PLOS Medicine recently published

by Laura Slade, Maya Blackman, Hiten D. Mistry, Jeffrey N. Bone, Milly Wilson, Nuhaat Syeda, Lucilla Poston, Peter von Dadelszen, Laura A. Magee, SCOPE Consortium

Background

In 2017, the American College of Cardiology and American Heart Association (ACC/AHA) lowered blood pressure (BP) thresholds to define hypertension in adults outside pregnancy. If used in pregnancy, these lower thresholds may identify women at increased risk of adverse outcomes, which would be particularly useful to risk-stratify nulliparous women. In this secondary analysis of the SCOPE cohort, we asked whether, among standard-risk nulliparous women, the ACC/AHA BP categories could identify women at increased risk for adverse outcomes.

Methods and findings

Included were pregnancies in the international SCOPE cohort with birth at ≥20 weeks’ gestation, 2004 to 2008. Women were mostly of white ethnicity, in their 20s, and of normal-to-overweight body mass index (BMI). Excluded were pregnancies ending in fetal loss at <20 weeks’ gestation, and those terminated at any point in pregnancy. Women were categorized by highest BP during pregnancy, using ACC/AHA criteria: normal (BP <120/80 mmHg), “Elevated BP” (BP 120 to 129 mmHg/<80 mmHg), “Stage-1 hypertension” (systolic BP [sBP] 130 to 139 mmHg or diastolic BP [dBP] 80 to 89 mmHg), and “Stage-2 hypertension” that was non-severe (sBP 140 to 159 mmHg or dBP 90 to 109 mmHg) or severe (sBP ≥160 mmHg or dBP ≥110 mmHg). Primary outcomes were preterm birth (PTB), low birthweight, postpartum hemorrhage, and neonatal care admission. Adjusted relative risks (aRRs) and diagnostic test properties were calculated for each outcome, according to: each BP category (versus “normal”), and using the lower limit of each BP category as a cut-off. RRs were adjusted for maternal age, BMI, smoking, ethnicity, and alcohol use. Of 5,628 women in SCOPE, 5,597 were included in this analysis. When compared with normotension, severe “Stage 2 hypertension” was associated with PTB (24.0% versus 5.3%; aRR 4.88, 95% confidence interval, CI [3.46 to 6.88]), birthweight <10th centile (24.4% versus 8.8%; aRR 2.70 [2.00 to 3.65]), and neonatal unit admission (32.9% versus 8.9%; aRR 3.40 [2.59 to 4.46]). When compared with normotension, non-severe “Stage 2 hypertension” was associated with birthweight <10th centile (16.1% versus 8.8%; aRR 1.82 [1.45 to 2.29]) and neonatal unit admission (15.4% versus 8.9%; aRR 1.65 [1.31 to 2.07]), but no association with adverse outcomes was seen with BP categories below “Stage 2 hypertension.” When each BP category was assessed as a threshold for diagnosis of abnormal BP (compared with BP values below), only severe “Stage 2 hypertension” had a useful (good) likelihood ratio (LR) of 5.09 (95% CI [3.84 to 6.75]) for PTB. No BP threshold could rule-out adverse outcomes (i.e., had a negative LR <0.2). Limitations of our analysis include lack of ethnic diversity and use of values from clinical notes for BP within 2 weeks before birth. This study was limited by: its retrospective nature, not all women having BP recorded at all visits, and the lack of detail about some outcomes.

Conclusions

In this study, we observed that 2017 ACC/AHA BP categories demonstrated a similar pattern of association and diagnostic test properties in nulliparous women, as seen in the general obstetric population. BP thresholds below the currently used “Stage 2 hypertension” were not associated with PTB, low birthweight, postpartum hemorrhage, or neonatal unit admission. This study does not support implementation of lower BP values as abnormal in nulliparous pregnant women.

by Aleksandra Turkiewicz, Karin Magnusson, Simon Timpka, Ali Kiadaliri, Andrea Dell-Isola, Martin Englund

Background

Cardiovascular, respiratory, and musculoskeletal disease are among the leading causes of disability in middle-aged and older people. Health and lifestyle factors in youth have known associations with cardiovascular or respiratory disease in adulthood, but largely unknown associations with musculoskeletal disease.

Methods and findings

We included approximately 40,000 18-year-old Swedish males, who completed their conscription examination in 1969 to 1970, followed up until age of 60 years. Exposures of interest were physical health: body mass and height, blood pressure, pulse at rest, muscle strength, cardiorespiratory fitness, and hematocrit; self-reported lifestyle: smoking, alcohol, and drug use; self-reported health: overall, headache and gastrointestinal. We followed the participants through the Swedish National Patient Register for incidence of common musculoskeletal (osteoarthritis, back pain, shoulder lesions, joint pain, myalgia), cardiovascular (ischemic heart disease, atrial fibrillation), and respiratory diseases (asthma, chronic obstructive pulmonary disease, bronchitis). We analyzed the associations using general estimating equations Poisson regression with all exposures included in one model and adjusted for parental education and occupation. We found that higher body mass was associated with higher risk of musculoskeletal (risk ratio [RR] per 1 standard deviation [SD] 1.12 [95% confidence interval, CI 1.09, 1.16]), cardiovascular (RR 1.22 [95% CI 1.17, 1.27] per 1 SD) and respiratory diseases (RR 1.14 [95% CI 1.05, 1.23] per 1 SD). Notably, higher muscle strength and cardiorespiratory fitness were associated with higher risk of musculoskeletal disease (RRs 1.08 [95% CI 1.05, 1.11] and 1.06 [95% CI 1.01, 1.12] per 1 SD difference in exposure), while higher cardiorespiratory fitness was protective against both cardiovascular and respiratory diseases (RRs 0.91 [95% CI 0.85, 0.98] and 0.85 [95% CI 0.73, 0.97] per 1 SD exposure, respectively). We confirmed the adverse effects of smoking, with risk ratios when comparing 11+ cigarettes per day to non-smoking of 1.14 (95% CI 1.06, 1.22) for musculoskeletal, 1.58 (95% CI 1.44, 1.74) for cardiovascular, and 1.93 (95% CI 1.60, 2.32) for respiratory diseases. Self-reported headache (category “often” compared to “never”) was associated with musculoskeletal diseases (RR 1.38 [95% CI 1.21, 1.58]) and cardiovascular diseases (RR 1.29 [95% CI 1.07, 1.56]), but had an inconclusive association with respiratory diseases (RR 1.13 [95% CI 0.79, 1.60]). No large consistent associations were found for other exposures. The most notable associations with specific musculoskeletal conditions were for cardiorespiratory fitness and osteoarthritis (RR 1.23 [95% CI 1.15, 1.32] per 1 SD) and for muscle strength and back pain (RR 1.18 [95% CI 1.12, 1.24] per 1 SD) or shoulder diseases (RR 1.27 [95% CI 1.19, 1.36] per 1 SD). The main limitations include lack of adjustment for genetic factors and environmental exposures from childhood, and that the register data were available for males only.

Conclusions

While high body mass was a risk factor for all 3 studied groups of diseases, high cardiorespiratory fitness and high muscle strength in youth were associated with increased risk of musculoskeletal disease in middle age. We speculate that these associations are mediated by chronic overload or acute trauma.

by Romain Ragonnet, Angus E. Hughes, David S. Shipman, Michael T. Meehan, Alec S. Henderson, Guillaume Briffoteaux, Nouredine Melab, Daniel Tuyttens, Emma S. McBryde, James M. Trauer

Background

School closures have been a prominent component of the global Coronavirus Disease 2019 (COVID-19) response. However, their effect on viral transmission, COVID-19 mortality and health care system pressure remains incompletely understood, as traditional observational studies fall short in assessing such population-level impacts.

Methods and findings

We used a mathematical model to simulate the COVID-19 epidemics of 74 countries, incorporating observed data from 2020 to 2022 and historical school closure timelines. We then simulated a counterfactual scenario, assuming that schools remained open throughout the study period. We compared the simulated epidemics in terms of Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) infections, deaths, and hospital occupancy pressure. We estimated that school closures achieved moderate to significant burden reductions in most settings over the period 2020 to 2022. They reduced peak hospital occupancy pressure in nearly all countries, with 72 out of 74 countries (97%) showing a positive median estimated effect, and median estimated effect ranging from reducing peak hospital occupancy pressure by 89% in Brazil to increasing it by 19% in Indonesia. The median estimated effect of school closures on COVID-19 deaths ranged from a 73% reduction in Thailand to a 7% increase in the United Kingdom. We estimated that school closures may have increased overall COVID-19 mortality (based on median estimates) in 9 countries (12%), including several European nations and Indonesia. This is attributed to changes in population-level immunity dynamics, leading to a concentration of the epidemic during the Delta variant period, alongside an upward shift in the age distribution of infections. While our estimates were associated with significant uncertainty, our sensitivity analyses exploring the impact of social mixing assumptions revealed robustness in our country-specific conclusions. The main study limitations include the fact that analyses were conducted at the national level, whereas school closure policies often varied by region. Furthermore, some regions, including Africa, were underrepresented due to insufficient data informing the model.

Conclusions

Our analysis revealed nuanced effects of school closures on COVID-19 dynamics, with reductions in COVID-19 impacts in most countries but negative epidemiological effects in a few others. We identified critical mechanisms for consideration in future policy decisions, highlighting the unpredictable nature of emerging variants and potential shifts in infection demographics associated with school closures.

by Si-Jing Chen, Jian-Yu Que, Ngan Yin Chan, Le Shi, Shirley Xin Li, Joey Wing Yan Chan, Weizhen Huang, Chris Xie Chen, Chi Ching Tsang, Yuen Lam Ho, Charles M. Morin, Ji-Hui Zhang, Lin Lu, Yun Kwok Wing

Background

Increasing evidence suggests that insomnia plays an important role in the development of depression, supporting insomnia intervention as a promising approach to prevent depression in youth. This randomized controlled trial evaluated the effectiveness of app-based cognitive behavioral therapy for insomnia (CBT-I) in preventing future onset of major depressive disorder (MDD) in youth.

Methods and findings

This was a randomized, assessor-blind, parallel group-controlled trial in Chinese youth (aged 15−25 years) with insomnia disorder and subclinical depressive symptoms. Participants were randomly assigned (1:1) to 6-week app-based CBT-I or 6-week app-based health education (HE) delivered through smartphones. Online assessments and telephone clinical interviews were conducted at baseline, post-intervention, 6- and 12-month follow-ups. The primary outcome was time to onset of MDD. The secondary outcomes included depressive symptoms and insomnia at both symptom and disorder levels. Between September 9, 2019, and November 25, 2022, 708 participants (407 females [57%]; mean age, 22.1 years [SD = 1.9]) were randomly allocated to app-based CBT-I group (n = 354) or app-based HE group (n = 354). Thirty-seven participants (10%) in the intervention group and 62 participants (18%) in the control group developed new-onset MDD throughout the 12-month follow-up, with a hazard ratio of 0.58 (95% confidence interval 0.38–0.87; p = 0.008). The number needed to treat to prevent MDD at 1 year was 10.9 (6.8–26.6). The app-based CBT-I group has higher remission rates of insomnia disorder than the controls at post-intervention (52% versus 28%; relative risk 1.83 [1.49–2.24]; p < 0.001) and throughout 12-month follow-up. In addition, the CBT-I group reported a greater decrease in depressive (adjusted difference −1.0 [−1.6 to −0.5]; Cohen’s d = 0.53; p < 0.001) and insomnia symptoms (−2.0 [−2.7 to −1.3], d = 0.78; p < 0.001) than the controls at post-intervention and throughout 6-month follow-up. Insomnia was a mediator of intervention effects on depression. No adverse events related to the interventions were reported.

Conclusions

App-based CBT-I is effective in preventing future onset of major depression and improving insomnia outcomes among youth with insomnia and subclinical depression. These findings highlight the importance of targeting insomnia to prevent the onset of MDD and emphasize the need for wider dissemination of digital CBT-I to promote sleep and mental health in the youth population.

Trial registration

ClinicalTrials.Gov (NCT04069247).

by Lorenz von Seidlein

In this Perspective article, Lorenz von Seidlein outlines the promise of two malaria vaccines, and discusses some of the considerations for their roll out.

by Abhishek Bhatia, Alexander J. Preiss, Xuya Xiao, M. Daniel Brannock, G. Caleb Alexander, Robert F. Chew, Hannah Davis, Megan Fitzgerald, Elaine Hill, Elizabeth P. Kelly, Hemalkumar B. Mehta, Charisse Madlock-Brown, Kenneth J. Wilkins, Christopher G. Chute, Melissa Haendel, Richard Moffitt, Emily R. Pfaff, the N3C Consortium

Background

Nirmatrelvir with ritonavir (Paxlovid) is indicated for patients with Coronavirus Disease 2019 (COVID-19) who are at risk for progression to severe disease due to the presence of one or more risk factors. Millions of treatment courses have been prescribed in the United States alone. Paxlovid was highly effective at preventing hospitalization and death in clinical trials. Several studies have found a protective association in real-world data, but they variously used less recent study periods, correlational methods, and small, local cohorts. Their estimates also varied widely. The real-world effectiveness of Paxlovid remains uncertain, and it is unknown whether its effect is homogeneous across demographic strata. This study leverages electronic health record data in the National COVID Cohort Collaborative’s (N3C) repository to investigate disparities in Paxlovid treatment and to emulate a target trial assessing its effectiveness in reducing severe COVID-19 outcomes.

Methods and findings

This target trial emulation used a cohort of 703,647 patients with COVID-19 seen at 34 clinical sites across the United States between April 1, 2022 and August 28, 2023. Treatment was defined as receipt of a Paxlovid prescription within 5 days of the patient’s COVID-19 index date (positive test or diagnosis). To emulate randomization, we used the clone-censor-weight technique with inverse probability of censoring weights to balance a set of covariates including sex, age, race and ethnicity, comorbidities, community well-being index (CWBI), prior healthcare utilization, month of COVID-19 index, and site of care provision. The primary outcome was hospitalization; death was a secondary outcome. We estimated that Paxlovid reduced the risk of hospitalization by 39% (95% confidence interval (CI) [36%, 41%]; p < 0.001), with an absolute risk reduction of 0.9 percentage points (95% CI [0.9, 1.0]; p < 0.001), and reduced the risk of death by 61% (95% CI [55%, 67%]; p < 0.001), with an absolute risk reduction of 0.2 percentage points (95% CI [0.1, 0.2]; p < 0.001). We also conducted stratified analyses by vaccination status and age group. Absolute risk reduction for hospitalization was similar among patients that were vaccinated and unvaccinate, but was much greater among patients aged 65+ years than among younger patients. We observed disparities in Paxlovid treatment, with lower rates among black and Hispanic or Latino patients, and within socially vulnerable communities. This study’s main limitation is that it estimates causal effects using observational data and could be biased by unmeasured confounding.

Conclusions

In this study of Paxlovid’s real-world effectiveness, we observed that Paxlovid is effective at preventing hospitalization and death, including among vaccinated patients, and particularly among older patients. This remains true in the era of Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) Omicron subvariants. However, disparities in Paxlovid treatment rates imply that the benefit of Paxlovid’s effectiveness is not equitably distributed.

by Nathaniel Z. Counts, Noemi Kreif, Timothy B. Creedon, David E. Bloom

Background

Federal policy impact analyses in the United States do not incorporate the potential economic benefits of adolescent mental health policies. Understanding the extent to which economic benefits may offset policy costs would support more effective policymaking. This study estimates the relationship between adolescent psychological distress and later health and economic outcomes and uses these estimates to determine the potential economic effects of a hypothetical policy.

Methods and findings

This analysis estimated the relationship between psychological distress in those aged 15 to 17 years in 2000 and economic and health outcomes approximately 10 years later, accounting for an array of explanatory variables using machine learning–enabled methods. The cohort was from the National Longitudinal Study of Youth 1997 and nationally representative of those aged 12 to 18 years in 1997. The cohort included 3,343 individuals under age 18 years in round 4 who completed the Mental Health Inventory-5 (MHI-5). Round 1 captured 50 explanatory variables that covered domains of potential confounders, including basic demographics, neighborhood environment, family resources, family processes, physical health, school quality, and academic skills. The exposure included a binary variable of clinically significant psychological distress (MHI-5 score of less than or equal to 3) and a categorical variable of symptom severity on the MHI-5. Outcomes covered domains of employment, income, total assets at age 30 years, education, and health approximately 10 years later.Forty-seven percent of the cohort were black and Hispanic, and 4.4% had past-month clinically significant psychological distress. Past-month clinically significant psychological distress in adolescence led to a 6-percentage-point (95% confidence interval [CI] [−0.08, −0.03]) reduction in past-year labor force participation 10 years later and $5,658 (95% CI [−6,772, −4,545]) USD fewer past-year wages earned. We used these results to model the labor market impacts of a hypothetical policy that expanded access to mental health preventive care and reached 10% of youth who would have otherwise developed clinically significant psychological distress. We found that the hypothetical policy could lead to $52 (95% credible interval [51,54]) billion USD in federal budget benefits over 10 years from labor supply impacts alone. This study faced limitations, including potential unmeasured confounding, missing data, and challenges to generalizability.

Conclusions

Our findings showed the impacts of adolescent mental health policies on the federal budget and found potentially large effects on the economy if policies achieve population-level change.

by Karin Källén, Mikael Norman, Charlotte Elvander, Christina Bergh, Verena Sengpiel, Henrik Hagberg, Teresia Svanvik, Ulla-Britt Wennerholm

Background

The risk of perinatal death and severe neonatal morbidity increases gradually after 41 weeks of pregnancy. We evaluated maternal and perinatal outcomes after a national shift from expectancy and induction at 42+0 weeks to a more active management of late-term pregnancies in Sweden offering induction from 41+0 weeks or an individual plan aiming at birth or active labour no later than 42+0 weeks.

Methods and findings

Women with a singleton pregnancy lasting 41+0 weeks or more with a fetus in cephalic presentation (N = 150,370) were included in a nationwide, register-based cohort study. Elective cesarean sections were excluded. Outcomes during period 1, January 2017 to December 2019 (before the shift) versus outcomes during period 2, January 2020 to October 1, 2023 (after the shift) were analysed. For comparison, outcomes of pregnancies lasting 39+0 to 40+6 weeks (N = 358,548) were also studied.Primary outcomes were: First, peri/neonatal death (stillbirth or neonatal death before 28 days); second, composite adverse peri/neonatal outcome (peri/neonatal death, Apgar score <4 at 5 min, hypoxic ischemic encephalopathy grades 1–3, meconium aspiration syndrome, birth trauma, or admission to a neonatal intensive care unit (NICU) ≥4 days); third, composite adverse peri/neonatal outcome excluding admission to NICU; and fourth, emergency cesarean section. Secondary outcomes included the components of the primary composite outcomes. Relative risks (RRs) with 95% confidence intervals (CIs) for binary outcomes period 2 versus period 1 were computed using modified Poisson regression analyses with adjustments for maternal age, parity, body mass index (BMI), smoking, and educational level.Induction rates among pregnancies lasting 41+0 weeks or more increased from 33.7% in period 1 to 52.4% in period 2. Mean (standard deviation) gestational age at birth decreased from 290.7 (2.9) days to 289.6 (2.3) days. Infants born during period 2 were at lower risk of peri/neonatal death compared to infants born during period 1; 0.9/1,000 versus 1.7/1,000 born infants (adjusted RR 0.52; 95% CI [0.38, 0.69]; p < 0.001), and they had a lower risk of having the composite adverse neonatal outcome, both including (50.5/1,000 versus 53.9/1,000, adjusted RR 0.92; 95% CI [0.88, 0.96]; p < 0.001) or excluding NICU admission (18.5/1,000 versus 22.5/1,000, adjusted RR 0.79; 95% CI [0.74, 0.85]; p < 0.001). The cesarean section rate increased from 10.5% in period 1 to 11.9% in period 2 (adjusted RR 1.07; 95% CI [1.04, 1.10]; p < 0.001). For births at 39 to 40 weeks the adjusted RR for peri/neonatal death was 0.86 (95% CI [0.72, 1.02]). One limitation of the study is that we had no data on to what extent monitoring of fetal health was performed.

Conclusions

A more active management of pregnancies lasting 41+0 weeks or more was associated with a decrease in peri/neonatal deaths, and a decrease in composite adverse peri/neonatal outcomes. Increased rate of emergency cesarean sections was observed. Women with pregnancies advancing towards 41 gestational weeks should be given balanced information on the benefits and risks of induction of labour at 41 weeks compared to expectant management until 42 weeks and be offered induction of labour at 41 weeks or active surveillance of pregnancies from 41 weeks in order to decrease peri/neonatal mortality.

by Raphaele Houlbracq, Camille Le Ray, Béatrice Blondel, Nathalie Lelong, Anne Alice Chantry, Thomas Desplanches, ENP2021 Study Group

Background

The French guidelines have recommended a restrictive policy of episiotomy since 2005. We aimed to assess variations in the prevalence of both episiotomy and obstetric anal sphincter injury (OASI) from the 2010, 2016, and 2021 National Perinatal Surveys.

Methods and findings

A total of 29,750 women who had given birth to a live infant by vaginal delivery were included. For instance, in 2021, 22.3% of women were over 35 years old, 17.7% were born outside of France, 11.3% had a body mass index (BMI) of 30 kg/m2 or higher, and 39.9% were primiparous. Episiotomy and OASI (third- and fourth-degree tears) were identified from medical records. We described the overall prevalence of outcomes, and then by obstetrical clinical contexts using a seven-group obstetric classification of women. Variations between 2010 (reference), 2016, and 2021 were analyzed by Cochran–Armitage tests and using Poisson regression models adjusted for maternal age, BMI, country of birth, antenatal classes, suspicion of fetal macrosomia, and neuroaxial analgesia during labor, the professional who attended the birth, the annual number of deliveries, and the maternity unit status to account for changes in women’s characteristics and obstetric practices.The overall prevalence of episiotomy decreased significantly from 25.8% (95% confidence interval (CI) 25.0 to 26.7) in 2010, to 20.1% (95% CI 19.3 to 20.9) in 2016, and 8.3% (95% CI 7.8 to 8.9) in 2021 (adjusted risk ratio (aRR) 0.33, 95% CI 0.30 to 0.35). This reduction was observed in all groups of the classification (Cochran–Armitage tests P < 0.001), ranging from −33.0% in Group 2a [nulliparous term cephalic singleton with forceps delivery] to −94.0% in Group 7 [multiple pregnancy]. The difference in overall prevalence of OASI between 2010 (0.7%) and 2021 (1.0%) was not statistically significant after adjustment (aRR 1.24, 95% CI 0.91 to 1.68). By groups of classification, the prevalence of OASI increased significantly only in Group 2b [nulliparous term cephalic singleton with spatula delivery] from 2.6% (95% CI 1.2 to 5.6) in 2010 to 9.6% (95% CI 6.2 to 14.7) in 2021 (aRR 3.69, 95% CI 1.50 to 9.09), and did not differ statistically significantly in Group 2a [nulliparous term cephalic singleton with forceps delivery] from 3.2% (95% CI 1.8 to 5.7) in 2010 to 5.7% (95% CI 3.4 to 9.5) in 2021 (aRR 1.78, 95% CI 0.81 to 3.90).The main limitations of this study include the failure to take into account some potential confounding factors and the inability to analyze some groups of the studied population (8.5% of the sample) because of the very small number of events in these groups.

Conclusions

The significant overall reduction in the prevalence of episiotomy in France has not been followed by an overall increase in OASI. However, subgroup analyses revealed a significant rise in OASI among nulliparous women giving birth by spatula (Group 2b), and a clinically relevant but statistically nonsignificant rise among nulliparous women delivering by forceps (Group 2a), while the prevalence of episiotomy significantly decreased. These results should be interpreted with caution given the low prevalence of OASI in some subgroups. Further research is needed to predict the optimal rate of episiotomy for instrumental deliveries. In hospitals with high episiotomy rates, our findings suggest that episiotomy could be safely reduced for spontaneous vaginal deliveries to comply with international guidelines and women’s requests.

by Sun Kim, Melike Hazal Can, Tefera B. Agizew, Andrew F. Auld, Maria Elvira Balcells, Stephanie Bjerrum, Keertan Dheda, Susan E. Dorman, Aliasgar Esmail, Katherine Fielding, Alberto L. Garcia-Basteiro, Colleen F. Hanrahan, Wakjira Kebede, Mikashmi Kohli, Anne F. Luetkemeyer, Carol Mita, Byron W. P. Reeve, Denise Rossato Silva, Sedona Sweeney, Grant Theron, Anete Trajman, Anna Vassall, Joshua L. Warren, Marcel Yotebieng, Ted Cohen, Nicolas A. Menzies

Background

Globally, over one-third of pulmonary tuberculosis (TB) disease diagnoses are made based on clinical criteria after a negative bacteriological test result. There is limited information on the factors that determine clinicians’ decisions to initiate TB treatment when initial bacteriological test results are negative.

Methods and findings

We performed a systematic review and individual patient data meta-analysis using studies conducted between January 2010 and December 2022 (PROSPERO: CRD42022287613). We included trials or cohort studies that enrolled individuals evaluated for TB in routine settings. In these studies, participants were evaluated based on clinical examination and routinely used diagnostics and were followed for ≥1 week after the initial test result. We used hierarchical Bayesian logistic regression to identify factors associated with treatment initiation following a negative result on an initial bacteriological test (e.g., sputum smear microscopy (SSM), Xpert MTB/RIF).Multiple factors were positively associated with treatment initiation: male sex [adjusted odds ratio (aOR) 1.61 (1.31, 1.95)], history of prior TB [aOR 1.36 (1.06, 1.73)], reported cough [aOR 4.62 (3.42, 6.27)], reported night sweats [aOR 1.50 (1.21, 1.90)], and having HIV infection but not on ART [aOR 1.68 (1.23, 2.32)]. Treatment initiation was substantially less likely for individuals testing negative with Xpert [aOR 0.77 (0.62, 0.96)] compared to smear microscopy and declined in more recent years. We were not able assess why clinicians made treatment decisions, as these data were not available.

Conclusions

Multiple factors influenced decisions to initiate TB treatment despite negative test results. Clinicians were substantially less likely to treat in the absence of a positive test result when using more sensitive, PCR-based diagnostics.

by Jewel Gausman, Richard Adanu, Delia A. B. Bandoh, Neena R Kapoor, Ernest Kenu, Ana Langer, Magdalene A. Odikro, Thomas Pullum, R. Rima Jolivet

Background

Sustainable Development Goal (SDG) Indicator 5.6.2 is the “Number of countries with laws and regulations that guarantee full and equal access to women and men aged 15 years and older to sexual and reproductive health care, information, and education.” This indicator plays a key role in tracking global progress toward achieving gender equity and empowerment, ensuring its validity is essential. Significant challenges related to the indicator’s calculation have been noted, which have important implications for the indicator’s validity in measuring progress towards meeting the SDG target. Recommendations have been made to revise the scoring of the indicator. This study examines the indicator’s validity by proposing a revision to the indicator’s calculation that addresses these global concerns and comparing the resulting values.

Methods and findings

This is an observational, validation study which used secondary data from the 2022 United Nations Population Fund’s Sexual and Reproductive Health and Rights Country Profiles from 75 countries. To address global recommendations, we proposed making 2 changes to the indicator’s calculation. First, we re-expressed all barriers and enablers to take positive values. Second, we used a weighted additive approach to calculate the total score, rather than the mean of the 13 individual component scores, which assigns equal weight to the substantive domains rather than the components. Our main outcome measures are the indicator values obtained from both scoring approaches examined. We assessed the indicator’s convergent validity by comparing the value obtained using the indicator’s current formula to the proposed formula using the Bland–Altman approach. We examined and interpreted changes in the indicator’s overall score that result from comparing the existing indicator with the proposed alternative. Differences in the total value of the indicator comparing the alternative versus the current formulation range from −7.18 percentage points in Mali to 26.21 percentage points in South Sudan. The majority of countries (n = 47) had an increase in total indicator score as a result of the alternative formula, while 27 countries had a decrease in score. Only 1 country, Sweden, saw no change in score, as it scored 100% of the possible indicator value under both rubrics. The mean difference between the scores produced by the 2 measures is 2.28 suggesting that the 2 methods may produce systematically different results. Under the alternative formulation, the most substantial changes were observed in the scores for “Component 3: Abortion.” The indicator’s current calculation results in 16 countries being assigned a score of zero, for “Component 3: Abortion” which masks important differences in the number of legal barriers present and whether women can be criminally charged for illegal abortion. After re-expressing barriers on a positive scale following the proposed formulation, only 4 countries have a score of zero for Component 3. The main limitation of our methodology is that there is no gold standard for measurement of the phenomenon under study, and thus we are unable to specify with total certainty which indicator performs better.

Conclusions

Our results illustrate underlying challenges with the current indicator formulation that impact its interpretability. The proposed changes could alter the way the current legal landscape governing sexual and reproductive health is understood, thereby pointing to different programmatic and policy priorities that may better support countries in achieving full and equal access to sexual and reproductive health and rights globally.