUDY DESIGN: We used data from the Merative MarketScan® Commercial Claims and Encounters Database. We included 275,937 commercially insured women aged 12-55 years who had a live birth or stillbirth delivery hospitalization between 2017-2018 and continuous insurance enrollment from 3 months before the estimated start of pregnancy to 6 months after delivery discharge. Using International Classification of Diseases 10th Revision Clinical Modification codes, we identified hypertensive disorders of pregnancy from inpatient or outpatient claims from 20 weeks gestation through delivery hospitalization and identified chronic hypertension from inpatient or outpatient claims from the beginning of the continuous enrollment period through delivery hospitalization. Distributions of time-to-event survival curves (time-to-first outpatient postpartum visit with a women's health, primary care, or cardiology provider) were compared between the hypertension types using Kaplan-Meier estimators and log rank tests. We used Cox proportional hazards models to estimate adjusted hazard ratios (aHR) and 95% confidence intervals (CI). Time points of interest (3, 6, and 12 weeks) were evaluated per clinical postpartum care guidelines. RESULTS: Among commercially insured women, the prevalences of hypertensive disorders of pregnancy, chronic hypertension, and no documented hypertension were 11.7%, 3.4%, and 84.8%, respectively. The proportions of women with a visit within 3 weeks of delivery discharge were 28.5%, 26.4%, and 16.0% for hypertensive disorders of pregnancy, chronic, and no documented hypertension, respectively. By 12 weeks, the proportions increased to 62.4%, 64.5%, and 54.2%, respectively. Kaplan-Meier analyses indicated significant differences in utilization by hypertension type and interaction between hypertension type and time before and after 6 weeks. In adjusted Cox proportional hazards models, the utilization rate before 6 weeks among women with hypertensive disorders of pregnancy was 1.42 times the rate for women with no documented hypertension [aHR=1.42, 95% CI (1.39-1.45)]. Women with chronic hypertension also had higher utilization rates compared to women with no documented hypertension before 6 weeks [aHR=1.28, 95% CI: (1.24-1.33)]. Only chronic hypertension was significantly associated with utilization compared to the no documented hypertension group after 6 weeks [aHR=1.09, 95% CI: (1.03-1.14)]. CONCLUSIONS: In the 6 weeks following delivery discharge, women with hypertensive disorders of pregnancy and chronic hypertension attended outpatient postpartum care visits sooner than women with no documented hypertension. However, after 6 weeks this difference extended only to women with chronic hypertension. Overall, postpartum care utilization remained around 50-60% by 12 weeks in all groups. Addressing barriers to postpartum care attendance can ensure timely care for women at high risk for cardiovascular disease. |
Implementation of BPaL in the United States: Experience using a novel all-oral treatment regimen for treatment of rifampin-resistant or rifampin-intolerant TB disease
Haley CA , Schechter MC , Ashkin D , Peloquin CA , Cegielski JP , Andrino BB , Burgos M , Caloia LA , Chen L , Colon-Semidey A , DeSilva MB , Dhanireddy S , Dorman SE , Dworkin FF , Hammond-Epstein H , Easton AV , Gaensbauer JT , Ghassemieh B , Gomez ME , Horne D , Jasuja S , Jones BA , Kaplan LJ , Khan AE , Kracen E , Labuda S , Landers KM , Lardizabal AA , Lasley MT , Letzer DM , Lopes VK , Lubelchek RJ , Macias CP , Mihalyov A , Misch EA , Murray JA , Narita M , Nilsen DM , Ninneman MJ , Ogawa L , Oladele A , Overman M , Ray SM , Ritger KA , Rowlinson MC , Sabuwala N , Schiller TM , Schwartz LE , Spitters C , Thomson DB , Tresgallo RR , Valois P , Goswami ND . Clin Infect Dis 2023 77 (7) 1053-1062 BACKGROUND: Rifampin-resistant tuberculosis is a leading cause of morbidity worldwide; only one-third of persons initiate treatment and outcomes are often inadequate. Several trials demonstrate 90% efficacy using an all-oral, six-month regimen of bedaquiline, pretomanid, and linezolid (BPaL), but significant toxicity occurred using 1200 mg linezolid. After U.S. FDA approval in 2019, some U.S. clinicians rapidly implemented BPaL using an initial linezolid 600 mg dose adjusted by serum drug concentrations and clinical monitoring. METHODS: Data from U.S. patients treated with BPaL between 10/14/2019 and 4/30/2022 were compiled and analyzed by the BPaL Implementation Group (BIG), including baseline examination and laboratory, electrocardiographic, and clinical monitoring throughout treatment and follow-up. Linezolid dosing and clinical management was provider-driven, and most had linezolid adjusted by therapeutic drug monitoring (TDM). RESULTS: Of 70 patients starting BPaL, two changed to rifampin-based therapy, 68 (97.1%) completed BPaL, and two of these 68 (2.9%) patients relapsed after completion. Using an initial 600 mg linezolid dose daily adjusted by TDM and careful clinical and laboratory monitoring for side effects, supportive care, and expert consultation throughout BPaL treatment, three (4.4%) patients with hematologic toxicity and four (5.9%) with neurotoxicity required a change in linezolid dose or frequency. The median BPaL duration was 6 months. CONCLUSIONS: BPaL has transformed treatment for rifampin-resistant or intolerant tuberculosis. In this cohort, effective treatment required less than half the duration recommended in ATS/CDC/ERS/IDSA 2019 guidelines for drug-resistant tuberculosis. Use of individualized linezolid dosing and monitoring likely enhanced safety and treatment completion. The BIG cohort demonstrates that early implementation of new tuberculosis treatments in the U.S. is feasible. |
Racial and ethnic differences in timing of diagnosis and clinical services received in Duchenne muscular dystrophy
Mann JR , Zhang Y , McDermott S , Wang Y , Cai B , Conway KM , Paramsothy P , Royer J , Venkatesh S , Howard JF Jr , Ciafaloni E . Neuroepidemiology 2023 57 (2) 90-99 INTRODUCTION: Racial/ethnic differences in diagnostic and treatment services have been identified for a range of health conditions and outcomes. The current study aimed to analyze whether there are racial/ethnic differences in the timing of diagnostic testing and treatments for males with Duchenne muscular dystrophy (DMD). METHODS: Diagnostic and clinical data for male individuals with DMD born during 1990-2010 were analyzed from eight sites (Arizona, Colorado, Georgia, Iowa, Piedmont Region of North Carolina, Western New York, South Carolina, and Utah) of the Muscular Dystrophy Surveillance, Tracking, and Research Network (MD STARnet). Seven milestones related to diagnosis/treatment experiences were selected as outcomes. Times to each milestone were estimated and compared by four racial/ethnic groups using Kaplan-Meier estimation and Cox proportional-hazards models. Times between initial evaluation or diagnostic testing and later milestones were also compared by race/ethnicity. RESULTS: We identified 682 males with definite or probable DMD of whom 61.7% were non-Hispanic white, 20.5% Hispanic, 10.6% other, and 7.2% non-Hispanic black. Seven milestone events were studied (initial evaluation, first neurology/neuromuscular visit, diagnosis, corticosteroid treatment first offered, corticosteroid treatment started, first electrocardiogram or echocardiogram, and first pulmonary function test). The first five milestone events occurred at an older age for non-Hispanic black individuals compared to non-Hispanic white individuals. Time to first offering of corticosteroids and initiation of corticosteroid therapy was later for Hispanic individuals compared to non-Hispanic white individuals. When accounting for timing of initial evaluation/diagnosis, offering of corticosteroids continued to occur later, but first pulmonary testing occurred earlier, among Hispanic individuals compared to non-Hispanic whites. No significant delays remained for non-Hispanic black individuals after accounting for later initial evaluation/diagnosis. CONCLUSION: We described racial/ethnic differences in ages at selected diagnostic and treatment milestones. The most notable differences were significant delays for five of seven milestones in non-Hispanic black individuals, which appeared to be attributable to later initial evaluation/diagnosis. Findings for Hispanic individuals were less consistent. Efforts to address barriers to early evaluation and diagnosis for non-Hispanic black children with DMD may promote more timely initiation of recommended disease monitoring and interventions. |
Attitudes towards COVID-19 vaccination among incarcerated persons in the Federal Bureau of Prisons, June-July 2021
Fukunaga R , Kaplan ZE , Rodriguez T , Hagan L , Aarvig K , Dusseau C , Crockett M , Long M . Vaccine 2023 41 (24) 3604-3610 OBJECTIVE: To understand the attitudes towards COVID-19 vaccination and trusted sources of vaccination-related information among persons incarcerated in the Federal Bureau of Prisons. METHODS: From June-July 2021, persons incarcerated across 122 facilities operated by the Federal Bureau of Prisons were invited to participate in a survey asking their reasons for receiving or declining COVID-19 vaccination and the information sources they relied upon to make these decisions. Descriptive analyses were conducted. RESULTS: A total of 130,789 incarcerated persons with known vaccination status were invited to participate in the survey. At the time of survey, 78,496 (62%) were fully vaccinated; 3,128 (3%) were partially vaccinated and scheduled to complete their second dose, and 44,394 (35%) had declined either a first or second dose. 7,474 (9.5%) of the fully vaccinated group and 2,302 (4.4%) of the group declining either a first or second dose chose to participate in the survey; an overall survey return rate of 7.6% (n = 9,905). Among vaccinated respondents, the most common reason given for accepting vaccination was to protect their health (n = 5,689; 76.1%). Individuals who declined vaccination cited concerns about vaccine side effects (n = 1,304; 56.6%), mistrust of the vaccine (n = 1,256; 54.6%), and vaccine safety concerns (n = 1,252; 54.4%). Among those who declined, 21.2% (n = 489) reported that they would choose to be vaccinated if the vaccine was offered again. Those who declined also reported that additional information from outside organizations (n = 1128; 49.0%), receiving information regarding vaccine safety (n = 841; 36.5%), and/or speaking with a trusted medical advisor (n = 565; 24.5%) may influence their decision to be vaccinated in the future. CONCLUSION: As the COVID-19 pandemic continues, it is important to increase vaccine confidence in prisons, jails, and detention facilities to reduce transmission and severe health outcomes. These survey findings can inform the design of potential interventions to increase COVID-19 vaccine uptake in these settings. |
Remdesivir for the Treatment of Covid-19 - Final Report
Beigel JH , Tomashek KM , Dodd LE , Mehta AK , Zingman BS , Kalil AC , Hohmann E , Chu HY , Luetkemeyer A , Kline S , Lopez de Castilla D , Finberg RW , Dierberg K , Tapson V , Hsieh L , Patterson TF , Paredes R , Sweeney DA , Short WR , Touloumi G , Lye DC , Ohmagari N , Oh MD , Ruiz-Palacios GM , Benfield T , Fätkenheuer G , Kortepeter MG , Atmar RL , Creech CB , Lundgren J , Babiker AG , Pett S , Neaton JD , Burgess TH , Bonnett T , Green M , Makowski M , Osinusi A , Nayak S , Lane HC , ACTT-1 Study Group Members , Uyeki Timothy . N Engl J Med 2020 383 (19) 1813-1826 BACKGROUND: Although several therapeutic agents have been evaluated for the treatment of coronavirus disease 2019 (Covid-19), no antiviral agents have yet been shown to be efficacious. METHODS: We conducted a double-blind, randomized, placebo-controlled trial of intravenous remdesivir in adults who were hospitalized with Covid-19 and had evidence of lower respiratory tract infection. Patients were randomly assigned to receive either remdesivir (200 mg loading dose on day 1, followed by 100 mg daily for up to 9 additional days) or placebo for up to 10 days. The primary outcome was the time to recovery, defined by either discharge from the hospital or hospitalization for infection-control purposes only. RESULTS: A total of 1062 patients underwent randomization (with 541 assigned to remdesivir and 521 to placebo). Those who received remdesivir had a median recovery time of 10 days (95% confidence interval [CI], 9 to 11), as compared with 15 days (95% CI, 13 to 18) among those who received placebo (rate ratio for recovery, 1.29; 95% CI, 1.12 to 1.49; P<0.001, by a log-rank test). In an analysis that used a proportional-odds model with an eight-category ordinal scale, the patients who received remdesivir were found to be more likely than those who received placebo to have clinical improvement at day 15 (odds ratio, 1.5; 95% CI, 1.2 to 1.9, after adjustment for actual disease severity). The Kaplan-Meier estimates of mortality were 6.7% with remdesivir and 11.9% with placebo by day 15 and 11.4% with remdesivir and 15.2% with placebo by day 29 (hazard ratio, 0.73; 95% CI, 0.52 to 1.03). Serious adverse events were reported in 131 of the 532 patients who received remdesivir (24.6%) and in 163 of the 516 patients who received placebo (31.6%). CONCLUSIONS: Our data show that remdesivir was superior to placebo in shortening the time to recovery in adults who were hospitalized with Covid-19 and had evidence of lower respiratory tract infection. (Funded by the National Institute of Allergy and Infectious Diseases and others; ACTT-1 ClinicalTrials.gov number, NCT04280705.). |
Predicting daily COVID-19 case rates from SARS-CoV-2 RNA concentrations across a diversity of wastewater catchments
Zulli A , Pan A , Bart SM , Crawford FW , Kaplan EH , Cartter M , Ko AI , Sanchez M , Brown C , Cozens D , Brackney DE , Peccia J . FEMS Microbes 2021 2 xtab022 We assessed the relationship between municipality COVID-19 case rates and SARS-CoV-2 concentrations in the primary sludge of corresponding wastewater treatment facilities. Over 1700 daily primary sludge samples were collected from six wastewater treatment facilities with catchments serving 18 cities and towns in the State of Connecticut, USA. Samples were analyzed for SARS-CoV-2 RNA concentrations during a 10 month time period that overlapped with October 2020 and winter/spring 2021 COVID-19 outbreaks in each municipality. We fit lagged regression models to estimate reported case rates in the six municipalities from SARS-CoV-2 RNA concentrations collected daily from corresponding wastewater treatment facilities. Results demonstrate the ability of SARS-CoV-2 RNA concentrations in primary sludge to estimate COVID-19 reported case rates across treatment facilities and wastewater catchments, with coverage probabilities ranging from 0.94 to 0.96. Lags of 0 to 1 days resulted in the greatest predictive power for the model. Leave-one-out cross validation suggests that the model can be broadly applied to wastewater catchments that range in more than one order of magnitude in population served. The close relationship between case rates and SARS-CoV-2 concentrations demonstrates the utility of using primary sludge samples for monitoring COVID-19 outbreak dynamics. Estimating case rates from wastewater data can be useful in locations with limited testing availability, testing disparities, or delays in individual COVID-19 testing programs. |
Informative censoring-a cause of bias in estimating COVID-19 mortality using hospital data
Lin HM , Liu STH , Levin MA , Williamson J , Bouvier NM , Aberg JA , Reich D , Egorova N . Life (Basel) 2023 13 (1) Background: Several retrospective observational analyzed treatment outcomes for COVID-19; (2) Methods: Inverse probability of censoring weighting (IPCW) was applied to correct for bias due to informative censoring in database of hospitalized patients who did and did not receive convalescent plasma; (3) Results: When compared with an IPCW analysis, overall mortality was overestimated using an unadjusted Kaplan-Meier curve, and hazard ratios for the older age group compared to the youngest were underestimated using the Cox proportional hazard models and 30-day mortality; (4) Conclusions: An IPCW analysis provided stabilizing weights by hospital admission. |
Retention and predictors of attrition among HIV-infected children on antiretroviral therapy in Cte d'Ivoire between 2012 and 2016
Touré F , Etheredge GD , Brennan C , Parris K , Diallo MO , Ouffoue AF , Ekra A , Prao H , Assamoua NV , Gnongoue C , Kone F , Koffi C , Kamagaté F , Rivadeneira E , Carpenter D . Pediatr Infect Dis J 2023 42 (4) 299-304 BACKGROUND: An estimated 21,000 children aged 0-14 years were living with HIV in Côte d'Ivoire in 2020, of whom only 49% have been diagnosed and are receiving antiretroviral therapy (ART). Retention in HIV care and treatment is key to optimize clinical outcomes. We evaluated pediatric retention in select care and treatment centers (CTCs) in Côte d'Ivoire. METHODS: We retrospectively reviewed medical records using 2-stage cluster sampling for children under 15 years initiated on ART between 2012 and 2016. Kaplan-Meier time-to-event analysis was done to estimate cumulative attrition rates per total person-years of observation. Cox proportional hazard regression was performed to identify factors associated with attrition. RESULTS: A total of 1198 patient records from 33 CTCs were reviewed. Retention at 12, 24, 36, 48 and 60 months after ART initiation was 91%, 84%, 74%, 72% and 70%, respectively. A total of 309 attrition events occurred over 3169 person-years of follow-up [266 children were lost to follow-up (LTFU), 29 transferred to another facility and 14 died]. LTFU determinants included attending a "public-private" CTC [adjusted hazard ratio (aHR) 6.05; 95% confidence interval (CI): 4.23-8.65], receiving care at a CTC without an on-site laboratory (aHR: 4.01; 95% CI: 1.70-9.46) or attending a CTC without an electronic medical record (EMR) system (aHR: 2.22; 95% CI: 1.59-3.12). CONCLUSIONS: In Cote d'Ivoire, patients attending a CTC that is public-private, does not have on-site laboratory or EMR system were likely to be LTFU. Decentralization of laboratory services and scaling use of EMR systems could help to improve pediatric retention. |
Measuring oral pre-exposure prophylaxis (PrEP) continuation through electronic health records during program scale-up among the general population in Zambia
Heilmann E , Okuku J , Itoh M , Hines JZ , Prieto JT , Phiri M , Watala K , Nsofu C , Luhana-Phiri M , Vlahakis N , Kabongo M , Kaliki B , Minchella PA , Musonda B . AIDS Behav 2022 27 (7) 2390-2396 HIV pre-exposure prophylaxis (PrEP) is being scaled-up in Zambia, but PrEP continuation data are limited by paper-based registers and aggregate reports. Utilization of Zambia's electronic health record (EHR) system, SmartCare, may address this gap. We analyzed individuals aged ≥ 15 years who initiated PrEP between October 2020 and September 2021 in four provinces in Zambia in SmartCare versus aggregate reports. We measured PrEP continuation using Kaplan-Meier survival analysis and Cox proportional hazards models. SmartCare captured 29% (16,791/58,010) of new PrEP clients; 49% of clients continued at one month, and 89% discontinued PrEP by February 2022. Women were less likely than men to discontinue PrEP (adjusted hazard ratio [aHR]: 0.89, 95% CI 0.86-0.92, z = - 6.99, p < 0.001), and PrEP clients aged ≥ 50 years were less likely to discontinue PrEP compared to clients 15-19 years (aHR: 0.53, 95% CI 0.48-0.58, z = - 13.04, p < 0.001). Zambia's EHR is a valuable resource for measuring individual-level PrEP continuation over time and can be used to inform HIV prevention programs. |
Informatics modeling the relationship between proxy measures of respondent burden and survey response rates in a household panel survey
Earp M , Kaplan R , Toth D . J Off Stat 2022 38 (4) 1145-1175 Respondent burden has important implications for survey outcomes, including response rates and attrition in panel surveys. Despite this, respondent burden remains an understudied topic in the field of survey methodology, with few researchers systematically measuring objective and subjective burden factors in surveys used to produce official statistics. This research was designed to assess the impact of proxy measures of respondent burden, drawing on both objective (survey length and frequency), and subjective (effort, saliency, and sensitivity) burden measures on response rates over time in the Current Population Survey (CPS). Exploratory Factor Analysis confirmed the burden proxy measures were interrelated and formed five distinct factors. Regression tree models further indicated that both objective and subjective proxy burden factors were predictive of future CPS response rates. Additionally, respondent characteristics, including employment and marital status, interacted with these burden factors to further help predict response rates over time. We discuss the implications of these findings, including the importance of measuring both objective and subjective burden factors in production surveys. Our findings support a growing body of research suggesting that subjective burden and individual respondent characteristics should be incorporated into conceptual definitions of respondent burden and have implications for adaptive design. © 2022 Morgan Earp et al. |
Therapeutic efficacies of artemether-lumefantrine and dihydroartemisinin-piperaquine for the treatment of uncomplicated Plasmodium falciparum and chloroquine and dihydroartemisinin-piperaquine for uncomplicated Plasmodium vivax infection in Ethiopia
Assefa A , Mohammed H , Anand A , Abera A , Sime H , Minta AA , Tadesse M , Tadesse Y , Girma S , Bekele W , Etana K , Alemayehu BH , Teka H , Dilu D , Haile M , Solomon H , Moriarty LF , Zhou Z , Svigel SS , Ezema B , Tasew G , Woyessa A , Hwang J , Murphy M . Malar J 2022 21 (1) 359 BACKGROUND: Routine monitoring of anti-malarial drugs is recommended for early detection of drug resistance and to inform national malaria treatment guidelines. In Ethiopia, the national treatment guidelines employ a species-specific approach. Artemether-lumefantrine (AL) and chloroquine (CQ) are the first-line schizonticidal treatments for Plasmodium falciparum and Plasmodium vivax, respectively. The National Malaria Control and Elimination Programme in Ethiopia is considering dihydroartemisinin-piperaquine (DHA/PPQ) as an alternative regimen for P. falciparum and P. vivax. METHODS: The study assessed the clinical and parasitological efficacy of AL, CQ, and DHA/PPQ in four arms. Patients over 6 months and less than 18 years of age with uncomplicated malaria mono-infection were recruited and allocated to AL against P. falciparum and CQ against P. vivax. Patients 18 years or older with uncomplicated malaria mono-infection were recruited and randomized to AL or dihydroartemisinin-piperaquine (DHA/PPQ) against P. falciparum and CQ or DHA/PPQ for P. vivax. Patients were followed up for 28 (for CQ and AL) or 42 days (for DHA/PPQ) according to the WHO recommendations. Polymerase chain reaction (PCR)-corrected and uncorrected estimates were analysed by Kaplan Meier survival analysis and per protocol methods. RESULTS: A total of 379 patients were enroled in four arms (n = 106, AL-P. falciparum; n = 75, DHA/PPQ- P. falciparum; n = 142, CQ-P. vivax; n = 56, DHA/PPQ-P. vivax). High PCR-corrected adequate clinical and parasitological response (ACPR) rates were observed at the primary end points of 28 days for AL and CQ and 42 days for DHA/PPQ. ACPR rates were 100% in AL-Pf (95% CI: 96-100), 98% in CQ-P. vivax (95% CI: 95-100) at 28 days, and 100% in the DHA/PPQ arms for both P. falciparum and P. vivax at 42 days. For secondary endpoints, by day three 99% of AL-P. falciparum patients (n = 101) cleared parasites and 100% were afebrile. For all other arms, 100% of patients cleared parasites and were afebrile by day three. No serious adverse events were reported. CONCLUSION: This study demonstrated high therapeutic efficacy for the anti-malarial drugs currently used by the malaria control programme in Ethiopia and provides information on the efficacy of DHA/PPQ for the treatment of P. falciparum and P. vivax as an alternative option. |
Immunity to poliovirus in Afghanistan: A household sampling method for serological assessment based on geographical information systems
Mendes A , Whiteman A , Nygren B , Kaplan B , Hussain I , Soofi S , Martinez M , Farag NH . Geospat Health 2022 17 (2) Afghanistan continues to experience challenges affecting polio eradication. Mass polio vaccination campaigns, which aim to protect children under the age of 5, are a key eradication strategy. To date, the polio program in Afghanistan has only employed facility-based seroprevalence surveys, which can be subject to sampling bias. We describe the feasibility in implementing a cross-sectional household poliovirus seroprevalence survey based on geographical information systems (GIS) in three districts. Digital maps with randomly selected predetermined starting points were provided to teams, with a total target of 1,632 households. Teams were instructed to navigate to predetermined starting points and enrol the closest household within 60 m. To assess effectiveness of these methods, we calculated percentages for total households enrolled with valid geocoordinates collected within the designated boundary, and whether the Euclidean distance of households were within 60 m of a predetermined starting point. A normalized difference vegetation index (NDVI) image ratio was conducted to further investigate variability in team performances. The study enrolled a total of 78% of the target sample with 52% of all households within 60 m of a pre-selected point and 79% within the designated cluster boundary. Success varied considerably between the four target areas ranging from 42% enrolment of the target sample in one place to 90% enrolment of the target sample in another. Interviews with the field teams revealed that differences in security status and amount of non-residential land cover were key barriers to higher enrolment rates. Our findings indicate household poliovirus seroprevalence surveys using GIS-based sampling can be effectively implemented in polio endemic countries to capture representative samples. We also proposed ways to achieve higher success rates if these methods are to be used in the future, particularly in areas with concerns of insecurity or spatially dispersed residential units. |
COVID-19-Related manuscripts: lag from preprint to publication.
Drzymalla E , Yu W , Khoury MJ , Gwinn M . BMC Res Notes 2022 15 (1) 340 OBJECTIVE: Preprints have had a prominent role in the swift scientific response to COVID-19. Two years into the pandemic, we investigated how much preprints had contributed to timely data sharing by analyzing the lag time from preprint posting to journal publication. RESULTS: To estimate the median number of days between the date a manuscript was posted as a preprint and the date of its publication in a scientific journal, we analyzed preprints posted from January 1, 2020, to December 31, 2021 in the NIH iSearch COVID-19 Portfolio database and performed a Kaplan-Meier (KM) survival analysis using a non-mixture parametric cure model. Of the 39,243 preprints in our analysis, 7712 (20%) were published in a journal, after a median lag of 178 days (95% CI: 175-181). Most of the published preprints were posted on the bioRxiv (29%) or medRxiv (65%) servers, which allow authors to choose a subject category when posting. Of the 20,698 preprints posted on these two servers, 7358 (36%) were published, including approximately half of those categorized as biochemistry, biophysics, and genomics, which became published articles within the study interval, compared with 29% categorized as epidemiology and 26% as bioinformatics. |
The procurement and supply chain strengthening project: improving public health supply chains for better access to HIV medicines, Uganda 2011-2016
Muyingo S , Etoori D , Lotay P , Malamba S , Olweny J , Keesler K , Wiersma S , Jjemba P , Settaala R . J Pharm Policy Pract 2022 15 (1) 72 BACKGROUND: With countries moving towards reaching the UNAIDS 90-90-90 goal to achieve HIV epidemic control, there are going to be an unprecedented number of persons who will need to be tested, treated, and regularly monitored for viral suppression. However, most of the countries with the greatest burden of HIV/AIDS experience regular stock outages which could be detrimental to reaching these targets. ART and other commodities such as HIV test kits and laboratory supplies need to be readily and consistently available to achieve these targets. The main objective was to improve access to HIV/AIDS related commodities and strengthening institutional capacity for the management of HIV/AIDS logistics services through the MAUL procurement and supply chain strengthening project (PSSP) that rolled out four interventions on mentorship and support supervision, stock level monitoring, spatial visualization of stock indicators using GIS, and using WhatsApp to submit order reports as photo images. METHODS: Medical Access Uganda Limited, a private-not-for-profit supply chain management company in Uganda, implemented these interventions as part of a procurement and supply chain strengthening project (PSSP). These interventions were evaluated using performance monitoring indicators from 2011-2016. We tested for the significance in the change in scores of performance monitoring indicators using the test for difference in proportions. Health facilities were scored on 6 categories and accredited as bronze, silver or gold based on their total scores. Kaplan-Meier estimates were computed for time to silver, and gold ranking and univariate and multivariate Cox proportional hazards models were computed for time to gold ranking. RESULTS: We observed a significant reduction in reported stock-outs from 46 to 4% (p < 0.001) in the analysis period. Accurate stock card inventory rose from 79 to 91% (p < 0.001); adequate stock levels rose from 54 to 71% (p = 0.002) and stock reporting rates from 91 to 100% (p < 0.001). The stock order fill rate improved from a high of 93% to 97% (p = 0.375). Patient load (medium vs low adjusted hazard ratio (aHR): 2.19, p = 0.026; high vs low aHR: 2.97, p = 0.034) and number of support supervision visits (6-10 aHR: 3.33, p = 0.024; > 10 aHR: 5.78, p = 0.003) were associated with better stock management ranking scores. CONCLUSIONS: Improvements in supply chain management in countries committed to achieving the 90-90-90 goals are crucial to achieving HIV epidemic control. Health system strengthening and mentorship investments in Uganda were feasible and are essential for sustainable disease control efforts. |
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