Patient-reported Global Impression Of Change Research Articles

Litigation, Performance Validity Testing, and Treatment Outcomes in Adults With Mild Traumatic Brain Injury.

To investigate whether involvement in litigation and performance validity test (PVT) failure predict adherence to treatment and treatment outcomes in adults with persistent symptoms after mild traumatic brain injury (mTBI). Outpatient concussion clinics in British Columbia, Canada. Participants were assessed at intake (average 12.9 weeks postinjury) and again following 3 to 4 months of rehabilitation. Adults who met the World Health Organization Neurotrauma Task Force definition of mTBI. Litigation status was known for 69 participants ( n = 21 reported litigation), and 62 participants completed a PVT ( n = 13 failed the Test of Memory Malingering) at clinic intake. Secondary analysis of a clinical trial (ClinicalTrials.gov #NCT03972579). Outcomes included number of completed sessions, homework adherence, symptoms (Rivermead Post Concussion Symptoms Questionnaire), disability ratings (World Health Organization Disability Assessment Schedule 2.0), and patient-rated global impression of change. We did not observe substantial differences in session and homework adherence associated with litigation or PVT failure. Disability and postconcussion symptoms generally improved with treatment. Involvement in litigation was associated with a smaller improvement in outcomes, particularly disability ( B = 2.57, 95% confidence interval [CI] [0.25-4.89], P = .03) and patient-reported global impression of change (odds ratio [OR] = 4.19, 95% CI [1.40-12.57], P = .01). PVT failure was not associated with considerable differences in treatment outcomes. However, participants who failed the PVT had a higher rate of missing outcomes (31% vs 8%) and perceived somewhat less global improvement (OR = 3.47, 95% CI [0.86-14.04]; P = .08). Adults with mTBI who are in litigation or who failed PVTs tend to adhere to and improve following treatment. However, involvement in litigation may be associated with attenuated improvements, and pretreatment PVT failure may predict lower engagement in the treatment process.

RANDOMIZED, CONTROLLED TRIAL OF EXHALATION DELIVERY SYSTEM WITH FLUTICASONE FOR CHRONIC RHINOSINUSITIS WITHOUT NASAL POLYPS

<h3>Introduction</h3> There are no FDA-approved medications for the >20 million chronic rhinosinusitis patients without nasal polyps. The Exhalation Delivery System with Fluticasone (EDS-FLU) is an intranasal steroid in a device that delivers drug to regions above the inferior turbinate and behind the nasal valve. <h3>Methods</h3> In this phase 3, 24-week, randomized, controlled trial evaluating EDS-FLU versus EDS-placebo twice daily in chronic sinusitis without polyps, co-primary endpoints were combined symptom score (CSS; week 4) and average of percentages of CT-opacified volume across ethmoid/maxillary sinuses (APOV; week 24). Other outcomes included Quality-of-Life (SNOT-22, SF-36), Sleep (PSQI), and Patient-reported Global Impression of Change (PGIC). <h3>Results</h3> Baseline scores suggest moderate-severe disease: mean CSS=6.0; APOV=62.0%. Both EDS-FLU doses [186µg (n=74) and 372µg (n=74)] significantly reduced both symptoms and sinus opacification versus EDS-placebo (n=75): CSS least-square (LS) mean change, EDS-placebo, -0.81; EDS-FLU 186µg, -1.54 (p<.05); EDS-FLU 372µg, -1.74, (p<.001); APOV LS mean change +1.19, -7.00 (p<.001), -5.14 (p<.01), respectively. EDS-FLU (n=145) vs EDS-placebo (n=75) also significantly improved secondary measures at Week 24 including SNOT-22 (LS mean -17.5 vs -8.7, p=.001); SF-36v2 (LS Mean PCS 4.9 vs 1.8, p=.002); PSQI Global score (LS mean -1.54 vs -.33; p<.001); and PGIC (60% vs 25% much/very much improved; p<.001). Adverse events (≥3% of patients and >EDS-placebo) were COVID-19, epistaxis, headache, and depression. <h3>Conclusion</h3> EDS-FLU is the first and only drug to show improvement in a phase 3 trial in both symptoms and sinus opacification in chronic rhinosinusitis without nasal polyps.

Validation of the Kansas City Cardiomyopathy Questionnaire in Symptomatic Obstructive Hypertrophic Cardiomyopathy

BackgroundThe primary goal for treating patients with obstructive hypertrophic cardiomyopathy (oHCM) is to improve their symptoms, function, and quality of life. Although the Kansas City Cardiomyopathy Questionnaire (KCCQ) is a valid, reliable, and sensitive measure for other etiologies of heart failure, its appropriateness for patients with oHCM is unknown. ObjectivesThe purpose of this study was to establish the interpretability, validity, reliability, and responsiveness of the KCCQ in patients with oHCM. MethodsCognitive debriefing of the KCCQ was performed in 26 patients with oHCM. The validity, reliability, responsiveness, and interpretability of the KCCQ were tested in 196 participants from the EXPLORER-HCM trial by comparing each scale with relevant comparators, describing the internal reliability and the mean change in stable patients, and comparing the mean change in patients who reported different degrees of clinical change using a patient-reported global impression of change (PGIC). ResultsAll KCCQ domains demonstrated strong correlations with external standards of symptoms, function, social limitation, and quality of life, including a recently designed instrument measuring symptoms not captured by the KCCQ (P < 0.0001 for all). Mean changes in stable patients were nonsignificant, ranging from 0.21 to 2.3 points (P > 0.30 for all), with high intraclass correlation coefficients. The mean changes in patients with small, moderate, and large clinical changes were consistent with the 5-, 10-, and 20-point mean differences observed in other etiologies of heart failure. ConclusionsThe KCCQ is well understood by patients with oHCM and has strong evidence of good psychometric performance. It can not only serve as a relevant endpoint in clinical trials of oHCM therapy, but may also prove useful in the clinical care of patients with oHCM. (Clinical Study to Evaluate Mavacamten [MYK-461] in Adults With Symptomatic Obstructive Hypertrophic Cardiomyopathy [EXPLORER-HCM]; NCT03470545)

Efficacy and Safety of "On-Demand" Dapoxetine in Treatment of Patients with Premature Ejaculation: A Meta-Analysis.

BackgroundThe aim of this study was to assess the efficacy and safety of “on-demand” dapoxetine in the treatment of premature ejaculation (PE).Material/MethodsWe performed a meta-analysis of intravaginal ejaculatory latency time (IELT), patient-reported global impression of change (PGIC), perceived control over ejaculation (PCOE), and drug-related adverse effects (AEs). We searched Medline, PubMed, Embase, CNKI, Wanfang, and VIP databases up to May 30, 2018 with the following search terms: “dapoxetine” or “SSRIs” and “premature ejaculation” or “sexual dysfunction”.ResultsOur analysis included 11 RCTs (8521 cases and 4338 controls). We found that IELT, PGIC, and PCOE in PE patients with “on-demand” dapoxetine were significantly higher than in the control group, and we observed higher proportions in 60 mg vs. 30 mg dapoxetine. The AEs were mild and tolerable.Conclusions“On-demand” dapoxetine is effective and safe for patients with PE, and a dose of 60 mg may be more effective than 30 mg.

Improving Patient Reported Outcomes and Preventing Depression and Anxiety in Older Adults With Knee Osteoarthritis: Results of a Sequenced Multiple Assignment Randomized Trial (SMART) Study

Older adults with knee osteoarthritis (OA) and comorbid subsyndromal depressive symptoms are at elevated risk for incidental major depression or anxiety disorders. Using an indicated prevention paradigm, the authors conducted a sequenced multiple assignment randomized trial (SMART) to: 1) evaluate the effect of cognitive behavioral therapy (CBT) and physical therapy (PT), together with the temporal ordering of these interventions, on patient-reported global impression of change (P-GIC), mood, anxiety, and pain; and 2) compare the strategies' impact on incidence of common psychiatric disorders over 12-months. This intervention development trial compared four adaptive strategies delivered in two stages (each up to 8 weeks), contrasted with enhanced usual care (EUC). The strategies were CBT followed by an increased dose of CBT (CBT-CBT), CBT followed by PT (CBT-PT), PT followed by an increased dose of PT (PT-PT), and PT followed by CBT (PT-CBT). Participants (n = 99) were aged 60 years and older and met clinical criteria for knee OA and subthreshold depression. Response was defined as at least "much better" on the P-GIC. Participants were assessed quarterly for 12 months for incidence of psychiatric disorders. Stage 1 response was higher for PT (47.5%) compared to CBT (20.5%). Non-responders receiving an additional dose of the same intervention experienced a response rate of 73%, higher than for switching to a different intervention. All strategies were superior to EUC (5%). Although not powered to detect effects on disorders, neither intervention strategy nor response status affected 12-month incidence of depression and anxiety disorders. As response rates were similar for PT-PT and CBT-CBT, it may be dose and not type of these interventions that are necessary for clinical benefit. For non-responders, this finding may guide providers to stay the clinical course for up to 12 weeks before switching. These results support future trials of SMART designs in late-life depression prevention.

Can Intraprostatic Injection of OnabotulinumtoxinA be Benefi cial to Treat Premature Ejaculation? Results of a Prospective Study

We prospectively evaluated efficacy and adverse effects of intraprostatic injections of onabotulinumtoxinA to treat premature ejaculation. Twenty-four men ≥19 years-old with premature ejaculation for ≥ 6 months and intravaginal ejaculation latency time ≤ 2 minutes underwent transurethral intraprostatic injections of onabotulinumtoxinA (100 U). Primary endpoint was change of intravaginal ejaculation latency time at 3-months. Secondary endpoints included changes in premature ejaculation profile and patient-reported global impression of change (PGI). Mean baseline ejaculation latency time has significantly increased at 1-, 3- and 6-months, respectively. In premature ejaculation profile “perceived control over ejaculation”, significant improvement was reported at 3-months, while non-significant changes were reported at 1- and 6-months. Patients reported non-significant changes of “personal distress related to ejaculation” and “interpersonal difficulty related to ejaculation”. Only 8.3%, 12.5% and 12.5% of men reported “better” at 1-, 3- and 6-months, respectively, while all other patients reported “no change” or “slightly better” in patient-reported global impression of change. No serious adverse effects were observed. Improvements of intravaginal ejaculation latency time were not clinically meaningful, as most men reported “no change” or “slightly better” in patient-reported global impression of change. These marginal improvements did not support using onabotulinumtoxinA intraprostatic injections to remedy premature ejaculation.

The role of dapoxetine hydrochloride on-demand for the treatment of men with premature ejaculation.

Premature ejaculation (PE) is the most common male sexual dysfunction. Dapoxetine hydrochloride, belonging to a class of drugs known as selective serotonin reuptake inhibitors or, was the first drug originally approved for the on-demand treatment of men with PE. We aimed to compare the intravaginal ejaculatory latency time (IELT), patient-reported global impression of change (PGIC), and adverse effect (AE) incidence associated with the use of dapoxetine (30 mg and 60 mg) versus placebo, and evaluate the differences in administering 60 mg versus 30 mg as on-demand medical oral therapy for the treatment of PE via a literature review and meta-analysis. Relevant randomized controlled trials (RCTs) were identified from PubMed, EMBASE, and Cochrane Central Register of Controlled Trials (Cochrane Library) databases. Ultimately, a total of seven RCTs with 8039 patients were included. Our meta-analysis demonstrated that dapoxetine (in the 30 mg and 60 mg subgroup) resulted in significantly higher IELT, PGIC, and AE incidence relative to the placebo, with higher proportions observed for 60 mg versus 30 mg of dapoxetine administration. The most common AEs were mild and tolerable. We conclude that dapoxetine (particularly the 60 mg dosage) may be considered a safe and effective drug for patients with PE.

The Efficacy and Safety of Opioids in Inflammatory Arthritis: A Cochrane Systematic Review

To determine the efficacy and safety of opioid analgesics in inflammatory arthritis (IA). We searched Medline, Embase, and Central to May 2010. Randomized controlled trials in adults with IA that compared opioids (administered via any route) to another intervention or placebo were included. Studies in the immediate postoperative setting were excluded. Two authors independently extracted data and assessed risk of bias. Primary endpoints were pain and adverse events (AE). Categorical data were pooled using RevMan5 and reported as relative risks (RR) or odds ratios (OR) with 95% confidence intervals (95% CI). Eleven studies were included, all in patients with RA. The risk of bias of all studies was high. No study was longer than 6 weeks in duration and 4 studies used single doses of study drugs. Seven studies were between 1 and 6 weeks in duration and assessed 6 different oral opioids. Only 1 study investigated a strong opioid. Data could be pooled from 4 studies comparing weak opioids to placebo: there was no difference in withdrawals due to inadequate analgesia (RR 0.82, 95% CI 0.34, 2.01), but patient-reported global impression of change was superior with opioids (RR 1.44, 95% CI 1.03, 2.03). Opioids were more likely than placebo to cause AE (OR 3.90, 95% CI 2.31, 6.56). There was no difference between opioids and placebo in net efficacy after adjustment for AE. Based on 11 heterogeneous studies of short duration and high risk of bias, there is weak evidence that opioids are effective analgesics in RA. AE are common and may offset the benefits. The relative risks and benefits of opioids in IA beyond 6 weeks are unknown.

Opioid therapy for treating rheumatoid arthritis pain

Despite improvements in the management of rheumatoid arthritis (RA), pain control is often inadequate even when inflammation is well controlled. To assess the efficacy and safety of opioid analgesics for treating pain in patients with RA. We searched the Cochrane Central Register of Controlled Trials (CENTRAL) (The Cochrane Library), MEDLINE and EMBASE for studies to May 2010. We also searched the 2008 to 2009 American College of Rheumatology (ACR) and European League against Rheumatism (EULAR) abstracts and performed a handsearch of the reference lists of articles. Studies were included if they were randomized or quasi-randomized controlled trials (RCTs or CCTs) which compared opioid therapy to another therapy (active or placebo) for pain in patients with RA. Outcomes of interest were pain, adverse effects, function and quality of life. Two review authors independently selected the studies for inclusion, extracted the data, and performed a risk of bias assessment. Eleven studies (672 participants) were included in the review. Four studies assessed the efficacy of single doses of various opioid and non-opioid analgesics; a pooled analysis of these studies was not performed but in each study opioids reduced pain more than placebo. There were no differences between analgesic drugs in these studies.Seven studies were between one and six weeks in duration and assessed six different oral opioids (dextropropoxyphene, codeine, tramadol, tilidine, pentazocine, morphine), either alone or combined with non-opioid analgesics. The only strong opioid investigated was controlled-release morphine sulphate, in a single study with 20 participants. Six studies compared an opioid to placebo. Opioids were superior to placebo in patient-reported global impression of change (3 studies, 324 participants: relative risk (RR) 1.44, 95% CI 1.03 to 2.03) but not for the number of withdrawals due to inadequate analgesia (4 studies, 345 participants: RR 0.82, 95% CI 0.34 to 2.0). Adverse events (most commonly nausea, vomiting, dizziness and constipation) were more frequent in patients receiving opioids compared to placebo (4 studies, 371 participants: odds ratio 3.90, 95% CI 2.31 to 6.56); the pooled risk ratio for withdrawal due to adverse events was 2.67 (3 studies, 331 participants: 95% CI 0.52 to 13.75). One study compared an opioid (codeine with paracetamol) to an NSAID (diclofenac) and found no difference in efficacy or safety between interventions. There is limited evidence that weak oral opioids may be effective analgesics for some patients with RA, but adverse effects are common and may offset the benefits of this class of medications. There is insufficient evidence to draw conclusions regarding the use of weak opioids for longer than six weeks, or the role of strong opioids.

Treatment benefit of dapoxetine for premature ejaculation: results from a placebo‐controlled phase III trial

To evaluate the overall treatment benefit of dapoxetine for premature ejaculation (PE), with specific emphasis on improvements in personal distress and interpersonal difficulty related to ejaculation. Although these factors are key elements of numerous sets of diagnostic criteria for PE, they have rarely been evaluated as outcome measures in clinical trials. In this randomized, double-blind, placebo-controlled, phase III trial we enrolled men aged > or =18 years, from the USA and Canada, who had a Diagnostic and Statistical Manual of Mental Disorders, fourth edition, text revision, diagnosis of PE (1238 men). Men were randomized to receive placebo or dapoxetine 60 mg as needed or once daily for 9 weeks. The once-daily treatment arm was included for analysis of withdrawal symptoms (primary endpoint; presented elsewhere). Patients completed the Premature Ejaculation Profile (PEP) on day 1 (before dosing), and on days 28 and 63 (or study endpoint), which comprised the outcome measures for perceived control over ejaculation, satisfaction with sexual intercourse, and personal distress and interpersonal difficulty related to ejaculation. The patient-reported global impression of change in PE was reported on day 63 (or study endpoint). Treatment benefit measures included the composite criteria of at least a two-category increase in perceived control over ejaculation and at least a one-category decrease in personal distress related to ejaculation from baseline at study endpoint. At baseline, approximately 5% of patients in any treatment group reported 'not at all' or 'a little bit' of personal distress related to ejaculation, which increased to 54.3% of those receiving dapoxetine (vs 35.3% with placebo; P < 0.001). Similarly, 43.0% and 40.9% of men in the placebo and dapoxetine groups, respectively, reported 'not at all' or 'a little bit' of interpersonal difficulty related to ejaculation at baseline, which increased to 76.8% and 64.2% of those with dapoxetine and placebo, respectively (P < 0.001). The percentage of men who achieved the composite criteria with dapoxetine 'as needed' was 47.6%, vs 21.7% with placebo (difference from placebo, 25.9%; P < 0.001). The distribution of responses for the PEP among men who achieved the composite criteria was similar to that reported for men without PE in a previous observational study in the USA. The most common adverse events were nausea, dizziness, headache, diarrhoea and insomnia, which were more common with dapoxetine than with placebo. Dapoxetine reduced the personal distress and interpersonal difficulty associated with PE, and was associated with patient-reported improvements in their condition. The percentage of patients who achieved a composite of a two-category or greater increase in perceived control over ejaculation and a one-category or greater decrease in personal distress related to ejaculation was substantially greater than with placebo, as were all outcome measures.

The Premature Ejaculation Profile: validation of self‐reported outcome measures for research and practice

To evaluate the reliability and validity of the Premature Ejaculation Profile (PEP), a self-reported outcome instrument for evaluating domains of PE and its treatment, comprised of four single-item measures, a profile, and an index score. Data were from men participating in observational studies in the USA (PE, 207 men; non-PE, 1380) and Europe (PE, 201; non-PE, 914) and from men with PE (1238) participating in a phase III randomized, placebo-controlled clinical trial of dapoxetine. The PEP contains four measures: perceived control over ejaculation, personal distress related to ejaculation, satisfaction with sexual intercourse, and interpersonal difficulty related to ejaculation, each assessed on five-point response scales. Test-retest reliability, known-groups validity, and ability to detect a patient-reported global impression of change (PGI) in condition were evaluated for the individual PEP measures and a PEP index score (the mean of all four measures). Profile analysis was conducted using multivariate analysis of variance. All PEP measures showed acceptable reliability (intraclass correlation coefficients ranged from 0.66 to 0.83) and mean scores for all measures differed significantly between PE and non-PE groups (P < 0.001). Men who reported a reduction in PE with treatment in the phase III trial had significantly greater scores on each of the four measures. The PEP profiles of men with and without PE differed significantly (P < 0.001) in both observational studies; higher levels of PGI were associated with higher PEP profiles (P < 0.001). The PEP index score also showed acceptable reliability and was significantly different between the PE and non-PE groups (P < 0.001). Men who reported an improvement in PE with treatment in the phase III trial had significantly greater PEP index scores. In the phase III trial, nausea was the most common adverse event with dapoxetine. The PEP provides a reliable, valid, and interpretable measure for use in monitoring outcomes of men with PE.

Perceived control over ejaculation is central to treatment benefit in men with premature ejaculation: results from phase III trials with dapoxetine

To assess the utility of perceived control over ejaculation ('control') in the evaluation of treatment benefit in men with premature ejaculation (PE), and to compare effects associated with a two-category or greater increase in this variable between men receiving dapoxetine and placebo. This subanalysis used combined data from all treatment groups in an integrated analysis of two identically designed, 12-week, double-blind, randomized, placebo-controlled trials of dapoxetine. Men (2614) met the Diagnostic and Statistical Manual of Mental Disorders (fourth edition, text revision) criteria for PE, had a stopwatch-measured intravaginal ejaculatory latency time (IELT) of < or =2 min in > or =75% of events in a 2-week baseline period, and self-reported moderate or severe PE. Men received placebo or dapoxetine 30 or 60 mg, 1-3 h before intercourse. The stopwatch-measured IELT was recorded for each episode; the patient-reported global impression of change (PGI; 7-point scale, 'much worse' to 'much better'), control and satisfaction with sexual intercourse (5-point scales, 'very poor' to 'very good') were assessed monthly. The utility of a two-category or greater increase in control was evaluated by examining the relationship of this variable with IELT and satisfaction with sexual intercourse. Of 2341 men with baseline and endpoint assessments, 96.8% reported 'very poor' or 'poor' control at baseline, and 748 (32%) reported a two-category or greater increase in control after treatment. More than 95% of those men rated their PE as 'slightly better', 'better', or 'much better' on the PGI; 67.1% gave ratings of 'better' or 'much better.' They also had greater improvements in IELT than men with less than a two-category increase in control, with a mean (sd) change from baseline of 3.7 (4.3) vs 0.77 (1.8) min, respectively, and a greater percentage reported good or very good satisfaction with sexual intercourse than men with less than a two-category increase in control (74% vs 19%, respectively). Nausea, headache and upper respiratory tract infection were the most common adverse events reported by men with a two-category or greater increase in control (15.8%, 7.4% and 6.6%, respectively) and those without (8.5%, 5.5% and 6.5%, respectively). The proportions of men with a two-category or greater increase in control with dapoxetine 30 and 60 mg were 36.3% and 44.5%, respectively (vs 15% with placebo). A two-category or greater increase in control (5-point scale) is useful for assessing the treatment benefit in men with PE; it corresponds with improvements in the man's perception of his condition, substantially greater prolongation of IELT, and higher levels of satisfaction with sexual intercourse.