Nevin Manimala

JAMA Netw Open. 2022 Jul 1;5(7):e2220563. doi: 10.1001/jamanetworkopen.2022.20563.

ABSTRACT

IMPORTANCE: Electroacupuncture (EA) is a widely recognized therapy for depression and sleep disorders in clinical practice, but its efficacy in the treatment of comorbid insomnia and depression remains uncertain.

OBJECTIVE: To assess the efficacy and safety of EA as an alternative therapy in improving sleep quality and mental state for patients with insomnia and depression.

DESIGN, SETTING, AND PARTICIPANTS: A 32-week patient- and assessor-blinded, randomized, sham-controlled clinical trial (8-week intervention plus 24-week observational follow-up) was conducted from September 1, 2016, to July 30, 2019, at 3 tertiary hospitals in Shanghai, China. Patients were randomized to receive EA treatment and standard care, sham acupuncture (SA) treatment and standard care, or standard care only as control. Patients were 18 to 70 years of age, had insomnia, and met the criteria for depression as classified in the Diagnostic and Statistical Manual of Mental Disorders (Fifth Edition). Data were analyzed from May 4 to September 13, 2020.

INTERVENTIONS: All patients in the 3 groups were provided with standard care guided by psychiatrists. Patients in the EA and SA groups received real or sham acupuncture treatment, 3 sessions per week for 8 weeks, for a total of 24 sessions.

MAIN OUTCOMES AND MEASURES: The primary outcome was change in Pittsburgh Sleep Quality Index (PSQI) from baseline to week 8. Secondary outcomes included PSQI at 12, 20, and 32 weeks of follow-up; sleep parameters recorded in actigraphy; Insomnia Severity Index; 17-item Hamilton Depression Rating Scale score; and Self-rating Anxiety Scale score.

RESULTS: Among the 270 patients (194 women [71.9%] and 76 men [28.1%]; mean [SD] age, 50.3 [14.2] years) included in the intention-to-treat analysis, 247 (91.5%) completed all outcome measurements at week 32, and 23 (8.5%) dropped out of the trial. The mean difference in PSQI from baseline to week 8 within the EA group was -6.2 (95% CI, -6.9 to -5.6). At week 8, the difference in PSQI score was -3.6 (95% CI, -4.4 to -2.8; P < .001) between the EA and SA groups and -5.1 (95% CI, -6.0 to -4.2; P < .001) between the EA and control groups. The efficacy of EA in treating insomnia was sustained during the 24-week postintervention follow-up. Significant improvement in the 17-item Hamilton Depression Rating Scale (-10.7 [95% CI, -11.8 to -9.7]), Insomnia Severity Index (-7.6 [95% CI, -8.5 to -6.7]), and Self-rating Anxiety Scale (-2.9 [95% CI, -4.1 to -1.7]) scores and the total sleep time recorded in the actigraphy (29.1 [95% CI, 21.5-36.7] minutes) was observed in the EA group during the 8-week intervention period (P < .001 for all). No between-group differences were found in the frequency of sleep awakenings. No serious adverse events were reported.

CONCLUSIONS AND RELEVANCE: In this randomized clinical trial of EA treatment for insomnia in patients with depression, quality of sleep improved significantly in the EA group compared with the SA or control group at week 8 and was sustained at week 32.

TRIAL REGISTRATION: ClinicalTrials.gov Identifier: NCT03122080.

PMID:35797047 | DOI:10.1001/jamanetworkopen.2022.20563

JAMA Otolaryngol Head Neck Surg. 2022 Jul 7. doi: 10.1001/jamaoto.2022.1573. Online ahead of print.

ABSTRACT

IMPORTANCE: Recent studies suggest that theophylline added to saline nasal irrigation (SNI) can be an effective treatment for postviral olfactory dysfunction (OD), a growing public health concern during the COVID-19 pandemic.

OBJECTIVE: To evaluate the efficacy and safety of theophylline added to SNI compared with placebo for COVID-19-related OD.

DESIGN, SETTING, AND PARTICIPANTS: This triple-blinded, placebo-controlled, phase 2 randomized clinical trial was conducted virtually between March 15 and August 31, 2021. Adults residing in Missouri or Illinois were recruited during this time period if they had OD persisting for 3 to 12 months following suspected COVID-19 infection. Data analysis was conducted from October to December 2021.

INTERVENTIONS: Saline sinus rinse kits and bottles of identical-appearing capsules with either 400 mg of theophylline (treatment) or 500 mg of lactose powder (control) were mailed to consenting study participants. Participants were instructed to dissolve the capsule contents into the saline rinse and use the solution to irrigate their nasal cavities in the morning and at night for 6 weeks.

MAIN OUTCOMES AND MEASURES: The primary outcome was the difference in the rate of responders between the treatment and the control arms, defined as a response of at least slightly better improvement in the Clinical Global Impression-Improvement scale posttreatment. Secondary outcome measures included changes in the University of Pennsylvania Smell Identification Test (UPSIT), the Questionnaire for Olfactory Disorders, the 36-Item Short Form Health Survey on general health, and COVID-19-related questions.

RESULTS: A total of 51 participants were enrolled in the study; the mean (SD) age was 46.0 (13.1) years, and 36 (71%) participants were women. Participants were randomized to SNI with theophylline (n = 26) or to SNI with placebo (n = 25). Forty-five participants completed the study. At the end of treatment, 13 (59%) participants in the theophylline arm reported at least slight improvement in the Clinical Global Impression-Improvement scale (responders) compared with 10 (43%) in the placebo arm (absolute difference, 15.6%; 95% CI, -13.2% to 44.5%). The median difference for the UPSIT change between baseline and 6 weeks was 3.0 (95% CI, -1.0 to 7.0) for participants in the theophylline arm and 0.0 (95% CI, -2.0 to 6.0) for participants in the placebo arm. Mixed-model analysis revealed that the change in UPSIT scores through study assessments was not statistically significantly different between the 2 study arms. Eleven (50%) participants in the theophylline arm and 6 (26%) in the placebo arm had a change of 4 or more points in UPSIT scores from baseline to 6 weeks. The difference in the rate of responders as measured by the UPSIT was 24% (95% CI, -4% to 52%) in favor of theophylline.

CONCLUSIONS AND RELEVANCE: This randomized clinical trial suggests that the clinical benefit of theophylline nasal irrigations on olfaction in participants with COVID-19-related OD is inconclusive, though suggested by subjective assessments. Larger studies are warranted to investigate the efficacy of this treatment more fully.

TRIAL REGISTRATION: ClinicalTrials.gov Identifier: NCT04789499.

PMID:35797024 | DOI:10.1001/jamaoto.2022.1573

Adv Ther. 2022 Jul 7. doi: 10.1007/s12325-022-02227-w. Online ahead of print.

ABSTRACT

INTRODUCTION: There is a paucity of literature on the efficacy and safety of ultrafiltration in Chinese patients with heart failure (HF). Therefore, we aimed to compare the efficacy and safety of ultrafiltration with diuretics and provide information and evidence as to the best approach for patients with HF.

METHODS: In this single-center, non-randomized interventional study patients with HF either received diuretics or ultrafiltration. The efficacy outcomes included changes in the weight, dyspnea score, and 6-min walk distance from baseline to 48 h after treatment. Safety outcomes were evaluated in both the groups with respect to changes in systolic blood pressure, heart rate, serum creatinine, blood urea nitrogen, blood potassium ion concentration, and blood sodium ion concentration.

RESULTS: A total of 149 patients with HF (diuretics, 73; ultrafiltration, 76) were included. At 48 h, patients in the ultrafiltration group showed significantly greater weight loss and better improvement in dyspnea score and 6-min walk distance compared to patients in the control group (P < 0.05). However, the two groups showed no statistically significant difference in terms of safety outcomes such as systolic blood pressure, heart rate, serum creatinine, blood urea nitrogen, blood potassium ion concentration, and blood sodium ion concentration, suggesting similar safety profiles of both the groups.

CONCLUSION: Ultrafiltration was associated with greater weight loss and better dyspnea score and 6-min walk distance with similar safety profiles as compared with diuretics. Ultrafiltration can be considered as an optimal option for Chinese patients with HF.

PMID:35797003 | DOI:10.1007/s12325-022-02227-w

Acta Neurol Belg. 2022 Jul 7. doi: 10.1007/s13760-022-02012-0. Online ahead of print.

ABSTRACT

INTRODUCTION: Aerobic exercise training after stroke has positive effects on quality of life, motor recovery, and aerobic endurance. The aim of this study was to investigate the effectiveness of anti-gravity treadmill gait training and underwater walking therapy on cardiorespiratory fitness, gait and balance in stroke survivors.

METHODS: The study included 39 patients with a history of stroke who were admitted to our center between July 2017 and January 2018. The patients were randomly assigned to anti-gravity treadmill training, underwater walking therapy, or a control group. The aerobic capacity of the participants was evaluated with the 6-min walk test and cycle ergometer testing before and after the treatment. Balance was examined using the Berg Balance Scale (BBS).

RESULTS: There was a statistically significant increase from pre- to post-treatment with regard to maximum heart rate and length of walking distance during 6-min walk test parameters in patients who underwent anti-gravity treadmill training (p < 0.05). The cycle ergometer training results showed significant improvements compared to baseline after treatment in patients who underwent anti-gravity training in terms of maximum heart rate attained during exercise stress testing, time to complete the test, rates of metabolic equivalents of task scores and peak oxygen consumption (p < 0.05). Improvements were also observed in ventricular repolarization indices including corrected QT intervals (QTc), Tp-e interval and Tp-e/QT, Tp-e/QTc ratio in the anti-gravity group (p < 0.05). BBS results showed no statistically significant difference in all groups (p > 0.05).

CONCLUSION: The data of this study showed that anti-gravity treadmill training has favorable effects on cardiorespiratory fitness in stroke survivors.

PMID:35797000 | DOI:10.1007/s13760-022-02012-0

Qual Life Res. 2022 Jul 7. doi: 10.1007/s11136-022-03178-z. Online ahead of print.

ABSTRACT

PURPOSE: To estimate the association between changes in BMI and changes in Health-Related Quality of Life (EQ-5D-3L).

METHODS: The WRAP trial was a multicentre, randomised controlled trial with parallel design and recruited 1267 adults (BMI ≥ 28 kg/m²). Participants were allocated to Brief Intervention, a Commercial weight management Programme (WW, formerly Weight Watchers) for 12 weeks, or the same Programme for 52 weeks. Participants were assessed at 0, 3, 12, 24, and 60 months. We analysed the relationship between BMI and EQ-5D-3L, adjusting for age and comorbidities, using a fixed effects model. Test for attrition, model specification and missing data were conducted. Secondary analyses investigated a non-symmetric gradient for weight loss vs. regain.

RESULTS: A unit increase in BMI was associated with a – 0.011 (95% CI – 0.01546, – 0.00877) change in EQ-5D-3L. A unit change in BMI between periods of observation was associated with – 0.016 017 (95% CI – 0.0077009, – 0.025086) change in EQ-5D-3L. The negative association was reduced during weight loss, as opposed to weight gain, but the difference was not statistically significant.

CONCLUSIONS: We have identified a strong and statistically significant negative relationship between BMI changes and HRQoL. These estimates could be used in economic evaluations of weight loss interventions to inform policymaking.

CLINICAL TRIAL REGISTRATION: This trial was registered with Current Controlled Trials, number ISRCTN82857232.

PMID:35796997 | DOI:10.1007/s11136-022-03178-z

Aging Clin Exp Res. 2022 Jul 7. doi: 10.1007/s40520-022-02179-9. Online ahead of print.

ABSTRACT

BACKGROUND: Fatigue is a common and often debilitating symptom experienced by many stroke survivors. Significant post stroke fatigue may predispose individuals to other health complications, such as falls, which can lead to fractures and soft tissue injuries. Only limited research has examined the association between fatigue and falls in stroke survivors.

METHODS: Data were obtained from the Sax Institute’s 45 and Up Study, from a subset of individuals who had experienced a stroke. The Modified Fatigue Impact Scale-5-item version (MFIS-5) was used to measure the level of fatigue. A logistic regression model, adjusted for stroke characteristics and comorbidities, was used to determine the magnitude of association between change in fatigue score and odds of having had a fall.

RESULTS: A total of 576 participants completed the questionnaire. A total of 214 (37.2%) participants reported having had a fall in the previous 12 months. There was a statistically significant association between fatigue scores and fall status (p < 0.001). Specifically, for every 1-point increase in the fatigue score (MFIS-5) (i.e. higher level of fatigue), the odds of a person having a fall is 1.10 times greater (AOR = 1.10; 95% CI 1.05, 1.15; p < 0.001).

CONCLUSION: This study revealed an association between an increasing risk of falls with increasing severity of post stroke fatigue. Accurate detection and management of fatigue may help reduce the risk of falls and should be the focus of future research.

PMID:35796976 | DOI:10.1007/s40520-022-02179-9

Methods Mol Biol. 2022;2509:361-393. doi: 10.1007/978-1-0716-2380-0_22.

ABSTRACT

Phase separation is one of the fundamental processes to compartmentalize biomolecules in living cells. RNA-protein complexes (RNPs) often scaffold biomolecular condensates formed through phase separation. We here present a statistical thermodynamics approach to investigate intracellular phase separation. We first present the statistical thermodynamic theory of the liquid-liquid phase separation (LLPS) of two molecules (such as proteins and solvent molecules) and of a polymer solution (such as RNPs and solvent molecules). Condensates produced by LLPS show coarsening and/or coalescence to minimize their total surface area. In addition to the LLPS, there are other types of self-assembly, such as microphase separation, micellization, emulsification, and vesiculation, with which the growth of the assembly stops with optimal size and shape. We also describe a scaling theory of micelles of block copolymers, where their structures are analogous to the core-shell structure of paraspeckle nuclear bodies scaffolded by RNPs of NEAT1_2 long noncoding RNAs (lncRNAs) and RNA-binding proteins (RBPs). These theories treat the self-assembly of polymers in the thermodynamic equilibrium, where their concentrations and compositions do not change with time. In contrast, RNPs are produced according to the transcription of RNAs and are degraded with time. We therefore take into account the dynamical aspect of the production of RNPs in an extension of the theory of the self-assembly of soft matter. Finally, we discuss the structure of paraspeckles as an example to demonstrate that an approach combining experiment and theory is powerful to investigate the mechanism of intracellular phase separation.

PMID:35796975 | DOI:10.1007/978-1-0716-2380-0_22

Neurol Ther. 2022 Jul 7. doi: 10.1007/s40120-022-00377-1. Online ahead of print.

ABSTRACT

INTRODUCTION: Results from several clinical trials suggest there is a dose-response effect for beta interferon-1a (INFβ1a) in multiple sclerosis (MS).

METHODS: Our objective was to confirm these results through a retrospective analysis of patients with MS who had breakthrough disease (BD) on intramuscular (IM) INFβ1a (Avonex®) once per week (QW), who were switched to twice per week (BIW) IM INFβ1a between 1995 and 2015. The primary outcome measure was no further BD for at least 24 months. A secondary outcome measure was decrease in mean percentage of disease activity over time. BD was defined as continued relapses, new T2 or enhanced lesions on magnetic resonance imaging (MRI) of the brain, or worsening of the Expanded Disability Status Scale (EDSS) or the neurological examination.

RESULTS: Among 92 patients on QW IM INFβ1a, 53 patients with BD were switched to BIW IM INFβ1a. Of these 53 patients, 44 had adequate follow-up for at least 2 years. Twenty-three of these had no further BD for 24 months or more (range 24-192 months). Beta interferon neutralizing antibody testing was negative in 19 patients. An intent-to-treat analysis of the uncensored data from 52 switched patients also supported a treatment benefit.

CONCLUSION: For patients with MS having breakthrough disease on QW INFβ1a, switching to more frequently administered INFβ may be an option. Advantages to using IM INFβ1a for this include no skin reactions and a lower incidence of neutralizing antibodies. Further pragmatic, observational, larger-group studies comparing treatment with Avonex® and higher dosed IM INFβ1a, such as the recently FDA-approved IM peginterferon beta-1a, may be indicated.

PMID:35796951 | DOI:10.1007/s40120-022-00377-1

Obes Surg. 2022 Jul 7. doi: 10.1007/s11695-022-06189-4. Online ahead of print.

ABSTRACT

INTRODUCTION: Vertical banded gastroplasty (VBG) is associated with high weight regain; Roux-en-Y gastric bypass (RYGB) is used as a revision procedure in patients with VBG experiencing weight regain. This study compared the 5-year follow-up outcomes of primary (PRYGB) and revision RYGB after VBG (RRYGB).

METHODS: Patients who underwent PRYGB or RRYGB after VBG from 2008 to 2016 were enrolled. Data on weight regain, weight loss (WL), food tolerance (FT), early and late complications, and resolution or improvement in associated medical conditions were analyzed.

RESULTS: PRYGB and RRYGB groups had 558 and 156 patients, respectively, after exclusion of the lost to follow-up patients. PRYGB group showed significantly lower mean body mass index (over the entire follow-up period), early complications, reintervention rates for late complications, and overall reintervention rates than that of the RRYGB group. On the other hand, FT scores, odds of late complications, and improvements (in the fifth year) in associated medical conditions were comparable between the two groups.

CONCLUSION: RRYGB in patients with VBG who regained weight showed comparable safety and resolution of associated diseases to that of PRYGB over the 5-year follow-up period. The WL in the RRYGB group was acceptable despite being less than that of the PRYGB group. FT was better after RRYGB than that of PRYGB in the first year; however, both were comparable at the fifth year follow-up. Patients with VBG undergoing RYGB should receive attentive treatment and evaluation of associated factors.

PMID:35796945 | DOI:10.1007/s11695-022-06189-4

J Neurooncol. 2022 Jul 7. doi: 10.1007/s11060-022-04044-1. Online ahead of print.

ABSTRACT

PURPOSE: Cognitive functioning represents an essential determinant of quality of life. Since significant advances in neuro-oncological treatment have led to prolonged survival it is important to reliably identify possible treatment-related neurocognitive dysfunction in brain tumor patients. Therefore, the present study specifically evaluates the effects of standard treatment modalities on neurocognitive functions in glioma patients within two years after surgery.

METHODS: Eighty-six patients with World Health Organization (WHO) grade 1-4 gliomas were treated between 2004 and 2012 and prospectively followed within the German Glioma Network. They received serial neuropsychological assessment of attention, memory and executive functions using the computer-based test battery NeuroCog FX. As the primary outcome the extent of change in cognitive performance over time was compared between patients who received radiotherapy, chemotherapy or combined radio-chemotherapy and patients without any adjuvant therapy. Additionally, the effect of irradiation and chemotherapy was assessed in subgroup analyses. Furthermore, the potential impact of the extent of tumor resection and histopathological characteristics on cognitive functioning were referred to as secondary outcomes.

RESULTS: After a median of 16.8 (range 5.9-31.1) months between post-surgery baseline neuropsychological assessment and follow-up assessment, all treatment groups showed numerical and often even statistically significant improvement in all cognitive domains. The extent of change in cognitive functioning showed no difference between treatment groups. Concerning figural memory only, irradiated patients showed less improvement than non-irradiated patients (p = 0.029, η² = 0.06). Resected patients, yet not patients with biopsy, showed improvement in all cognitive domains. Compared to patients with astrocytomas, patients with oligodendrogliomas revealed a greater potential to improve in attentional and executive functions. However, the heterogeneity of the patient group and the potentially selected cohort may confound results.

CONCLUSION: Within a two-year post-surgery interval, radiotherapy, chemotherapy or their combination as standard treatment did not have a detrimental effect on cognitive functions in WHO grade 1-4 glioma patients. Cognitive performance in patients with adjuvant treatment was comparable to that of patients without.

PMID:35796933 | DOI:10.1007/s11060-022-04044-1