Clinical factors associated with relapse in depression in a sample of UK primary care patients who have been on long-term antidepressant treatment.

BACKGROUND: This paper investigates whether age of onset of depression, duration of the last episode, number of episodes, and residual symptoms of depression and anxiety are associated with depression relapse in primary care patients who have been on long-term maintenance antidepressant treatment and no longer meet ICD10 criteria for depression. METHODS: An observational cohort using data from ANTLER (N = 478), a double-blind placebo-controlled trial. The primary outcome was time to relapse using the retrospective CIS-R. Participants were followed for 12 months. RESULTS: Primary outcome was available for 468 participants. Time to relapse in those with more than five previous episodes of depression was shorter, hazard ratio (HR) 1.84 (95% confidence interval [CI] 1.23-2.75) compared to people with two episodes; HR 1.57 (95% CI 1.01-2.43) after adjustment. The residual symptoms of depression at baseline were also associated with increased relapse: HR 1.05 (95% CI 1.01-1.09) and HR 1.06 (95% CI 1.01-1.12) in the adjusted model. There was evidence of reduced rate of relapse in older age of onset group: HR 0.86 (95% CI 0.78-0.95); HR attenuated after adjustment HR 0.91 (95% CI 0.81-1.02). There was no evidence of an association between duration of the current episode and residual anxiety symptoms with relapse. CONCLUSIONS: The number of previous episodes and residual symptoms of depression were associated with increased likelihood of relapse. These factors could inform joint decision making when patients are considering tapering off maintenance antidepressant treatment or considering other treatments to prevent relapse.

Fifteen years of real-world data on the use of vigabatrin in individuals with infantile epileptic spasms syndrome.

OBJECTIVE: This study was undertaken to evaluate our treatment algorithm for infantile epileptic spasms syndrome (IESS) used between 2000 and 2018. We initiated vigabatrin (VGB), and steroids were added if the electroclinical response (spasms and electroencephalogram [EEG]) to VGB was not obtained or incomplete. METHODS: Individuals with IESS treated with VGB were recruited from our hospital clinical data warehouse based on electronic health records (EHRs) generated since 2009 and containing relevant keywords. We confirmed the diagnosis of IESS. Clinical, EEG, imaging, and biological data were extracted from the EHRs. We analyzed factors associated with short-term response, time to response, relapse, time to relapse of spasms, and the presence of spasms at last follow-up. RESULTS: We collected data from 198 individuals (female: 46.5%, IESS onset: 6 [4.5-10.3] months, follow-up: 4.6 [2.5-7.6] years, median [Q1-Q3]) including 129 (65.2%) with identifiable etiology. VGB was started 17 (5-57.5) days after IESS diagnosis. A total of 113 individuals were responders (57.1% of the cohort), 64 with VGB alone and 38 with VGB further combined with steroids (56.6% and 33.6% of responders, respectively). Among responders, 33 (29%) experienced relapses of spasms, mostly those with later onset of spasms (p = .002) and those who received VGB for <24 months after spasms cessation compared to a longer duration on VGB (45% vs. 12.8%, p = .003). At follow-up, 92 individuals were seizure-free (46.5% of the whole cohort), including 26 free of therapy (13.1%). One hundred twelve individuals (56.6%) were still receiving VGB, with a duration of 3.2 (1.75-5.7) years. SIGNIFICANCE: Our sequential protocol introducing VGB then adding steroids is an effective alternative to a combined VGB-steroids approach in IESS. It avoids steroid-related adverse events, as well as those from VGB-steroid combination. According to our data, a period of 7 days seems sufficient to assess VGB response and enables the addition of steroids rapidly if needed. Continuing VGB for 2 years may balance the risk of relapse and treatment-induced adverse events.

An investigation of treatment return after psychological therapy for depression and anxiety.

BACKGROUND: Some patients return for further psychological treatment in routine services, although it is unclear how common this is, as scarce research is available on this topic. AIMS: To estimate the treatment return rate and describe the clinical characteristics of patients who return for anxiety and depression treatment. METHOD: A large dataset (N=21,029) of routinely collected clinical data (2010-2015) from an English psychological therapy service was analysed using descriptive statistics. RESULTS: The return rate for at least one additional treatment episode within 1-5 years was 13.7%. Furthermore, 14.5% of the total sessions provided by the service were delivered to treatment-returning patients. Of those who returned, 58.0% continued to show clinically significant depression and/or anxiety symptoms at the end of their first treatment, while 32.0% had experienced a demonstrable relapse before their second treatment. CONCLUSIONS: This study estimates that approximately one in seven patients return to the same service for additional psychological treatment within 1-5 years. Multiple factors may influence the need for additional treatment, and this may have a major impact on service activity. Future research needs to further explore and better determine the characteristics of treatment returners, prioritise enhancement of first treatment recovery, and evaluate relapse prevention interventions.

Treatment of patients with crowding of the anterior group of teeth by circumferential supracrestal fiberotomy.

OBJECTIVE: Aim: To evaluate the effectiveness of the use of circumferential supracrestal fiberotomy in the treatment of tortoanomalies to improve the effectiveness of treatment, prevent recurrence and increase the stability of the achieved result. PATIENTS AND METHODS: Materials and Methods: Our study consists in determining the effectiveness of the use of methods that prevent the recurrence of tortoanomalies - circumferential supracrestal fiberotomy (CSF) in patients over the age of 16 years and the effect of CSF on the gingival junction in the treatment of tortoanomalіes with fixed orthodontic multibonding equipment. RESULTS: Results: The high level of stability of results proves expediency operations circumferential supracrestal fiberotomy and papilla splitting at orthodontic treatment of frontal teeth density at patients older 16 years and for increasing stability of results of treatment by prevention of relapse tortoanomalies. Efficiency of the offered ways of treatment is proved clinically and anthropometrically on the early and remote terms of supervision (1, 6, 12 months). CONCLUSION: Conclusions: The high level of stability of results proves expediency operations circumferential supracrestal fiberotomy and papilla splitting at orthodontic treatment of frontal teeth density at patients older 16 years and for increasing stability of results of treatment by prevention of relapse tortoanomalies. Efficiency of the offered ways of treatment is proved clinically and anthropometrically on the early and remote terms of supervision (1, 6, 12 months).

Inactivated SARS-CoV-2 vaccine does not increase the risk of relapse in patients with clinically inactive adult-onset Still's disease.

OBJECTIVE: A succession of cases have reported flares of adult-onset Still's disease (AOSD) after vaccination against severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), raising concerns. We aimed to investigate the impact of inactivated SARS-CoV-2 vaccines on disease activity in patients with AOSD. METHODS: We prospectively enrolled clinically inactive AOSD patients visiting the outpatient clinics of our department. The patients received SARS-CoV-2 vaccines (BBIBP-CorV, Sinopharm, Beijing, China) voluntarily. The occurrence of relapse in the participants was recorded during the follow-up period, and a propensity score matching (PSM) method was used to compare the relapse rates between vaccinated and unvaccinated patients. Localized and systemic symptoms were assessed in the vaccinated patients. RESULTS: A total of 122 patients with inactive AOSD were included, of which 49.2% (n = 60) voluntarily received the inactivated SARS-CoV-2 vaccine. The relapse rate did not increase significantly in vaccinated patients in comparison with unvaccinated patients (after PSM: 6.8% vs 6.8%), and no relapse occurred within 1 month after vaccination. No obvious adverse reactions were reported in 75.0% of the participants, and none of the patients reported severe reactions. CONCLUSION: Increased disease activity or relapse following vaccination with inactivated SARS-CoV-2 was rare in patients with inactive AOSD. Local and systemic adverse reactions were found to be mild and self-limiting. These safety profiles of inactivated SARS-CoV-2 vaccines in patients with AOSD may assist in eliminating vaccine hesitancy and increase the vaccination rate against SARS-CoV-2.

Relapse prevention through health technology program reduces hospitalization in schizophrenia.

BACKGROUND: Psychiatric hospitalization is a major driver of cost in the treatment of schizophrenia. Here, we asked whether a technology-enhanced approach to relapse prevention could reduce days spent in a hospital after discharge. METHODS: The Improving Care and Reducing Cost (ICRC) study was a quasi-experimental clinical trial in outpatients with schizophrenia conducted between 26 February 2013 and 17 April 2015 at 10 different sites in the USA in an outpatient setting. Patients were between 18 and 60 years old with a diagnosis of schizophrenia, schizoaffective disorder, or psychotic disorder not otherwise specified. Patients received usual care or a technology-enhanced relapse prevention program during a 6-month period after discharge. The health technology program included in-person, individualized relapse prevention planning with treatments delivered via smartphones and computers, as well as a web-based prescriber decision support program. The main outcome measure was days spent in a psychiatric hospital during 6 months after discharge. RESULTS: The study included 462 patients, of which 438 had complete baseline data and were thus used for propensity matching and analysis. Control participants (N = 89; 37 females) were enrolled first and received usual care for relapse prevention followed by 349 participants (128 females) who received technology-enhanced relapse prevention. During 6-month follow-up, 43% of control and 24% of intervention participants were hospitalized (χ2 = 11.76, p<0.001). Days of hospitalization were reduced by 5 days (mean days: b = -4.58, 95% CI -9.03 to -0.13, p = 0.044) in the intervention condition compared to control. CONCLUSIONS: These results suggest that technology-enhanced relapse prevention is an effective and feasible way to reduce rehospitalization days among patients with schizophrenia.

Vaccines and nephrotic syndrome: efficacy and safety.

Vaccines represent the most important medical evolution in the last two centuries allowing prevention and formally eradication of a wide number of infectious diseases. Safety and effectiveness are main issues that still require an open discussion. A few clinical reports described a critical temporal relationship between vaccination and acute nephrotic syndrome, indirectly suggesting an association. For this review, the literature was reviewed to identify articles reporting associations of nephrotic syndrome with vaccines against a vast array of infectious diseases (including bacteria, virus and Sars-Cov-2). As specific aims, we evaluated effectiveness and safety in terms of occurrence of either "de novo" nephrotic syndrome in health subjects or "relapse" in those already affected by the disease. In total, 377 articles were found; 166 duplicates and 71 non-full text, animal studies or non-English language were removed. After excluding another 50 articles not containing relevant data on generic side effects or on relapses or new onset nephrotic syndrome, 90 articles met the search criteria. Overall, studies reported the effect of vaccines in 1015 patients, plus 4 nationwide epidemiologic investigations. Limited experience on vaccination of NS patients with measles, mumps, and rubella live attenuated vaccines does not allow any definitive conclusion on their safeness. VZV has been administered more frequently without side effects. Vaccines utilizing virus inactivated, recombinant, and toxoid can be utilized without risks in NS. Vaccines for influenza reduce the risk of infections during the pandemic and are associated with reduced risk of relapse of NS typically induced by the infection. Vaccines for SARS-CoV-2 (all kinds) offer a concrete approach to reduce the pandemic. "De novo" NS or recurrence are very rare and respond to common therapies.

Efficacy of low-dose rituximab in minimal change disease and prevention of relapse.

BACKGROUND: Minimal change disease (MCD) is a major cause of nephrotic syndrome (NS) in children and a minority of adults. The higher tendency to relapse put patients at risk for prolonged exposure to steroids and other immunosuppressive agents. B cell depletion with rituximab (RTX) may be beneficial to the treatment and prevention of frequently relapsing MCD. Therefore, this study aimed to verify the therapeutic/preventive effects of low-dose RTX on the relapse in adult with MCD. METHODS: A total of 33 adult patients were selected for the study, including 22 patients with relapsing MCD in relapse treatment group who were treated with low-dose RTX (200 mg per week × 4 following by 200 mg every 6 months) and 11 patients in relapse prevention group with complete remission (CR) after steroid therapy were treated with RTX (200 mg ×1 every 6 months) for preventing the relapse of MCD. RESULTS: Of the 22 patients with MCD in relapse treatment group, there were 21 cases (95.45%) of remission [2 (9.09%) partial remission (PR), 19 (86.36%) CR], 1 (4.56%) no remission (NR) and 20 (90.90%) relapse-free. The Median duration of sustained remission was 16.3 months (3, 23.5 months, inter quartile range (IQR)). 11 patients in the relapse prevention group during a follow-up of 12 months (9-31 months) had no relapse. The average dose of prednisone in two groups after RTX treatment was significantly lower than before treatment. CONCLUSION: The results of this study suggested low-dose RTX can significantly reduce relapse rate and steroid dose in adults with MCD with fewer side effects. Low-dose RTX regimens may be beneficial for the treatment of relapsing MCD in adults and may be the preferred regimen for patients at high risk for the development of adverse events from corticosteroids.

[Long-term probiotic administration for irritable bowel syndrome: a legal need].

BACKGROUND: Irritable bowel syndrome (IBS) is one of the most common functional diseases of the gastrointestinal tract. Violations in the intestinal microbiocenosis play a significant role in the pathogenesis of this suffering. The probiotic strain Bifidobacterium longum 35624® has a strong evidence base for use in the management of patients with IBS. The duration of probiotic therapy and the need for repeated courses of probiotics require further study, which determined the need for this observational study. AIM: To compare the results of prolonged (12 weeks) and usual duration of courses of probiotic Bifidobacterium longum 35624® in patients with IBS. MATERIALS AND METHODS: 42 patients with a verified diagnosis of IBS of moderate and severe severity who met the inclusion criteria were recruited into the study. Patients were prescribed probiotic Bifidobacterium longum 35624® at a dose of 1 capsule (1×109 CFU), 1 time per day for 12 weeks. The course of the disease was assessed using the visual analogue scale, visceral sensitivity index (VSI), IBS symptom severity scale (IBS-SSS), quality of life indicators were assessed using the IBS-QoL questionnaire scales. Evaluation of indicators was carried out at the inclusion visit, on days 14, 28, 56, 84 of probiotic intake and on day 112 (28 days after the last dose of Bifidobacterium longum 35624®). RESULTS: The results obtained confirmed the ability of the probiotic Bifidobacterium longum 35624® to positively influence the course of IBS. The addition of the main therapy with a probiotic made it possible to achieve a significant decrease in the severity of abdominal pain, bloating, and stool disorders. The severity of IBS significantly decreased according to the results of IBS-SSS. Reliable positive dynamics of indicators on the scales IBS-QoL, VSI is shown. The most pronounced changes were observed by the end of the third month of taking Bifidobacterium longum 35624®. Thus, according to the IBS-SSS indicators, only by the end of the third month of observation, some patients achieved remission of the disease. All described changes were persistent and persisted one month after the end of the probiotic intake. CONCLUSION: The addition of a prolonged course of the probiotic Bifidobacterium longum 35624® to the basic therapy in patients with IBS allows a more pronounced and lasting effect to be achieved. A "post-probiotic" effect was shown - a decrease in VSI after the end of the intake of the probiotic strain. Given the chronic relapsing course of IBS, the use of repeated probiotic courses was proposed to prevent exacerbation of the disease.

[Optimization of monitoring of pregnant women with various risk of dental caries relapse]. / Monitoring stomatologicheskogo statusa beremennykh s razlichnym riskom retsidiva kariesa zubov.

OBJECTIVE: The aim of the study is determination of the effectiveness of technologies for predicting the progressive course of dental caries in pregnant women. MATERIAL AND METODS: We examined 511 pregnant women aged 18-40 years with dental caries (304 were included in a main group, 207 were enrolled in controls), who were assessed the DMFT index sequentially in the 1st, 2nd and 3rd trimesters of pregnancy. The prognosis of recurrence of dental caries was determined by the method of two-stage clinical and laboratory prognosis. RESULTS: The prevalence of dental caries in the main group was 89.1% (271 out of 304 patients), in the control group - 87.9% (182 out of 207 patients). In the third trimester of pregnancy 36.2% of women in the main group had a recurrence of caries (vs 43.0% in the control group). Early examination of patients in the 1st trimester of pregnancy, followed by monitoring of the state of the organs and tissues of the mouth, made it possible to achieve timely treatment of dental caries and prevent its recurrence. In the third trimester of pregnancy, the DMFT-index in the dispensary group, in contrast to the control group, was statistically significantly (p<0.05) lower by 12.3%, which indicated the effective use of the proposed monitoring. CONCLUSION: The use of a system for providing dental treatment and preventive care in the form of screening, dynamic forecasting and assessment of the risk of recurrence of caries in pregnant women with dental caries and a high risk of its progression makes it possible to stop the development of this process and ensure the preservation of dental health.

Prevention of disease flares by risk-adapted stratification of therapy withdrawal in juvenile idiopathic arthritis: results from the PREVENT-JIA trial.

OBJECTIVES: To investigate the ability of high-sensitivity C-reactive protein (hsCRP) and S100A12 to serve as predictive biomarkers of successful drug withdrawal in children with clinical remission of juvenile idiopathic arthritis (JIA). METHODS: This multicentre trial (PREVENT-JIA) enrolled 119 patients with JIA in clinical remission, and 100 patients reached the intervention phase in which the decision whether to continue or stop treatment was based on S100A12 and hsCRP levels. Patients were monitored for 12 months after stopping medication for flares of disease. Results were compared with withdrawal of therapy without biomarker-based stratification in patients from the German Biologika in der Kinderrheumatologie (BiKeR) pharmacovigilance registry. RESULTS: In the PREVENT-JIA group, 49 patients had a flare, and 45% of patients stopping medication showed flares within the following 12 months. All patients (n=8) continuing therapy due to permanently elevated S100A12/hsCRP at more than one visit flared during the observation phase. In the BiKeR control group, the total flare rate was 62%, with 60% flaring after stopping medication. The primary outcome, time from therapy withdrawal to first flare (cumulative flare rate after therapy withdrawal), showed a significant difference in favour of the PREVENT-JIA group (p=0.046; HR 0.62, 95% CI 0.38 to 0.99). As additional finding, patients in the PREVENT-JIA trial stopped therapy significantly earlier. CONCLUSION: Biomarker-guided strategies of therapy withdrawal are feasible in clinical practice. This study demonstrates that using predictive markers of subclinical inflammation is a promising tool in the decision-making process of therapy withdrawal, which translates into direct benefit for patients. TRIAL REGISTRATION NUMBER: ISRCTN69963079.

Treatment for relapsed acute promyelocytic leukemia.

The advent of all-trans retinoic acid (ATRA) and arsenic trioxide (ATO) has significantly improved the outcomes of acute promyelocytic leukemia (APL); nevertheless, a small fraction of patients still experience relapse. Due to the infrequency of APL relapse coupled with the rapid change in the therapeutic landscape, there are limited available data regarding the treatment of relapsed APL. In this situation, however, ATO-based therapy has been shown to result in high rates of hematological and molecular complete remission (CR). Autologous hematopoietic cell transplantation (HCT) is considered the postremission therapy of choice when patients achieve molecular CR, whereas recent studies have suggested that molecular CR is not prerequisite for the success of autologous HCT. Allogeneic HCT can be reserved for selected patients, i.e., those who cannot achieve CR and those who relapse after autologous HCT, because of high toxicities and the expectation of highly favorable outcomes with autologous HCT during CR. For patients who are ineligible for HCT, prolonged administration of ATRA + ATO would be a viable option. To further refine the therapy for patients with relapsed APL, it is imperative to aggregate clinical data of patients who relapse after the ATRA + ATO frontline therapy within the framework of national and international collaboration.

Research Review: A meta-analysis of relapse rates in cognitive behavioral therapy for anxiety and related disorders in youth.

BACKGROUND: Cognitive behavioral therapy (CBT) is an effective treatment for youth with anxiety and related disorders, with a 59% remission rate at post-treatment. Results of reviews and meta-analyses indicate that treatment gains are maintained across long-term follow-up, at least in terms of symptom improvement. Less is known about relapse, defined as patients who initially achieve remission status but then experience a return of symptoms after a follow-up period. METHOD: The current study used meta-analysis to determine the overall rate of relapse in CBT for children and adolescents (age 18 years or younger) with anxiety and related disorders. Potential moderating factors of relapse rates, including demographic, methodological, and clinical/intervention characteristics, were also examined. Out of a pool of 78 abstracts, 13 full-text articles were retained for meta-analysis. An additional two articles were identified from other sources (total N = 535 patients). RESULTS: Results showed an overall relapse rate of 10.5% (including comorbid autism spectrum disorder) and 8% (excluding comorbid autism spectrum disorder) across studies. Moderator analyses demonstrated that relapse rates were higher among younger and more racially diverse samples, as well as among patients with comorbid externalizing disorders and those taking psychiatric medications. There were no differences in relapse rates as a function of primary diagnosis. CONCLUSIONS: Taken together, the findings indicate that relapse rates in CBT for anxious youth are relatively low, suggesting that treatment development and refinement efforts should focus on improving treatment response and remission rates for this population.

Real-world effectiveness and safety of fingolimod in patients with multiple sclerosis in the Czech Republic: results from core and extension parts of the GOLEMS study up to 48 months.

BACKGROUND: Fingolimod, an oral sphingosine 1-phosphate receptor immunomodulator, is approved in Europe for people with multiple sclerosis (pwMS) with highly active disease despite a full and adequate course of treatment with ≥ 1 disease-modifying therapy or patients with rapidly evolving severe relapsing-remitting MS. GOLEMS, a national, multicenter, non-interventional, single-arm, real-world study showed a favorable benefit-risk profile of 12-month treatment with fingolimod in pwMS in the Czech Republic. Here, we evaluated the long-term effectiveness and safety of fingolimod and its impact on disability progression and work capability for up to 48 months in pwMS. METHODS: The endpoints assessed were the incidence and severity of MS relapses in fingolimod-treated patients and the proportion of relapse-free patients up to 48 months of fingolimod treatment, change from baseline in the Expanded Disability Status Scale (EDSS) score, and change from baseline in work capability assessment. Efficacy outcomes were analyzed in the completed and efficacy sets, and safety was evaluated in all the enrolled patients. RESULTS: Of 240 enrolled patients, 237 were included into efficacy set. Patients with a minimum of a 12-month observation period in the core study who continued fingolimod treatment, were eligible to participate in the extension phase. Of 211 patients enrolled in extension study, 155 were evaluated in the completed set. Based on analysis of 48-month period of fingolimod treatment, 95/237 patients (40.1%) in the efficacy set, 54/155 (34.8%) in the completed set were free of relapses. The majority of relapses reported were moderate in intensity. Mean EDSS score remained stable throughout 48-month study period (Baseline, 3.4; Month 48, 3.6). No trend was observed in changes in work capability assessment or number of missed days of work. Of 240 enrolled patients, 147 (61.3%) had ≥ 1 treatment-emergent adverse event (AE) and 20 (8.3%) reported serious AEs. In total, 45 patients (18.8%) permanently discontinued treatment because of AEs related to study drug; two patients reported pregnancy after treatment initiation and subsequently discontinued the treatment; no deaths were reported. CONCLUSION: GOLEMS study demonstrated the sustained effectiveness and manageable safety profile of fingolimod under real-world conditions over 48 months in patients with MS. TRIAL REGISTRATION: Not applicable.

Brucellosis relapse causing thoracic aortic ulcers and aneurysm formation: a case report.

BACKGROUND: Brucellosis is an infectious disease caused by Brucella spp, which can involve the cardiovascular, digestive, and respiratory systems. Cardiovascular involvement is a rare occurrence, it has an extremely high mortality rate. CASE PRESENTATION: A 67-year-old Chinese man presented with thoracic aortic multiple ulcers and partial aneurysm formation that caused symptoms of left waist and left buttock pain. The man was admitted to our hospital due to abdominal aorta pseudoaneurysms 5 years ago. The diagnosis was made by thoracic computed tomography angiography (CTA), previous history, and positive culture of Brucella, and the patient was successfully treated by thoracic aortic covered stent-graft implantation and specific medical treatment. CONCLUSIONS: People who have a history of contact with cattle and sheep, should beware of the possibility of Brucella infection. If chest and abdominal pain occur, timely medical treatment is recommended, aortic aneurysm, the disease with a high risk of death, can be identified or excluded by CTA. Early treatment and prevention of disease progression are more beneficial to patients.

Delayed crises following benzodiazepine withdrawal: deficient adaptive mechanisms or simple pharmacokinetics? Detoxification assisted by serum-benzodiazepine elimination tracking.

OBJECTIVE: Rapid relapses after successful withdrawal occur even in apparently motivated benzodiazepine (BZD)-dependent patients. Regardless of known personality or biological (re-adaptation) issues, the aim of this open-label, single-arm, seminaturalistic study was to search for any detoxification errors contributing to failures. METHODS: The data came from 350 inpatients. Based on serum-BZD evolution criteria, the procedure was divided into four stages: substitution, accumulation, elimination and post-elimination observation. After switching the patients to a long-acting substitute (diazepam), to prevent data falsification due to unwanted overaccumulation, the doses were expeditiously reduced under laboratory feedback until accumulation stopped. With the start of effective elimination, the tapering rate slowed and was individually adjusted to the patient's current clinical state. The tracking of both serum-BZD concentration and the corresponding intensity of withdrawal symptoms was continued throughout the entire elimination phase, also following successful drug withdrawal. Detoxification was concluded only after the patient's post-elimination stabilization. RESULTS: Regardless of various initial serum-BZD concentration levels and the customized dose-reduction rate, and despite the novel lab-driven actions preventing initial overaccumulation, elimination was systematically proven to be protracted and varied within the 2- to 95-day range after the final dose. Within this period, withdrawal syndrome culminated several times, with varying combinations of symptoms. The last crisis occurrence (typically 2-3 weeks after withdrawal) correlated with the final serum-BZD elimination. The factors that prolonged elimination and delayed the final crisis were patient age, duration of addiction, adjunct valproate medication and elimination stage start parameters growing with former overaccumulation. CONCLUSIONS: The low-concentration detoxification stage is critical for patients' confrontations with recurring withdrawal symptoms. Underestimated elimination time following drug withdrawal and premature conclusions of detoxification expose patients to unassisted withdrawal crises. Concentration tracking defines proper limits for medical assistance, preventing early relapses.

Update on the treatment of steroid-sensitive nephrotic syndrome.

Steroid-sensitive nephrotic syndrome (SSNS) is a rare condition that develops primarily in preadolescent children after the age of 1 year. Since the 1950s, oral corticosteroids have been the mainstay of treatment of all children presenting with nephrotic syndrome, with most patients responding within 4 weeks to an oral course of prednisone (PDN). However, corticosteroids have important side effects and 60-80 % of patients relapse, developing frequently relapsing or steroid-dependent forms. For these reasons, many patients require second-line steroid-sparing immunosuppressive medications that have considerably improved relapse-free survival, while avoiding many PDN-related toxicities. Since most patients will eventually heal from their disease with a normal kidney function, the morbidity of SSNS is primarily related to side effects of drugs that are used to maintain prolonged remission. Therefore, treatment is essentially based on balancing the use of different drugs to achieve permanent remission with the lowest cumulative number of side effects. Treatment choice is based on the severity of SSNS, on patient age, and on drug tolerability. This review provides an update of currently available therapeutic strategies for SSNS.

Optimizing relapse prevention and changing habits (REACH+) in anorexia nervosa.

INTRODUCTION: Relapse rates in anorexia nervosa (AN) are high, even after full weight restoration. This study aims to develop a relapse prevention treatment that specifically addresses persistent maladaptive behaviors (habits). Relapse Prevention and Changing Habits (REACH+) aims to support patients in developing routines that promote weight maintenance, encourage health, and challenge habits that perpetuate illness. The clinical trial design uses the Multiphase Optimization STrategy (MOST) framework to efficiently identify which components of treatment contribute to positive outcomes. METHODS: Participants will be 60 adults with AN who have achieved weight restoration in an inpatient setting. Treatment will consist of 6 months of outpatient telehealth sessions. REACH+ consists of behavior, cognitive, and motivation components, as well as food monitoring and a skill consolidation phase. A specialized online platform extends therapy between sessions. Participants will be randomly assigned to different versions of each component in a fractional factorial design. Outcomes will focus on maintenance of remission, measured by rate of weight loss and end-of-trial status. Interventions that contribute to remission will be included in an optimized treatment package, suitable for a large-scale clinical trial of relapse prevention in AN.

Implementation and Outcomes of a Maternal Smoking Cessation Program for a Multi-ethnic Cohort in California, USA, 2012-2019.

Smoking during pregnancy remains one of the most significant risk factors for poor birth outcomes. During 2012-2019, the Loma Linda University Health Comprehensive Tobacco Treatment Program (CTTP) used a multicomponent behavioral intervention for tobacco cessation for 1402 pregnant smokers with components of known efficacy (i.e., incentives, biomarker testing, feedback, and motivational interviewing). The CTTP cohort includes a multi-ethnic sample of pregnant women with a mean age of 27 years referred by collaborating community-based healthcare providers in San Bernardino county. Evaluation of program outcomes from 7 years of follow-up (2012-2019) creates a rich cohort dataset for implementation science research to examine the real-world effectiveness of the program. In this report, we provide a cohort profile, and 8-week prolonged abstinence (8-week PA) and relapse findings from the first year of follow-up (n = 233). We found: (1) 28.4% achieved 8-week PA, (2) At a median of 6.2 months of follow-up after achieving 8-week PA, 23.2% of enrolled subjects reported tobacco cessation, and (3) a high rate of loss to follow-up (44%). In addition, our modeling indicated that the odds of relapse/smoking after enrollment was significantly higher in young mothers, non-Hispanic mothers (White, Black/African-American), mothers in the first and third trimester, and rural mothers. Formative quantitative and qualitative research on the CTTP cohort will consider the effects of a range of implementation science (number of intervention sessions, addition of a mHealth component, distance to care) and individual (partner/household smoking, birth outcomes, NICU) outcome measures for the purpose of scaling up the CTTP model.

E-Prevention: Advanced Support System for Monitoring and Relapse Prevention in Patients with Psychotic Disorders Analyzing Long-Term Multimodal Data from Wearables and Video Captures.

Wearable technologies and digital phenotyping foster unique opportunities for designing novel intelligent electronic services that can address various well-being issues in patients with mental disorders (i.e., schizophrenia and bipolar disorder), thus having the potential to revolutionize psychiatry and its clinical practice. In this paper, we present e-Prevention, an innovative integrated system for medical support that facilitates effective monitoring and relapse prevention in patients with mental disorders. The technologies offered through e-Prevention include: (i) long-term continuous recording of biometric and behavioral indices through a smartwatch; (ii) video recordings of patients while being interviewed by a clinician, using a tablet; (iii) automatic and systematic storage of these data in a dedicated Cloud server and; (iv) the ability of relapse detection and prediction. This paper focuses on the description of the e-Prevention system and the methodologies developed for the identification of feature representations that correlate with and can predict psychopathology and relapses in patients with mental disorders. Specifically, we tackle the problem of relapse detection and prediction using Machine and Deep Learning techniques on all collected data. The results are promising, indicating that such predictions could be made and leading eventually to the prediction of psychopathology and the prevention of relapses.