Tag: nevin manimala

J Ophthalmic Inflamm Infect. 2022 Jun 18;12(1):18. doi: 10.1186/s12348-022-00297-z.

ABSTRACT

OBJECTIVES: This study aimed to evaluate the retinal and choroidal changes in the macular region of patients with Coronavirus Disease 2019 (COVID-19) using structural spectral-domain optical coherence tomography (SD-OCT) analysis.

METHODS: This cross-sectional observational case-control study included patients recovered from COVID-19. The COVID-19 in all participants was confirmed using the reverse transcription-polymerase chain reaction (RT-PCR) technique. The participants had mild to moderate degree of disease without a history of hospitalization, steroid usage, or blood saturation below 92%. Macular SD-OCT was performed at least two weeks and up to one month after recovery from systemic COVID-19. Quantitative and qualitative changes detected by macular SD-OCT imaging were evaluated in COVID-19 recovered patients and compared with the results of age-matched normal controls.

RESULTS: Participants in this study included 30 cases (60 eyes) and 60 healthy controls (120 eyes). In total, 17 (28.3%) eyes in patient group showed at least one abnormal finding indicated by macular SD-OCT imaging included hyperreflective lesions in different retinal layers. In addition, dilated choroidal vessels and retinal pigment epitheliopathy were evident in 41 (68.3.6%) and 4 (6.6%) eyes in patient group, respectively, and their OCT findings resembled those with pachychoroid spectrum. No statistically significant differences were observed in retinal layers or retinal volume between the two groups. The mean ± SD subfoveal choroidal thickness (SFCT) was determined at 380.3 ± 12.40 μm, which was significantly thicker than that in control group (310.7 ± 57.5 μm) (P < 0.001).

CONCLUSION: Regarding retinal thickness, no significant change was observed in different retina layers of patients with COVID-19; however, there were striking qualitative changes, such as hyperreflective lesions in different retinal layers. The evaluation of choroidal structure and thickness demonstrated remarkable abnormal pachyvessels and significant thickening of the SFCT but the clinical significance of these findings is unknown.

PMID:35716213 | DOI:10.1186/s12348-022-00297-z

Int Urogynecol J. 2022 Jun 18. doi: 10.1007/s00192-022-05278-3. Online ahead of print.

ABSTRACT

INTRODUCTION AND HYPOTHESIS: Increased post-voiding residual volume (PVRV), known as covert postpartum urinary retention (PUR), is an asymptomatic condition with unknown long-term adverse effects. The objectives were to determine the frequency of this phenomenon 3 days after delivery and to examine the associated risk factors and consequences of the increased residuum on women´s health 6 weeks postpartum.

METHODS: We carried out a prospective observational study including a total of 926 primiparous women, giving birth to singletons. All participants underwent ultrasound determination of PVRV on day 3 postpartum. Then, risk factors were determined using logistic regression analysis. After 6 weeks, participants were invited to return for PVRV determination and to complete urogynecological and general health questionnaires. Using these data, the consequences of increased PVRV were determined.

RESULTS: A total of n=90 women were diagnosed with abnormal PVRV. Mean age in the studied population was 30.4 years, BMI prior to delivery 27.8, weight of the newborn 3,420 g, and percentage of cesarean sections 15.9%. Gestational week (p=0.043), vaginal tear (p=0.032), and induction of labor (p=0.003) were risk factors for covert PUR. Puerperal incidence of urinary tract infection was 1.1% (6 out of 526) and of urinary incontinence 29.2% (155 out of 530), with no differences between the groups. In the second examination, covert PUR was no longer present, and the values of residual urine decreased for all patients in the case group. No statistically significant differences were observed in questionnaire scores in general health and wellbeing perceptions between the groups.

CONCLUSIONS: We have found a few significant obstetrical-pediatric risk factors for abnormal PVRVs. Data from the follow-up suggest that covert PUR has no impact on morbidity and quality of life 6 weeks postpartum. Therefore, abnormal PVRV is a self-limited phenomenon with a tendency toward self-correction. Our findings support those of previous studies that advocate against screening for asymptomatic retention in the postpartum period, despite some similar previous recommendations.

PMID:35716199 | DOI:10.1007/s00192-022-05278-3

Stat Med. 2022 Jun 18. doi: 10.1002/sim.9501. Online ahead of print.

ABSTRACT

Counterfactual-model-based mediation analysis can yield substantial insight into the causal mechanism through the assessment of natural direct effects (NDEs) and natural indirect effects (NIEs). However, the assumptions regarding unmeasured mediator-outcome confounding and intermediate mediator-outcome confounding that are required for the determination of NDEs and NIEs present practical challenges. To address this problem, we introduce an instrumental blocker, a novel quasi-instrumental variable, to relax both of these assumptions, and we define a swapped direct effect (SDE) and a swapped indirect effect (SIE) to assess the mediation. We show that the SDE and SIE are identical to the NDE and NIE, respectively, based on a causal interpretation. Moreover, the empirical expressions of the SDE and SIE are derived with and without an intermediate mediator-outcome confounder. Then, a multiply robust estimation method is derived to mitigate the model misspecification problem. We prove that the proposed estimator is consistent, asymptotically normal, and achieves the semiparametric efficiency bound. As an illustration, we apply the proposed method to genomic datasets of lung cancer to investigate the potential role of the epidermal growth factor receptor in the treatment of lung cancer.

PMID:35716042 | DOI:10.1002/sim.9501

Stat Med. 2022 Jun 18. doi: 10.1002/sim.9498. Online ahead of print.

ABSTRACT

The existence of items not susceptible to the event of interest is of both theoretical and practical importance. Although researchers may provide, for example, biological, medical, or sociological evidence for the presence of such items (cured), statistical models performing well under the existence or not of a cured proportion, frequently offer a necessary flexibility. This work introduces a new reparameterization of a flexible family of cure models, which not only includes among its special cases, the most studied cure models (such as the mixture, bounded cumulative hazard, and negative binomial cure model) but also classical survival models (ie, without cured items). One of the main properties of the proposed family, apart from its computationally tractable closed form, is that the case of zero cured proportion is not found at the boundary of the parameter space, as it typically happens to other families. A simulation study examines the (finite) performance of the suggested methodology, focusing to the estimation through EM algorithm and model discrimination, by the aid of the likelihood ratio test and Akaike information criterion; for illustrative purposes, analysis of two real life datasets (on recidivism and cutaneous melanoma) is also carried out.

PMID:35716033 | DOI:10.1002/sim.9498

Stat Med. 2022 Jun 18. doi: 10.1002/sim.9491. Online ahead of print.

ABSTRACT

In precision medicine, the ultimate goal is to recommend the most effective treatment to an individual patient based on patient-specific molecular and clinical profiles, possibly high-dimensional. To advance cancer treatment, large-scale screenings of cancer cell lines against chemical compounds have been performed to help better understand the relationship between genomic features and drug response; existing machine learning approaches use exclusively supervised learning, including penalized regression and recommender systems. However, it would be more efficient to apply reinforcement learning to sequentially learn as data accrue, including selecting the most promising therapy for a patient given individual molecular and clinical features and then collecting and learning from the corresponding data. In this article, we propose a novel personalized ranking system called Proximal Policy Optimization Ranking (PPORank), which ranks the drugs based on their predicted effects per cell line (or patient) in the framework of deep reinforcement learning (DRL). Modeled as a Markov decision process, the proposed method learns to recommend the most suitable drugs sequentially and continuously over time. As a proof-of-concept, we conduct experiments on two large-scale cancer cell line data sets in addition to simulated data. The results demonstrate that the proposed DRL-based PPORank outperforms the state-of-the-art competitors based on supervised learning. Taken together, we conclude that novel methods in the framework of DRL have great potential for precision medicine and should be further studied.

PMID:35716038 | DOI:10.1002/sim.9491

Muscle Nerve. 2022 Jun 18. doi: 10.1002/mus.27662. Online ahead of print.

ABSTRACT

INTRODUCTION/AIMS: Pulmonary decline is an important issue in patients with Duchenne muscular dystrophy (DMD). Eteplirsen is a US-approved treatment for patients with DMD and exon 51 skip-amenable mutations. Previous analyses have shown that eteplirsen is associated with statistically significant attenuation of pulmonary decline. This study evaluates the effect of eteplirsen treatment from newly available data sources on pulmonary function over time in patients with DMD.

METHODS: This study uses a post hoc pooled analysis to compare the percentage of predicted forced vital capacity (FVC%p) and projected time to pulmonary function milestones in patients with DMD and exon 51 skip-amenable mutations receiving eteplirsen (Studies 204 and 301) or standard of care (SoC; Cooperative International Neuromuscular Research Group Duchenne Natural History Study). A mixed model for repeated measures framework was applied to evaluate the impact of eteplirsen.

RESULTS: An average annual rate of FVC%p decline for eteplirsen-treated patients was estimated to be 3.47%, which was a statistically significant attenuation from the 5.95% rate of decline estimated in SoC patients (P = 0.0001). Using linear extrapolations of the model-estimated decline in FVC%p, the attenuation in FVC%p decline for eteplirsen-treated patients corresponded to a delay of 5.72 years in time to needing continuous ventilation, 3.31 years in time to needing nighttime ventilation, and 2.11 years in time to needing a cough assist device compared with SoC patients.

DISCUSSION: The attenuation of FVC%p decline suggests that eteplirsen-treated patients experienced statistically significant and clinically meaningful attenuations in pulmonary decline compared with SoC patients. This article is protected by copyright. All rights reserved.

PMID:35715998 | DOI:10.1002/mus.27662

J Med Radiat Sci. 2022 Jun 18. doi: 10.1002/jmrs.602. Online ahead of print.

ABSTRACT

INTRODUCTION: The magnitude and impact of rotational error is unclear in rectal cancer radiation therapy. This study evaluates rotational errors in rectal cancer patients, and investigates the feasibility of planning target volume (PTV) margin reduction to decrease organs at risk (OAR) irradiation.

METHODS: In this study, 10 patients with rectal cancer were retrospectively selected. Rotational errors were assessed through image registration of daily cone beam computed tomography (CBCT) and planning CT scans. Two reference treatment plans (TP_R ) with PTV margins of 5 mm and 10 mm were generated for each patient. Pre-determined rotational errors (±1°, ±3°, ±5°) were simulated to produce six manipulated treatment plans (TP_M ) from each TP_R . Differences in evaluated dose-volume metrics between TP_R and TP_M of each rotation were compared using Wilcoxon Signed-Rank Test. Clinical compliance was investigated for statistically significant dose-volume metrics.

RESULTS: Mean rotational errors in pitch, roll and yaw were -0.72 ± 1.81°, -0.04 ± 1.36° and 0.38 ± 0.96° respectively. Pitch resulted in the largest potential circumferential displacement of clinical target volume (CTV) at 1.42 ± 1.06 mm. Pre-determined rotational errors resulted in statistically significant differences in CTV, small bowel, femoral heads and iliac crests (P < 0.05). Only small bowel and iliac crests failed clinical compliance, with majority in the PTV 10 mm margin group.

CONCLUSION: Rotational errors affected clinical compliance for OAR dose but exerted minimal impact on CTV coverage even with reduced PTV margins. Both PTV margin reduction and rotational correction decreased irradiated volume of OAR. PTV margin reduction to 5 mm is feasible, and rotational corrections are recommended in rectal patients to further minimise OAR irradiation.

PMID:35715996 | DOI:10.1002/jmrs.602

Obesity (Silver Spring). 2022 Jun 17. doi: 10.1002/oby.23453. Online ahead of print.

ABSTRACT

OBJECTIVE: Metabolic bariatric procedures are potentially efficacious treatment options in patients with type 2 diabetes mellitus (T2DM). Previous meta-analyses focused on individual operative approaches rather than the mechanistic pathways behind different bariatric procedures. This updated network meta-analysis aimed to synthesize new evidence and comparatively evaluate the efficacy of metabolic surgery against restrictive procedures and standard first-line treatment for patients with T2DM.

METHODS: Embase, MEDLINE, and trial registries were searched for randomized controlled trials on bariatric surgeries in patients with T2DM on September 3, 2021. A Bayesian network meta-analysis was conducted. The primary outcome was T2DM remission. Secondary outcomes included changes in BMI, lipoprotein levels, and blood pressure.

RESULTS: Thirty-two articles were included. Metabolic surgery was statistically superior to restrictive procedures (risk ratio [RR]: 2.57, 95% credibility intervals [CrI]: 1.36-5.43), medical therapy (RR: 35.29, 95% Crl: 10.56-183.23), and lifestyle intervention (RR: 40.51, 95% Crl: 5.32-402.59) in T2DM remission. Metabolic surgery significantly lowered BMI and blood pressure compared with other interventions. Restrictive procedures significantly increased high-density lipoprotein compared with metabolic surgery. Lifestyle intervention and metabolic surgery were statistically superior to restrictive procedures in reducing low-density lipoprotein.

CONCLUSIONS: The superiority in diabetes remission and favorable metabolic profile support the choice of metabolic surgery over restrictive bariatric procedures.

PMID:35715979 | DOI:10.1002/oby.23453

Health Soc Care Community. 2022 Jun 17. doi: 10.1111/hsc.13862. Online ahead of print.

ABSTRACT

As behavioural health occupations have diversified, more specialists such as social workers and counsellors are involved in providing substance use disorder treatment services. This study examined the association between changes in the number of different types of behavioural health professionals and changes in drug and opioid overdose deaths in the United States. Using publicly available state-level data from 2008 to 2017, we constructed multivariate linear regression models with state- and year fixed-effects to examine the effect of changes in the number of different types of behavioural health professionals (i.e. psychiatrists, psychologists, social workers and counsellors) on changes in drug and opioid overdose deaths at the state level, controlling for state population characteristics and other state-level factors. After controlling for confounding factors, a 1% increase in the number of social workers and counsellors at the state level was significantly associated with a 0.215% reduction in drug overdose deaths per 100,000 state population and with a 0.358% reduction in opioid overdose deaths per 100,000 state population. We did not find statistically significant associations between changes in drug overdose death rates and increases in the number of psychiatrists or psychologists alone. Our findings suggest efforts to facilitate a prepared and skilled workforce, such as expanding the capacity of social workers and counsellors, to maximise access to substance use disorder treatment services.

PMID:35715970 | DOI:10.1111/hsc.13862

Biophys J. 2022 Jun 16:S0006-3495(22)00477-5. doi: 10.1016/j.bpj.2022.06.018. Online ahead of print.

ABSTRACT

Missense mutations that compromise the plasma membrane expression (PME) of integral membrane proteins are the root cause of numerous genetic diseases. Differentiation of this class of mutations from those that specifically modify the activity of the folded protein has proven useful for the development and targeting of precision therapeutics. Nevertheless, it remains challenging to predict the effects of mutations on the stability and/ or expression of membrane proteins. In this work, we utilize deep mutational scanning data to train a series of artificial neural networks to predict the PME of transmembrane domain variants of G-protein coupled receptors (GPCRs) from structural and/ or evolutionary features. We show that our best performing network, which we term PMEpred, can recapitulate mutagenic trends within rhodopsin and can differentiate pathogenic transmembrane domain variants that cause it to misfold from those that compromise its’ signaling. This network also generates statistically significant predictions for the relative PME of transmembrane domain variants for another class A GPCR (β₂ adrenergic receptor) but not for an unrelated voltage-gated potassium channel (KCNQ1). Notably, our analyses of these networks suggest structural features alone are generally sufficient to recapitulate the observed mutagenic trends. Moreover, our findings imply that networks trained in this manner may be generalizable to proteins that share a common fold. Implications of our findings for the design of mechanistically specific genetic predictors are discussed.

PMID:35715957 | DOI:10.1016/j.bpj.2022.06.018