Understanding treatment goals and their application in clinical trial design for patients with Alzheimer disease and caregivers.

Background: As research continues towards improved treatments for Alzheimer disease (AD), there is growing interest in the views and needs from patients and caregivers on AD treatments. Methods: In this study, we surveyed patients with AD and caregivers to determine the treatment goals that are most important to them. Patients with AD and caregivers were independently recruited in Europe and North America to complete a web-based survey. Eligible participants were ≥18 years old and diagnosed with mild cognitive impairment or mild-to-moderate AD (patient-reported group) or persons involved in the care of patients with AD (caregiver-reported group). A total of 322 patients and 614 caregivers completed the survey. Results: The demographic characteristics of patients in the patient-reported and the caregiver-reported groups were similar. Disease severity of patients was greater in the caregiver-reported group compared with the patient-reported group (72.1% versus 46.9% moderate AD). The most important goal of AD treatment in both groups was maintenance of quality of life (QoL) (patient-reported group 31.1% and caregiver-reported group 38.8%; p=0.01). This was consistent across disease stages or symptom severity except for patients with mild cognitive impairment in the caregiver-reported group where slowing the progression of memory loss was the most important treatment goal. Conclusions: Patient QoL was consistently the most relevant treatment goal for patients with AD and caregivers. In AD clinical trials, patient-relevant outcomes, for example, QoL, should be given high priority to reflect the needs and demands of patients with AD and their caregivers.A preliminary report of this work was presented at the 14th Clinical Trials on Alzheimer's Disease meeting (November 9-12, 2021).

Impact of Endometriosis on Fatigue and Productivity Impairment in a Cross-Sectional Survey of Canadian Women.

OBJECTIVE: To evaluate fatigue burden and productivity impairments in Canadian women with a self-reported diagnosis of endometriosis (DxE). METHODS: From December 2018 to January 2019, Canadian women aged 18-49 years completed an online survey assessing fatigue via the Patient-Reported Outcomes Measurement Information System (PROMIS) Fatigue Short Form 6a questionnaire. Fatigue T-scores were compared between women with and without a DxE, by age and endometriosis symptom severity, using t tests. Women with a DxE completed the Work Productivity and Activity Impairment - Specific Health Problem (WPAI-SHP) questionnaire. The effects of age and hallmark endometriosis symptoms on productivity impairments were assessed via analysis of variance. RESULTS: Survey data included 2004 women with and 26 528 women without a DxE. Mean fatigue T-scores were 58.5 ± 10.1 in women with a DxE and 59.2 ± 10.1 in women with hallmark endometriosis symptoms (i.e., menstrual or non-menstrual pelvic pain/cramping, dyspareunia) versus 55.2 ± 9.4 in women without a DxE (both P < 0.001). Women with moderate or severe endometriosis symptoms had a mean T-score of 61.2 ± 9.4 versus 55.9 ± 10.1 for women with mild symptoms (P < 0.001). Women with moderate or severe hallmark endometriosis symptoms had mean T-scores of 59.6-62.9 versus 57.0-58.2 for women with mild or no symptoms (all comparisons P < 0.01). Women with a DxE reported 17.1% of work time missed, 41.8% impaired work ability, 46.5% overall work impairment, and 41.4% activity impairment per the WPAI-SHP. Women with a DxE aged 30-34 and 35-39 years consistently experienced the greatest effects of fatigue and productivity impairments. CONCLUSIONS: Canadian women with a DxE experience a substantial fatigue burden and significant productivity impairments.

Cross-Sectional Survey of the Impact of Endometriosis Symptoms on Health-Related Quality of Life in Canadian Women.

OBJECTIVE: To characterize the health-related quality of life (HRQOL) of Canadian women with a self-reported diagnosis of endometriosis (DxE). METHODS: Canadian women aged 18-49 years completed a survey from December 2018 through January 2019 in which HRQOL was assessed via the 12-item Short Form Health Survey (SF-12) and Endometriosis Health Profile-30 (EHP-30) questionnaire. We used t tests to compare SF-12 scores between women with and without a self-reported DxE, as well as the severity of hallmark endometriosis symptoms, including menstrual pelvic pain/cramping, non-menstrual pelvic pain/cramping, and dyspareunia, for women with a DxE (moderate/severe vs. mild/none). The effects of overall endometriosis symptom severity on HRQOL were assessed via analysis of variance. RESULTS: In total, 26 528 women without a DxE and 2004 women with a self-reported DxE were included. SF-12 scores were significantly lower for women with versus without a DxE (Mental Component Summary: 38.6 vs. 41.2; Physical Component Summary: 47.3 vs. 52.1; both P < 0.001), indicating reduced HRQOL. Moderate/severe hallmark endometriosis symptoms were associated with low SF-12 scores (i.e., worse HRQOL), with the greatest impact from non-menstrual pelvic pain/cramping. EHP-30 scores for women with a DxE ranged from 40.6 to 46.8, with the greatest impairment in self-image. Women with severe endometriosis symptoms had EHP-30 scores 1.3- and >2-fold higher (i.e., worse) than those with moderate and mild symptoms, at 67.5-74.6 versus 51.3-56.9 and 25.6-32.9, respectively. CONCLUSION: Canadian women with a self-reported diagnosis of endometriosis had significantly impaired health-related quality of life, which was inversely correlated with endometriosis symptom severity. This finding highlights a substantial unmet need among women with endometriosis.

Prevalence, Symptomatic Burden, and Diagnosis of Endometriosis in Canada: Cross-Sectional Survey of 30 000 Women.

OBJECTIVE: This study sought to estimate the prevalence of diagnosis of endometriosis (DxE) in Canada and to assess the symptomatic and diagnostic experience of Canadian women with DxE. METHOD: A cross-sectional, online survey of women in Canada aged 18 to 49 was conducted from December 7, 2018 through January 24, 2019. Survey data were weighted by Canadian population statistics to estimate the prevalence, symptomatic burden, and diagnostic experience of DxE. Logistic regressions were used to assess differences in symptom burden between women with and without DxE. RESULTS: The estimated prevalence of DxE was 7.0% (2004 women of 28 532 women surveyed). Almost half (47.5%) of women with DxE were aged 18 to 29 when they received an endometriosis diagnosis, and 84.1% experienced symptoms before diagnosis. More women with versus without DxE experienced menstrual pelvic pain or cramping (70.3% vs. 50.7%), non-menstrual pelvic pain or cramping (49.5% vs. 18.7%), dyspareunia (52.5% vs. 28.0%), and infertility (22.3% vs. 6.3%). Women with DxE were more likely to report severe menstrual pelvic pain or cramping (odds ratio [OR] 2.9; 95% confidence interval [CI] 2.5-3.3), non-menstrual pelvic pain or cramping (OR 3.4; 95% CI 2.8-4.2), general abdominal pain (OR 3.0; 95% CI 2.5-3.6), and pelvic pressure (OR 3.0; 95% CI 2.3-3.8). Women with DxE reported an average 5.4-year diagnostic delay, with a 3.1-year delay from onset of symptoms to physician consultation and a 2.3-year delay between physician consultation and diagnosis. CONCLUSION: Self-reported DxE is prevalent among Canadian women and is associated with a substantial symptomatic burden. The 5.4-year diagnostic delay reported here indicates an important unmet need for more timely diagnosis of endometriosis in Canada.

A survey of care pathway and health-related quality of life impact for children with central precocious puberty.

Objective: To describe the timeline to diagnosis for children with central precocious puberty (CPP) and evaluate their psychosocial and health-related quality of life (HRQoL).Methods: A cross-sectional survey was used to prospectively collect data from caregivers, recruited via the MAGIC Foundation, of children with CPP. The control (non-CPP) group was recruited from a national panel of parents/caregivers. After completing a screening survey, respondents completed a burden of illness survey. Respondents in both groups completed the Pediatric Quality of Life Inventory (PedsQL) and Patient-Reported Outcomes Measurement Information System (PROMIS) peer relationship instruments.Results: Responses from 142 caregivers of children with and 300 without CPP were assessed. Mean time to treatment after a child's visit to the pediatric endocrinologist was 220 days and time from onset of symptoms to initiating treatment was approximately 2 years. Responses to HRQoL inventories were all lower in children with CPP versus non-CPP. Adjusted mean (± standard error) PedsQL total (65.3 ± 1.8 versus 75.7 ± 1.2), Psychosocial Health Summary (62.4 ± 1.8 versus 73.4 ± 1.2), and Physical Health Summary (70.7 ± 2.2 versus 79.9 ± 1.5) scores were significantly lower (p < .01) in CPP versus non-CPP group. PROMIS peer relationship T score (± standard error) was numerically lower for the CPP versus non-CPP group (45.4 ± 1.0 versus 47.4 ± 0.7, p = .11).Conclusions: In clinical practice, there is a longer than expected delay between CPP symptom onset and referral to an endocrinologist and ultimate treatment. Children with CPP experience a substantial disease burden with a significant impact on emotional, social, and physical functioning compared with children without CPP.

Current practice patterns in CIDP: A cross-sectional survey of neurologists in the United States.

To evaluate how neurologists make decisions regarding chronic inflammatory demyelinating polyneuropathy (CIDP), we conducted a cross-sectional quantitative survey of 100 community neurologists in the United States. Only 13% cited using the European Federation of Neurological Societies/Peripheral Nerve Society guideline. In addition, variability in treatment approaches existed regarding the dose of IVIg used, the length of IVIg therapy before determining response, the outcome measures used to determine IVIg response, and the protocol for weaning off therapy. Forty-three percent reported giving doses that were lower than the recommended IVIg loading dose for CIDP. Many reported giving nonspecific patient education about the rationale of IVIg use and treatment duration. The finding that approximately half of community neurologists endorsed electrodiagnostic criteria that do not support CIDP diagnosis indicated difficulties relying heavily upon neurophysiologic studies in diagnostic guidelines. More education on CIDP diagnosis and treatment and a clear, actionable, clinically focused guideline would enhance best practices, particularly in the midst of high information flow and multiple guidelines.

Fluid resuscitation practices in cardiac surgery patients in the USA: a survey of health care providers.

BACKGROUND: Fluid resuscitation during cardiac surgery is common with significant variability in clinical practice. Our goal was to investigate current practice patterns of fluid volume expansion in patients undergoing cardiac surgeries in the USA. METHODS: We conducted a cross-sectional online survey of 124 cardiothoracic surgeons, cardiovascular anesthesiologists, and perfusionists. Survey questions were designed to assess clinical decision-making patterns of intravenous (IV) fluid utilization in cardiovascular surgery for five types of patients who need volume expansion: (1) patients undergoing cardiopulmonary bypass (CPB) without bleeding, (2) patients undergoing CPB with bleeding, (3) patients undergoing acute normovolemic hemodilution (ANH), (4) patients requiring extracorporeal membrane oxygenation (ECMO) or use of a ventricular assist device (VAD), and (5) patients undergoing either off-pump coronary artery bypass graft (OPCABG) surgery or transcatheter aortic valve replacement (TAVR). First-choice fluid used in fluid boluses for these five patient types was requested. Descriptive statistics were performed using Kruskal-Wallis test and follow-up tests, including t tests, to evaluate differences among respondent groups. RESULTS: The most commonly preferred indicators of volume status were blood pressure, urine output, cardiac output, central venous pressure, and heart rate. The first choice of fluid for patients needing volume expansion during CPB without bleeding was crystalloids, whereas 5% albumin was the most preferred first choice of fluid for bleeding patients. For volume expansion during ECMO or VAD, the respondents were equally likely to prefer 5% albumin or crystalloids as a first choice of IV fluid, with 5% albumin being the most frequently used adjunct fluid to crystalloids. Surgeons, as a group, more often chose starches as an adjunct fluid to crystalloids for patients needing volume expansion during CPB without bleeding. Surgeons were also more likely to use 25% albumin as an adjunct fluid than were anesthesiologists. While most perfusionists reported using crystalloids to prime the CPB circuit, one third preferred a mixture of 25% albumin and crystalloids. Less interstitial edema and more sustained volume expansion were considered the most important colloid traits in volume expansion. CONCLUSIONS: Fluid utilization practice patterns in the USA varied depending on patient characteristics and clinical specialties of health care professionals.

Fluid resuscitation practice patterns in intensive care units of the USA: a cross-sectional survey of critical care physicians.

BACKGROUND: Fluid resuscitation is a cornerstone of intensive care treatment, yet there is a lack of agreement on how various types of fluids should be used in critically ill patients with different disease states. Therefore, our goal was to investigate the practice patterns of fluid utilization for resuscitation of adult patients in intensive care units (ICUs) within the USA. METHODS: We conducted a cross-sectional online survey of 502 physicians practicing in medical and surgical ICUs. Survey questions were designed to assess clinical decision-making processes for 3 types of patients who need volume expansion: (1) not bleeding and not septic, (2) bleeding but not septic, (3) requiring resuscitation for sepsis. First-choice fluid used in fluid boluses for these 3 patient types was requested from the respondents. Descriptive statistics were performed using a Kruskal-Wallis test to evaluate differences among the physician groups. Follow-up tests, including t tests, were conducted to evaluate differences between ICU types, hospital settings, and bolus volume. RESULTS: Fluid resuscitation varied with respect to preferences for the factors to determine volume status and preferences for fluid types. The 3 most frequently preferred volume indicators were blood pressure, urine output, and central venous pressure. Regardless of the patient type, the most preferred fluid type was crystalloid, followed by 5 % albumin and then 6 % hydroxyethyl starches (HES) 450/0.70 and 6 % HES 600/0.75. Surprisingly, up to 10 % of physicians still chose HES as the first choice of fluid for resuscitation in sepsis. The clinical specialty and the practice setting of the treating physicians also influenced fluid choices. CONCLUSIONS: Practice patterns of fluid resuscitation varied in the USA, depending on patient characteristics, clinical specialties, and practice settings of the treating physicians.

Restless legs syndrome (RLS) augmentation associated with dopamine agonist and levodopa usage in a community sample.

OBJECTIVE: Assess the rate of augmentation as it occurs during standard long-term dopaminergic treatment of RLS, potential risk factors or predictors of augmentation, the relationship between treatment duration and augmentation, and the clinical impact of augmentation on subjects' health outcomes. METHODS: Two hundred sixty-six patients with dopamine-treated RLS completed a one-time online survey. All subjects were recruited by their PCP/neurologist and were 18 or older. Augmentation was assessed using NIH guidelines and an augmentation classification system was developed through this research. RESULTS: Overall, 20% of the patients were classified as having definitive or highly suggestive clinical indications of augmentation. Five factors were considered likely to reflect increased risk of developing augmentation, including more frequent RLS symptoms pre-treatment, greater discomfort with RLS symptoms before treatment, and longer treatment duration. RLS augmentation occurred at a rate of about 8% each year for at least the first 8 years of dopamine treatment. Subjects reporting definite or highly suggestive clinical indicators of augmentation had an average IRLS score of 23.6, indicating generally inadequate treatment with generally poor clinical outcomes. Only 25% of the patients reported no indications of augmentation and they were the only group to show on average a low (<15) IRLS score and good clinical outcomes. CONCLUSIONS: As currently used, long term dopaminergic treatment for an average ± SD of 2.7 ± 2.4 years produced significant augmentation problems in at least 20% of the patients and only 25% of the patients were totally free of this problem. It is important for physicians to carefully screen patients for changes in RLS symptoms for as long as they are on dopamine agents, with particular attention paid to those patients who present with the most severe RLS symptoms prior to treatment initiation. Given the marked increase in suffering with augmentation, a method for early detection and intervention would be an important contribution to the effective management and treatment of RLS.