Search

Purpose: The aim of the present study was to examine the acute and chronic effects of wild blueberry supplementation on mood, executive function, and serum biomarkers of neuroplasticity, inflammation, and oxidative stress in emerging adults with moderate-to-severe depressive symptoms. Methods: In this double-blind trial, 60 emerging adults (Mage = 20.0 years, 32% male) with self-reported depressive symptoms were randomly assigned to receive a single blueberry drink (acute phase), followed by 6 weeks of daily blueberry supplementation (chronic phase), or a matched placebo drink. The primary outcome was Beck Depression Inventory-II (BDI-II) scores at 6-week follow-up. Further measures included momentary affect (PANAS-X) and accuracy on an executive function task. The data were analyzed using ANCOVAs adjusted for baseline values, sex, and habitual fruit and vegetable intake. Estimated marginal means were calculated to compare the treatment arms. Results: The blueberry drink significantly improved positive affect (p = 0.026) and executive function (p = 0.025) at 2 h post-ingestion, with change scores being positively correlated in the blueberry group (r = 0.424, p = 0.017). However, after six weeks of supplementation the reduction in BDI-II scores was greater in the placebo group by 5.8 points (95% CI: 0.8–10.7, p = 0.023). Generalized anxiety and anhedonia also decreased significantly more in the placebo group. No significant differences were found for any of the biomarkers. Conclusions: Six weeks of wild blueberry supplementation were inferior to placebo in reducing depressive symptoms. Nevertheless, the correlated improvements in positive affect and executive function after a single dose of blueberries point to a beneficial, albeit transient, psychological effect. These contrasting results suggest a biphasic, hormetic-like response that warrants further investigation. Trial registration: NCT04647019, dated 30 November, 2020. [ABSTRACT FROM AUTHOR]

We report midline impacts of a community-randomized cash transfer intervention to 1857 vulnerable mothers in 140 rural cocoa-farming communities of Côte d'Ivoire. Compared to mothers in the comparison group who participated in village savings and loan associations (VSLAs), treatment mothers participated in VSLAs and received 8 € each week for up to one year with no conditions attached (the midway point of a two-year program). We find small- to moderate-sized treatment effects on four of six indicators of economic well-being (d = 0.23–0.75), as well as small reductions in maternal stress (d = −0.27). We find no statistically detectable impacts on educational engagement, educational aspirations, or educational expectations for children. Results suggest that cash transfer programs in rural West African communities can improve economic well-being and reduce maternal stress. Implications for children and families and for future cash transfer evaluations are discussed. [ABSTRACT FROM AUTHOR]

Mastectomy serves as the main surgical treatment for both invasive and in situ breast carcinoma and large phyllodes tumors. It is associated with skin necrosis, seroma, and surgical site infection in up to 30% of patients. In the present trial, we compared the complications in patients undergoing skin flap elevation by one of the 4 techniques: thick skin flap raised by scalpel(group1), thin skin flap raised with scalpel (group 2), thick skin flap raised with diathermy (group 3), and thin skin flap raised with diathermy (group 4). A randomized trial with superiority hypothesis and 2 × 2 factorial design was conducted at All India Institute of Medical Sciences New Delhi. Mastectomy skin flap necrosis (MSN) was recorded as the main outcome of interest. MSN was noted in 2.5% in group1, 10% in group 2, 7.5% in group 3, and 30% in group 4. MSN was observed in 5% cases with thick flap compared to 20% cases with a thin skin flap (p = 0.007). Raising the flap with scalpel was associated with MSN in 6.25% compared to 18.75% in the diathermy group (p = 0.029). We conclude that raising a thick flap with scalpel is associated with lowest risk of skin flap necrosis. Trial Registration: Clinical Trial Registry- India CTRI/2014/09/004978 [ABSTRACT FROM AUTHOR]

Objective: Mirtazapine and SSRIs are widely prescribed as first-line agents for late-life depression. However, evidence for these drugs is mostly based on non-elderly patients. Therefore, we reanalyzed a randomized controlled trial of mirtazapine versus SSRIs for depression in a sub-population of late-life patients. Methods: A randomized controlled trial was conducted with 141 patients, of whom 41 were elderly, and 100 were non-elderly. This study compared SSRIs and mirtazapine in late-life depression, examined late-onset and early adult-onset separately and compared elderly and non-elderly patients for each drug. Treatment effects and adverse events were assessed using the Hamilton Depression Rating Scale and the Udvalg for Kliniske Undersøgelser Side Effect Rating Scale, respectively. Results: In late-life depression, mirtazapine showed faster HAM-D total score improvement (3.3 points difference, p = 0.021) and higher improvement in insomnia (1.7 points difference, p = 0.001) and appetite (1.2 points difference, p = 0.020). Similar findings were observed for late-onset depression with the HAM-D total score (4.3 points difference, p = 0.007) and appetite (0.9 points difference, p = 0.004), favoring mirtazapine. Depressive symptoms were generally less improved in late-life depression than in non-late-life depression. Regarding the effect of mirtazapine on appetite, late-life depression showed greater improvement (0.7 points difference, p = 0.008). Nausea and micturition disturbances were more common with SSRIs in late-life depression than in non-late-life depression. In contrast, somnolence was less common in late-life depression with mirtazapine. Conclusion: The potential usefulness of mirtazapine in elderly patients was demonstrated. The results also showed differences in the treatment response to SSRIs and mirtazapine between elderly and non-elderly patients. [ABSTRACT FROM AUTHOR]

Purpose: To test the hypothesis that daily supplementation with low-dose B vitamins plus betaine could significantly reduce plasma homocysteine concentrations in Chinese adults with hyperhomocysteinemia and free from background mandatory folic acid fortification. Methods: One hundred apparently healthy adults aged 18–65 years with hyperhomocysteinemia were recruited in South China from July 2019 to June 2021. They were randomly assigned to either the supplement group (daily supplementation: 400 μg folic acid, 8 mg vitamin B6, 6.4 μg vitamin B12 and 1 g betaine) or the placebo group for 12 weeks. Fasting venous blood was collected at baseline, week 4 and week 12 to determine the concentrations of homocysteine, folate, vitamin B12 and betaine. Generalized estimation equations were used for statistical analysis. Results: Statistically significant increments in blood concentrations of folate, vitamin B12 and betaine after the intervention in the supplement group indicated good participant compliance. At baseline, there were no significant differences in plasma homocysteine concentration between the two groups (P = 0.265). After 12-week supplementation, compared with the placebo group, there was a significant reduction in plasma homocysteine concentrations in the supplement group (mean group difference − 3.87; covariate-adjusted P = 0.012; reduction rate 10.1%; covariate-adjusted P < 0.001). In the supplement group, the decreased concentration of plasma homocysteine was associated with increments of blood concentrations of both folate (β = –1.680, P = 0.004) and betaine (β = –1.421, P = 0.020) after 12 weeks of supplementation. Conclusions: Daily supplementation with low-dose B vitamins plus betaine for 12 weeks effectively decreased plasma homocysteine concentrations in Chinese adults with hyperhomocysteinemia. Trial registration: This trial was registered at clinicaltrials.gov as NCT03720249 on October 25, 2018. Website:https://clinicaltrials.gov/ct2/show/NCT03720249. [ABSTRACT FROM AUTHOR]

Cyclical mastalgia of moderate to severe degree requires systemic drug therapy. Tamoxifen is the drug of choice worldwide. A novel molecule, centchroman/Ormeloxifene, developed in India, was found to be equally effective in previous studies. However, its optimal dose regimen is uncertain. We conducted three-arm randomized controlled trial to compare the effectiveness in relieving breast pain. Group 1 received tamoxifen 10 mg daily, and groups 2 and 3 received centchroman 30 mg twice and 30 mg thrice a week, respectively, for 3 months with a follow-up of 3 more months. Breast pain score, nodularity score, sonographic evaluation of the breasts and ovaries, quality of life scores, and adverse events were recorded. The number of patients enrolled was 32, 31, and 30 in group 1, group 2, and group 3, respectively. All three groups had significant improvement in breast pain scores [group 1 (5 → 2), group 2 (5 → 2), group 3 (6 → 2), p < 0.001)], nodularity scores [group1 (1 → 0), group 2 (1 → 0), group 3 (1 → 0), p < 0.001)] and in the quality of life scores over time. However, no significant differences were observed in-between the groups. Transient ovarian cyst formation and menstrual irregularities were more common with a higher dose of centchroman. Centchroman in the dosages of 30 mg twice or thrice a week is as effective as a daily dose of tamoxifen 10 mg in relieving pain, nodularity, and improving quality of life scores. The dose of centchroman 30 mg twice a week for 12 weeks has the least adverse effects and should be accepted as the optimal dosage regimen. There is a need of further study with a greater number of participants and longer follow-up. Trial registration number: CTRI/2018/02/012043 (Registered on: 21/02/2018). [ABSTRACT FROM AUTHOR]

Children with chronic illness (CI) are at risk for internalizing problems, which reduce their quality of life, hamper treatment, and increase family stress. Accordingly, behavioral interventions are provided at the family level. However, the effects of parental involvement on child outcomes are not consistently beneficial. Therefore, it is relevant to study the working mechanisms. In the present study, we tested child coping and parenting stress as underlying mechanisms of the effect of an intervention for children and an additional group intervention for parents. Data were analyzed from a randomized controlled trial. Families of children with chronic illness (N = 120, child M age = 12.11 years, range 7.98–18.07) participated in a cognitive-behavioral-based group intervention and were randomized in the child-only intervention or parent–child intervention. Primary outcomes were parent- and child-reported internalizing problems, whereas the mediators were the use of child active coping skills and parenting stress. The causal model was tested with multilevel mediation analysis. Active coping skills and parenting stress stood out as significant mediators of the effect of the intervention on parent- and child-reported internalizing behavior (Cohen's d effect size range 0.29–1.57). When parents were involved in the intervention, children increased their use of active coping skills and parents decreased in parenting stress, which in turn improved child internalizing problems. Knowing that coping skills and parenting stress underlie the benefit of involving parents can be used for optimizing interventions for children with CI and addressing the risk of internalizing problems. Highlights: Parental involvement in interventions for children with chronic illness can be beneficial, however explanations are still unclear. In this randomized efficacy trial, child use of active coping skills and parenting stress appeared significant temporal mediators. Parental involvement supported child coping and diminished parenting stress, which in turn decreased child internalizing problems. Interventions for children with internalizing problems might be optimized by focusing on determined active components. [ABSTRACT FROM AUTHOR]

While there is a large body of evidence drawn from randomised controlled trials supporting the efficacy of SSGT in autistic adolescents, the control arms of these studies are almost exclusively treated either as usual or waitlist. Addressing this limitation, 90 verbal autistic adolescents (70% male) aged 12–17 years (M = 13.77, SD = 1.6) with IQ > 70 participated in this pragmatic two-armed randomised controlled trial design study evaluating the efficacy of sixteen 90-min sessions of SSGT KONTAKT® (n = 46) in comparison to a manualised interactive group cooking programme (n = 44) of equal dosage controlling for the potentially confounding effects of exposure to a social group context. The primary outcome was the adolescents' progress towards achieving their personally meaningful social goals at follow-up. Secondary outcomes were changes in autistic traits, quality of life, facial emotion recognition skills, social anxiety, and loneliness. Assessments were conducted at baseline, post intervention and 12-week follow-up. The interaction between time point and group allocation was investigated through a random-effects regression model (linear mixed model) to examine changes in the dependent outcomes. While intention-to-treat analysis (N = 90) demonstrated that both SSGT (ES = 1.36, p <.001) and active control (ES = 1.10, p <.001) groups made progress towards their personally meaningful social goals at follow-up, KONTAKT® participants demonstrated greater progress in social goal attainment than their peers in the active control group (ES = 0.35, p =.04). Findings suggest that KONTAKT® is efficacious in supporting autistic adolescents to achieve their personally meaningful social goals compared to other prosocial group activities. Trial registration: (1) Australian New Zealand Clinical Trials Registry (ANZCTR): ACTRN12617001117303, registered 31 July 2017, anzctr.org.au; (2) ClinicalTrials.gov: NCT03294668 registered 22 September 2017, https://clinicaltrials.gov. [ABSTRACT FROM AUTHOR]

Lactational breast abscess results from inadequate or partially treated mastitis. Recently, needle aspiration or catheter suction drainage is being adopted in place of incision and drainage. We planned to evaluate the effectiveness of needle aspiration versus vacuum suction drainage in resolution of puerperal breast abscess. One-hundred-twelve mothers with lactational breast abscess were randomized to either ultrasound-guided needle aspiration or vacuum suction drainage. These patients were followed up on alternate days and assessed for complete resolution of breast abscess, pain in the breast on Visual Analog Scale (VAS) of 0–10, day of return to normal breast feeding, number of aspirations needed, recurrence of abscess and total cost of care. In the suction drain group, 98% of mothers enjoyed complete resolution within 10 days as compared to 87% of mothers treated with needle aspiration. Mean VAS at first follow-up was 2.89 in aspiration group and 2.62 in suction group. The VAS reduced to 0.74 in aspiration group and 0.53 in suction drainage group, at the last follow-up. The mean day of recovery was 7 days for aspiration and 5.73 days for suction. Most patients required 3 aspirations. The mean drainage time was 4.5 days. Vacuum suction drainage is the more effective method for achieving resolution of lactational breast abscess and offers greater patient satisfaction compared to needle aspiration. [ABSTRACT FROM AUTHOR]

Purpose: This study investigated whether UVB-exposed wheat germ oil (WGO) is capable to improving the vitamin D status in healthy volunteers. Methods: A randomized controlled human-intervention trial in parallel design was conducted in Jena (Germany) between February and April. Ultimately, 46 healthy males and females with low mean 25-hydroxyvitamin D (25(OH)D) levels (34.9 ± 10.6 nmol/L) were randomized into three groups receiving either no WGO oil (control, n = 14), 10 g non-exposed WGO per day (– UVB WGO, n = 16) or 10 g WGO, which was exposed for 10 min to ultraviolet B-light (UVB, intensity 500–630 µW/cm2) and provided 23.7 µg vitamin D (22.9 µg vitamin D2 and 0.89 µg vitamin D3) (+ UVB WGO, n = 16) for 6 weeks. Blood was obtained at baseline, after 3 and 6 weeks and analyzed for serum vitamin D-metabolite concentrations via LC–MS/MS. Results: Participants who received the UVB-exposed WGO were characterized by an increase of circulating 25(OH)D2 after 3 and 6 weeks of intervention. However, the 25(OH)D3 concentrations decreased in the + UVB WGO group, while they increased in the control groups. Finally, the total 25(OH)D concentration (25(OH)D2 + 25(OH)D3) in the + UVB WGO group was lower than that of the non-WGO receiving control group after 6 weeks of treatment. In contrast, circulating vitamin D (vitamin D2 + vitamin D3) was higher in the + UVB WGO group than in the control group receiving no WGO. Conclusion: UVB-exposed WGO containing 23.7 µg vitamin D can increase 25(OH)D2 levels but do no improve total serum levels of 25(OH)D of vitamin D-insufficient subjects. Trial registration: ClinicalTrials.gov: NCT03499327 (registered, April 13, 2018). [ABSTRACT FROM AUTHOR]

Robust clinical evidence has not been available for melatonin, a drug commonly administered for treating sleep problems of children with autism spectrum disorder (ASD). In a phase 3 randomized, placebo-controlled clinical trial, we administered 1-mg melatonin (n = 65), 4-mg melatonin (n = 65), or placebo (n = 66) to196 children with ASD once daily before bedtime under adequate sleep hygiene interventions. The primary outcome was sleep onset latency (SOL) assessed with the electronic sleep diary. SOL shortened significantly in the 1- and 4-mg melatonin groups compared to the placebo group (− 22.0, − 28.0, and − 5.0 min, respectively; p < 0.0001 each). This therapeutic regimen of melatonin is a reasonable clinical approach to cope with ASD-emergent difficulties in children with ASD. [ABSTRACT FROM AUTHOR]

Cognitive-Behavioral Therapy for Insomnia (CBT-I) is the gold-standard treatment for insomnia, which is common among breast cancer survivors (BCS). This pilot randomized controlled trial tested the first CBT-I intervention for Spanish-speaking BCS delivered using eHealth. Participants (N = 30) were Spanish-speaking BCS with insomnia symptoms recruited in Puerto Rico and randomized to a 6-week eHealth CBT-I group intervention or a waitlist control. Primary outcomes were acceptability (recruitment, treatment satisfaction) and feasibility (retention, attendance). Secondary outcomes were group differences in sleep outcomes post-treatment (i.e., insomnia symptoms, sleep disturbance, sleep efficiency). Recruitment (95%) and retention (97%) were excellent. All CBT-I participants (100%) attended ≥ 3 of 6 sessions. Satisfaction with CBT-I was acceptable. Post-intervention, there were medium to large group differences for average insomnia symptoms (d = 1.02), sleep disturbance (d = 1.25), and sleep efficiency (d = 0.77) favoring CBT-I. There were small/medium to medium/large group differences for the proportion of participants with clinically significant insomnia symptoms (d = 0.52), sleep disturbance (d = 0.67), and low sleep efficiency (d = 0.33) favoring CBT-I. Spanish-language eHealth CBT-I for BCS was acceptable and feasible and showed preliminary efficacy. ClinicalTrials.gov TRN: NCT04101526 (Posted September 24, 2019). [ABSTRACT FROM AUTHOR]

Purpose: Lutetium-177 prostate-specific membrane antigen-617 (177Lu-PSMA-617) in end-stage metastatic castration-resistant prostate cancer (mCRPC) has reported favourable outcomes. In this study, we aimed to prospectively compare the efficacy and safety of 177Lu-PSMA-617 and docetaxel in chemotherapy-naïve mCRPC patients. Methods: This was a randomized, parallel-group, open-label, phase 2, and non-inferiority trial. Chemotherapy-naïve patients with mCRPC and high PSMA-expressing lesions on 68 Ga-PSMA-11 PET/CT were randomly assigned in 1:1 ratio to 177Lu-PSMA-617 (6.0–7.4 GBq/cycle, every 8 weeks, up to 4 cycles) or docetaxel (75 mg/m2/cycle, every 3 weeks, up to 10 cycles). The primary end-point was best prostate-specific antigen response rate (PSA-RR), defined according to Prostate Cancer Clinical Trials Working Group-3 as proportion of patients achieving ≥ 50% decline in PSA from baseline. Non-inferiority margin of − 15% was pre-specified for PSA-RR. Results: Between December 2019 and March 2021, 40 of the 45 patients assessed for eligibility underwent randomization. Fifteen of 20 patients in 177Lu-PSMA-617 arm and 20/20 patients in docetaxel arm received treatment per protocol. Of these, best PSA-RR in the 177Lu-PSMA-617 arm was 60% (9/15) versus 40% (8/20) in the docetaxel arm. The difference in the PSA-RRs between the two arms was 20% (95% confidence interval, CI: − 12–47, P = 0.25), meeting the pre-specified criterion for non-inferiority in per-protocol analysis. Further, progression-free survival rates at 6 months were 30% and 20% in the 177Lu-PSMA-617 and docetaxel arms respectively (difference 10%, 95% CI: − 18–38, P = 0.50). Overall, treatment-emergent grade ≥ 3 adverse events occurred less frequently with 177Lu-PSMA-617 than with docetaxel (6/20, 30% versus 10/20, 50%, respectively, P = 0.20). Quality-of-life outcomes improved significantly in 177Lu-PSMA-617 arm compared to docetaxel arm (P < 0.01). Conclusion: 177Lu-PSMA-617 was demonstrated to be safe and non-inferior to docetaxel in the treatment of mCRPC and could, thus, be potentially employed earlier in the disease course rather than being solely reserved for advanced end-stage disease. Clinical trial registration: Clinical Trials Registry-India, CTRI/2019/12/022282. [ABSTRACT FROM AUTHOR]

Objective: The present study aimed to evaluate the efficacy and safety of aripiprazole once-monthly (AOM) compared to oral aripiprazole in treating acute schizophrenia. Methods: This randomized, double-blind, non-inferiority study recruited patients from 15 trial sites across China from May 2017 to April 2019. Patients with an acute psychotic episode received AOM at 400 mg or oral aripiprazole at 10–20 mg for 12 weeks. The primary and secondary efficacy endpoints were the difference in scores from baseline to week 10, as assessed on the Positive and Negative Syndrome Scale (PANSS) and Clinical Global Impressions—Severity (CGI-S) scores, respectively. Results: A total of 436 patients were randomized. Among them, 159/218 (72.9%) and 165/218 (75.7%) in the AOM and oral aripiprazole groups completed 10 weeks of treatment, respectively. The least-squares (LS) mean changes from baseline to endpoint (week 10) in PANSS were − 33.6 for the AOM group and − 34.8 in the oral aripiprazole group, respectively, with a difference of − 1.2 (95% CI: − 4.1, 1.7). The non-inferiority margin of AOM to oral aripiprazole was − 4.1, which was above the lower limit of the pre-defined margin. The altered CGI-S score was − 2.2 and − 2.3 in the AOM and oral aripiprazole groups, respectively. The incidence of treatment-emergent adverse events (TEAEs) was similar in both groups. The rate of discontinuation due to TEAEs was 2.3% and 3.2% in the AOM and oral aripiprazole groups, respectively. Conclusions: This study confirmed the efficacy and safety of AOM for the treatment of Chinese patients with acute schizophrenia. The non-inferiority of AOM to oral aripiprazole was established, with comparable efficacy and tolerability. These findings suggested that AOM could be used as a treatment option for patients experiencing an acute episode of schizophrenia. Trial registration: ClinicalTrials.gov identifier: NCT03172871. [ABSTRACT FROM AUTHOR]

Pivotal Response Treatment (PRT) is promising for children with Autism Spectrum Disorder (ASD), but more methodologically robust designed studies are needed. In this randomized controlled trial, forty-four children with ASD, aged 9–15 years, were randomly allocated to PRT (n = 22) or treatment-as-usual (TAU; n = 22). Measurements were obtained after 12- and 20-weeks treatment, and 2-month follow-up. PRT resulted in significant greater improvements on parent-rated social-communicative skills after 12 weeks treatment (p =.004, partial η2 = 0.22), compared to TAU. Furthermore, larger gains in PRT compared to TAU were observed on blindly rated global functioning, and parent-rated adaptive socialization skills and attention problems. Implications for clinical practice and suggestions for future research are discussed. [ABSTRACT FROM AUTHOR]

Purpose: Pregnant women in Sweden are mildly iodine deficient. We investigated the effect of daily iodine supplementation on the iodine and thyroid status of pregnant women. Methods: In this pilot, randomized, double-blind trial, 200 thyroid-healthy pregnant women were recruited at mean (standard deviation) pregnancy week 8.85 (1.62) and assigned (1:1) to daily intake of a multivitamin tablet with or without 150 μg of iodine. Urine and serum samples were collected at baseline and once during the second and third trimesters. Urinary iodine concentration (UIC), serum thyroglobulin (Tg), thyroid-stimulating hormone (TSH), free thyroxine (FT4), and thyroid peroxidase antibodies (TPOabs) were analyzed. Neonatal TSH data were collected. UIC and Tg were also analyzed in a group of 89 thyroid-healthy non-pregnant women of reproductive age (WRA). Results: At baseline, the intervention and the control groups had similar median UIC (interquartile range (IQR)): 110 μg/L (74–119) and 111 μg/L (66–168), respectively. The intervention group reached iodine sufficiency with median UIC (IQR) 139 μg/L (89–234) and 136 μg/L (91–211) in the second and third trimester, respectively, without significant difference from the lower limit of the recommended range, i.e. 150–250 μg/L (p = 0.42 and p = 0.87, respectively). The intervention group had higher median UIC and lower median Tg compared to the control group during the second (p < 0.001 and p = 0.019, respectively) and third trimester (p < 0.001 and p = 0.003, respectively), whereas thyroid hormones, serum TPOabs, and neonatal TSH were similar. The WRA group presented median UIC (IQR) 65 μg/L (30–98) and median Tg (IQR) 18 μg/L (13–27). Conclusion: A daily supplement containing 150 μg of iodine to a group of pregnant women with mild iodine deficiency improved the iodine status from mild ID to iodine sufficiency. This improvement seems to have had a positive impact on maternal thyroglobulin. This study is now under extension to investigate the children's neuropsychological development. Trial registration: ClinicalTrials.gov Identifier NCT02378246, May 3, 2015, retrospectively registered. [ABSTRACT FROM AUTHOR]