Overt hepatic encephalopathy: development of a novel clinician reported outcome tool and electronic caregiver diary.

Clinical management and clinical trials of patients with overt hepatic encephalopathy (OHE) are compromised by lack of standardized and reproducible tools for its clinical diagnosis or for caregiver (CG) identification of OHE manifestations which merit medical evaluation. Using an iterative Delphi method, Steering Committee and international hepatologist panel, the West Haven (WH) scale was modified to develop and operationalize a clinician tool for OHE identification and grading (HE Grading Instrument, HEGI™). Major diagnostic criteria included disorientation to time, place, and person, asterixis, lethargy, and coma. Minimum HEGI requirements for OHE diagnosis included: (1) disorientation, or (2) presence of both lethargy and asterixis, or (3) coma. Inter- and intra-rater HEGI reproducibility were 97 % and 98 %, respectively. When applied to a phase II clinical trial population of 178 patients with 388 OHE episodes, HEGI demonstrated excellent concordance with investigator judgement. Additionally, a multi-stage study was conducted to develop a daily CG e-diary, based on OHE manifestations recognizable by CG including speech difficulties, unusual behavior, forgetfulness, confusion, disorientation and level of consciousness. The e-diary was designed for use on smart phone, laptop or desktop, utilized branching logic and skip patterns, incorporated automatic daily completion reminders and real time alerts to clinical sites to facilitate daily standardized CG input and was found to be user friendly and understandable. The HEGI and e-diary, which were developed using methodology accepted by regulatory authorities, are designed to facilitate the design and interpretation of clinical trials for OHE and improve outcomes for OHE patients in clinical practice.

The impact of opioid-induced constipation among chronic pain patients with sufficient laxative use.

BACKGROUND: The impact of sufficient laxative use on opioid-induced constipation (OIC) is not known. AIM: To understand the experience and symptom burden over time among chronic non-cancer pain patients with OIC who are sufficient laxative users. METHODS: A prospective longitudinal study was conducted in United States, Canada, Germany and UK which included medical record abstraction, patient surveys and physician surveys. Patients on daily opioid therapy for ≥ 4 weeks for chronic non-cancer pain with OIC were recruited from physician offices and completed the survey at Baseline and Weeks 2, 4, 6, 8, 12, 16, 20 and 24. Sufficient laxative use was defined as at least one laxative remedy 4 or more times in the prior 2 weeks. RESULTS: Of the 489 patients who completed the Baseline survey and met OIC criteria, 234 (48%) were categorised as sufficient laxative users; 65% were female; 90% were white and 75 (32%) maintained sufficient laxative use for > 7 of the 8 follow-up periods. Patient Assessment of Constipation-Symptom (PAC-SYM) and Patient Assessment of Constipation-Quality of Life (PAC-QOL) scores indicated moderate symptom severity and impact. PAC-SYM and PAC-QOL scores remained relatively unchanged over time with a maximum score change of 0.5 points. Work productivity and activity impairment remained relatively constant. Mean per cent activity impairment because of constipation was 37% at Baseline and 34% at Week 24. CONCLUSIONS: These findings demonstrate constipation persists despite sufficient laxative use with little improvement in symptoms, HRQL or activity impairment. This ongoing burden emphasises the need to identify more efficacious constipation therapies for this chronic pain patient population.

Validation of a 3-item OAB awareness tool.

AIM: The purpose of this study was to validate a short awareness tool to assist patients in identifying if they have bothersome overactive bladder (OAB) symptoms. METHODS: This secondary analysis study utilised data from a cross-sectional study of adult patients presenting for primary care visits. Patients completed an 8-item OAB screener. The clinician probed for urinary frequency, urgency, nocturia and urgency urinary incontinence. If the patient screened positive or reported the presence of at least one OAB symptom, additional questions were asked regarding lifestyle and coping issues. The clinician then diagnosed the patient as having No OAB, Possible OAB, or Probable OAB. Multivariate logistic regressions were performed to assess the feasibility of deriving a shorter screener to raise awareness of OAB among primary care patients. RESULTS: The 1,260 patients in this study were 51.6±17.0 years old; 62% were women; and most (89%) were Caucasian. Clinicians diagnosed 12.1% of patients with Probable OAB, 19.7% with Possible OAB and 68.3% with No OAB. The logistic regression models were performed with OAB clinical diagnosis as the dependent variable comparing No OAB versus Probable OAB. Three items which included the symptoms of urinary frequency, urinary urgency and urine loss associated with a strong desire to urinate performed well as an awareness tool. A cut-point of four provided the most appropriate sensitivity (82%) and specificity (91%) when identifying Probable OAB and yielded adequate model fit. The final 3-item OAB Awareness Tool (OAB-V3) is gender neutral. CONCLUSION: The 3-item OAB Awareness Tool (OAB-V3) correctly identified patients with symptoms of OAB with high sensitivity and specificity and can be used as a conversation starter for patients with symptoms of OAB.