Category: Nevin Manimala

J Clin Oncol. 2023 Jan 9:JCO2201485. doi: 10.1200/JCO.22.01485. Online ahead of print.

ABSTRACT

PURPOSE: The results in terms of side effects vary among the published accelerated partial-breast irradiation (APBI) studies. Here, we report the 5-year results for cosmetic outcomes and toxicity of the IRMA trial.

METHODS: We ran this randomized phase III trial in 35 centers. Women with stage I-IIA breast cancer treated with breast-conserving surgery, age ≥ 49 years, were randomly assigned 1:1 to receive either whole-breast irradiation (WBI) or external beam radiation therapy APBI (38.5 Gy/10 fraction twice daily). Patients and investigators were not masked to treatment allocation. The primary end point was ipsilateral breast tumor recurrence. We hereby present the analysis of the secondary outcomes, cosmesis, and normal tissue toxicity. All side effects were graded with the Radiation Therapy Oncology Group/European Organisation for Research and Treatment of Cancer Radiation Morbidity Scoring Schema. Analysis was performed with both intention-to-treat and as-treated approaches.

RESULTS: Between March 2007 and March 2019, 3,309 patients were randomly assigned to 1,657 WBI and 1,652 APBI; 3,225 patients comprised the intention-to-treat population (1,623 WBI and 1,602 APBI). At a median follow-up of 5.6 (interquartile range, 4.0-8.4) years, adverse cosmesis in the APBI patients was higher than that in the WBI patients at 3 years (12.7% v 9.2%; P = .009) and at 5 years (14% v 9.8%; P = .012). Late soft tissue toxicity (grade ≥ 3: 2.8% APBI v 1% WBI, P < .0001) and late bone toxicity (grade ≥ 3: 1.1% APBI v 0% WBI, P < .0001) were significantly higher in the APBI arm. There were no significant differences in late skin and lung toxicities.

CONCLUSION: External beam radiation therapy-APBI with a twice-daily IRMA schedule was associated with increased rates of late moderate soft tissue and bone toxicities, with a slight decrease in patient-reported cosmetic outcomes at 5 years when compared with WBI, although overall toxicity was in an acceptable range.

PMID:36623246 | DOI:10.1200/JCO.22.01485

J Clin Oncol. 2023 Jan 9:JCO2201359. doi: 10.1200/JCO.22.01359. Online ahead of print.

ABSTRACT

PURPOSE: Although level 1 evidence supports 45-Gy twice-daily radiotherapy as standard for limited-stage small-cell lung cancer, most patients receive higher-dose once-daily regimens in clinical practice. Whether increasing radiotherapy dose improves outcomes remains to be prospectively demonstrated.

METHODS: This phase III trial, CALGB 30610/RTOG 0538 (ClinicalTrials.gov identifier: NCT00632853), was conducted in two stages. In the first stage, patients with limited-stage disease were randomly assigned to receive 45-Gy twice-daily, 70-Gy once-daily, or 61.2-Gy concomitant-boost radiotherapy, starting with either the first or second (of four total) chemotherapy cycles. In the second stage, allocation to the 61.2-Gy arm was discontinued following planned interim toxicity analysis, and the study continued with two remaining arms. The primary end point was overall survival (OS) in the intention-to-treat population.

RESULTS: Trial accrual opened on March 15, 2008, and closed on December 1, 2019. All patients randomly assigned to 45-Gy twice-daily (n = 313) or 70-Gy once-daily radiotherapy (n = 325) are included in this analysis. After a median follow-up of 4.7 years, OS was not improved on the once-daily arm (hazard ratio for death, 0.94; 95% CI, 0.76 to 1.17; P = .594). Median survival is 28.5 months for twice-daily treatment, and 30.1 months for once-daily treatment, with 5-year OS of 29% and 32%, respectively. Treatment was tolerable, and the frequency of severe adverse events, including esophageal and pulmonary toxicity, was similar on both arms.

CONCLUSION: Although 45-Gy twice-daily radiotherapy remains the standard of care, this study provides the most robust information available to help guide the choice of thoracic radiotherapy regimen for patients with limited-stage small-cell lung cancer.

PMID:36623230 | DOI:10.1200/JCO.22.01359

Proc Natl Acad Sci U S A. 2023 Jan 17;120(3):e2218957120. doi: 10.1073/pnas.2218957120. Epub 2023 Jan 9.

NO ABSTRACT

PMID:36623183 | DOI:10.1073/pnas.2218957120

Proc Natl Acad Sci U S A. 2023 Jan 17;120(3):e2207595120. doi: 10.1073/pnas.2207595120. Epub 2023 Jan 9.

ABSTRACT

Over the past two decades, multiple countries with high vaccine coverage have experienced resurgent outbreaks of mumps. Worryingly, in these countries, a high proportion of cases have been among those who have completed the recommended vaccination schedule, raising alarm about the effectiveness of existing vaccines. Two putative mechanisms of vaccine failure have been proposed as driving observed trends: 1) gradual waning of vaccine-derived immunity (necessitating additional booster doses) and 2) the introduction of novel viral genotypes capable of evading vaccinal immunity. Focusing on the United States, we conduct statistical likelihood-based hypothesis testing using a mechanistic transmission model on age-structured epidemiological, demographic, and vaccine uptake time series data. We find that the data are most consistent with the waning hypothesis and estimate that 32.8% (32%, 33.5%) of individuals lose vaccine-derived immunity by age 18 y. Furthermore, we show using our transmission model how waning vaccine immunity reproduces qualitative and quantitatively consistent features of epidemiological data, namely 1) the shift in mumps incidence toward older individuals, 2) the recent recurrence of mumps outbreaks, and 3) the high proportion of mumps cases among previously vaccinated individuals.

PMID:36623178 | DOI:10.1073/pnas.2207595120

Nano Lett. 2023 Jan 9. doi: 10.1021/acs.nanolett.2c05004. Online ahead of print.

ABSTRACT

Bernal-stacked bilayer graphene exhibits a wealth of interaction-driven phenomena, including robust even-denominator fractional quantum Hall states. We construct Fabry-Pérot interferometers using a split-gate design and present measurements of the Aharonov-Bohm oscillations. The edge state velocity is found to be approximately 6 × 10⁴ m/s at filling factor ν = 2 and decreases with increasing filling factor. The dc bias and temperature dependence of the interference point to electron-electron interaction induced decoherence mechanisms. These results pave the way for the quest of fractional and non-Abelian braiding statistics in this promising device platform.

PMID:36622939 | DOI:10.1021/acs.nanolett.2c05004

Am J Occup Ther. 2022 Nov 1;76(6):7606205100. doi: 10.5014/ajot.2022.049295.

ABSTRACT

IMPORTANCE: Interventions to reduce anxiety are needed for patients with anorexia nervosa (AN) and avoidant- restrictive food intake disorder (ARFID). Weighted blankets are one such intervention.

OBJECTIVE: To evaluate the impact of weighted blankets on anxiety for patients with AN and ARFID.

DESIGN: Randomized controlled trial conducted between November 2018 and March 2019. Patients were randomized into the control group or the intervention group.

SETTING: Inpatient setting; medical stabilization unit.

PARTICIPANTS: Patients (N = 23) diagnosed with AN or ARFID and experiencing moderate anxiety. The majority were female (91%), with a mean age of 26 yr (SD = 9.3), and the mean length of hospitalization was 22 days (SD = 17.3).

INTERVENTIONS: Control group participants received usual care, which included occupational therapy services. Intervention group participants received a weighted blanket along with usual care.

OUTCOMES AND MEASURES: Mixed-effects regression models were conducted. Primary outcomes included improvement in Beck Anxiety Inventory (BAI) scores by discharge.

RESULTS: Intervention group patients had a greater, non-statistically significant decrease in BAI score over time (B = 1.16, p = .83) than control group patients.

CONCLUSIONS AND RELEVANCE: Weighted blankets may be an effective tool for reducing anxiety among patients with AN or ARFID. What This Article Adds: The use of a weighted blanket, in conjunction with occupational therapy interventions, is potentially a beneficial non-pharmacological option for patients with anorexia nervosa (AN) and avoidant-restrictive food intake disorder (ARFID). The current study adds an additional modality to the multidisciplinary treatment approach for eating disorders.

PMID:36622934 | DOI:10.5014/ajot.2022.049295

J Hosp Palliat Nurs. 2023 Jan 6. doi: 10.1097/NJH.0000000000000931. Online ahead of print.

ABSTRACT

The palliative care team identified a lack of knowledge and confidence for nurses providing end-of-life care in a hospital. The team completed a quality improvement project establishing significant improvement in knowledge and self-efficacy after a 2-hour educational intervention. The next step was to study the impact on practice. Clinical management of pain, dyspnea, secretions, and agitation was compared for a 3-month period before and after intervention. Thirty-six patients were identified in the preintervention group, and 46 patients were in the postintervention group. A 2-sample proportion Z test (α = .05, 2-tailed) showed no statistical significance in the number of doses of opioids administered between preintervention and postintervention groups; however, the number of patients in the postintervention group that received an opioid orally was significantly greater (z = -2.098, P = .0357). A significantly lower proportion of the postintervention group received benzodiazepines (z = -4.334, P < .00001). The postintervention group had a statistically significant lower proportion of anticholinergics administered (z = -4.189, P < .00001). Significantly more patients in the postintervention group had oxygen titrated (z = -3.196, P = .0014) and were on room air at the time of death (z = -3.891, P = .0001). A 2-hour training led to statistically significant changes in the use of evidence-based interventions.

PMID:36622898 | DOI:10.1097/NJH.0000000000000931

Cephalalgia. 2023 Jan;43(1):3331024221132008. doi: 10.1177/03331024221132008.

ABSTRACT

BACKGROUND: It has been suggested that patients with migraine have a higher risk of stroke. Despite considerable research on this topic in younger populations, a clear answer is still lacking for older individuals. We studied the association between migraine and the risk of stroke in a middle-aged and elderly population.

METHODS: Within the ongoing prospective population-based Rotterdam Study, the presence of migraine was assessed using a validated questionnaire in a structured interview between 2006 and 2011, which formed the baseline. The association between migraine and the risk of stroke was analyzed using Cox proportional-hazards models with adjustments for age, sex, and cardiometabolic risk factors.

RESULTS: A total of 6925 (mean age 65.7 ± 11.3 years, 57.8% females) stroke-free participants were included. At baseline, 1030 (14.9%) participants had lifetime history of migraine. During a median follow-up of 6.2 years, 195 participants developed a stroke (163 ischemic stroke). Analyzing the association between migraine and stroke, we found a hazard ratio of 1.44 with a 95% confidence interval of 0.96-2.15. The results were similar for the ischemic stroke (HR 1.50, CI: 0.97-2.32).

CONCLUSION: Our data suggested an association between migraine and the risk of stroke in a middle-aged and elderly population, but this was not statistically significant.

PMID:36622876 | DOI:10.1177/03331024221132008

Transl Vis Sci Technol. 2023 Jan 3;12(1):13. doi: 10.1167/tvst.12.1.13.

ABSTRACT

PURPOSE: Retinal microvascular abnormalities measured on retinal images are a potential source of prognostic biomarkers of vascular changes in the neurodegenerating brain. We assessed the presence of these abnormalities in Alzheimer’s dementia and mild cognitive impairment (MCI) using ultra-widefield (UWF) retinal imaging.

METHODS: UWF images from 103 participants (28 with Alzheimer’s dementia, 30 with MCI, and 45 with normal cognition) underwent analysis to quantify measures of retinal vascular branching complexity, width, and tortuosity.

RESULTS: Participants with Alzheimer’s dementia displayed increased vessel branching in the midperipheral retina and increased arteriolar thinning. Participants with MCI displayed increased rates of arteriolar and venular thinning and a trend for decreased vessel branching.

CONCLUSIONS: Statistically significant differences in the retinal vasculature in peripheral regions of the retina were observed among the distinct cognitive stages. However, larger studies are required to establish the clinical importance of our findings. UWF imaging may be a promising modality to assess a larger view of the retinal vasculature to uncover retinal changes in Alzheimer’s disease.

TRANSLATIONAL RELEVANCE: This pilot work reports an investigation into which retinal vasculature measurements may be useful surrogate measures of cognitive decline, as well as technical developments (e.g., measurement standardization), that are first required to establish their recommended use and translational potential.

PMID:36622689 | DOI:10.1167/tvst.12.1.13

JAMA Netw Open. 2023 Jan 3;6(1):e2249568. doi: 10.1001/jamanetworkopen.2022.49568.

ABSTRACT

IMPORTANCE: Little is known about the long-term economic and social outcomes for children with longitudinally assessed comorbid externalizing and internalizing symptoms, especially compared with children with externalizing symptoms or internalizing symptoms only.

OBJECTIVE: To examine the association between childhood trajectories of externalizing, internalizing, and comorbid symptoms and long-term economic and social outcomes.

DESIGN, SETTING, AND PARTICIPANTS: A 32-year prospective cohort study linked with administrative data was conducted in school-aged participants aged 6 to 12 years in the Québec Longitudinal Study of Kindergarten Children (N = 3017) followed up from 1985 to 2017. Data analysis was conducted between August 1, 2021, and March 31, 2022.

EXPOSURES: Teacher-rated behavioral symptoms were used to categorize children from age 6 to 12 years into developmental profiles using group-based trajectory modeling.

MAIN OUTCOMES AND MEASURES: Multivariable regression models were used to test the association between childhood symptom profile group and adult employment earnings, welfare receipt, intimate partnership status, and having children living in the household. Participant sex, IQ, and socioeconomic background were adjusted for.

RESULTS: Of 3017 participants in this sample, 1594 (52.8%) were male and 1423 (47.2%) were female. Per confidentiality rules established by Statistics Canada, income variables were rounded to base 100 and count variables were rounded to base 10; the mean (SD) age was 37 (0.29) years at follow-up. Four symptom profiles were identified: no/low (n = 1369 [45.4%]), high externalizing (882 [29.2%]), high internalizing (354 [11.7%]), and comorbid (412 [13.7%]) symptoms. Compared with the no/low symptom profile, participants in the high externalizing-only profile earned $5904 (95% CI, -$7988 to -$3821) less per year and had 2.0 (95% CI, 1.58-2.53) times higher incidence of welfare receipt, while participants in the high internalizing group earned $8473 (95% CI, -$11 228 to -$5717) less per year, had a 2.07 (95% CI, 1.51-2.83) higher incidence of welfare receipt, and had a lower incidence of intimate partnership (incident rate ratio [IRR], 0.89; 95% CI, 0.80-0.99). Participants in the comorbid profile fared especially poorly: they earned $15 031 (95% CI, -$18 030 to -$12 031) less per year, had a 3.79 (95% CI, 2.75-5.23) times higher incidence of annual welfare receipt, and were less likely to have an intimate partner (IRR, 0.71; 95% CI, 0.63-0.79) and children living in the household (IRR, 0.86; 95% CI, 0.80-0.92). Estimated lost earnings over a 40-year working career were $140 515 for the high externalizing, $201 657 for the high internalizing, and $357 737 for the comorbid profiles.

CONCLUSIONS AND RELEVANCE: In this cohort study, children exhibiting sustained childhood high externalizing, high internalizing, or comorbid symptoms were at increased risk of poor economic and social outcomes into middle age. These findings suggest that children exhibiting comorbid problems were especially vulnerable and that early detection and support are indicated.

PMID:36622675 | DOI:10.1001/jamanetworkopen.2022.49568