Effectiveness of a Therapeutic Educational Oral Health Program for Persons with Schizophrenia: A Cluster Randomized Controlled Trial and Qualitative Approach.

BACKGROUND: The oral health of people with schizophrenia (PWS) is very poor, suggesting a need for oral health promotion programmes with a high level of evidence. The aim of the EBENE study (Clinicaltrials.gov: NCT02512367) was to develop and evaluate the effectiveness of a multidisciplinary therapeutic educational programme in oral health (TEPOH) for PWS. METHODS: A multicentre cluster randomised controlled trial, with outpatient psychiatry centres as the unit of randomisation, was designed to compare the effectiveness of TEPOH (intervention group) versus standard care (control group). The trial was conducted in 26 outpatient psychiatry centres in France (14 in the intervention group, 12 in the control group). Eligible patients with a diagnosis of schizophrenia were enroled between 2016 and 2020 and followed for 6 months. The TEPOH group received a multicomponent intervention (comprising an introductory session, three educational sessions, and a debriefing session). The primary endpoint was the evaluation of periodontal disease as a community periodontal index (CPI) score ≥ 3 at Month 6. The trial was completed using a qualitative approach based on semi-structured interviews with caregivers conducted between July 2018 and December 2019. The trial was stopped early due to difficulties in recruiting patients. RESULTS: Overall, 81 patients (of 250 planned) were included, and 54 patients completed the trial: 40 in the TEPOH group and 14 in the control group. At baseline, the percentage of CPI ≥ 3 was 42.5% in the TEPOH group and 9.1% in the control group. At Month 6, the percentage of CPI ≥ 3 was 20% in the TEPOH group and 14.3% in the control group. The qualitative evaluation underlined that the professionals emphasised the "seriousness" and "assiduity" of the patients' participation in this programme and that the TEPOH reinforced carers' investment in oral hygiene. It also highlighted structural factors (lack of resources for professionals, lack of teeth in PWS, COVID-19 pandemic) that may have exacerbated the difficulties with enrolment and follow-up. CONCLUSIONS: The effectiveness of this TEPOH, developed for PWS as part of the EBENE study, has not been demonstrated. Certain aspects of the programme's content and implementation need to be reconsidered. In particular, an adapted subjective measurement scale should be developed.

Efficacy of repetitive transcranial magnetic stimulation (rTMS) for reducing consumption in patients with alcohol use disorders (ALCOSTIM): study protocol for a randomized controlled trial.

BACKGROUND: The number of people with an alcohol use disorder (AUD) was recently estimated to be 63.5 million worldwide. The global burden of disease and injury attributable to alcohol is considerable: about 3 million deaths, namely one in 20, were caused by alcohol in 2015. At the same time, AUD remains seriously undertreated. In this context, alternative or adjunctive therapies such as brain stimulation could play an important role. The early results of studies using repetitive transcranial magnetic stimulation (rTMS) suggest that stimulations delivered to the dorsolateral prefrontal cortex significantly reduce cravings and improve decision-making processes in various addictive disorders. We therefore hypothesize that rTMS could lead to a decrease in alcohol consumption in patients with AUD. METHODS/DESIGN: We report the protocol of a randomized, double-blind, placebo-controlled, parallel-group trial to evaluate the efficacy of rTMS on alcohol reduction in individuals diagnosed with AUD. The study will be conducted in 2 centers in France. Altogether, 144 subjects older than 18 years and diagnosed with AUD will be randomized to receive 5 consecutive twice-daily sessions of either active or sham rTMS (10 Hz over the right DLPFC, 2000 pulses per day). The main outcomes of the study will be changes in alcohol consumption within the 4 weeks after the rTMS sessions. Secondary outcome measures will include changes in alcohol consumption within the 24 weeks, alcohol cravings, clinical and biological improvements, effects on mood and quality of life, and cognitive and safety assessments, and, for smokers, an assessment of the effects of rTMS on tobacco consumption. DISCUSSION: Several studies have observed a beneficial effect of rTMS on substance use disorders by reducing craving, impulsivity, and risk-taking behavior and suggest that rTMS may be a promising treatment in addiction. However, to date, no studies have included sufficiently large samples and sufficient follow-up to confirm this hypothesis. The results from this large randomized controlled trial will give a better overview of the therapeutic potential of rTMS in AUD. TRIAL REGISTRATION: ClinicalTrials.gov NCT04773691. Registered on 26 February 2021 https://clinicaltrials.gov/ct2/show/NCT04773691?term=trojak&draw=2&rank=5 .

Corporeal Compression at the Onset of Septic shock (COCOONs): a compression method to reduce fluid balance of septic shock patients.

Fluid overload in septic intensive care unit (ICU) patients is common and strongly associated with poor outcome. There is currently no treatment for capillary leak, which is mainly responsible for high positive fluid balance (FB) in sepsis. We hypothesized that increasing interstitial pressure with extensive corporeal compression would reduce FB. The objective of this study was to evaluate the feasibility, efficacy, and safety of a compression treatment during sepsis. This pilot, two-center, single-arm trial enrolled critically ill, non-surgical, septic patients receiving mechanical ventilation. The therapeutic intervention was the early application of compression bandages on more than 80% of the body surface. The primary outcome was negative net FB on day 7. The primary endpoint was reached in 29 of 45 patients (64%) with available data, for a planned objective of 26. By day 4, cumulative FB was 7280 ml [3300-9700]. SOFA- and aged-matched patients from a historical cohort had a significantly higher FB at 1, 2 and 7 days. Tolerance was good, although low-stage pressure ulcers were observed in 16 patients (26%). No effect on intra-abdominal pressure or respiratory plateau pressure was observed. In conclusion, corporeal compression demonstrated potential efficacy in limiting FB during septic shock, with acceptable feasibility and tolerance.

Central retinal thickness following panretinal photocoagulation using a multispot semi-automated pattern-scanning laser to treat ischaemic diabetic retinopathy: Treatment in one session compared with four monthly sessions.

PURPOSE: To compare central retinal thickness (CRT) after panretinal photocoagulation (PRP) with a multispot semi-automated PAttern-SCAnning Laser (PASCAL) in one session (SS-PRP) versus four monthly sessions (MS-PRP) in diabetic retinopathy. METHODS: Multicentre, prospective, randomized, single-blinded, controlled trial evaluating the noninferiority of SS-PRP versus MS-PRP for CRT measured with macular spectral-domain optical coherence tomography (SD-OCT), with a 9-month follow-up in patients presenting severe nonproliferative diabetic retinopathy (DR) or mild proliferative DR without macular oedema (ME) at baseline. RESULTS: Ninety-seven eyes of 97 participants with a mean age of 57.0 ± 14.2 years were included. The mean change of CRT from baseline to 9 months was not statistically different in SS-PRP or in MS-PRP: +16.9 ± 28.3 µm versus +24.7 ± 31.8 µm, respectively (p = 0.224). The variation in mean best-corrected visual acuity (BCVA) from baseline to 9 months was similar in both groups: -1.1 ± 6.5 letters versus -0.6 ± 6.2 letters (p = 0.684). The number of patients with stabilization of DR was not statistically different between the two groups. No severe complication was recorded in either group. CONCLUSION: This study showed the noninferiority of PRP performed in one session versus four monthly sessions with a PASCAL concerning central retinal thickness for treating mild proliferative or severe nonproliferative DR without ME at baseline.

Randomized controlled trial comparing embryo culture in two incubator systems: G185 K-System versus EmbryoScope.

OBJECTIVE: To study whether the closed culture system, as compared with a benchtop incubator with similar culture conditions, has a positive impact on intracytoplasmic sperm injection (ICSI) outcomes. DESIGN: Randomized controlled trial. SETTING: University hospital. PATIENT(S): A total of 386 patients undergoing ICSI cycles with at least six mature oocytes were randomized. INTERVENTION(S): Of these patients, 195 were assigned to the group with culture in a time-lapse imaging (TLI) system (EmbryoScope) and 191 to the group with culture in the G185 K-System (G185). MAIN OUTCOME MEASURE(S): Rate of implantation (primary endpoint) and embryo morphology grade. RESULT(S): No significant differences were found in the implantation rates. The proportion of high-grade embryos on day 2 was significantly higher in the TLI group compared with the G185 group (40.4% vs. 35.2%). The impact of the incubator on embryo morphology remained significant in multivariate analysis, which took into account the woman's age, the rank of attempt, and the smoking status (TLI vs. G185: odds ratio = 1.27; 95% confidence interval, [1.04-1.55]). No difference was found in the mean number of frozen embryos, even though the total proportion of frozen embryos was significantly higher in the TLI group than in the G185 group (29.5% vs. 24.8%). CONCLUSION(S): No difference in implantation rate was found between the two incubators for fresh cycles. It remains to be determined whether the observed differences in embryo morphology and the total number of embryos cryopreserved would translate into higher cumulative outcomes with subsequent frozen embryo transfers. CLINICAL TRIAL REGISTRATION NO: NCT02722252.

Effects of Transcranial Magnetic Stimulation on the Hypothalamic-Pituitary Axis in Depression: Results of a Pilot Study.

Some studies have reported that repetitive transcranial magnetic stimulation (rTMS) applied to the dorsolateral prefrontal cortex (DLPFC) is able to induce changes in the hypothalamic-pituitary axis in subjects with major depression. The causes of these neuroendocrine effects are unknown and deserve to be studied. The authors monitored neuroendocrine hormones in 15 subjects with major depression treated by 1-Hz rTMS on the right DLPFC and explored a correlation with mood improvement. Unlike previous studies, no changes in serum cortisol, prolactin, and thyroid hormone levels were found. However, the authors did observe short-term changes in growth hormone levels in nonresponsive subjects.

Efficacy of transcranial direct current stimulation (tDCS) in reducing consumption in patients with alcohol use disorders: study protocol for a randomized controlled trial.

BACKGROUND: Approximately 15 million persons in the European Union and 10 million persons in the USA are alcohol-dependent. The global burden of disease and injury attributable to alcohol is considerable: worldwide, approximately one in 25 deaths in 2004 was caused by alcohol. At the same time, alcohol use disorders remain seriously undertreated. In this context, alternative or adjunctive therapies such as brain stimulation may play a prominent role. The early results of studies using transcranial direct current stimulation found that stimulations delivered to the dorsolateral prefrontal cortex result in a significant reduction of craving and an improvement of the decision-making processes in various additive disorders. We, therefore, hypothesize that transcranial direct current stimulation can lead to a decrease in alcohol consumption in patients suffering from alcohol use disorders. METHODS/DESIGN: We report the protocol of a randomized, double-blind, placebo-controlled, parallel-group trial, to evaluate the efficacy of transcranial direct current stimulation on alcohol reduction in patients with an alcohol use disorder. The study will be conducted in 14 centers in France and Monaco. Altogether, 340 subjects over 18 years of age and diagnosed with an alcohol use disorder will be randomized to receive five consecutive twice-daily sessions of either active or placebo transcranial direct current stimulation. One session consists in delivering a current flow continuously (anode F4; cathode F3) twice for 13 minutes, with treatments separated by a rest interval of 20 min. Efficacy will be evaluated using the change from baseline (alcohol consumption during the 4 weeks before randomization) to 24 weeks in the total alcohol consumption and number of heavy drinking days. Secondary outcome measures will include alcohol craving, clinical and biological improvements, and the effects on mood and quality of life, as well as cognitive and safety assessments, and, for smokers, an assessment of the effects of transcranial direct current stimulation on tobacco consumption. DISCUSSION: Several studies have reported a beneficial effect of transcranial direct current stimulation on substance use disorders by reducing craving, impulsivity, and risk-taking behavior, and suggest that transcranial direct current stimulation may be a promising treatment in addiction. However, to date, no studies have included sufficiently large samples and sufficient follow-up to confirm the hypothesis. Results from this large randomized controlled trial will give a better overview of the therapeutic potential of transcranial direct current stimulation in alcohol use disorders. TRIAL REGISTRATION: Clinical Trials Gov, NCT02505126 (registration date: July 15 2015).

Early versus delayed intravitreal betamethasone as an adjuvant in the treatment of presumed postoperative endophthalmitis: a randomised trial.

AIM: To compare early versus delayed intravitreal betamethasone as an adjuvant in the treatment of presumed acute postoperative endophthalmitis after phacoemulsification. METHODS: Patients with presumed postcataract surgery endophthalmitis were included in this prospective, randomised, multicentre study. On admission, patients received intravitreal vancomycin and ceftazidime, and were randomly assigned to intravitreal betamethasone injection (early-IVB) group or no immediate injection (delayed-IVB) group. After 48 h, a second intravitreal antibiotic injection associated with intravitreal betamethasone was given to all patients. In patients with severe endophthalmitis or clinical deterioration, a prompt or delayed vitrectomy was performed. The primary outcome was the proportion of patients achieving a visual acuity (VA) of 20/40 or better at 12 months. The secondary outcomes were the rate of delayed vitrectomy and the rate of complications (retinal detachment and phthisis). RESULTS: Ninety-seven eyes of 97 patients were included, 45 in the early-IVB group and 52 in the delayed-IVB group. Overall, 62.9% of patients achieved a VA ≥20/40 at 1 year. There was no statistically significant difference in the visual outcome between the two groups at 1 year, whatever their baseline VA or light perception or hand motion or more (p=0.55 and p=0.10, respectively). The rates of delayed vitrectomy, retinal detachment and phthisis bulbi were not significantly different between the two groups (p=0.42, p=0.37 and p=0.44, respectively). CONCLUSIONS: Early intravitreal betamethasone had no clear advantage versus delayed injection in the management of presumed postoperative endophthalmitis.

Interest of targeting either cortical area Brodmann 9 or 46 in rTMS treatment for depression: a preliminary randomized study.

OBJECTIVE: To assess the interest of specifically targeting Brodmann Areas (BA) 9 or 46 for rTMS treatment of depression. METHODS: Patients with Treatment-Resistant Depression were randomly assigned to two treatment groups to receive either rTMS on BA 9 or on BA 46. Each patient underwent 10 sessions of 1Hz-rTMS for 2weeks. The Hamilton and Montgomery-Asberg Depression Rating Scales (HDRS, MADRS) were used under blind conditions to assess the therapeutic response (50% improvement). A Wilcoxon signed-rank test was used to compare the depression rating scales scores obtained before and after the 10 rTMS sessions for each of the two groups. The therapeutic results in the two groups were compared using the Mann-Whitney-Wilcoxon test. We also reported the effect sizes using Hedges's g. RESULTS: Fifteen patients were included. Stimulation of both BA 9 (n=7) and BA 46 (n=8) led to similar therapeutic responses in the two groups (with moderate effect size), such as the mean decrease in HDRS (BA 9: p=0.015; BA 46: p=0.010) and MADRS (BA 9: p=0.042; BA 46: p=0.038) scores. CONCLUSION: Our results do not come out in favor of one or the other BA. SIGNIFICANCE: Stimulation of BA 9 and BA 46 appears to be equally effective in the treatment of depression.