Patient Dropout Rates Research Articles

Efficacy and acceptability of different probiotic products plus laxatives for pediatric functional constipation: a network meta-analysis of randomized controlled trials

The prevalence of pediatric constipation ranges from 0.7 to 29.6% across different countries. Functional constipation accounts for 95% of pediatric constipation, and the efficacy of pharmacotherapy is limited, with a success rate of 60%. Several randomized controlled trials (RCTs) have shown the benefits of probiotic supplements in treating this condition. However, the reported strains of probiotics varied among the RCTs. We aimed to compare the efficacy and acceptability of different probiotic supplements for pediatric functional constipation. The current frequentist model–based network meta-analysis (NMA) included RCTs of probiotic supplements for functional constipation in children. The primary outcome was changes in bowel movement or stool frequency; acceptability outcome was all-cause discontinuation. Nine RCTs were included (N = 710; mean age = 5.5 years; 49.4% girls). Most probiotic products, used either alone or combined with laxatives, were associated with significantly better improvement in bowel movement or stool frequency than placebo/control. Protexin plus laxatives (standardized mean difference (SMD) = 1.87, 95% confidence interval (95% CI) = 0.85 to 2.90) were associated with the greatest improvement in bowel movement or stool frequency among all the investigated probiotic products. For the single probiotic interventions, only Lactobacillus casei rhamnosus Lcr35 was associated with significant efficacy compared to placebo/control treatments (SMD = 1.37, 95% CI: 0.32 to 2.43). All the investigated probiotic products had fecal incontinence and patient drop-out rates similar to those of placebo/control treatments. Conclusion: The results of our NMA support the application of an advanced combination of probiotics and laxatives for pediatric functional constipation if there is no concurrent contraindication. Registration: PROSPERO (CRD42022298724).What is Known:• Despite of the high prevalence of pediatric constipation, which ranges from 0.7% to 29.6%, the efficacy of pharmacotherapy is limited, with a success rate of 60%. Several randomized controlled trials (RCTs) have shown the benefits of probiotic supplements in treating this condition. However, the reported strains of probiotics varied among the RCTs. The widely heterogeneous strains of probiotics let the traditional meta-analysis, which pooled all different strains into one group, be nonsense and insignificant.What is New:• By conducting a comprehensive network meta-analysis, we aimed to compare the efficacy and acceptability of different strains of probiotic supplements for pediatric functional constipation. Network meta-analysis of nine randomized controlled trials revealed that the most probiotic products, used either alone or combined with laxatives, were associated with significantly better improvement in bowel movement or stool frequency than placebo/control. Protexin plus laxatives was associated with the greatest improvement in bowel movement or stool frequency among all the investigated probiotic products. For the single probiotic interventions, only Lactobacillus casei rhamnosus Lcr35 was associated with significant efficacy compared to placebo/control treatments. All the investigated probiotic products had fecal incontinence and patient drop-out rates similar to those of placebo/control treatments.

Retrospective Review of the Factors Limiting Optune Initiation in GBM patients

Tumor Treating Fields (TTFields) are a proven treatment that prolongs survival in Glioblastoma Multiforme (GBM) patients. The duration of usage of TTFields correlates with its effectiveness. This study aims to identify socioeconomic and clinical factors that prevent GBM patients at a single institution from starting and remaining on TTFields treatment. This is a retrospective review from a single institution. Data were analyzed for each patient with a diagnosis of GBM that was seen in new patient consultation with a radiation oncologist. Data from 2015 to present were available. 178 patients were included in the study. Insurance status (private vs Medicare/Medicaid vs uninsured), zip code, expected income status, race, ethnicity, preferred primary language, work status, performance status (KPS) at time of diagnosis, and family support at home (Spouse vs Other) were analyzed. For those that initiated TTFields, we examined the duration of treatment, usage rates, patient reported tolerability, and reasons for discontinuation. Early termination of treatment was defined as treatment with TTFields for less than 3 months. Of the 178 diagnosed GBM patients, 96 (54%) were offered TTFields and 48 (27%) agreed to treatment, with 46 actually starting. Of 89 Non-Hispanic patients, 53 were offered TTFields (60%) whereas of 73 Hispanic patients, 35 were offered TTFields (48%) (no statistically significant difference). The number one reason for refusing TTFields treatment was rapid deterioration (14/48 patients). The next most common reason was the patient feeling overwhelmed by managing or wearing the device (10/48) as well as the patient's decision to participate in any other clinical trial (10/48). The 3-month dropout rate for patients who received TTFields was 35% (17/48). 5 of the 17 stopped early due to skin rash or annoyance with the device. Patient's median income and insurance status did not predict whether they would start TTFields. 33 out of 109 (31%) patients with spousal support at home started treatment with TTFields compared to 13 of 69 (19%) of those without spousal support (p = .0895, Chi-Square test). TTFields were offered to more patients each successive year, but many patients had no documented discussion offering TTFields, which may indicate room for improvement at our institution. Median income and insurance status did not play a role in patient access to TTFields, most likely due to Novocure sponsorship of un- or under-insured patients. Among those who declined treatment, 21% did so because of perceived difficulty managing the device. The strongest single trend predictive of successful initiation of TTFields is spousal support at home. Further interventions may focus on improving patient support at home, such as home health nursing visits or community support.

Telemedicine for Monitoring Nutritional Intake in Malnourished Community-Dwelling Elderly: A Scoping Review of Clinical Trials

Malnutrition is part of the geriatric giant and a major concern among community-dwelling elderly individuals. Improper intervention of this problem can have detrimental effects on the elderly. Monitoring nutritional intake plays a vital role in managing malnutrition. Telemedicine has been widely applied for managing chronic diseases and gained prominence during the COVID-19 pandemic as a remote health monitoring method. This scoping review aims to identify the advantages and limitations of implementing telemedicine for addressing malnutrition in community-dwelling elderly. This study reviewed the literature obtained through a systematic search of PubMed and ScienceDirect databases, supplemented by manual searches based on specific inclusion criteria. Two randomized controlled trials (RCTs) assessing the application of telemedicine for malnutrition were identified. The forms of telemedicine used were telecare and set-top boxes on television. The interventions included nutritional monitoring and specific interventions for each patient. However, high patient dropout rates indicated low patient compliance. Nevertheless, the application of telemedicine demonstrated improved patient compliance with nutritional intake guidelines. Limitations of telemedicine implementation included low motivation, technological constraints, and physiological constraints. Telemedicine may be used as a tool for monitoring nutritional intake among malnourished geriatric populations.

#4312 CHANGES OF PATIENT CARE DURING THE COVID 19 PANDEMIC AND ITS IMPACT ON THE ADVANCED STAGE OF CKD PATIENTS

Abstract Background and Aims With the COVID-19 pandemic from the end of 2019, due to the tightening of medical care resources and intermittent lockdowns, CKD patients could not receive the full patients care or educations. However, on CKD management, patient care and education by the nephrologist and multiple professions are known to be important, especially for the late stage of CKD patients. We assessed changes of CKD patients’ management during the COVID-19 pandemic and clarify its impact on their medical conditions. Method Retrospective single center cohort study was conducted. From 2018 to 2021, CKD stage 4 to 5, non-dialyzed patients, who were followed in CKD out-patients clinic in St. Luke's International Hospital, Tokyo, Japan, were included. We definite the pre post pandemic periods as: pre-pandemic: Pre-C, from January 2018 to December 2019, and post-pandemic; Post-C, January 2020 to December 2021. The following data was compared between the 2 periods: Number of nephrology visits per patient; Rate of using telemedicine; Rate of receiving multidisciplinary educational support; Rate of drop-out patients; and Number of patients who initiate renal replacement therapy, newly. Clinical information and laboratory data were obtained from hospital medical record, eGFR were calculated according to MDRD formula modified for Japanese. This study was approved by research ethics committee in St. Lukes’ International hospital. Results Two hundreds and eighty nine individual patients were eligible for the analysis. The baseline data were as follows: mean age 67.9±14 years, 63.5% male, mean eGFR 22.2±5.9 ml/min and 40.2% comorbid DM. The number of nephrology visits and receiving multidisciplinary support was decreased in Post-C periods: Nephrology visits; Pre-C: 9.8±5.1 visits/year, Post-C 7.7±5.2 visits/year, P<0.001, Multidisciplinary support; Pre-C: 78%, Post-C 32%, P<0.001. Multi professional educational support was provided mainly for CKD stage 5 patients during the Post-C. More, the rate of using telemedicine and dropout increased in Post-C. Especially, the dropout rate of elderly patients over 70 years old was significant: 8% in Pre-C and 17% in Post-C, P<0.001. On the other hand, clinical indicators such RRT initiation rate remained unchanged. More, there were no difference of RRT initiation rate, between on-visit and telemedicine patients. Conclusion Frequency of nephrology visits and multidisciplinary educational care has been decreased with COVID-19, there was no difference in the short-term prognosis of CKD patients, from our study. During the pandemic of COVID-19 infection, human conversation or contact, was restricted to prevent its spread, in all over the world. In Japan, a national survey reported that the number of outpatient hospital visits in 2020 was on average 70% of those in 2019. Our clinic also recognized the phenomenon. Some patients switched their visit to telemedicine. Telemedicine has some evidence which has equivalent value to face to face education. From our study, needs for more IT-based, contact-less device-based medical treatment and care in the future was suggested. On the other hand, the dropout rate in the elderly was increased, and these population could no easily use telemedicine. The prognosis of these patients needs to be followed up and verified.

Psychotherapies for the Youth: Evolution, Progress, and On Way to Eclecticism

Psychotherapies for the youth have resulted from the confluence of 3 major disciplines: adult psychology and psychiatry, developmental neurology and pediatrics, and developmental psychology and ethology. Since their humble origins in the psychoanalytically oriented play therapy and the related theories in the pre-War Germany, over more than a century, they have embraced diverse theoretical views that include but not limited to the integration of developmental issues, evolution of the child guidance movement, and the various influences of institutional and social policies. Such a rich journey has eventually resulted in evidence-based practices (EBPs)—powerful interventions for children and families for complex behavioral problems. In this chapter, we attempt to trace the blooming field of youth psychotherapies in their historical contexts, provide an account of the existing gaps of knowledge, briefly narrate the modern-day developments, mostly regarding the multimodal/eclectic treatment aspects and finally, given their rapid growth, we speculate about their (positive) future. Child and adolescent therapies have progressed considerably, as reflected in the number of controlled studies, their methodological quality, and identification of evidence-based treatments. Despite the methodological difficulties in outcome studies, the field has witnessed major advances regarding the efficacy of selected treatments in child and adolescent psychotherapy and good quality meta-analyses do suggest that 75% of children and young people who attend therapy benefit from it. However, despite the comforting data related to efficacy, major challenges still remain, especially in regard to patient engagement and dropout rates, gap in knowledge about what works and why it works, cultural sensitivity, and data of cost- effectiveness—just to quote a few. Several key areas have been neglected in research, such as the mechanisms of change, the moderators of treatment outcome, and the generalizability of the research findings to the clinical practice arena—this has greatly limited what we know about treatment and partly explains the relative lack of personalized psychotherapies and scarcity in their dissemination/generalization despite the documented evidence on their efficacy. Tailoring treatment more specifically to each patient may be necessary to reduce this nonresponsiveness and dropping outs, as one treatment does not fit all. This necessitates the need for eclecticism—to combine youth psychotherapies with other modes of treatments, such as medications, neuromodulation interventions, and Yoga and mindfulness-based cognitive therapy. Future practice for treatment of mental health conditions in the youth will likely adapt to this huge need for development of eclectic modalities and also reflect cost effectiveness and cultural sensitivity to an increasingly diverse population.

Introducing the fragility index-A case study using the Term Breech Trial.

The fragility index (FI) is a sensitivity analysis of the statistically significant result of a clinical study. It is the number of hypothetical changes in the primary event of one of the two cohorts in a 1-to-1 comparative trial to render the statistically significant result non-significant (ie, to alter the P-value from ≤0.05 to >0.05). The FI can be compared with the patient drop-out rates and protocol violations, which, if much higher than the FI, may arguably suggest less robustness/stability of the trial's results. To illustrate the concept, we have chosen the Term Breech Trial (TBT) as a case study. The TBT results favor planned cesarean birth, as opposed to planned vaginal delivery, in the term singleton fetus with breech presentation. Our analysis shows that the FI of the TBT is 21, which is small in comparison to the number (hundreds) of protocol violations present. Some experts have suggested the inclusion of the FI in data analysis and subsequent discussion of clinical trial data. Routine use of such a metric may be valuable in encouraging readers to maintain a healthy degree of skepticism, especially when interpreting trial results which may directly influence clinical practice.

Psychiatric treatment conducted via telemedicine versus in-person consultations in mood, anxiety and personality disorders: a protocol for a systematic review and meta-analysis

IntroductionMajor advancements in technology have led to considerations how telemedicine (TM) and other technology platforms can be meaningfully integrated in treatment for psychiatric disorders. The COVID-19 pandemic has placed a...

Can electronic monitoring with a digital smart spacer support personalised medication adherence and inhaler technique education in patients with asthma?: Protocol of the randomised controlled OUTERSPACE trial

IntroductionMedication adherence and inhaler technique in patients with asthma remain suboptimal. A digital, smart spacer may support personalised adherence and inhaler technique education. The aim of this study is to...

Memantine in the Prevention of Radiation-Induced Brain Damage: A Narrative Review.

Simple SummaryDecline in cognitive function is a major problem for patients undergoing whole-brain radiotherapy (WBRT). Scientific interest has increased due to the high dropout rate of patients in the first months after WBRT and the early onset of cognitive decline. Therefore, the study of antiglutamatergic pharmacological prophylaxis and hippocampal-sparing WBRT techniques has been deepened based on the knowledge of the mechanisms of hyperglutamatergic neurotoxicity and the role of some hippocampal areas in cognitive decline. In order to provide a summary of the evidence in this field, and to foster future research in this setting, this literature review presents current evidence on the prevention of radiation-induced cognitive decline and particularly on the role of memantine.Preserving cognitive functions is a priority for most patients with brain metastases. Knowing the mechanisms of hyperglutamatergic neurotoxicity and the role of some hippocampal areas in cognitive decline (CD) led to testing both the antiglutamatergic pharmacological prophylaxis and hippocampal-sparing whole-brain radiotherapy (WBRT) techniques. These studies showed a relative reduction in CD four to six months after WBRT. However, the failure to achieve statistical significance in one study that tested memantine alone (RTOG 0614) led to widespread skepticism about this drug in the WBRT setting. Moreover, interest grew in the reasons for the strong patient dropout rates in the first few months after WBRT and for early CD onset. In fact, the latter can only partially be explained by subclinical tumor progression. An emerging interpretation of the (not only) cognitive impairment during and immediately after WBRT is the dysfunction of the limbic and hypothalamic system with its immune and hormonal consequences. This new understanding of WBRT-induced toxicity may represent the basis for further innovative trials. These studies should aim to: (i) evaluate in greater detail the cognitive effects and, more generally, the quality of life impairment during and immediately after WBRT; (ii) study the mechanisms producing these early effects; (iii) test in clinical studies, the modern and advanced WBRT techniques based on both hippocampal-sparing and hypothalamic-pituitary-sparing, currently evaluated only in planning studies; (iv) test new timings of antiglutamatergic drugs administration aimed at preventing not only late toxicity but also acute effects.

Estrogen valerate pretreatment with the antagonist protocol does not increase oocyte retrieval in patients with low ovarian response: a randomized controlled trial

Abstract STUDY QUESTION Does luteal phase estrogen valerate pretreatment improve oocyte yield and clinical outcomes in patients with low ovarian response during ovarian stimulation with the antagonist protocol? SUMMARY ANSWER Pretreatment with oral estrogen valerate from Day 7 after ovulation to Day 2 of the next menstrual cycle did not increase oocyte yield in patients with a low ovarian response compared to no pretreatment. WHAT IS KNOWN ALREADY Previous studies showed that patients with a normal ovarian response can obtain better clinical outcomes after pretreatment with estrogen in the antagonist protocol. For patients with advanced age and low ovarian response, it remains unclear if estrogen valerate pretreatment with the antagonist protocol yields more oocytes and improves pregnancy outcomes. STUDY DESIGN, SIZE, DURATION This non-blinded randomized controlled trial (RCT) was conducted between November 2017 and March 2021. Participants were 552 women with low response who requested IVF treatment. The primary endpoint was comparison of the total number of retrieved oocytes between the two groups. The secondary endpoints were the total number of retrieved metaphase II (MII) oocytes, duration and total dosage of recombinant FSH (rFSH), good-quality embryo rate and clinical pregnancy rate. PARTICIPANTS/MATERIALS, SETTING, METHODS The study was conducted at a reproductive center. The RCT enrolled 552 infertile women with a low ovarian response (according to the Bologna criteria) who were undergoing IVF. In the study group, on Day 7 after ovulation patients were administered oral estrogen valerate (2 mg twice a day) until Day 2 of their next menstruation. Ovary stimulation was performed using rFSH, and a GnRH antagonist (0.25 mg/day) was started when a dominant follicle had a mean diameter ≥13 mm. MAIN RESULTS AND THE ROLE OF CHANCE No significant difference was observed in the number (mean [SD]) of oocytes retrieved from the estrogen valerate pretreatment and control group (3.2 [2.8] versus 3.4 [2.6], respectively). The treatment difference was −0.18 (95% CI −0.67, 0.32, P = 0.49). No significant differences were observed in the number of MII oocytes (2.9 [2.5] versus 3.1 [2.4], mean difference −0.23, 95% CI (−0.69, 0.23), P = 0.16) and good-quality embryos (1.0 [1.3] versus 1.20 [1.6], mean difference −0.23, 95% CI (−0.50, 0.04), P = 0.19) between the two groups. The duration of rFSH treatment was significantly longer in the estrogen valerate pretreatment group than in the control group (10.3 [2.2] versus 8.6 [2.1] days, mean difference 1.7, 95% CI (1.3, 2.2), P = 0.00), and the total rFSH dosage was significantly higher in the estrogen valerate pretreatment group than in the control group (3081 [680] versus 2548 [649] IU, mean difference 553.7, 95% CI (405.8, 661.6), P = 0.00). The clinical pregnancy rate in the pretreatment group (19.3% [23/119]) was not significantly different from that in the control group (28.7% [43/150]). The mean difference was −0.09, 95% CI (−0.20, 0.01), P = 0.08. LIMITATIONS, REASONS FOR CAUTION The major limitation was the high dropout rate of patients. Some patients did not return to the hospital for treatment because of predicted low success rates and for economic reasons. In addition, it is possible that the fixed dose of 300 IU rFSH was not sufficient to see differences in oocyte yield between the groups. WIDER IMPLICATIONS OF THE FINDINGS Estrogen valerate pretreatment with an antagonist protocol did not increase oocyte yield in patients with low ovarian response. Similar to the number of retrieved oocytes, there was no significant difference in clinical pregnancy rate between estrogen pretreatment group and control group. More research is needed on whether patients with low ovarian response need pretreatment and which pretreatment is more appropriate. STUDY FUNDING/COMPETING INTEREST(S) This study was supported in part by a research grant from the Investigator-Initiated Studies Program of MSD (China) Holding Co., Ltd. and Organon (Shanghai) Pharmaceutical Technology Co., Ltd. (Grant number: IIS 56284). The authors declare that they have no competing interests regarding authorship or publication of this study. TRIAL REGISTRATION NUMBER ClinicalTrials.gov NCT03300518. TRIAL REGISTRATION DATE 28 September 2017. DATE OF FIRST PATIENT’S ENROLMENT 15 November 2017.

Does Confinement Affect Treatment Dropout Rates in Patients With Gambling Disorder? A Nine-Month Observational Study.

Background and Aims: COVID-19 pandemic and confinement have represented a challenge for patients with gambling disorder (GD). Regarding treatment outcome, dropout may have been influenced by these adverse circumstances. The aims of this study were: (a) to analyze treatment dropout rates in patients with GD throughout two periods: during and after the lockdown and (b) to assess clinical features that could represent vulnerability factors for treatment dropout.Methods: The sample consisted of n=86 adults, mostly men (n=79, 91.9%) and with a mean age of 45years old (SD=16.85). Patients were diagnosed with GD according to DSM-5 criteria and were undergoing therapy at a Behavioral Addiction Unit when confinement started. Clinical data were collected through a semi-structured interview and protocolized psychometric assessment. A brief telephone survey related to COVID-19 concerns was also administered at the beginning of the lockdown. Dropout data were evaluated at two moments throughout a nine-month observational period (T1: during the lockdown, and T2: after the lockdown).Results: The risk of dropout during the complete observational period was R=32/86=0.372 (37.2%), the Incidence Density Rate (IDR) ratio T2/T1 being equal to 0.052/0.033=1.60 (p=0.252). Shorter treatment duration (p=0.007), lower anxiety (p=0.025), depressive symptoms (p=0.045) and lower use of adaptive coping strategies (p=0.046) characterized patients who abandoned treatment during the lockdown. Briefer duration of treatment (p=0.001) and higher employment concerns (p=0.044) were highlighted in the individuals who dropped out after the lockdown. Treatment duration was a predictor of dropout in both periods (p=0.005 and p<0.001, respectively).Conclusion: The present results suggest an impact of the COVID-19 pandemic on treatment dropout among patients with GD during and after the lockdown, being treatment duration a predictor of dropout. Assessing vulnerability features in GD may help clinicians identify high-risk individuals and enhance prevention and treatment approaches in future similar situations.

Psychological Impacts of Infertility and Other Reproductive Technologies

Individuals and couples all over the world find incapacity to conceive children to be a distressing circumstance. Infertility has a wide range of implications, including societal pressure as well as personal distress. Advances in assisted reproductive technologies, like as IVF, can give many couples hope where treatment is accessible, yet there are still challenges to overcome in terms of medical coverage and expense. The medicalization of infertility has unknowingly resulted in a dismissal of couples' emotional responses, which include distress, loss of control, stigmatization, and a disruption in their adult developmental trajectory. Evidence is accumulating that there is a link between fertility treatment stress and patient drop-out and pregnancy rates. Fortunately, psychological therapies for infertility patients, particularly those emphasizing stress management and coping-skills training, have been demonstrated to be useful.

Effect of patient-led cooperative follow-up by general practitioners and community pharmacists on osteoporosis treatment persistence.

Osteoporosis is a major risk factor for fractures. Poor persistence with osteoporosis medication hampers outcomes. This study assessed whether encouraging the formation of patient-led follow-up cooperatives between general practitioners (GPs) and community pharmacists improved medication persistence. All consecutive patients who attended an osteoporosis patient education program were invited to participate. They were given a logbook containing questionnaires they would bring to 6-monthly visits to their GP and pharmacist. The effect of this 3-year cooperative follow-up on persistence with medication and lifestyle changes was assessed. In total, 121 patients (average age, 67years; 93% female) participated. Poor cooperation between GPs and pharmacists was noted. Nevertheless, medication persistence ranged from 83% to 91% over the 6 visits. However, since patient drop-out rates were high and questionnaire return rates were low, a post-study medical chart review was performed. This confirmed that persistence was high (74%-83%) at 3years post-enrollment, even for oral bisphosphonate-treated patients (73%-76%). However, adoption of anti-osteoporosis lifestyle changes was poor throughout the study: one- to two-thirds of the patients did not alter their diet, physical activity, or surroundings to prevent falls. One study goal, namely, to encourage GPs and pharmacists to cooperate in patient follow-up, was not achieved. However, high medication persistence was observed. This may reflect the education program, patient empowerment, personalized attention from study personnel, and being in a study. Patient-centered approaches can thus significantly increase medication persistence in osteoporosis. Ongoing education may be needed to improve patient adoption of and persistence with lifestyle changes.

A systematic review of interventions to support transitions from intensive treatment for adults with anorexia nervosa and/or their carers

In the short term, intensive treatment focusing on restoring weight for anorexia nervosa can remediate many symptoms. However, there is a high level of relapse after discharge. This paper examines interventions developed to bridge the transition from intensive to less intensive forms of treatment for adult anorexia nervosa. We undertook a systematic review of the literature on interventions aimed at providing transition support. The Template for Intervention Description and Replication was used to describe components of the transition interventions. Patient's drop-out rates, weight, eating disorder psychopathology and mood data were extracted at end of treatment and follow-up to describe preliminary efficacy. Fourteen studies were selected: nine used psychological interventions delivered through face-to-face talking therapy or guided self-help, three examined the use of fluoxetine and two assessed stepped-care approaches. Transition support was delivered to patients in 11 studies, to patients and carers in two studies, and carers alone in another study. There was a great heterogeneity in the content and structure of the transition interventions evaluated. Overall, drop-out rates were lower for psychological support than pharmacological interventions or stepped-care approaches. Changes in eating disorder outcomes and mood were small to moderate throughout for studies that included a comparison group.

Double or dual stimulation in poor ovarian responders: where do we stand?

Recent advances in our recognition of two to three follicular waves of development in a single menstrual cycle has challenged the dogmatic approach of ovarian stimulation for in vitro fertilization starting in the early follicular phase. First shown in veterinary medicine and thereafter in women, luteal phase stimulation–derived oocytes are at least as competent as those retrieved following follicular phase stimulation. Poor ovarian responders still remain a challenge for many decades simply because they do not respond to ovarian stimulation. Performing follicular phase stimulation and luteal phase stimulation in the same menstrual cycle, named as double stimulation/dual stimulation, clearly increases the number of oocytes, which is a robust surrogate marker of live birth rate in in vitro fertilization across all female ages. Of interest, apart from one study, the bulk of evidence reports significantly higher number of oocytes following luteal phase stimulation when compared with follicular phase stimulation; hence, performing double stimulation/dual stimulation doubles the number of oocytes leading to a marked decrease in patient drop-out rate which is one of the major factors limiting cumulative live birth rates in such poor prognosis patients. The limited data with double stimulation/dual stimulation-derived embryos is reassuring for obstetric and neonatal outcome. The mandatory requirement of freeze-all and lack of cost-effectiveness data are limitations of this novel approach. Double stimulation/dual stimulation is an effective strategy when the need to obtain oocytes is urgent, including patients with malignant diseases undergoing oocyte cryopreservation and patients of advanced maternal age or with reduced ovarian reserve.

Does hip or knee joint replacement decrease chances to complete an ultra-trail race? Study in participants at the Ultra-Trail du Mont Blanc®

IntroductionThe number of patients with hip or knee joint replacements is increasing. Some of these patients want to practice sport, including in high-impact sports such as ultra-trails. Is the proportion of drop-out higher among runners after a hip or knee replacement? What are the symptoms of these patients? HypothesisHip or knee joint replacements are associated with a higher drop-out rate during an ultra-trail. Material and methodsWe conducted a monocentric retrospective epidemiological study. A questionnaire translated into French, English and Spanish were sent to all runners registered for one or more of the 5 races of the 2015 to 2017 Ultra-Trail du Mont-Blanc® (UTMB®) editions. There were no exclusion criteria. The drop-out rate of patients who responded to the questionnaire was calculated among patients with and without hip or knee joint replacement. Specific symptoms related to these joint replacements were identified before, during and after the race. ResultsOut of the 24,855 participants having run at least one of the 3 editions, 2,469 responded. Some of them ran several races: these 2469 runners were on 3171 start lines and 2548 finish lines (drop-out rate of 19.6%). Among these 2469 runners, 18 had hip and/or knee replacement and were on 27 start lines and 17 finish lines (drop-out rate of 37%). The race was finished by 3 of the 6 runners with a total hip arthroplasty (THA), all of the 8 runners with a hip resurfacing arthroplasty (HRA) and 3 of the 4 runners with a total knee arthroplasty (TKA). Among runners with THA, pubalgia or groin pain was described by one of them before the race, 3 during the race and 2 after the race. Among runners with HRA, pygalgia or groin pain was described by 2 of them during the race. As for the TKA, there was no specific symptom. No answering runner had a unicompartmental knee prosthesis. DiscussionRunning ultra-trail is possible after a hip or knee joint replacement. All of the 8 runners with HRA finished the race. We may remain cautious about the long-term survival of prostheses. Level of proofIV; monocentric retrospective epidemiological study.

Patient dropouts from sublingual allergen specific immunotherapy with house dust mites. Solving a problem.

Relevance. The insufficient effect of sublingual allergen-specific immunotherapy (SLIT) is caused, first of all, by non-compliance with the treatment regimen and premature treatment termination.&#x0D; Purpose of the study. Determining the frequency of patient drop-out rate during SLIT with house dust mites (HDM) allergens in children with allergic rhinitis (AR) or AR in combination with bronchial asthma (BA), with an analysis of the drop-out reasons, and approbation of the developed visit-to-visit patient management plan (Plan).&#x0D; Materials and methods. We analyzed 274 cases of treatment with HDM SLIT in children. 218 patients: 67.4% (147) boys, median age 11.33 years [7.26; 15.46], the proportion of patients with BA 43.1% (94 children) received HDM SLIT in 20132020. 56 patients: 71.4% (40) boys, median age 9.29 years [6.13; 15.93], the proportion of patients with BA 78.6% (44 children) received treatment in accordance with the Plan.&#x0D; Results. A relatively low frequency of treatment withdrawal was noted in the first 2 years of therapy (2 years after the start of treatment, 72.47% patients continue it). However, only 52.29% complete 3 years of therapy, and 14.67% complete 4 years of therapy. Implementation of the Plan increased patient retention in treatment at the 3rd year of treatment to 69.64% (p=0.031).&#x0D; Conclusions. Only half of the patients receive the required three-year minimum of treatment.&#x0D; The daily plan optimizes the patient management schedule for HDM ASIT; reduces patient dropout from treatment and can be recommended for practical healthcare.

FDA analysis of ECOG performance status and safety outcomes.

12024 Background: Patients with poor performance status are often excluded from clinical trials. The FDA has published several guidances on modernizing oncology clinical trial eligibility criteria to more accurately reflect the patient population. Many patients receiving novel oncology therapeutics are heavily pretreated, and often have comorbidities, organ dysfunction, and frailty syndromes. Little is known about the safety of novel therapeutics in patients with poor performance status. Methods: Data from six randomized trials (n=4465) leading to registration for several solid tumor and malignant hematologic cancers, including multiple therapeutic mechanisms of action, such as EGFR TKI’s, immune checkpoint inhibitors (ICI), and chemotherapy, were pooled. Cumulative incidence of Grade 3-5 adverse events and serious adverse events at Days 30, 90, and 180 were evaluated based on ECOG 0-2. Rates of treatment discontinuation by ECOG was also examined. Results: Cumulative incidence of toxicity events at days 30, 90, and 180 are shown in Table. Patient dropout rates due to death were 3.9%, 6.7%, and 10.9%; dropout rates due to disease progression were 66.5%, 66.6% and 56.9%; and dropout rates due to reasons other than progression or death were 29.7%, 26.7% and 32.1% for ECOG PS 0, 1 and 2, respectively. Conclusions: This FDA exploratory analysis of safety outcomes in registration trials based on ECOG suggests increasing rates of adverse events and rates of treatment discontinuation due to death with worsening performance status. Discontinuation rates due to disease progression and other reasons did not appear to be worse for ECOG 2 compared to 0-1. These findings were consistent across therapies (targeted therapy, ICI, chemotherapy). All trials in the analysis led to FDA approval, thus inclusion of patients with ECOG 2 did not adversely affect the trial outcome for this set of FDA approved agents. ECOG performance status eligibility criteria should be evaluated and modified on a frequent basis during drug development. Additional analysis of trials which enroll patients with ECOG 2 is needed. [Table: see text]

Impact of a three-phase ACLR post-operative rehabilitation pathway on patient drop-out rates and return to sport outcomes

Impact of a three-phase ACLR post-operative rehabilitation pathway on patient drop-out rates and return to sport outcomes

The Trend of Increasing Placebo Response and Decreasing Treatment Effect in Schizophrenia Trials Continues: An Update From the US Food and Drug Administration.

Concerns of increasing placebo response and declining treatment effect in acute schizophrenia trials have been reported for new drug applications (NDAs) submitted to the US Food and Drug Administration (FDA) during an 18-year period from 1991 through January 2009 (ie, the pre-2009 period). Current exploratory analyses provide an update in the trends observed in placebo response, treatment effect, and dropout rates for NDAs submitted from February 2009 to 2015 (ie, the post-2009 period). Clinical trial data from all acute schizophrenia trials that were submitted as part of NDAs to the US FDA during a 24-year period from 1991 to 2015. Aggregate trial-level efficacy data from multicenter, multiregional, randomized, placebo-controlled, 4- to 8-week, fixed- and flexible-dose trials in adult schizophrenia patients were compiled. There were 12 NDAs pre-2009 (32 trials, N = 11,567) and 3 NDAs post-2009 (14 trials, N = 6,434). Baseline demographic and disease variables and scores on the Positive and Negative Syndrome Scale (PANSS) were summarized and compared for the two time periods (pre-2009 and post-2009). The primary efficacy measure was mean change from baseline to endpoint in total PANSS score obtained by last-observation-carried-forward analysis. Regional differences in placebo response and treatment effect were explored for the two time periods based on baseline patient characteristics, sample size, and dropout rates. Trials were predominantly multiregional (10/14; 71%) during the post-2009 period compared to the pre-2009 period (11/32; 34%). The overall trial success rates were 57% (8/14) and 78% (25/32) during the post-2009 and pre-2009 periods, respectively. Comparing the pre-2009 and post-2009 periods, the mean placebo response (change from baseline in PANSS score) increased from -6.4 to -10.5 and the mean treatment effect (drug response - placebo response) declined from -8.6 to -5.8 , with substantial differences observed especially in North American trials. In North American trials, placebo response increased from -4.3 (pre-2009) to -8.5 (post-2009), and treatment effect decreased from -9.0 (pre-2009) to -3.4 (post-2009). The difference in placebo response (pre- and post-2009: -10.0 and -11.3 ) and treatment effect (pre and post-2009: -8.1 and -6.4 ) in multiregional trials for the two time periods remained minimal. Baseline disease severity remained similar in the pre- and post-2009 time periods, with PANSS scores ranging between 85 and 100. Trials with higher mean baseline PANSS scores tended to show higher treatment effect irrespective of the time period and region. Post-2009, dropout rates were higher (55%) in North American trials compared with 33% in multiregional trials, similar to the pre-2009 trend. The continuing trend of increasing placebo responses and decreasing treatment effects in schizophrenia trials over the 24-year period does remain of great concern, especially with respect to North American trials. However, given the current global nature of drug development, close attention to trial conduct and reexamination of design elements for future trials may be warranted.