Nevin Manimala

Stat Methods Med Res. 2023 Apr 6:9622802231167437. doi: 10.1177/09622802231167437. Online ahead of print.

ABSTRACT

Response-adaptive randomization allows the probabilities of allocating patients to treatments in a clinical trial to change based on the previously observed response data, in order to achieve different experimental goals. One concern over the use of such designs in practice, particularly from a regulatory viewpoint, is controlling the type I error rate. To address this, Robertson and Wason (Biometrics, 2019) proposed methodology that guarantees familywise error rate control for a large class of response-adaptive designs by re-weighting the usual $z$-test statistic. In this article, we propose an improvement of their method that is conceptually simpler, in the context where patients are allocated to the experimental treatment arms in a trial in blocks (i.e. groups) using response-adaptive randomization. We show the modified method guarantees that there will never be negative weights for the contribution of each block of data to the adjusted test statistics, and can also provide a substantial power advantage in practice.

PMID:37021480 | DOI:10.1177/09622802231167437

Clin Rehabil. 2023 Apr 6:2692155231166220. doi: 10.1177/02692155231166220. Online ahead of print.

ABSTRACT

OBJECTIVE: To investigate whether combination of corticosteroid subdeltoid injections and physiotherapy was more effective than either treatment alone in chronic subacromial bursitis.

DESIGN: Prospective, three-arm randomised controlled trial.

SETTING: Rehabilitation department of an academic hospital.

SUBJECTS: Patients with chronic subacromial bursitis.

INTERVENTIONS: Patients were divided into corticosteroid injection (N = 36), physiotherapy (N = 40) and combined (N = 35) groups. Two corticosteroid subdeltoid injections in corticosteroid group, 8-week physical therapy emphasising on therapeutic exercise in physiotherapy group, and combined both treatments in combined group.

MAIN OUTCOME MEASURES: The primary outcome measures were pain visual analogue scale and Shoulder Pain and Disability Index at 8 weeks after finishing treatment. The secondary outcome measures were active range of motion, Shoulder Disability Questionnaire, Western Ontario Rotator Cuff Index, patient’s evaluation of treatment effect, and symptom recurrence.

RESULTS: Group comparison showed significant statistical difference in shoulder flexion (P < 0.003) and patient’s evaluation of treatment effect (P < 0.001). The time and group interactions comparison revealed significant statistical differences in pain score (P < 0.024), external rotation (P < 0.044) and patient’s evaluation of treatment effect (P < 0.001). The above statistics were in favour of the corticosteroid and combined groups rather than physiotherapy group. The percentage of recurrence was 36.1, 7.5 and 17.1 in the corticosteroid, physiotherapy and combined groups, respectively (P < 0.001).

CONCLUSION: Corticosteroid subdeltoid injection, or combined with physiotherapy, was superior to physiotherapy alone, but the recurrence rate was least in the physiotherapy group.

PMID:37021475 | DOI:10.1177/02692155231166220

CNS Neurol Disord Drug Targets. 2023 Apr 4. doi: 10.2174/1871527322666230404114911. Online ahead of print.

ABSTRACT

BACKGROUND: Autism Spectrum Disorder (ASD) is a common child neurodevelopmental disorder, whose pathogenesis is not completely understood. Until now, there is no proven treatment for the core symptoms of ASD. However, some evidence indicates a crucial link between this disorder and GABAergic signals which are altered in ASD. Bumetanide is a diuretic that reduces chloride, shifts gamma-amino-butyric acid (GABA) from excitation to inhibition, and may play a significant role in the treatment of ASD.

OBJECTIVE: The objective of this study is to assess the safety and efficacy of bumetanide as a treatment for ASD.

METHODS: Eighty children, aged 3-12 years, with ASD diagnosed by Childhood Autism Rating Scale (CARS), ⩾30 were included in this double-blind, randomized, and controlled study. Group 1 received Bumetanide, Group 2 received a placebo for 6 months. Follow-up by CARS rating scale was performed before and after 1, 3, and 6 months of treatment.

RESULTS: The use of bumetanide in group 1 improved the core symptoms of ASD in a shorter time with minimal and tolerable adverse effects. There was a statistically significant decrease in CARS and most of its fifteen items in group 1 versus group 2 after 6 months of treatment (p-value <0.001).

CONCLUSION: Bumetanide has an important role in the treatment of core symptoms of ASD.

PMID:37021422 | DOI:10.2174/1871527322666230404114911

Nutr Health. 2023 Apr 6:2601060231166036. doi: 10.1177/02601060231166036. Online ahead of print.

ABSTRACT

AIM: To evaluate the association between sociodemographic factors and screen exposure during meals with the consumption of dietary markers in children treated at a university hospital in Rio de Janeiro.

METHODS: Cross-sectional study with children of both sexes between 2 and 9 years of age. Food consumption and screen exposure were assessed using specific forms. The socio-demographic data evaluated were age, maternal education, household composition, receipt of government benefits, and household food and nutrition security. The statistical analysis included simple and multivariate logistic regression with a confidence interval of 95%.

RESULTS: Among the 129 children evaluated, most of them were of preschool age (57.4%), 71.3% received some type of government benefit, and 69.8% ate meals in front of screens. Among the markers of a healthy diet, beans (86.0%) and fresh fruits (69.8%) were the most consumed, while among the markers of an unhealthy diet, the most common components were sweetened beverages (61.7%) and cookies, candies, or other sweets (54.7%). There was a higher consumption of sweetened beverages among the children whose families received a government benefit (OR 2.63; 95% CI: 1.13-6.13) and who were exposed to a screen during meals (2.27; 95% CI: 1.01-5, 14).

CONCLUSION: This study showed that in view of the high frequency of consumption of unhealthy foods and screen exposure during meals, it is imperative that food and nutrition education actions are taken to promote an adequate and healthy food environment in childhood.

PMID:37021415 | DOI:10.1177/02601060231166036

J Gerontol A Biol Sci Med Sci. 2023 Apr 6:glad099. doi: 10.1093/gerona/glad099. Online ahead of print.

ABSTRACT

BACKGROUND: Almost 60% of adults with amnestic mild cognitive impairment (aMCI) have obstructive sleep apnea (OSA). Treatment with continuous positive airway pressure (CPAP) may delay cognitive decline, but CPAP adherence is often suboptimal. In this study we report predictors of CPAP adherence in older adults with aMCI who have increased odds of progressing to dementia, particularly due to Alzheimer’s disease.

METHODS: The data are from Memories 2, “Changing the Trajectory of Mild Cognitive Impairment with CPAP Treatment of Obstructive Sleep Apnea”. Participants had moderate to severe OSA, were CPAP naïve, and received a telehealth CPAP adherence intervention. Linear and logistic regression models examined predictors.

RESULTS: The 174 participants (mean age 67.08 years, 80 Female, 38 Black persons) had a mean apnea-hypopnea index of 34.78, and 73.6% were adherent, defined as an average of ≥ 4 hours of CPAP use per night. Only 18 (47.4%) Black persons were CPAP adherent. In linear models, White race, moderate OSA, and participation in the tailored CPAP adherence intervention were significantly associated with higher CPAP use at 3 months. In logistic models, White persons had 9.94 times the odds of adhering to CPAP compared to Black persons. Age, sex, ethnicity, education, body mass index, nighttime sleep duration, daytime sleepiness, and cognitive status were not significant predictors.

CONCLUSIONS: Older patients with aMCI have high CPAP adherence, suggesting that age and cognitive impairment should not be a barrier to prescribing CPAP. Research is needed to improve adherence in Black patients, perhaps through culturally tailored interventions.

PMID:37021413 | DOI:10.1093/gerona/glad099

Europace. 2023 Apr 6:euad086. doi: 10.1093/europace/euad086. Online ahead of print.

ABSTRACT

AIMS: The development of intracardiac echocardiography (ICE) has enabled fluoroless atrial fibrillation (AF) ablation using three-dimensional electroanatomical mapping systems. However, fluoroless cryoballoon ablation (CBA) remains challenging, mainly because of the lack of a visual mapping system. Hence, this study aimed to investigate the safety and efficacy of fluoroless CBA for AF under ICE guidance.

METHODS AND RESULTS: Patients (n = 100) who underwent CBA for paroxysmal AF were randomly assigned to zero-fluoroscopic (Zero-X) and conventional groups. Intracardiac echocardiography was used to guide the transseptal puncture and catheter and balloon manipulation in all enrolled patients. The patients were prospectively followed for 12 months after CBA. The mean age was 60.4 years, and the left atrial (LA) size was 39.4 mm. Pulmonary vein isolation (PVI) was achieved in all patients. In the Zero-X group, fluoroscopy was used in only one patient because of unstable phrenic nerve capture during right-sided PVI. The procedure time and LA indwelling time in the Zero-X group were not statistically different compared with that in the conventional group. Fluoroscopic time (9.0 vs. 0.008 min) and radiation exposure (29.4 vs. 0.02 mGy) were significantly shorter in the Zero-X group than in the conventional group (P < 0.001). The complication rate did not differ between the two groups. During a mean follow-up of 663.3 ± 172.3 days, the recurrence rate was similar (16.0 vs. 18.0%; P = 0.841) between the groups. Multivariate analysis revealed that LA size was the only independent predictor of clinical recurrence.

CONCLUSION: Intracardiac echocardiography-guided fluoroless CBA for AF was a feasible strategy without compromising acute and long-term success or complication rates.

PMID:37021403 | DOI:10.1093/europace/euad086

Foot Ankle Spec. 2023 Apr 5:19386400231162409. doi: 10.1177/19386400231162409. Online ahead of print.

ABSTRACT

BACKGROUND: Given the lack of objective data on opioid use and the difficulty of addressing a patient’s postoperative pain, we sought to quantify patient’s narcotic use after hallux valgus surgery. The purpose of our study was to determine the average quantity and type of postoperative opioids consumed after hallux valgus surgery and to assess potential predictive factors for increased opioid consumption.

METHODS: At the preoperative visit, patients were consented and completed a demographical questionnaire. Data were collected from the operative record, 2, 6, and 12-week postoperative visits. Type and number of pills prescribed were recorded as well as number of pills consumed at each postoperative visit. A logistic regression was performed to determine the average quantity consumed postoperatively and any statistically significant correlations.

RESULTS: The average number of opioid pills collectively consumed at the 2-week and 12-week postoperative visit was 20 and 23, respectively. At the 2-week postoperative visit, only patient body mass index (BMI) showed a correlation with increased opioid use.

CONCLUSION: Patients consumed an average of 23 of 40 (57.5%) narcotic pain pills prescribed after hallux valgus reconstruction surgery through the 12-week postoperative period. Owing to the opioid epidemic and potential for narcotic diversion, surgeons should counsel their patients on proper nonopioid postoperative pain management.

LEVEL OF EVIDENCE: II Therapeutic.

PMID:37021374 | DOI:10.1177/19386400231162409

Global Spine J. 2023 Apr 5:21925682231166324. doi: 10.1177/21925682231166324. Online ahead of print.

ABSTRACT

STUDY DESIGN: A retrospective case-control study.

OBJECTIVE: This study aimed to compare the effects of the Wiltse approach of pedicle screw fixation (PSF) either in combination with or without vertebroplasty (VP) in the treatment of Genant III degree osteoporotic thoracolumbar fractures (Genant III-OTLFs).

METHODS: A retrospective study of Genant III-OTLFs was performed from January 2018 to December 2019, including 54 cases of PSF + VP and 56 cases of PSF. Clinical indicators [visual analog scale (VAS) score, Oswestry disability index (ODI)], radiographic parameters [local kyphosis angle (LKA), percentage of anterior, central, and posterior vertebral heights (AVH%, CVH%, and PVH%, respectively)] and follow-up complications [adjacent vertebral fracture (AVF), residual pain (RP), vertebral height loss (VHL), and internal fixation failure (IFF)] were compared between the 2 groups.

RESULTS: No differences in surgical outcomes, clinical indicators, and radiographic parameters were observed between the 2 groups during the preoperation period and 7 days post-operatively (P > .05). However, the VAS score [2.0 (.6), 1.9 (.5)], ODI [23.7 (4.0), 22.6 (3.0)], LKA [9.5 (1.8), 10.6 (3.0)], AVH% [90.1 (2.7), 87.7 (6.0)], CVH% [92.5 (2.6), 91.3 (3.7)], and PVH% [93.4 (2.0), 92.7 (2.4)] at 1 year post-operatively and last follow-up of the PSF + VP group were better than those of the PSF group [2.5 (.8), 3.1 (1.1), 26.6 (3.8), 29.6 (4.6), 12.2 (1.6), 16.6 (3.2), 84.9 (4.0), 69.9 (6.6), 88.1 (3.1), 78.2 (5.1), 89.7 (2.3), 84.8 (4.6)], respectively (P < .001). During follow-up, the incidence of AVF had no difference (P > .05), while that of RP (32.1 vs 14.8%), VHL (33.9 vs 9.3%) and IFF (17.9 vs 5.6%) had statistical differences between them (P < .05).

CONCLUSION: The Wiltse approach of PSF combined with VP for Genant III-OTLFs can not only effectively relieve pain, restore vertebral height, and correcte kyphosis, but also better maintain vertebral height, delay kyphosis progression, and reduce complications during follow-up.

PMID:37021369 | DOI:10.1177/21925682231166324

Comput Methods Biomech Biomed Engin. 2023 Apr 5:1-17. doi: 10.1080/10255842.2023.2194474. Online ahead of print.

ABSTRACT

Recent research has shown that individuals suffering from COVID-19 are accommodating an elevated level of blood viscosity due to the morphological changes in blood cells. As viscosity is a major flow parameter influencing the flow across a stenosis or an aneurysm, the examination of the significance of hyperviscosity in COVID patients is imperative in arterial pathologies. In this research, we have considered a patient-specific case in which the aneurysm is located along the abdominal aortal walls. Recent research on the side effects of COVID-19 voiced out the various effects on the circulatory system of humans. Also, as abdominal aneurysms exist very often among individuals, causing the death of 150-200 million every year, the hyper-viscous effects of blood on the flow across the diseased aorta are explored by considering the elevated viscosity levels. In vitro explorations contribute considerably to the clinical methods and treatments to be regarded. The objective of the present inquest is to research the flow field in aneurysmatic-COVID-affected patients considering the elastic nature of vessel walls, using the arbitrary Lagrangian-Eulerian approach. The study supports the various clinical findings that voiced the detrimental effects associated with blood hyperviscosity. The simulation results obtained, by solving the fluid mechanics’ equations coupled with the solid mechanics’ equations, employing a FEM solver suggest that the elevated stress imparted by the hyper-viscous flows on the walls of the aneurysmal aorta can trigger the fastening of the aneurysmal sac enlargement or rupture.

PMID:37021363 | DOI:10.1080/10255842.2023.2194474

Stat Med. 2023 Apr 5. doi: 10.1002/sim.9734. Online ahead of print.

ABSTRACT

In adaptive clinical trials, the conventional end-of-trial point estimate of a treatment effect is prone to bias, that is, a systematic tendency to deviate from its true value. As stated in recent FDA guidance on adaptive designs, it is desirable to report estimates of treatment effects that reduce or remove this bias. However, it may be unclear which of the available estimators are preferable, and their use remains rare in practice. This article is the second in a two-part series that studies the issue of bias in point estimation for adaptive trials. Part I provided a methodological review of approaches to remove or reduce the potential bias in point estimation for adaptive designs. In part II, we discuss how bias can affect standard estimators and assess the negative impact this can have. We review current practice for reporting point estimates and illustrate the computation of different estimators using a real adaptive trial example (including code), which we use as a basis for a simulation study. We show that while on average the values of these estimators can be similar, for a particular trial realization they can give noticeably different values for the estimated treatment effect. Finally, we propose guidelines for researchers around the choice of estimators and the reporting of estimates following an adaptive design. The issue of bias should be considered throughout the whole lifecycle of an adaptive design, with the estimation strategy prespecified in the statistical analysis plan. When available, unbiased or bias-reduced estimates are to be preferred.

PMID:37021359 | DOI:10.1002/sim.9734