Patient-rated Severity Research Articles

Impact of possible tardive dyskinesia on physical wellness and social functioning: results from the real-world RE-KINECT study

BackgroundTardive dyskinesia (TD) is a persistent and potentially disabling movement disorder associated with antipsychotic use. Data from RE-KINECT, a real-world study of antipsychotic-treated outpatients, were analyzed to assess the effects of possible TD on patient health and social functioning.MethodsAnalyses were conducted in Cohort 1 (patients with no abnormal involuntary movements) and Cohort 2 (patients with possible TD per clinician judgment). Assessments included: EuroQoL’s EQ-5D-5L utility (health); Sheehan Disability Scale (SDS) total score (social functioning); patient- and clinician-rated severity of possible TD (“none”, “some”, “a lot”); and patient-rated impact of possible TD (“none”, “some”, “a lot”). Regression models were used to analyze the following: associations between higher (worse) severity/impact scores and lower (worse) EQ-5D-5L utility (indicated by negative regression coefficients); and associations between higher (worse) severity/impact scores and higher (worse) SDS total score (indicated by positive regression coefficients).ResultsIn Cohort 2 patients who were aware of their abnormal movements, patient-rated TD impact was highly and significantly associated with EQ-5D-5L utility (regression coefficient: − 0.023, P < 0.001) and SDS total score (1.027, P < 0.001). Patient-rated severity was also significantly associated with EQ-5D-5L utility (− 0.028, P < 0.05). Clinician-rated severity was moderately associated with both EQ-5D-5L and SDS, but these associations were not statistically significant.ConclusionsPatients were consistent in evaluating the impacts of possible TD on their lives, whether based on subjective ratings (“none”, “some”, “a lot”) or standardized instruments (EQ-5D-5L, SDS). Clinician-rated severity of TD may not always correlate with patient perceptions of the significance of TD.

A pilot single-blind parallel randomised controlled trial comparing kinesiology tape to compression in the management of subacute hand oedema after trauma

BackgroundHand oedema is a common consequence of hand trauma or surgery. There are numerous methods to reduce hand oedema but lack high-quality evidence to support best practice. The primary objective of this pilot trial was to assess study feasibility when comparing treatments for subacute hand oedema after trauma.MethodsA parallel two-arm pilot randomised controlled trial was conducted in the hand therapy department at a regional hospital in Norfolk between October 2017 and July 2018. Patients were eligible if 18 years or over, referred to hand therapy with subacute hand oedema. Randomisation was on a 1:1 basis to treatment as usual (TAU) (compression, elevation and massage) or trial treatment (TT) (kinesiology tape, elevation and massage). One blinded assessor completed all assessments (prior to randomisation, 4 and 12 weeks later). Data on study feasibility, adherence and acceptability of treatments were collected. The primary outcome measure was hand volume (volumetry). Patient-rated severity (0–5 Likert scale), hand health profile of the Patient Evaluation Measure (PEM) and quality of life (EQ-5D-5L) were also recorded.ResultsForty-five patients were screened for eligibility and 26 consented and were randomised with 13 patients in each treatment arm. Twelve participants were lost to follow-up leaving 7 participants in each group included in the analysis. Assessor blinding was maintained in 64% of participants (9/14). Total mean acceptability scores, out of 100, were higher for TAU (87.9) than TT (76.1). Health resource use results showed TT was marginally cheaper (~£2 per patient) than TAU.Individual adherence ranged between 39 and 100%, with higher levels of overall adherence seen in the TAU group. Four participants (28%) reported adverse effects (TT group n = 3, TAU group n = 1).ConclusionThis pilot trial has identified that modifications are required in order to make a full-scale trial feasible. They include a formal assessment of treatment fidelity, research staff assisting with screening and recruitment of participants and multiple blinded assessors at each study site. Whilst not designed as an efficacy trial, it should be acknowledged that the small sample size and high loss to follow-up meant very small numbers were included in the final analysis resulting in wide confidence intervals and therefore low precision in parameter estimates.Trial registrationInternational Standard Randomised Controlled Trial Number: 94083271. Date of registration 16th August 2017.Trial fundingNational Institute for Health Research Trainees Co-ordinating Centre (TCC); Grant Codes: CDRF-2014-05-064

RE-KINECT: A Prospective Study of the Presence and Healthcare Burden of Tardive Dyskinesia in Clinical Practice Settings.

RE-KINECT (NCT03062033) was designed to assess the presence and impact of possible tardive dyskinesia (TD) in antipsychotic-treated outpatients. The study included adults with 3 or more months of lifetime antipsychotic exposure and 1 or more psychiatric disorder. Based on clinician observation and assessment, patients were assigned to cohort 1 (without involuntary movements or with non-TD involuntary movements) or cohort 2 (with involuntary movements confirmed by clinician as possible TD). Baseline assessments included the following: patient characteristics; location/severity of involuntary movements; and impact of possible TD on health-related quality of life, including the EuroQoL 5-Dimensions 5-Level questionnaire. Of 739 eligible patients, 204 (27.6%) had clinician-confirmed possible TD (cohort 2). Compared with cohort 1, patients in cohort 2 were significantly older (P < 0.0001), more likely to have schizophrenia or schizoaffective disorder (P < 0.0001) and longer lifetime exposure to antipsychotics (P < 0.0001), and less likely to be working or studying, based on clinician perception (P = 0.0010). Clinician- and patient-rated severity of possible TD movements was significantly correlated in each of 4 body regions (head/face, neck/trunk, upper extremities, lower extremities), for maximum severity in any region, and for total number of affected regions (P < 0.001 for all correlations). For the patient-rated EuroQoL 5-Dimensions 5-Level, the health state visual analog scale score was significantly lower (worse) in cohort 2 versus cohort 1 (66.8 vs 69.7; P = 0.0002), as was the utility index score (0.71 vs 0.76; P < 0.0175). Results from this real-world population indicate that TD occurs frequently and can significantly reduce quality of life in patients with a psychiatric disorder.

PND84 FACTORS THAT IMPACT HEALTH-RELATED QUALITY OF LIFE IN PATIENTS WITH TARDIVE DYSKINESIA: REGRESSION ANALYSES OF DATA FROM THE REAL-WORLD RE-KINECT STUDY

RE-KINECT, an ongoing study of tardive dyskinesia (TD) in antipsychotic-treated outpatients, includes 2 cohorts: patients with visible uncontrollable movements that are clinician-confirmed as possible TD (C2); and patients with no visible movements or with non-TD movements (C1). Data from the EuroQoL 5-Dimension 5-Level (EQ-5D-5L) questionnaire, administered before cohort assignment, were analyzed to assess health-related quality of life (HRQoL) in C2 vs. C1 and the effects of possible TD on HRQoL (C2 only). To eliminate non-TD as a confounding factor, patients who presented with (or reported having) any uncontrollable movements not confirmed as TD were excluded from C1. A linear regression model (adjusted for confounding factors: age, gender, overall health, psychiatric severity, functional status, psychiatric diagnosis) was used to analyze the difference in EQ-5D-5L utility score (0=health state equivalent to death; 1=perfect health) between C2 (n=204) and C1 (n=450). Analyses were also conducted based on C2 patients who rated themselves as having “a lot” of overall TD severity (n=53) or “a lot” of TD impact on daily activities (n=41). In C2, the effects of TD severity (patient-rated, clinician-rated) and TD impact (patient-rated) on EQ-5D-5L utility were analyzed. The difference (±SE) between C2 and C1 was significant for EQ-5D-5L utility (-0.04±0.02, P<0.05). Larger significant differences were found when the model was limited to C2 patients with “a lot” of TD severity (-0.09±0.03; P<0.001) or TD impact (-0.15±0.03, P<0.001). EQ-5D-5L utility was most strongly associated with patient-rated TD impact (-0.021, P<0.001), followed by patient-rated TD severity (-0.028, P<0.05]). No significant association was found between EQ-5D-5L utility and clinician-rated TD severity (-0.007, P>0.05), which was significantly lower (less severe) than patient-rated severity (difference±SE: -0.28±0.12, P<0.05). TD is associated with measurably worse HRQoL, especially from the perspective of patients versus clinicians and particularly in patients who self-reported greater TD severity/TD impact.

Quality of Life in Hand Eczema Questionnaire: Validation of the Japanese version of a disease-specific measure of quality of life for hand eczema patients.

Hand eczema (HE) is a common skin disease that impairs health-related quality of life (HRQOL). Impairments in HRQOL have already been reported in Japanese HE patients using the Skindex-16. Recently, an instrument to measure disease-specific HRQOL in HE patients was developed by an international expert group, consisting of domains for: (i) symptoms; (ii) emotions; (iii) functioning; and (iv) treatment and prevention. The objective of this study is to translate the English-language version of the Quality of Life Hand Eczema Questionnaire (QOLHEQ) to Japanese and then to validate the Japanese version. The Japanese version of the QOLHEQ, the Dermatological Life Quality Index (DLQI) and a questionnaire regarding basic demographic information, including patient ratings of HE severity, were distributed to Japanese HE patients. Additionally, a dermatologist evaluated patients' HE severity using the Physician Global Assessment. A total of 124 patients with a mean age of 43.7 years were included in the analysis, and 78% of the sample was female. Cronbach's alphas for the domains symptoms, emotions, functioning, and treatment and prevention were 0.76, 0.89, 0.88 and 0.81, respectively. The total QOLHEQ score showed a strong correlation with the DLQI, a moderate correlation with patient-rated severity and weak correlations with dermatologist-rated severity and the number of consultations. The Japanese version of the QOLHEQ showed excellent reliability and high validity. The Japanese version of the QOLHEQ is ready for use in epidemiological studies to evaluate HRQOL impairments in HE patients.

Discordance Between Physician- and Patient-Reported Disease Severity in Adults with Atopic Dermatitis: A US Cross-Sectional Survey.

BackgroundThere is limited understanding of severity rating of atopic dermatitis in clinical practice.ObjectivesTo evaluate the agreement between physician- and patient-rated severity of atopic dermatitis.MethodsData were collected from the 2014 Adelphi US Atopic Dermatitis Disease Specific Programme, a cross-sectional survey of physicians and their patients with a history of moderate-to-severe atopic dermatitis; patients voluntarily completed a questionnaire. Current disease severity (mild/moderate/severe), based on personal judgment, was rated independently by patients and their physicians. The weighted kappa statistic identified level of agreement between physicians and patients. Bivariate analyses characterized agreement; multi-nomial logistic regression identified factors associated with discordance.ResultsOverall, 678 patients were included (369 [54.4%] were women, 525 [77.4%] were White, mean age was 39.3 years). Agreement was moderate (weighted kappa = 0.52): compared with physician ratings, patient-rated severity was higher in 76 patients (11.2%), lower in 137 patients (20.2%), and matched in 465 patients (68.6%). There were no differences in the rates of agreement between physician and patient ratings based on physician specialty (p = 0.6781), objective severity measures [Eczema Area and Severity Index score (p = 0.5308), percent body surface area affected (p = 0.9872), and current systemic immunosuppressant use (p = 0.9197)]. Multivariate analysis showed patients with a worse quality of life (Dermatology Life Quality Index) were more likely to rate a higher severity (relative risk ratio 1.04, 95% confidence interval 1.00–1.08; p = 0.0460). Physicians were more likely to rate a higher severity with a greater physician-reported sleep disturbance (relative risk ratio 1.71, 95% confidence interval 1.01–2.89; p = 0.0440).ConclusionsAlmost one-third of patients rated atopic dermatitis severity differently from their physicians, supporting the importance of the patient perspective in the severity assessment of atopic dermatitis and the need for greater communication between patients and physicians.Electronic supplementary materialThe online version of this article (doi:10.1007/s40257-017-0284-y) contains supplementary material, which is available to authorized users.

Development and validation of the hand-foot reaction and quality of life (HF-QoL) questionnaire for oncology.

e20537 Background: Skin toxicity (hand-foot syndrome and hand-foot skin reaction, HFS/R) related to antineoplastic therapy is a significant issue in oncology practice with potentially large impacts on health-related quality of life (HRQL). Methods: A brief, patient self-reported questionnaire, The Hand-Foot Quality of Life (HF-QoL), was developed to measure HFS/R symptoms associated with cancer therapeutic agents and their effect on daily activities. The validity and reliability of the HF-QoL was tested in a phase 2b trial of sorafenib in 223 patients with locally advanced or metastatic breast cancer. Other measures completed included a patient rating of condition severity, the FACT-B, and the clinician-rated NCI-CTCAE [version 3.0] grading for rash. Psychometric properties tested included factor loadings, internal consistency, construct and discriminant validity, and responsiveness. The minimal clinically important difference (MCID) was estimated. Results: The final HF-QoL instrument comprises a 20-item Symptom rating scale and an 18-item Daily Activities scale. Each scale demonstrated excellent measurement properties and strongly discriminated between NCI-CTCAE grade and patient-rated condition severity with moderate to large effect sizes (&gt;0·50 standard deviation). The Daily Activities domain had excellent internal consistency (Cronbach’s alpha 0·96) and was correlated with FACT-B, FACT-G (both r=-0·53) and Symptom scores (r=0·82). Both HF-QoL scores increased notably and linearly with increasing patient-rated condition severity (p&lt;0·001). The MCIDs were estimated as 4 units for Daily Activities and 6 units for Symptoms means. Conclusions: The HF-QoL is a valid and reliable measure of symptoms associated with HFS/R and its effects on daily activities in this population of patients with advanced breast cancer. The HF-QoL is thus suitable for assessing HRQL impairment associated with HFS/R with cancer chemotherapeutic agents.

Age at Onset in Trichotillomania

Trichotillomania (TTM), or compulsive hair pulling, is a common psychiatric disorder characterized by psychosocial impairment and reduced quality of life. The aim of this retrospective study was to characterize the impact of age at TTM onset on clinical variables and neuropsychological function using a variety of clinical and neurocognitive measures. The study sample included 98 adult treatment-seeking individuals with a DSM-IV diagnosis of TTM. Correlates were explored by grouping participants into childhood-onset (onset at ≤ 11 years old, n = 42) or later-onset (≥ 12 years old, n = 56) TTM and via linear regression. All subjects underwent a semistructured clinical interview with a psychiatrist and completed a variety of paper-pencil tests regarding TTM severity and quality of life. A subset (n = 44) of subjects underwent neurocognitive testing assessing motor inhibition and set-shifting compared to a sample (n = 27) of age- and gender-matched healthy controls. Data were collected from September 2006 through July 2011. Postpubertal age at onset was significantly associated with greater TTM symptom severity. Clinically, the later-onset group pulled their hair for a significantly greater amount of time daily (P = .008), had higher clinician-rated TTM severity on the Clinical Global Impressions-Severity of Illness scale (P = .042), and had higher patient-rated severity on the Massachusetts General Hospital Hairpulling Scale (P = .022) compared to healthy controls. On the neurocognitive tasks, later-onset TTM was characterized by stop-signal impairments (P = .020) and relatively spared set-shifting, consistent with previous studies in the literature. In contrast, the childhood-onset manifestation was associated with set-shifting deficits in stages of the task completed and total errors adjusted (both P < .001) but relatively spared stop-signal performance compared to healthy controls. Results indicate that childhood-onset of TTM is common, as confirmed by the fact that 42.9% of our sample met childhood-onset criteria, and may differ neurobiologically from the prototypical later-onset form. Future neurobiological and treatment studies should measure age at onset and explore further these putative differences.Trial Registration ClinicalTrials.gov identifiers: NCT00354770 and NCT00775229.

Association of patient-rated severity with other outcomes in patients with painful diabetic peripheral neuropathy

ObjectiveTo evaluate the association of patient-reported severity of painful diabetic peripheral neuropathy (pDPN) with other outcomes in a European population of patients using the Adelphi Disease Specific Programme for pDPN (DSP III, 2008).MethodsThe severity of patients’ pDPN (mild, moderate, or severe) was rated independently by both patients and physicians. Relationships were evaluated between patient-reported pDPN severity and other patient-reported outcomes including pain, sleep, function, and work productivity. Physicians rated the severity of patients’ pDPN (1 = mild, 2 = moderate, 3 = severe) and sleep interference.ResultsPatient-reported data were available from 634 individuals (56.2% male, mean age 63 years) from France, Germany, Italy, and the UK, of whom only 22.2% reported that they were currently employed. pDPN severity was rated as mild, moderate, and severe by 22.2%, 60.9%, and 16.9% of the patients, respectively. There was a significant association between patient-rated and physician-rated pDPN severity (P < 0.0001), although there were discrepancies in agreement (kappa = 0.37, 95% confidence interval [CI] 0.31, 0.43; weighted kappa = 0.43, 95% CI 0.37, 0.48) among physician and patient ratings in a substantial proportion of patients across severity categories. Higher pDPN severity was associated with greater interference of daily function including sleep (P < 0.0001 for all pairwise comparisons). Among employed patients, percent of pDPN-related impairment while at work (presenteeism) and overall work impairment increased with greater pDPN severity, resulting in indirect costs that increased significantly with pDPN severity; $8266, $15,449, and $24,300 for mild, moderate, and severe pDPN, respectively (overall P < 0.001).ConclusionSeverity of patient-rated pDPN was significantly associated with outcomes, including function and productivity; poorer function and lower productivity were reported at higher pDPN severity levels. Moreover, physicians rated pDPN severity different from patients in a substantial proportion of patients.

Efficacy and safety study of arbaclofen placarbil in patients with spasticity due to spinal cord injury

Randomized, double-blind, placebo-controlled, two-period crossover. To evaluate the efficacy and safety of arbaclofen placarbil (AP) in patients with spasticity secondary to spinal cord injury (SCI). United States and Canada. Patients received extended-release AP tablets 10, 20 or 30 mg every 12 h in one of two AP/placebo sequences, with 26 days of each treatment. The primary analysis compared Ashworth scale assessments of muscle tone between AP and placebo for the muscle group with maximum baseline Ashworth score. Secondary endpoints included a patient-rated Severity of Spasticity Scale. In the primary analysis, AP significantly improved Ashworth scores compared with placebo over the dosing interval: least-squares mean reduction versus placebo was 0.60 for AP 20 mg (P=0.0059) and 0.88 for AP 30 mg (P=0.0007). The difference was significant for the pre-morning dose time point, 12 h after the prior evening dose, indicating that efficacy was maintained throughout the dosing interval. Treatment differences for AP 10 mg versus placebo were not significant. Severity of Spasticity ratings were significantly reduced for the combined 20/30-mg group versus placebo (P=0.018). No statistically significant differences between AP and placebo were observed for muscle strength. AP-related AEs were generally mild to moderate in intensity, and none led to early withdrawal or were serious. AP was well tolerated at all investigated dosages and, when administered at doses of 20 or 30 mg twice daily, was efficacious in reducing spasticity due to SCI.

Relationship between patient-reported disease severity and other clinical outcomes in osteoarthritis: a European perspective

Objective:To determine how patient-rated osteoarthritis (OA) severity correlates with other patient-reported and clinical outcomes in the European clinical setting.Methods:We used the Adelphi Arthritis VII (2008) Disease Specific Program (DSP). OA severity was patient-rated using the question ‘How bad would you say your arthritis is now?’ with responses of ‘mild,’ ‘moderate,’ and ‘severe.’ Patient-reported outcomes included a 0–100 mm pain visual analogue scale (VAS); questions on daily functioning; Work Productivity and Activity Impairment (WPAI) scale; and EuroQoL (EQ-5D). Regression models and chi-square analyses evaluated relationships between self-rated OA severity and other outcomes.Results:Patient-reported data were available from 1739 individuals (63.1% female, mean age 64.4 [standard deviation 11.9] years) from France, Germany, Italy, Spain, and the UK. With increasing OA severity; mild (24.5%), moderate (56.3%), severe (19.2%), statistically significant differences (p < 0.05) were observed with higher pain VAS scores (28.3, 49.9, 69.2, respectively), reduced function, and greater overall work impairment due to OA (24.3%, 38.5%, 68.6%, respectively). Significant associations of patient-reported OA severity with function and health status were indicated, including the EQ-5D health state index; 0.77 (mild), 0.62 (moderate), 0.30 (severe) (p < 0.0001). Physicians tended to overestimate patients who rated their OA as mild, and underrate patients who rated their OA as severe.Conclusions:In five European countries, patient-rated OA severity was associated with other patient-reported outcomes, and may be of benefit in the clinical setting when choosing treatment options aimed at improving pain, function and productivity, providing an accurate and tangible assessment of patient’s perceptions of their disease.

Predictors of doctor‐rated and patient‐rated gout severity: gout impact scales improve assessment

Our objective was to describe the factors associated with doctor-rated and patient-rated gout severity to explain how doctor assessment involving patient-reported outcomes can improve the clinical management of gout. Patients completed a newly validated gout-specific health-related quality of life instrument, the Gout Impact Scale (GIS) and other questions regarding their gout. Both patients and their doctors gave an overall gout severity assessment. We conducted correlation analyses between each predictor of interest and the two different severity ratings (doctor-rated severity and patient-rated severity). Stepwise multiple regressions were performed to determine the best predictors for doctor-rated and patient-rated severity, respectively. Doctor-rated severity more closely correlated with objective clinical and laboratory findings, particularly the presence of tophi, which was not a leading factor in patient-rated severity assessments. Patient-rated severity more closely correlated with the domains of the GIS, which expressed the impact of gout on health-related quality of life. Doctors might have a better understanding of their patients' level of disease impact if they incorporate an instrument such as the GIS in their evaluation of gout severity and their decisions regarding aggressiveness of treatment. The increased use of patient-reported outcomes measures has the potential to improve quality of care and patient satisfaction, as well as reduce costs of health care utilization.

The development and validation of a Nocturnal Gastro‐oesophageal Reflux Disease Symptom Severity and Impact Questionnaire for adults

Current questionnaires for assessing gastro-oesophageal reflux disease (GERD) symptoms are limited in their ability to capture nocturnal symptoms. To develop and validate an instrument, the Nocturnal Gastro-oesophageal Reflux Disease Symptom Severity and Impact Questionnaire (N-GSSIQ), to assess severity and impact of nocturnal GERD symptoms. Two focus groups and 16 cognitive debriefing interviews were conducted among GERD patients to identify key issues about nocturnal symptoms. A draft instrument was tested in 196 patients at 11 clinics in the US to evaluate psychometric properties. Exploratory factor and item response theory analyses were conducted to finalize items and subscales. Internal consistency reliability, reproducibility and construct validity were examined. Mean age was 45 (s.d. = 13.8) years; 76% were female and 68% were Caucasian. Patient-rated severity was mild-moderate for 69% of participants; 48% reported symptoms on two to three nights the past week. The final questionnaire includes 20 items and three subscales: Nocturnal GERD Symptoms, Morning Impact of Nocturnal GERD and Concern about Nocturnal GERD. The subscales demonstrated internal consistency reliability (Cronbach's alpha 0.84-0.94) and were significantly correlated with similar measures and disease severity (0.41-0.81; P < 0.0001). The results support the reliability and validity of the N-GSSIQ as a measure of severity, morning impact and concern about nocturnal GERD.

Impact of asthma control on sleep, attendance at work, normal activities, and disease burden

The 2007 Expert Panel Report 3 asthma treatment guidelines place substantial emphasis on understanding the effectiveness of treatment strategies on outcomes such as disease control. To assess the impact of asthma control on patient-reported outcomes and disease burden in a real-world setting. Patients aged 18 to 64 years with moderate to severe asthma defined by medical and pharmaceutical use were asked to participate in a cross-sectional survey of asthma care, control, and burden. Patients were included if they had an International Classification of Diseases, Ninth Revision, Clinical Modification code for asthma, a prescription for an Expert Panel Report 3-defined controller medication (or combinations), and 24-month pre-index continuous eligibility. Patients with chronic obstructive pulmonary disease were excluded. Survey respondent data were linked to commercial health claims information to create the research database. The Asthma Therapy Assessment Questionnaire (ATAQ) was used as the measure of control. The ATAQ scores range from 0 to 4, with 0 indicating no asthma control problems. A total of 1,199 patients (73% women) completed the survey and had their claims data linked for analysis. Age, sex, and comorbidity index measures did not differ between respondents and nonrespondents. Only 12.2% of respondents scored 0 on the ATAQ, 77.0% scored 1 or 2, and 10.8% scored 3 or 4. The ATAQ scores were moderately correlated with patient-rated severity. Decreasing levels of asthma control were associated with greater prevalences of sleep problems, depression, functional impairment, and effect on work and regular activities. Approximately 88% of patients with moderate to severe asthma were not fully controlled despite anti-inflammatory drug treatment. Lack of asthma control is associated with substantial patient burden.

Efficacy and Safety of Prucalopride in Patients with Chronic Noncancer Pain Suffering from Opioid-Induced Constipation

BackgroundOpioid-induced constipation (OIC) has negative effects on quality of life (QOL). Prucalopride is a new, selective 5-HT4 agonist and enterokinetic with strong clinical data in chronic constipation. This study investigated the efficacy, safety, and tolerability of prucalopride in patients with noncancer pain and OIC.MethodsA phase II, double-blind, placebo-controlled study of 196 patients randomized to placebo (n = 66), prucalopride 2 mg (n = 66) or 4 mg (n = 64), for 4 weeks, was carried out. The primary endpoint was the proportion of patients with increase from baseline of ≥1 spontaneous complete bowel movement (SCBM)/week. Secondary endpoints [proportion of patients with ≥3 SCBM/week, weekly frequency of (SC)BM, severity of constipation, and efficacy of treatment], adverse events (AEs), and safety parameters were also monitored.ResultsMore patients had an increase from baseline of ≥1 SCBM per week (weeks 1–4) in the prucalopride groups [35.9% (2 mg) and 40.3% (4 mg)] versus placebo (23.4%), reaching statistical significance in week 1. Over weeks 1–4, more patients in the prucalopride groups achieved an average of ≥3 SBM per week versus placebo (60.7% and 69.0% versus 43.3%), reaching significance at week 1. Prucalopride 4 mg significantly improved patient-rated severity of constipation and effectiveness of treatment versus placebo. Patient Assessment of Constipation-Symptom (PAC-SYM) total scores and Patient Assessment of Constipation-Quality of Life (PAC-QOL) total and satisfaction subscale scores were improved. The most common AEs were abdominal pain and nausea. There were no clinically relevant differences between groups in vital signs, laboratory measures or electrocardiogram parameters.ConclusionIn this population with OIC, prucalopride improved bowel function and was safe and well tolerated.

Immediate versus Delayed Surgical Intervention for Reconstructive Therapy of HIV-Associated Facial Lipoatrophy: A Randomized Open-Label Study

We assessed the safety and efficacy of reconstructive therapy with facial fillers for the treatment of HIV-associated facial lipoatrophy (FLA) through a randomized, controlled, open-label single-center study. A total of 134 HIV-infected patients with severe FLA were randomly assigned to receive immediate (67 patients) or delayed (67 patients) facial injections of poly-l-lactic acid (PLA) or polyacrylamide gel (PAIG). Outcome measures included changes in physician and patient FLA severity scale, adverse events, and changes in health-related quality of life (HRQoL) and anxiety using validated measures. The mean average study follow-up was 27 weeks for the immediate and 25 weeks for the delayed subjects. Adverse events were mild and resolved after a mean of 4 days. Compared to patients randomized to the delayed treatment group, patients assigned to the immediate treatment group had significantly lower physician-rated (0.0 versus -3.0; p < 0.0001) and patient-rated (0.1 versus -1.8; p < 0.0001) FLA severity scores. By contrast, measures exploring HRQoL and anxiety did not show any significant difference between patients randomized to the immediate and deferred groups. Reconstructive therapy with facial fillers was effective and safe and led to significant improvements in FLA severity. However, no significant gains in HRQoL, relational and psychological consequences of body changes, and anxiety-related concerns were observed. Studies should be performed to identify patients who could maximally benefit from filling interventions for FLA.

Skin scar preconceptions must be challenged: Importance of self-perception in skin scarring

Greater objective scar severity and visibility should intuitively cause greater psychosocial distress for patients. Previous research is contradictory and has employed non-validated scar severity measures whilst neglecting patient-rated severity. The aim of this study was to assess the effects of objective and patient-rated scar severity, scar type and location on psychosocial distress. Skin scars were quantitatively assessed on two independent occasions using the 'Manchester Scar Scale' (MSS) - a validated measure. Scars were scored twice independently. Patients also rated their scars (from 'very good' [zero] to 'poor' [four]) and good completed the Derriford Appearance Scale (DAS24) and Dermatology Life Quality Index (DLQI). Eighty-two patients, with an average+/-SD (range) age of 34+/-15 (16-65) years were recruited. Mean psychosocial questionnaire scores were: DAS24 45.5+/-17.8 (15-91); DLQI 7.5+/-6.7 (0-26). Participants had 1.9+/-1.5 (1-8) scars with an MSS score of 31.3+/-24.0 (6.6-162.0) and subjective score of 2.6+/-1.2 (0-4). Correlation between psychosocial distress and objective severity was not significant (DAS24 0.14 p=0.11; DLQI 0.16 p=0.06). Correlation between psychosocial distress and subjective severity was significant (DAS24 0.48 p<0.0001; DLQI 0.46 p<0.0001). Patients with non-visible scars experienced greater psychosocial distress than patients with visible scars (DAS24 9.7 p=0.046; DLQI 4.2 p=0.014). Scar type was unrelated to psychosocial distress. Patient-rated scar severity and scar visibility are correlated with psychosocial distress rather than clinician's objective severity rating or scar type. Although counter-intuitive, results are consistent with research into other disfiguring conditions and patient self-assessment should therefore form an integral part of clinical assessment.

Effectiveness of a Time-Limited Cognitive Behavior Therapy Type Intervention Among Primary Care Patients With Medically Unexplained Symptoms

Patients seeking care for medically unexplained physical symptoms pose a major challenge at primary care sites, and there are very few well-accepted and properly evaluated interventions to manage such patients. We tested the effectiveness of a cognitive behavior therapy (CBT)-type intervention delivered in primary care for patients with medically unexplained physical symptoms. Patients were randomly assigned to receive either the intervention plus a consultation letter or usual clinical care plus a consultation letter. Physical and psychiatric symptoms were assessed at baseline, at the end of treatment, and at a 6-month follow-up. All treatments and assessments took place at the same primary care clinic where patients sought care. A significantly greater proportion of patients in the intervention group had physical symptoms rated by clinicians as "very much improved" or "much improved" compared with those in the usual care group (60% vs 25.8%; odds ratio = 4.1; 95% confidence interval, 1.9-8.8; P<.001). The intervention's effect on unexplained physical symptoms was greatest at treatment completion, led to relief of symptoms in more than one-half of the patients, and persisted months after the intervention, although its effectiveness gradually diminished. The intervention also led to significant improvements in patient-reported levels of physical symptoms, patient-rated severity of physical symptoms, and clinician-rated depression, but these effects were no longer noticeable at follow-up. This time-limited, CBT-type intervention significantly ameliorated unexplained physical complaints of patients seen in primary care and offers an alternative for managing these common and problematic complaints in primary care settings.

Assessment of severity of hand eczema: discrepancies between patient- and physician-rated scores

In clinical practice or trials on hand eczema the severity of this disease can be 'measured' in different ways: by means of a physician-rated clinical severity score, a patient-rated clinical severity score or by an indicator of the burden of disease. We assume that the patient-rated severity score corresponds more with the (change in) burden of disease than with the physician-rated severity score. To demonstrate how physicians and patients differ in their assessment of the severity of hand eczema as seen in a physician-rated severity score, patient-rated severity score and a burden of disease questionnaire. We used data from an open-label randomized controlled trial which was set up in two university hospital dermatology departments in the Netherlands, specializing in hand eczema. One hundred and fifty-eight patients with moderate to severe chronic hand eczema were included. The main outcome measures were the physician-rated severity score, based on five visible aspects of hand eczema (desquamation, erythema, vesicles, infiltration, fissures), the patient-rated severity score (a self-rating scale), a burden of disease questionnaire (the Dermatology Life Quality Index, DLQI) and the correlations between these parameters, both at inclusion and over time. Only desquamation and infiltration were significantly correlated with patient-rated severity score. Patient-rated severity score correlated with seven of 10 DLQI items, but it did not correlate with the items regarding influence on clothes worn, impairment of sporting activities, and problems associated with treatment of the skin. The majority of patients showed improvement in all parameters after treatment. However, the improvement in patient-rated severity score was not clearly correlated with changes in physician-rated severity score. Except for DLQI item 1 (itch, soreness, pain, stinging), none of the changes in burden of disease was correlated with changes in patient-rated severity score. For each DLQI item, change over time correlated weakly with decreases in several, but not all, components of the physician-rated severity score. Disease severity can be expressed by different scores; these scores are not clearly correlated, and measure different aspects. Patient satisfaction is not guaranteed when treatment is focused solely on the visible aspects of hand eczema. Instead, burden of disease has a greater impact.

Blinded placebo crossover study of gabapentin in primary orthostatic tremor

Primary orthostatic tremor (OT) is a rare but disabling condition characterized by leg tremor and feelings of instability during stance. Previous studies have reported a reduction in OT symptoms with gabapentin treatment. In this study, we report on the benefits of gabapentin treatment in a double-blind placebo-controlled crossover study of 6 OT patients. First, the maximally effective gabapentin dosage (600-2,700 mg/day) for each patient was determined during an initial dose-titration phase. Patients were then studied 7 days after drug withdrawal and again after two 2-week periods of treatment with either gabapentin or placebo, using force platform posturography to quantify postural sway and tremor. Other medications for OT were continued unchanged. Symptomatic response was assessed by a patient-rated severity scale and quality of life (QOL) questionnaire. All patients reported an increase in symptoms during the washout phase and symptom reduction (50%-75%) during gabapentin treatment. Tremor amplitude was reduced to 79% +/- 11% and sway area to 71% +/- 11% of the placebo state. QOL improved in all patients, no adverse drug effects were noted, and symptomatic benefit was maintained at follow-up (mean = 19 months). The findings confirm that gabapentin is an effective treatment for OT, reducing both tremor and postural instability and improving quality of life, and support its use as add-on or first-line therapy for OT.