Nevin Manimala

Nat Commun. 2022 Oct 2;13(1):5783. doi: 10.1038/s41467-022-33192-1.

ABSTRACT

Patient-level data from completed clinical studies or electronic health records can be used in the design and analysis of clinical trials. However, these external data can bias the evaluation of the experimental treatment when the statistical design does not appropriately account for potential confounders. In this work, we introduce a hybrid clinical trial design that combines the use of external control datasets and randomization to experimental and control arms, with the aim of producing efficient inference on the experimental treatment effects. Our analysis of the hybrid trial design includes scenarios where the distributions of measured and unmeasured prognostic patient characteristics differ across studies. Using simulations and datasets from clinical studies in extensive-stage small cell lung cancer and glioblastoma, we illustrate the potential advantages of hybrid trial designs compared to externally controlled trials and randomized trial designs.

PMID:36184621 | DOI:10.1038/s41467-022-33192-1

BMC Infect Dis. 2022 Oct 2;22(1):766. doi: 10.1186/s12879-022-07726-3.

ABSTRACT

BACKGROUND: We aimed to assess the prevalence of Salmonella Typhi through DNA and IgM-antibody detection methods as a prelude to extended surveillance activities at sites in Ghana, Madagascar, and Ethiopia.

METHODS: We performed species-specific real-time polymerase reaction (RT-PCR) to identify bacterial nucleic acid, and enzyme-linked immunosorbent assay (ELISA) for detecting HlyE/STY1498-, CdtB/STY1886-, pilL/STY4539- and Vi-antigens in blood and biopsy specimens of febrile and non-febrile subjects. We generated antigen-specific ELISA proxy cut-offs by change-point analyses, and utilized cumulative sum as detection method coupled with 1000 repetitive bootstrap analyses. We computed prevalence rates in addition to odds ratios to assess correlations between ELISA outcomes and participant characteristics.

RESULTS: Definitive positive RT-PCR results were obtained from samples of febrile subjects originating from Adama Zuria/Ethiopia (1.9%, 2/104), Wolayita Sodo/Ethiopia (1.0%, 1/100), Diego/Madagascar (1.0%, 1/100), and Kintampo/Ghana (1.0%, 1/100), and from samples of non-febrile subjects from Wolayita Sodo/Ethiopia (1%, 2/201). While IgM antibodies against all antigens were identified across all sites, prevalence rates were highest at all Ethiopian sites, albeit in non-febrile populations. Significant correlations in febrile subjects aged < 15 years versus ≥ 15 years were detected for Vi (Odds Ratio (OR): 8.00, p = 0.034) in Adama Zuria/Ethiopia, STY1498 (OR: 3.21, p = 0.008), STY1886 (OR: 2.31, p = 0.054) and STY4539 (OR: 2.82, p = 0.022) in Diego/Madagascar, and STY1498 (OR: 2.45, p = 0.034) in Kintampo/Ghana. We found statistical significance in non-febrile male versus female subjects for STY1498 (OR: 1.96, p = 0.020) in Adama Zuria/Ethiopia, Vi (OR: 2.84, p = 0.048) in Diego/Madagascar, and STY4539 (OR: 0.46, p = 0.009) in Kintampo/Ghana.

CONCLUSIONS: Findings indicate non-discriminatory stages of acute infections, though with site-specific differences. Immune responses among non-febrile, presumably healthy participants may mask recall and/or reporting bias leading to misclassification, or asymptomatic, subclinical infection signs induced by suppression of inflammatory responses. As most Ethiopian participants were ≥ 15 years of age and not at high-risk, the true S. Typhi burden was likely missed. Change-point analyses for generating ELISA proxy cut-offs appeared robust, though misclassification is possible. Our findings provided important information that may be useful to assess sites prior to implementing surveillance for febrile illness including Salmonella disease.

PMID:36184614 | DOI:10.1186/s12879-022-07726-3

BMC Pregnancy Childbirth. 2022 Oct 2;22(1):740. doi: 10.1186/s12884-022-05073-4.

ABSTRACT

BACKGROUND: Interventions targeting physical activity and sedentary behavior concurrently in pregnancy may be an ideal strategy to reduce the risk of pregnancy complications. We assessed the feasibility, acceptability, and preliminary efficacy of a single-arm, remotely-delivered health coaching intervention to promote physical activity and reduce sedentary behavior in pregnancy.

METHODS: Women (n = 34) between 8 and 12 weeks gestation were recruited to take part in the INcreasing Steps in PREgnancy (INSPiRE) study. Participants were given an activity tracker (Fitbit Inspire) and met virtually with their health coach throughout the second and third trimesters of pregnancy. Feasibility was based on enrollment, retention, and adherence rates. Acceptance was assessed using a process evaluation survey. Intervention efficacy was based on activPAL data obtained at baseline and the end of the second trimester.

RESULTS: Feasibility objectives were met, with greater than 70% enrollment, 97% retention, and 99% adherence. All participants reported high levels of satisfaction with the program. ActivPAL data indicated statistically significant increases in daily steps (+ 1715.8 steps/day, Cohen’s d = 0.97), stepping time (+ 1.9%, d = 0.75), standing time (+ 2.3%, d = 0.29), and decreases in total sedentary time (- 4.2%, d = 0.43) and sedentary bouts of 30 minutes (- 4.1%, d = 0.36) from baseline to the end of the second trimester, all p < 0.05. Decreases were also observed in sedentary bouts of 60 minutes (- 3.9%, d = 0.40), but this was not statistically significant.

CONCLUSIONS: The INSPiRE study demonstrated feasibility, high acceptability, and preliminary efficacy for improving movement behaviors in women during pregnancy, supporting future testing in a randomized controlled trial.

PMID:36184599 | DOI:10.1186/s12884-022-05073-4

BMC Pregnancy Childbirth. 2022 Oct 2;22(1):738. doi: 10.1186/s12884-022-05028-9.

ABSTRACT

OBJECTIVES: To study the correlations between facial profile markers and crown-lump length (CRL) in a Chinese population, and to evaluate the clinical value of these markers for abnormal fetuses during the first trimester (11 to 13⁺⁶ gestational weeks). METHODS: The facial profile markers were as followings: inferior facial angle (IFA), maxilla-nasion-mandible (MNM) angle, facial maxillary angle (FMA), frontal space (FS) distance and profile line (PL) distance. These markers were measured in facial mid-sagittal section through ViewPoint 6 software. The diagnostic value of these markers for abnormal fetuses was assessed by receiver operating characteristic (ROC) curves.

RESULTS: According to the first-trimester scanning (FTS) and follow-up, 31 fetuses were enrolled in the abnormal group, including 14 cases of trisomy 21, 7 cases of trisomy 18, 10 cases with cleft lip and palate (CLP), and 1000 normal fetuses were selected. Among the normal fetuses, the IFA, FS distance and PL distance had negative correlations with CRL. The MNM angle and FMA had positive correlations with CRL. The mean IFA values for fetuses with trisomy 21 and trisomy 18 were 74.11° (standard deviation (SD) 7.48) and 69.88° (SD 7.08), respectively, which were significantly smaller than the normal fetuses (p = 0.013; p = 0.003). The mean MNM angle of fetuses with trisomy 18 and CLP were 6.98° (SD 2.61) and 9.41° (SD 2.57), respectively, which were significantly greater than the normal fetuses (p = 0.005; p < 0.001). The mean FMA values of trisomy 18 fetuses were 63.95° (SD 4.77), which was significantly smaller than the normal fetuses (p < 0.001). The mean FS distance of CLP fetuses was -0.22 mm (SD 1.38), which was significantly smaller than the normal fetuses (p < 0.001). The mean PL distance of trisomy 21, trisomy 18 and CLP fetuses were 2.89 mm (SD 0.41), 2.91 mm (SD 0.56) and 2.71 mm (SD 0.37), respectively. The difference with the normal fetuses had no statistical significance (p = 0.56; p = 0.607; p = 0.54).

CONCLUSIONS: Fetal facial profile markers had excellent correlations with CRL during the first trimester. IFA had certain clinical significance in detecting trisomy 21. FMA, IFA and MNM angle were reliable indicators for screening trisomy 18. The abnormal MNM angle and FS distance could be used as sensitive indicators for CLP. However, PL distance was not the best markers for trisomy 21, trisomy 18 and CLP.

PMID:36184592 | DOI:10.1186/s12884-022-05028-9

BMC Infect Dis. 2022 Oct 2;22(1):767. doi: 10.1186/s12879-022-07740-5.

ABSTRACT

BACKGROUND: Clinical trials and individual-level observational data in Israel demonstrated approximately 95% effectiveness of mRNA-based vaccines against symptomatic SARS-CoV-2 infection. Individual-level data are not available in many countries, particularly low- and middle- income countries. Using a novel Poisson regression model, we analyzed ecologic data in Costa Rica to estimate vaccine effectiveness and assess the usefulness of this approach.

METHODS: We used national data from December 1, 2020 to May 13, 2021 to ascertain incidence, hospitalizations and deaths within ecologic units defined by 14 age groups, gender, 105 geographic areas, and day of the epidemic. Within each unit we used the proportions of the population with one and with two vaccinations, primarily tozinameran. Using a non-standard Poisson regression model that included an ecologic-unit-specific rate factor to describe rates without vaccination and a factor that depended on vaccine effectiveness parameters and proportions vaccinated, we estimated vaccine effectiveness.

RESULTS: In 3.621 million persons aged 20 or older, there were 125,031 incident cases, 7716 hospitalizations, and 1929 deaths following SARS-CoV-2 diagnosis; 73% of those aged ≥ 75 years received two doses. For one dose, estimated effectiveness was 59% (95% confidence interval 53% to 64%) for SARS-CoV-2 incidence, 76% (68% to 85%) for hospitalizations, and 63% (47% to 80%) for deaths. For two doses, the respective estimates of effectiveness were 93% (90% to 96%), 100% (97% to 100%), and 100% (97% to 100%).

CONCLUSIONS: These effectiveness estimates agree well with findings from clinical trials and individual-level observational studies and indicate high effectiveness in the general population of Costa Rica. This novel statistical approach is promising for countries where ecologic, but not individual-level, data are available. The method could also be adapted to monitor vaccine effectiveness over calendar time.

PMID:36184587 | DOI:10.1186/s12879-022-07740-5

Int Heart J. 2022;63(5):864-873. doi: 10.1536/ihj.22-265.

ABSTRACT

In patients with atrial septal defect (ASD), atrial left-to-right shunting causes left atrial (LA) remodeling and dysfunction, leading to atrial fibrillation (AF). In adults with ASD and concomitant AF, LA function should be evaluated after ASD closure plus AF radiofrequency catheter ablation (RFCA).This multicenter retrospective cohort study included patients who underwent transcatheter ASD closure at one of the four leading hospitals. Patients with a history of AF also underwent preceding RFCA. The association between AF history and LA ejection fraction (EF) (indicating LA global function) at 6-12 months following ASD closure was evaluated. To account for differences in baseline characteristics between patients with and without a history of AF, we conducted the following statistical methods: (1) multivariate regression analysis in the prepropensity score (PS)-matched cohort and (2) univariate comparisons in the PS-matched cohort.Overall, this study included 231 patients (30 with AF history, 201 without). Multiple regression analysis showed that AF history was independently associated with impaired LAEF (β = -10.425, P < 0.001, model created prior to propensity matching). A one-to-one PS matching (25 pairs) showed that the LAEF at 6-12 months following ASD closure was significantly impaired in patients with ASD and AF history compared to that in patients without history of AF (median LAEF, 37.5% (interquartile range [IQR] 29.4%-48.5%) versus 52.3 [IQR 50.0%-56.6%]; P < 0.001).LA function was impaired in patients with ASD and a history of AF at 6-12 months after successful transcatheter ASD closure and on maintenance of sinus rhythm by RFCA.

PMID:36184548 | DOI:10.1536/ihj.22-265

Rev Psiquiatr Salud Ment (Engl Ed). 2022 Sep 29:S2173-5050(22)00044-9. doi: 10.1016/j.rpsmen.2022.09.006. Online ahead of print.

ABSTRACT

INTRODUCTION: Psychological pain is understood as an intolerable and disturbing mental state characterized by an internal experience of negative emotions. This study was aimed at making a Spanish adaptation of the Psychache Scale by Holden and colleagues in a sample of young adults.

MATERIAL AND METHODS: The scale evaluates psychological pain as a subjective experience. It is composed of 13 items with a Likert-type response format. Following the guidelines of the International Tests Commission for the adaptation of the test, we obtained a version conceptually and linguistically equivalent to the original scale. Through an online questionnaire, participants completed the psychological pain scale along with other scales to measure depression (BDI-II), hopelessness (Beck’s scale of hopelessness) and suicide risk (Plutchik suicide risk scale). The participants were 234 people (94 men, 137 women and three people who identified as a different sex) from 18 to 35 years old.

RESULTS: The EFA showed a one-factor solution, and the FCA revealed adequate indexes of adjustment to the unifactorial model. It also showed good reliability of the test scores. The evidence of validity of the scale in relation to the other variables showed high, positive and statistically significant correlations with depression, hopelessness, suicidal ideation and suicidal risk.

CONCLUSION: In summary, this Spanish adaptation of the Psychache Scale could contribute to improving the evaluation of both the patient with suicide risk and the effectiveness of psychological therapy, as well as suicidal behaviour prevention and intervention.

PMID:36184539 | DOI:10.1016/j.rpsmen.2022.09.006

Eur Urol Focus. 2022 Sep 29:S2405-4569(22)00217-6. doi: 10.1016/j.euf.2022.09.010. Online ahead of print.

ABSTRACT

BACKGROUND: Quantitative Gleason grading appears to be a reliable prognostic parameter and provides broader risk stratification then the traditional Gleason grading in patients with prostate cancer (PCa) treated with radical prostatectomy (RP).

OBJECTIVE: To determine if quantification of Gleason pattern (GP) 4 for targeted and systematic biopsy (TBx + SBx) cores together with further clinical variables can identify the lowest quantitative GP 4 fraction on RP.

DESIGN, SETTING, AND PARTICIPANTS: A total of 548 patients underwent TBx + SBx of the prostate and then RP, with pathology revealing Gleason score 3 + 4, 4 + 3, or 4 + 4 disease.

INTERVENTION: TBx + SBx of the prostate followed by RP.

OUTCOME MEASUREMENTS AND STATISTICAL ANALYSIS: GP 4 fraction thresholds of ≤5%, ≤10%, ≤15%, ≤20%, and ≤25% were compared between the TBx + SBx and RP specimens. The sensitivity, specificity, negative predictive value (NPV), positive predictive value (PPV), and accuracy for predicting the GP 4 fraction in the RP specimen were determined. Logistic regression models were used to establish a probabilistic relationship between various combinations of clinical and biopsy variables and the GP 4 fraction in the RP specimen.

RESULTS AND LIMITATIONS: GP 4 fractions of ≤5%, ≤10%, ≤15%, ≤20%, and ≤25% was observed in 33%, 49%, 58%, 65%, and 70% of patients on TBx, and 18%, 41%, 53%, 63%, and 70% of patients on RP, respectively. The sensitivity, specificity, NPV, PPV, and accuracy were 75%, 67%, 91%, 39%, and 74% for a TBx GP 4 fraction of ≤5%, and 65%, 85%, 65%, 85%, and 79% for a TBx GP 4 fraction of ≤25%, respectively. A model combining quantified TBx + SBx GP 4 with clinical parameters demonstrated the highest diagnostic accuracy. Limitations include the retrospective study design.

CONCLUSIONS: Our results demonstrate that the combination of MRI-TBx + SBx and GP 4 quantification allowed precise detection of a low fraction of GP 4 when using RP specimens as the reference standard. Moreover, we found that clinical variables including Prostate Imaging-Reporting and Data System score without biopsy are limited in detection of low GP 4 fractions.

PATIENT SUMMARY: Combination of targeted biopsy alone as well as combined with systematic biopsy and quantitative Gleason grading of biopsy specimen showed high agreement with pathology findings after surgical removal of the prostate. This could help in identifying patients who are suitable for active surveillance.

PMID:36184537 | DOI:10.1016/j.euf.2022.09.010

J Card Surg. 2022 Oct 2. doi: 10.1111/jocs.16988. Online ahead of print.

ABSTRACT

BACKGROUND: While prior data have suggested worse outcomes in women after acute type A aortic dissection (ATAAD) repair when compared to men, results have been inconsistent across studies over time. This study sought to evaluate the impact of sex on short- and long-term outcomes after ATAAD repair.

METHODS: This was a retrospective study utilizing an institutional database of ATAAD repairs from 2007 to 2021. Patients were stratified according to sex. Kaplan-Meier survival estimation and multivariable Cox regression were performed. Supplementary analysis using propensity score matching was also performed.

RESULTS: Of the 601 patients who underwent ATAAD repair, 361 were males (60.1%) and 240 (39.9%) were females. Females were significantly older, more likely to have hypertension, and more likely to have chronic lung disease. Females were also significantly more likely than males to undergo hemiarch replacement, while males were significantly more likely than females to undergo total arch replacement and frozen elephant trunk. Operative mortality was 9.4% among males and 13.8% among females, though this was not a statistically significant difference (p = .098). Postoperative complications were comparable between groups. Kaplan-Meier survival estimates were similar for men and women, and, on multivariable Cox regression, sex was not significantly associated with long-term survival (hazard ratio: 1.00, 95% confidence interval: 0.73, 1.37, p = .986). Outcomes remained comparable after supplementary propensity score matched analysis.

CONCLUSION: ATAAD repair can be performed with comparable short-term and long-term outcomes in both men and women.

PMID:36183385 | DOI:10.1111/jocs.16988

J Card Surg. 2022 Oct 2. doi: 10.1111/jocs.16984. Online ahead of print.

ABSTRACT

BACKGROUND/AIM: A transposition complex with an interrupted aortic arch (IAA) is rare and surgically challenging because of its anatomical diversity and complexity. Herein, we aimed to present our 20-year experience with one-stage arterial switch surgery associated with IAA repair.

METHODS: From January 2000 to April 2017, 11 patients were diagnosed with transposition complex and IAA and underwent one-stage repair at our center. These patients were retrospectively reviewed. Two patients had transposition of the great arteries, while the others had double outlet right ventricles, of whom eight had subpulmonary ventricular septal defects (VSDs; Taussig-Bing anomalies), and one had a noncommitted VSD. In terms of the IAA, three patients underwent repair by extended end-to-end anastomosis, and one 16-mm prosthetic vascular graft was replaced in an elder patient. The remaining patients underwent autologous pericardial patch enlargement. All the variables were summarized and reported with descriptive statistics.

RESULTS: Three early deaths occurred in this study. The median follow-up time was approximately 5 years (range: 3-14 years). No late deaths were reported. Only one patient required percutaneous re-intervention for recurrent coarctation. Moderate aortic regurgitation was observed in three patients. However, there was no requirement for aortic valvuloplasty or valve replacement. One patient had more than moderate tricuspid regurgitation. The other survivors are presently healthy.

CONCLUSIONS: Although one-stage repair for transposition complex and IAA still has non-negligible mortality even in older children, the late outcomes of survivors are acceptable. Owing to the high rate of valve regurgitation, closer follow-up is necessary for these patients.

PMID:36183381 | DOI:10.1111/jocs.16984