Outpatient Trial Research Articles

Mobile e-diary application facilitates the monitoring of patient-reported outcomes and a high treatment adherence for clinical trials in dermatology.

BackgroundAssessment of treatment effects in clinical trials requires valid information on treatment adherence, adverse events and symptoms. Paper‐based diaries are often inconvenient and have limited reliability, particularly for outpatient trials.ObjectivesTo investigate the utility of an electronic diary (e‐diary) application for patients with skin diseases in outpatient clinical trials.MethodsAn e‐diary application was developed and technically validated. Treatment adherence was defined as topical administration by the patient, and patient‐reported outcomes, i.e. pain and itch, were evaluated by the e‐diary in six clinical trials on newly tested topical drugs. Additionally, the proportion of patients capturing the applied topical drug by camera and filling in the pain and itch scores was defined as e‐diary adherence, and patients’ perception of usefulness and acceptability of the e‐diary were evaluated.ResultsTreatment adherence rates of the included 256 patients were high (median 98%, range 97–99%). E‐diary adherence was also high with a median of 93% (range 87–97%) for capturing the applied drug by camera, and 89% (range 87–96%) and 94% (range 87–96%) for entering respectively the itch and pain score. Daily symptom scores provided good insights into the disease burden, and patients rated the e‐diary as good to excellent with respect to user acceptability.ConclusionsThe results suggest that the e‐diary is an excellent way to ensure proper treatment administration, indicated by both the high user acceptability scores and high treatment adherence. Moreover, the e‐diary may also be valuable for frequent and reliable monitoring of patient‐reported outcomes in daily clinical practice.

Guanfacine extended-release for cannabis use disorder: a pilot feasibility trial

ABSTRACT Background: Currently, there are no established pharmacotherapies for cannabis use disorders (CUDs). As a long-acting alpha-2-adrenergic receptor agonist, guanfacine extended-release (G-XR) could be useful in the treatment of CUDs by mitigating withdrawal and improving behavioral control. Objectives: To evaluate the feasibility and tolerability of G-XR as a treatment for CUDs. Methods: In an eight-week open-label outpatient pilot trial, we evaluated the safety and tolerability of G-XR in 22 cannabis dependent individuals. Using 2 different titration schedules, G-XR was gradually titrated to a dose of 4 mg or the highest dose tolerated. All participants received standard medication management. Results: Retention at week eight was 41%. Average daily amount of cannabis use (in grams: F1,86 = 8.74, p = .004; in dollars: F1,86 = 16.67, p < .0001) and cannabis using days (F1,86 = 7.67, p = .007) significantly reduced over the course of study participation. There were no significant differences between the titration schedules on emergence of side effects (Fisher exact test, p = .378) or retention (Log-Rank Test X2 1 = 0.021, p = .886). A total of 3 participants achieved 3 weeks or greater of total abstinence. Conclusions: G-XR is a feasible treatment for CUDs, and should be evaluated further in an efficacy trial.

Cost-benefit analysis of clinical pharmacist intervention in preventing adverse drug events in the general chronic diseases outpatients.

Clinical pharmacy services are vital in the prevention of adverse drug events (ADEs) in clinical practice, extending beyond the hospital to chronic disease management in outpatient settings. This study sought to evaluate the cost benefit of a clinical pharmacy intervention in resolving treatment-related problems (TRPs) among hospital outpatients with chronic diseases. From the hospital system perspective, the cost-benefit analysis was based on a randomized clinical trial in the general outpatients of the major hospital in Jordan. Eligible patients were randomly assigned to either an intervention or a control group. TRPs were identified in both study groups, but interventions were delivered only to the intervention group via a home medication management review (HMMR) by a clinical pharmacist. A follow-up in both groups took place 3months after recruitment. The total economic benefit was the sum of (a) cost savings due to intervention and (b) cost avoidance associated with preventable ADEs. The primary outcome measures were the net benefit and benefit-to-cost ratio with the clinical pharmacist-based HMMR. In both groups, 158 TRPs were identified, and 79 interventions were provided in the study group. The monthly cost of intervention was JD764 (US $1078), and the total monthly benefit was JD4570 (US $6444), leading to a benefit-to-cost ratio of 5.98 and an annual net benefit of JD45669 (US $64393). Sensitivity analyses confirmed the robustness of results. The RCT-based cost-benefit evaluation provided evidence-based insight into the economic benefit of a clinical pharmacist-provided HMMR for preventing ADEs in the general chronic diseases outpatients. This intervention method against the TRPs among outpatients is cost beneficial and offers substantial cost savings to the health care hospital payer in Jordan.

Modulation of striatal dopamine dynamics by cocaine self-administration and amphetamine treatment in female rats.

Despite decades of research into the neurobiological basis of cocaine abuse, pharmacotherapeutic treatments for cocaine addiction have been largely ineffective. Converging evidence from preclinical research and from outpatient clinical trials suggest that treatment with amphetamine is efficacious in reducing cocaine intake. Although it has been suggested that amphetamine treatment reduces cocaine intake as an agonist replacement therapy, we have shown recently that multiple aspects of dopamine signaling are altered by cocaine self-administration and returned to pre-cocaine function by amphetamine treatment in the nucleus accumbens of male rats. Here, we sought to determine if these effects were also evident in female subjects, and across regions of the striatum. Female rats performed 5days of cocaine self-administration (1.5mgkg-1 inj-1 , 40inj/day) and were treated with a single amphetamine (0.56mg/kg) or saline infusion 1hr prior to killing. We then used ex vivo fast-scan cyclic voltammetry in the nucleus accumbens core or dorsolateral caudate-putamen to examine dopamine signaling and cocaine potency. We found that in the nucleus accumbens core, cocaine self-administration decreased dopamine uptake rate and cocaine potency, and both alterations were restored by amphetamine treatment. In the dorsolateral caudate-putamen, neither cocaine self-administration nor amphetamine treatment altered dopamine uptake; however, cocaine potency was decreased by self-administration and returned to control levels by amphetamine. Together, these findings support a role for amphetamine treatment for cocaine addiction outside of agonist replacement therapy, and suggest that the development of cocaine tolerance is similar across sexes.

1053-P: Automated Adaptation of the Bionic Pancreas while Transitioning from Multiple Daily Injection Insulin Regimens

In a random-order, outpatient crossover trial we compared automated glycemic control with the insulin-only bionic pancreas (BP) to usual care in subjects with T1D. Subjects transitioned directly to the BP from CSII or MDI (insulins glargine n=6, detemir n=1, or degludec n=5). The BP continuously adapts to individual insulin needs and was initialized based on body mass only, without information about the baseline insulin regimen. The first 24 hours of BP control was compared to days 3-7 (the 5-day period considered for the primary outcome) to examine the effect of having received long-acting insulin the day prior to initiation of the BP. As shown in the Table, the mean CGM glucose and time-in-range did not differ between the first 24 hours and days 3-7 after starting the BP in subjects on MDI at baseline, while there was a reduction in mean and an increase in time-in-range among those on CSII at baseline. Subjects on MDI at baseline did not experience more hypoglycemia in the first 24 hours despite having long-acting insulin on board. Both subjects on MDI and CSII at baseline achieved good glucose control on the BP (see Table). Surprisingly, there was no difference in the insulin total daily dose (TDD) between the first 24 hours and days 3-7 in the MDI users despite an average TDD of basal insulin at baseline of 15 u/day. These results suggest that BP therapy can be safely initiated directly from MDI regimens. Disclosure J. Sherwood: None. C.A. Balliro: None. F. El-Khatib: Employee; Self; Beta Bionics. Stock/Shareholder; Self; Beta Bionics. L. Ekhlaspour: None. L. Hsu: None. B.A. Buckingham: Advisory Panel; Self; ConvaTec Inc., Novo Nordisk Inc., Profusa, Inc. Consultant; Self; Medtronic MiniMed, Inc. Research Support; Self; Beta Bionics, ConvaTec Inc., Dexcom, Inc., Insulet Corporation, Medtronic MiniMed, Inc., Tandem Diabetes Care. Other Relationship; Self; Insulet Corporation, Tandem Diabetes Care. E. Damiano: Advisory Panel; Self; Novo Nordisk A/S. Board Member; Self; Beta Bionics. Employee; Self; Beta Bionics. Stock/Shareholder; Self; Beta Bionics. Stock/Shareholder; Spouse/Partner; Beta Bionics. Other Relationship; Self; Ascensia Diabetes Care, Senseonics. S.J. Russell: Advisory Panel; Self; Companion Medical, Unomedical a/s. Consultant; Self; Flexion Therapeutics. Research Support; Self; Beta Bionics, MITRE Corporation, Novo Nordisk A/S, Zealand Pharma A/S. Other Relationship; Self; ADOCIA, Ascensia Diabetes Care, Ascensia Diabetes Care, Lilly Diabetes, Roche Diabetes Care, Senseonics. Funding National Institutes of Health (NIDDKUC4DK108612)

Two-Year Follow-Up after Treatment with the Cognitive Behavioral Analysis System of Psychotherapy versus Supportive Psychotherapy for Early-Onset Chronic Depression

Background: Evidence on the long-term efficacy of psychotherapeutic approaches for chronic depression is scarce. Objective: To evaluate the effects of the Cognitive Behavioral Analysis System of Psychotherapy (CBASP) compared to Supportive Psychotherapy (SP) 1 year and 2 years after treatment termination. Methods: In this study, we present 1- and 2-year follow-up assessments of a prospective, multicenter, evaluator-blinded, randomized clinical trial of outpatients with early-onset chronic major depression (n = 268). The initial treatment included 32 sessions of CBASP or SP over 48 weeks. The primary outcome was the rate of “well weeks” (Longitudinal Interval Follow-Up Evaluation; no/minimal symptoms) after 1 year and 2 years. The secondary outcomes were, among others, clinician- and self-rated depressive symptoms, response/remission rates, and quality of life. Results: Of the 268 randomized patients, 207 (77%) participated in the follow-up. In the intention-to-treat analysis, there was no statistically significant difference between CBASP and SP patients in experiencing well weeks (CBASP: mean [SD] of 48.6 [36.9] weeks; SP: 39.0 [34.8]; rate ratio 1.26, 95% CI 0.99–1.59, p = 0.057, d = 0.18) and in remission rates (CBASP: 1 year 40%, 2 years 40.2%; SP: 1 year 28.9%, 2 years 33%) in the 2 years after treatment. Statistically significant effects were found in favor of CBASP 1 year after treatment termination regarding the rate of well weeks, self-rated depressive symptoms, and depression-related quality of life. Conclusions: CBASP lost its superiority over SP at some point between the first and the second year. This suggests the necessity of maintenance treatment for early-onset chronically depressed patients remitted with CBASP during the acute therapy phase, as well as the sequential integration of other treatment strategies, including medication for those who did not reach remission.

PO 8472 EACCR-2 INSTITUTIONAL CLINICAL RESEARCH CAPACITY ASSESSMENT: CASE STUDY OF SIAYA COUNTY REFERRAL HOSPITAL, WESTERN KENYA

BackgroundInfrastructural inadequacies and lack of research management expertise impede optimal research participation by Ministries of Health in Africa. The East African Consortium for Clinical Research (EACCR-2) network champions research strengthening through capacity building and partnership with local institutions to improve research output in the region. The Siaya County Referral Hospital was evaluated for research needs in preparation for a future clinical trial.MethodsIn April 1018, we interviewed departmental in-charges or designees for administrative, financial and clinical data management, laboratory records and information technology (IT). Standardised assessment questionnaires were used.ResultsFive of the seven respondents interviewed were males. Patient populations such as children, adolescents and pregnant mothers were identified as having unique characteristics. They are to be considered for future inpatient and outpatient clinical trials. There is little research exposure among clinical, data and laboratory staff despite some of them receiving GCP and GCLP training.An Institutional Review Board (IRB) is in place and it reviews both academic research proposals and large multicentre clinical trials before studies are carried out. However, the members lack appropriate training in bioethics.Acute staff shortage, reagent stock-outs, space constraints, and faulty equipment limit the laboratory’s capacity. Insufficient IT support and internet access cause delays in data entry. A lack of expertise in monitoring, data analysis and statistics, of financial management systems and library services were also identified.ConclusionThe hospital’s capacity to conduct clinical research is low. Assessment findings highlighted funding constraints faced at the referral hospital in a country burdened by disease. North-South partnership through EDCTP will contribute towards addressing part of these gaps.

Multiple models for artificial pancreas predictions identified from free-living condition data: A proof of concept study

The artificial pancreas (AP) is a closed-loop system to automatically regulate the glucose concentration in patients with type 1 diabetes (T1D). Model predictive control (MPC) revealed to be one of the most promising approaches for this control problem. Several MPC algorithms have been tested in clinical trials with satisfactorily results. However, the inter-patient variability characterising T1D patients limits the performance of MPC algorithms synthesized on average models and calls for patient-tailored models. The availability of experimental data on long outpatient trials motivated the study of identification techniques applicable to free-living patient data. Moreover, a detailed data analysis can be used to improve model identification. Considered that the postprandial (PP) glucose control is one of the most critical aspects of glucose regulation, the analysis was focused on the PP period. The intra-day variability is investigated via ANOVA test that highlighted a correlation between PP glucose profiles and different day periods (DPs). A data-driven multiple-model predictor (MMP) based on real-data analysis is proposed in this work. It exploits different identified models on the basis of the knowledge acquired through the data analysis. In particular, the MMP uses three basic models specific of each DP. These models have been identified through the impulse-response technique that achieved promising results in model identification from real-data. The prediction capabilities of the MMP are compared to the performance of a predictor built using a single model identified on a daily subset, showing an improvement in terms of predictions capabilities in the breakfast DP.

Predictive modeling for response to lithium and quetiapine in bipolar disorder.

Lithium and quetiapine are known to be effective treatments for bipolar disorder. However, little information is available to inform prediction of response to these medications. Machine-learning methods can identify predictors of response by examining variables simultaneously. Further evaluation of models on a test sample can estimate how well these models would generalize to other samples. Data (N=482) were drawn from a randomized clinical trial of outpatients with bipolar I or II disorder who received adjunctive personalized treatment plus either lithium or quetiapine. Elastic net regularization (ENR) was used to generate models for lithium and quetiapine; these models were evaluated on a test set. Predictions from the lithium model explained 17.4% of the variance in actual observed scores of patients who received lithium in the test set, while predictions from the quetiapine model explained 32.1% of the variance of patients that received quetiapine. Of the baseline variables selected, those with the largest parameter estimates were: severity of mania; attention-deficit/hyperactivity disorder (ADHD) comorbidity; nonsuicidal self-injurious behavior; employment; and comorbidity with each of two anxiety disorders (social phobia/society anxiety and agoraphobia). Predictive accuracy of the ENR model outperformed the simple and basic theoretical models. ENR is an effective approach for building optimal and generalizable models. Variables identified through this methodology can inform future research on predictors of response to lithium and quetiapine, as well as future modeling efforts of treatment choice in bipolar disorder.

Abstract TP180: Comprehensive Assessment of Disability Post-stroke using the Newly Developed miFUNCTION Scale

Background and Purpose: The modified Rankin Scale (mRS) is the most widely used primary outcome measure in acute stroke trials. However, substantial inter-observer variability impairs outcome assessment and reduces power of clinical trials. Guided by the International Classification of Functioning, Disability and Health (ICF), we developed a comprehensive, hierarchical assessment tool (miFUNCTION) to address the shortcomings of the mRS and deliver a more thorough understanding of disability following stroke (figure 1). Methods: The construct validity of miFUNCTION was initially established in a pilot study of patients at an outpatient stroke prevention clinic that had been diagnosed with stroke within 60 days. To further assess criterion validity, miFUNCTION was compared against the mRS and other outcome measures within the ESCAPE trial. Logistic regression analysis with miFUNCTION as an outcome was used to demonstrate the benefit of endovascular treatment. Results: The pilot study showed moderate inter-observer agreement (k=0.585, p&lt;0.005) but near perfect correlation between miFUNCTION and mRS (ρ=0.821, p&lt;0.05). The correlation of miFUNCTION and mRS was near perfect again in the ESCAPE trial (ρ=0.944). Effect size of multivariable models using mRS (adjusted OR 3.45, 95% CI 2.05 – 5.78) and miFUNCTION (adjusted OR 3.32, 95% CI 1.99 – 5.55) as an outcome measure for the ESCAPE trial patients was similar. Conclusions: miFUNCTION is strongly associated with the degree of disability following stroke both in an outpatient setting and clinical trial. Further work remains to assess sensitivity to change and to improve the inter-observer reliability of the scale.

Pharmacological treatments for generalised anxiety disorder: a systematic review and network meta-analysis

Generalised anxiety disorder is a disease that can be associated with substantial dysfunction. Pharmacological treatment is often the first choice for clinicians because of the cost and resource constraints of psychological alternatives, but there is a paucity of comparative information for the multiple available drug choices. A systematic review and network meta-analysis was performed on randomised trials in adult outpatients with generalised anxiety disorder identified from MEDLINE, Web of Science, Cochrane Library, ClinicalTrials.gov, Chinese National Knowledge Infrastructure (CNKI), Wanfang data, Drugs@FDA and commercial pharmaceutical registries. Placebo and active control trials were included. Data were extracted from all manuscripts and reports. Primary outcomes were efficacy (mean difference [MD] in change in Hamilton Anxiety Scale Score) and acceptability (study discontinuations for any cause). We estimated summary mean treatment differences and odds ratios using network meta-analyses with random effects. This study is registered with PROSPERO, number CRD42018087106. Studies were published between Jan 1, 1994 and Aug 1, 2017, in which 1992 potential studies were screened for inclusion. This analysis is based on 89 trials, which included 25 441 patients randomly assigned to 22 different active drugs or placebo. Duloxetine (MD -3·13, 95% credible interval [CrI] -4·13 to -2·13), pregabalin (MD -2·79, 95% CrI -3·69 to -1·91), venlafaxine (MD -2·69, 95% CrI -3·50 to -1·89), and escitalopram (MD -2·45, 95% CrI -3·27 to -1·63) were more efficacious than placebo with relatively good acceptability. Mirtazapine, sertraline, fluoxetine, buspirone, and agomelatine were also found to be efficacious and well tolerated but these findings were limited by small sample sizes. Quetiapine (MD -3·60 95% CrI -4·83 to -2·39) had the largest effect on HAM-A but it was poorly tolerated (odds ratio 1·44, 95% CrI 1·16-1·80) when compared with placebo. Likewise, paroxetine and benzodiazepines were effective but also poorly tolerated when compared with placebo. Risk of reporting bias was considered low, and when possible all completed studies were included to avoid publication bias. To our knowledge, this is the largest contemporary review of pharmacological agents for the treatment of generalised anxiety disorder by use of network analysis. There are several effective treatment choices for generalised anxiety disorder across classes of medication. The failure of initial pharmacological therapy might not be a reason to abandon a pharmacological treatment strategy. No funding was received for this research.

Olanzapine Versus Placebo in Adult Outpatients With Anorexia Nervosa: A Randomized Clinical Trial.

This study evaluated the benefits of olanzapine compared with placebo for adult outpatients with anorexia nervosa. This randomized double-blind placebo-controlled trial of adult outpatients with anorexia nervosa (N=152, 96% of whom were women; the sample's mean body mass index [BMI] was 16.7) was conducted at five sites in North America. Participants were randomly assigned in a 1:1 ratio to receive olanzapine or placebo and were seen weekly for 16 weeks. The primary outcome measures were rate of change in body weight and rate of change in obsessionality, assessed with the Yale-Brown Obsessive Compulsive Scale (YBOCS). Seventy-five participants were assigned to receive olanzapine and 77 to receive placebo. A statistically significant treatment-by-time interaction was observed, indicating that the increase in BMI over time was greater in the olanzapine group (0.259 [SD=0.051] compared with 0.095 [SD=0.053] per month). There was no significant difference between treatment groups in change in the YBOCS obsessions subscale score over time (-0.325 compared with -0.017 points per month) and there were no significant differences between groups in the frequency of abnormalities on blood tests assessing potential metabolic disturbances. This study documented a modest therapeutic effect of olanzapine compared with placebo on weight in adult outpatients with anorexia nervosa, but no significant benefit for psychological symptoms. Nevertheless, the finding on weight is notable, as achieving change in weight is notoriously challenging in this disorder.

The Concise Health Risk Tracking-Self Report: Psychometrics within a placebo-controlled antidepressant trial among depressed outpatients.

While substantial prior research has evaluated the psychometric properties of the 12-item Concise Health Risk Tracking-Self Report (CHRT-SR12), a measure of suicide propensity and suicidal thoughts, no prior research has investigated its factor structure, sensitivity to change over time, and other psychometric properties in a placebo-controlled trial of antidepressant medication, nor determined whether symptoms change throughout treatment. Participants in the multi-site Establishing Moderators and Biosignatures of Antidepressant Response in Clinical Care (EMBARC) study ( n=278) provided data to evaluate the factor structure and sensitivity to change over time of the CHRT-SR12 through eight weeks of a clinical trial in which participants received either placebo or antidepressant medication (sertraline). Factor analysis confirmed two factors: propensity (comprised of first-order factors including pessimism, helplessness, social support, and despair) and suicidal thoughts. Internal consistency (α's ranged from 0.69-0.92) and external validity were both acceptable, with the total score and propensity factor scores significantly correlated with total scores and single-item suicidal-thoughts scores on the self-report Quick Inventory of Depressive Symptoms and the clinician-rated 17-item Hamilton Rating Scale for Depression. Through analyzing CHRT-SR12 changes over eight treatment weeks, the total score and both the factors decreased regardless of baseline suicidal thoughts. Change in clinician-rated suicidal thoughts was reflected by change in both the total score and propensity factor score. These results confirm the reliability, validity, and applicability of the CHRT-SR12 to a placebo-controlled clinical trial of depressed outpatients receiving antidepressant medication.

Psychoeducational Strategies During Outpatient Transition to Extended-Release Naltrexone for Patients With Opioid Use Disorder.

BACKGROUND: The United States is experiencing an opioid epidemic. Better approaches to encourage outpatient utilization of Food and Drug Administration-approved medications for the treatment of opioid use disorder, including extended-release naltrexone (XR-NTX), are needed. Withdrawal management before initiation of XR-NTX is challenging for clinicians and patients and represents a major barrier to treatment. AIMS: To review psychoeducational strategies that support patients during outpatient withdrawal management and transition to XR-NTX. METHOD: We reviewed the literature on psychoeducational strategies used during opioid withdrawal management and described the role that nurses can play in facilitating transition to XR-NTX in a Phase 3, placebo-controlled, outpatient trial comparing induction regimens. RESULTS: Supportive interventions include general psychoeducation on addiction, overcoming ambivalence, treatment adherence, anticipating XR-NTX induction, managing psychological and physiological aspects of opioid withdrawal, risks of opioid use, and sources of support during recovery. CONCLUSIONS: Psychoeducational strategies led by nurses can promote treatment adherence during withdrawal management and induction onto XR-NTX.

Antibiotics for exacerbations of chronic obstructive pulmonary disease.

Background Many patients with an exacerbation of chronic obstructive pulmonary disease (COPD) are treated with antibiotics. However, the value of antibiotics remains uncertain as systematic reviews and clinical trials have shown conflicting results. Objectives To assess the effects of antibiotics in the management of acute COPD exacerbations on treatment failure as observed between seven days and one month after treatment initiation (primary outcome) and on other patient-important outcomes (mortality, adverse events, length of hospital stay). Search methods We searched the Cochrane Central Register of Controlled Trials (CENTRAL), MEDLINE, EMBASE and other electronically available databases up to September 2012. Selection criteria Randomised controlled trials (RCTs) in people with acute COPD exacerbations comparing antibiotic therapy and placebo with a follow-up of at least seven days. Data collection and analysis Two review authors independently screened references and extracted data from trial reports. We kept the three groups of outpatients, inpatients and patients admitted to the intensive care unit (ICU) separate for benefit outcomes and mortality because we considered them to be clinically too different to be summarised in one group. We considered outpatients to have a mild to moderate exacerbation, inpatients to have a severe exacerbation and ICU patients to have a very severe exacerbation. Where outcomes or study details were not reported we requested missing data from the authors of the primary studies. We calculated pooled risk ratios (RR) for treatment failure, Peto odds ratios (OR) for rare events (mortality and adverse events) and weighted mean differences (MD) for continuous outcomes using fixed-effect models. We used GRADE to assess the quality of the evidence. Main results Sixteen trials with 2068 participants were included. In outpatients (mild to moderate exacerbations), there was evidence of low quality that antibiotics did statistically significantly reduce the risk for treatment failure between seven days and one month after treatment initiation (RR 0.75; 95% CI 0.60 to 0.94; I2 = 35%) but they did not significantly reduce the risk when the meta-analysis was restricted to currently available drugs (RR 0.80; 95% CI 0.63 to 1.01; I2 = 33%). Evidence of high quality showed that antibiotics statistically significantly reduced the risk of treatment failure in inpatients with severe exacerbations (ICU not included) (RR 0.77; 95% CI 0.65 to 0.91; I2 = 47%) regardless of whether restricted to current drugs. The only trial with 93 patients admitted to the ICU showed a large and statistically significant effect on treatment failure (RR 0.19; 95% CI 0.08 to 0.45; high-quality evidence). Evidence of low-quality from four trials in inpatients showed no effect of antibiotics on mortality (Peto OR 1.02; 95% CI 0.37 to 2.79). High-quality evidence from one trial showed a statistically significant effect on mortality in ICU patients (Peto OR 0.21; 95% CI 0.06 to 0.72). Length of hospital stay (in days) was similar in the antibiotics and placebo groups except for the ICU study where antibiotics statistically significantly reduced length of hospital stay (mean difference -9.60 days; 95% CI -12.84 to -6.36 days). One trial showed no effect of antibiotics on re-exacerbations between two and six weeks after treatment initiation. Only one trial (N = 35) reported health-related quality of life but did not show a statistically significant difference between the treatment and control group. Evidence of moderate quality showed that the overall incidence of adverse events was higher in the antibiotics groups (Peto OR 1.53; 95% CI 1.03 to 2.27). Patients treated with antibiotics experienced statistically significantly more diarrhoea based on three trials (Peto OR 2.62; 95% CI 1.11 to 6.17; high-quality evidence). Authors' conclusions Antibiotics for COPD exacerbations showed large and consistent beneficial effects across outcomes of patients admitted to an ICU. However, for outpatients and inpatients the results were inconsistent. The risk for treatment failure was significantly reduced in both inpatients and outpatients when all trials (1957 to 2012) were included but not when the analysis for outpatients was restricted to currently used antibiotics. Also, antibiotics had no statistically significant effect on mortality and length of hospital stay in inpatients and almost no data on patient-reported outcomes exist. These inconsistent effects call for research into clinical signs and biomarkers that help identify patients who benefit from antibiotics and patients who experience no effect, and in whom downsides of antibiotics (side effects, costs and multi-resistance) could be avoided.

Manualised Cognitive Behaviour Therapy for Anorexia Nervosa: Use of Treatment Modules in the ANTOP Study.

Standardised treatment manuals facilitate therapy planning and enhance comparability for research purposes. Within the Anorexia Nervosa Treatment of Out Patients (ANTOP) study, the largest multisite outpatient intervention trial in anorexia nervosa (AN) to date, manualised enhanced cognitive-behavioural therapy (CBT-E) was offered as one treatment modality. The manual consisted of 9 modules, of which Motivation, Nutrition, Formulation and Relapse Prevention were compulsory. Homework worksheets were provided, to ensure the transfer of therapeutic improvements to daily life. This study investigated the use of modules and worksheets in order to explore practice styles of trained therapists in the treatment of AN. This secondary analysis was based on log-sheets (n = 2604) CBT-E therapists completed after each session. Frequencies of modules and worksheets used across all sessions were calculated. Relationships, such as that between use of module and duration of illness, were examined. The most commonly used module was Motivation. In patients with longer illness duration, the module Self Esteem seemed to be particularly important. The worksheet Scales, balancing the pros and cons of AN, was prioritised by therapists. The results underline the importance of motivational work in the treatment of AN, including validating the ambivalence experienced by most AN patients. With increasing duration of illness, resource-oriented elements, such as self esteem stabilisation, should be of focus.

How whole-body vibration can help our COPD patients. Physiological changes at different vibration frequencies.

ObjectiveEvaluate cardiac, metabolic, and ventilatory changes during a training session with whole-body vibration training (WBVT) with 3 different frequencies in patients with chronic obstructive pulmonary disease (COPD).MethodsThis was a prospective, interventional trial in outpatients with severe COPD. Participants performed 3 vertical WBVT sessions once a week using frequencies of 35, 25 Hz and no vibration in squatting position (isometric). Cardiac, metabolic, and ventilator parameters were monitored during the sessions using an ergospirometer. Changes in oxygen pulse response (VO2/HR) at the different frequencies were the primary outcome of the study.ResultsThirty-two male patients with a mean forced expiratory volume in 1 second of 39.7% completed the study. Compared to the reference of 35 Hz, VO2/HR at no vibration was 10.7% lower (P=0.005); however, no statistically significant differences were observed on comparing the frequencies of 35 and 25 Hz. The median oxygen uptake (VO2) at 25 Hz and no vibration was 9.43% and 13.9% lower, respectively, compared to that obtained at 35 Hz (both comparisons P<0.0001). The median expiratory volume without vibration was 9.43% lower than the VO2 at the end of the assessment at 35 Hz vibration (P=0.002).ConclusionVertical WBVT training sessions show greater cardiac, metabolic, and respiratory responses compared with the squat position. On comparing the 2 frequencies used, we observed that the frequency of 35 Hz provides higher cardiorespiratory adaptation.

Educational Video Followed by Retelling Bowel Preparation Process to Improve Colonoscopy Bowel Preparation Quality: A Prospective Nursing Intervention Study.

BackgroundThis study investigated the effect of a patient education video followed by retelling the process of bowel preparation on colonoscopy bowel preparation quality.Material/MethodsThis was a prospective, randomized, controlled clinical trial of outpatients undergoing colonoscopy. Patients were randomized (1: 1) to the video + retelling group or the control group. The primary endpoint was to assess the bowel preparation quality using the Ottawa Bowel Preparation Quality scale (Ottawa score). Risk factors associated with poor bowel preparation were also evaluated.ResultThe video + retelling group had a higher percentage of patients with adequate colonoscopy bowel preparation (Ottawa score <6) than the control group (P<0.001). Mean Ottawa total scores significantly differed between the control group and the video + retelling group (4.18±1.4 vs. 3.05±1.3, P<0.001). The video + retelling group showed superior cleanliness in the right, middle, and recto-sigmoid colon segments (all Ps <0.001). Logistic regression analysis revealed that male gender (OR=2.10, 95%CI: 1.098–4.018, P=0.025), diabetes mellitus (OR=2.830, 95%CI: 1.257–6.372, P=0.012), and no educational video followed by retelling bowel preparation process (OR=3.02, 95%CI: 1.731–5.270, P<0.001) were independently associated with poor bowel preparation.ConclusionsUse of an educational video followed by asking patients to retell the process of bowel preparation after receiving regular instructions is a convenient and risk-free practice that enhances the compliance with bowel preparation guidance and improves bowel preparation quality.

Non-adjunctive flash glucose monitoring system use during summer-camp in children with type 1 diabetes: The free-summer study.

A factory-calibrated sensor for intermittently scanned continuous glucose monitoring (isCGM) is accurate and safe in children with type 1 diabetes (T1D). Data on isCGM effectiveness as a replacement for self-monitoring of blood glucose (SMBG) in this population is scarce. The aim of this study was to evaluate the non-adjunctive use of isCGM in children with T1D during 2 weeks in a challenging summer-camp setting. In this two-arm, parallel, randomized, outpatient clinical trial we enrolled 46 children (25 females, mean ± SD: age 11.1 ± 2.6 years, glycated hemoglobin (HbA1c) 7.4% ± 0.7%): 26 in the isCGM group were blinded for the SMBG and insulin dosing was isCGM-based, whereas 20 in the control group were blinded for isCGM and performed SMBG-based insulin dosing. The primary outcome of intention-to-treat analysis was between-group difference in the proportion of time within range 3.9 to 10 mmol/L (TIR). There was no significant difference in TIR (3.9-10 mmol/L) between the two groups. In participants with suboptimal metabolic control (HbA1c > 7%) we observed a significant reduction in time spent above 10 mmol/L (P < 0.05) and an improvement in TIR (P = 0.05) in the isCGM group. No severe hypoglycemic events or serious adverse events occurred. Overall mean absolute relative difference (MARD) between isCGM and SMBG was 18.3%, with median absolute relative difference (ARD) of 8%. Consensus error grid analysis demonstrated 82.2% and 95.2% of results in zone A, and zone A + B, respectively. The non-adjunctive use of isCGM was as safe and effective as SMBG, and reduced time spent in hyperglycemia in a sub-population of children with T1D with suboptimal glycemic control. NCT03182842.

Effect of 6 months hybrid closed-loop insulin delivery in young people with type 1 diabetes: a randomised controlled trial protocol

IntroductionAutomated insulin delivery (also known as closed loop, or artificial pancreas) has shown potential to improve glycaemic control and quality of life in people with type 1 diabetes (T1D). Automated...