Statistical considerations for cardiovascular clinical trials straddling the continuum of pandemic phases.

In 2020, the NIH and FDA issued guidance documents that laid the foundation for human subject research during an unprecedented pandemic. To bridge these general considerations to actual applications in cardiovascular interventional device trials, the PAndemic Impact on INTErventional device ReSearch (PAIINTERS) Working Group was formed in early 2021 under the Predictable And Sustainable Implementation Of National CardioVascular Registries (PASSION CV Registries). The PAIINTER's Part I report, published by Rymer et al. [5], provided a comprehensive overview of the operational impact on interventional studies during the first year of the Pandemic. PAIINTERS Part II focused on potential statistical issues related to bias, variability, missing data, and study power when interventional studies may start and end in different pandemic phases. Importantly, the paper also offers practical mitigation strategies to adjust or minimize the impact for both SATs and RCTs, providing a valuable resource for researchers and professionals involved in cardiovascular clinical trials.

Impact of chronic medication de-escalation in patients with cystic fibrosis taking elexacaftor, tezacaftor, ivacaftor: A retrospective review.

BACKGROUND: This single-center, retrospective study evaluated the effects of de-escalating cystic fibrosis (CF) supportive therapies in patients on elexacaftor/tezacaftor/ivacaftor (ETI). For many with CF, the clinical benefit of ETI exceeds that of supportive therapies. Therefore, we anticipated patients would desire to discontinue many of their supportive therapies, leading to the creation of a de-escalation algorithm. If patients were clinically improved and stable on ETI, CF supportive therapies could be de-escalated quarterly in accordance with the algorithm. METHODS: The primary objective was to assess non-inferiority of supportive therapies de-escalation by comparing the absolute change in percent predicted (ppFEV1) from baseline to month 1 versus the absolute change from baseline to month 12 after initiating ETI with patients serving as their own control. A chart review of patients initiated on ETI from September 2019 through December 2020 was conducted. Inclusion criteria included those six years and older with at least one copy of F508del. RESULTS: The study included 174 patients. The mean ppFEV1 at baseline, month 1, and month 12 was 67%, 78%, and 87% respectively. The mean difference in absolute change in ppFEV1 from baseline to month 1 compared to baseline to month 12 after the initiation of ETI was 1.53% (95% CI: -0.49 to 3.55) CONCLUSION: De-escalating supportive therapies for those on ETI was non-inferior to remaining on all supportive therapies. This suggests that medications may be able to be discontinued under the context of a de-escalation algorithm, which may decrease medication burden and cost and increase quality of life.

Elexacaftor-Tezacaftor-Ivacaftor Therapy for Chronic Sinus Disease in Cystic Fibrosis.

Importance: Cystic fibrosis (CF) is a multiorgan genetic disease with progressive upper and lower airway involvement. The effects of CF transmembrane conductance regulator (CFTR) modifier therapies on CF-related upper airway disease, specifically chronic rhinosinusitis (CRS), are not characterized. Objective: To determine the outcome of elexacaftor-tezacaftor-ivacaftor (ETI) on CRS as measured by changes in sinus computed tomography (CT) metrics and on clinical parameters in individuals with CF. Design, Setting, and Participants: This prospective longitudinal cohort study was conducted at the CF center of a tertiary care hospital between October 1, 2019, and July 31, 2021. A total of 64 participants with CF were included in the analysis. Intervention: Sinus CT was obtained within 1 month of initiation of ETI therapy (baseline), and within 1 month of 1 year of ETI therapy. Images were independently analyzed by pulmonology, radiology, and otolaryngology physicians, using the Lund-Mackay and Sheikh-Lind scoring systems. Percent predicted forced expiratory volume in 1 second (ppFEV1), body mass index (BMI), and microbiologic data collected at initiation of ETI therapy and 3-month intervals for 1 year were also measured. Main Outcomes and Measures: The study hypothesis was that ETI therapy will improve CRS as measured by changes in sinus CT at initiation and 1 year after ETI therapy and clinical parameters in individuals with CF. Results: Among the 64 participants (39 [60.9%] female; median age, 18.5 [IQR, 16.0-28.5] years; 64 [100%] White), improvement in CRS was noted by improvements in sinus CT scans using both sinus CT scoring systems after 1 year of ETI therapy. The reduction in the median total score using the Lund-Mackay sinus CT scoring system (from 5.8 [IQR, 5.0-7.0] to 3.3 [IQR, 2.6-4.2]) and the Sheikh-Lind scoring system (from 3.8 [IQR, 3.0-5.0] to 2.2 [IQR, 2.0-2.5]) was noted. Increases in ppFEV1 and BMI were also observed by 3 months of ETI therapy with persistent improvement through 1 year of treatment. Similarly, after 1 year of ETI therapy, participants with CF had reductions in positivity for Pseudomonas aeruginosa and Staphylococcus aureus in oropharyngeal cultures. Conclusion and Relevance: This cohort study found that use of ETI therapy was associated with improved CRS outcomes in participants with CF as quantified by improved sinus CT scans measured by 2 radiographic scoring systems and was also associated with improved clinical outcomes. Despite improvement in CT scan scores, most people with CF continue to have scores that indicate severe sinus disease.

Impact of Elexacaftor-Tezacaftor-Ivacaftor on lung disease in cystic fibrosis.

BACKGROUND: In people with cystic fibrosis (pwCF), the impact of cystic fibrosis transmembrane conductance regulator (CFTR) modulator therapies, such as Elexacaftor-Tezacaftor-Ivacaftor (ETI), on structural changes in the lungs is unclear. OBJECTIVE: To determine the impact of ETI on clinical parameters and on structural lung disease as measured by the changes in the chest computed tomography (CT) scans in pwCF. METHODS: Percent predicted forced expiratory volume in one second (ppFEV1), body mass index (BMI), and microbiologic data were collected at initiation and 3-month intervals for 1 year. Chest CT scans before starting ETI therapy (baseline) and at 1-year on ETI therapy were compared by two pulmonologists independently. RESULTS: The sample size was 67 pwCF, 30 (44.8%) males, median age of 25 (16, 33.5) years. Significant increases in ppFEV1 and BMI observed by 3 months of ETI therapy persisted throughout 1 year of ETI therapy (p < 0.001 at all-time points for both). After 1 year on ETI, pwCF had significant reductions in Pseudomonas aeruginosa (-42%) and MRSA (-42%) positivity. None of the pwCF had worsening of chest CT parameters during 1 year of ETI therapy. Comparing chest CT findings at baseline and at 1-year follow-up, bronchiectasis was present in 65 (97%) pwCF and at 1-year follow-up decreased in 7 (11%). Bronchial wall thickening 64 (97%), decreased in 53 (79%). Mucous plugging in 63 (96%), absent in 11 (17%), and decreased in 50 (77%). Hyperinflation/air trapping in 44 (67%), decreased in 11 (18%), absent in 27 (44%) CONCLUSIONS: ETI significantly improved clinical outcomes and lung disease as documented by improvement in chest CT scans.

Clinical change 2 years from start of elexacaftor-tezacaftor-ivacaftor in severe cystic fibrosis.

RATIONALE: Limited published research is available on the impact of elexacaftor/tezacaftor/ivacaftor (ETI) beyond the initial few months postdrug initiation, especially for those who initiated therapy via individual investigational new drug application. The experiences of patients with cystic fibrosis (CF) experiencing severe lung disease were reviewed for significant improvements in clinical symptoms and quality of life. OBJECTIVES: To examine clinical outcomes 2 years post-ETI in patients with CF and advanced lung disease. METHODS: This single center institutional review board-approved, retrospective chart review assessed clinical markers (percent predicted forced expiratory volume in 1 s, weight, sweat chloride), quality of life and computed tomography scans in patients with advanced lung disease who met criteria for compassionate use/expanded access program due to high risk of death or transplant need within 2 years. RESULTS: Eighteen identified patients (ages 15-49 years) initiated drug between July and September 2019. Clinical markers indicated that therapy was well tolerated, not discontinued by any participant, and lab values did not indicate medical concern or discontinuation. Monitoring results indicated the safety of modulator therapy as there were no adverse clinical occurrences and all patients presented universal stabilization. There were no deaths and no transplants by the end of the study. CONCLUSIONS: This study focused on patients with CF eligible for modulator therapy and were initiated due to advanced lung disease. Initiation of modulator therapy was deemed safe and resulted in objective positive changes in nutrition, cough, FEV1 , subjective reports of clinical status, level of activity, and a reduction in burden of treatment.

Accuracy of Three Commercial Home-Use Hemoglobin A1c Tests.

Background: The COVID-19 pandemic and the rapid expansion of telemedicine have increased the need for accurate and reliable capillary hemoglobin A1c (HbA1c) testing. Nevertheless, validation studies of commercially available products suitable for home use have been in short supply. Methods: Three commercial home-use capillary blood sample HbA1c tests (Home Access, CoreMedica, and A1cNow+) were evaluated in 219 participants with type 1 or type 2 diabetes (4-80 years years of age, HbA1c 5.1%-13.4% [32-123 mmol/mol]) at four clinical sites. Comparisons were made between HbA1c measurements from the commercial tests and paired venous samples for which HbA1c was measured at two central reference laboratories. The primary outcome was percentage of commercial HbA1c values within 5% of the corresponding reference values. Results: HbA1c values were within 5% (relative difference) of paired reference values for 82% of Home Access samples, 29% of CoreMedica samples, and 46% of A1cNow+ samples. Absolute differences were within 0.3% of the reference value for 75% of Home Access samples, 28% of CoreMedica samples, and 44% of A1cNow+ samples and exceeded 0.5% for 8%, 55%, and 37%, respectively. Conclusions: None of the commercial home-use HbA1c tests produced the National Glycohemoglobin Standardization Program goal of ≥90% measurements within 5% of a DCCT venous reference. However, the Home Access product performed substantially better than the CoreMedica or A1cNow+ products. Telemedicine is likely to persist as a mainstay of diabetes care well after the COVID-19 era. As such, accurate home-based HbA1c assessment represents an urgent need for the diabetes community.

An Evaluation of Two Capillary Sample Collection Kits for Laboratory Measurement of HbA1c.

Background: The COVID-19 pandemic has impacted the conduct of clinic visits. We conducted a study to evaluate two academic laboratories' fingerstick capillary blood collection kits suitable for home use for laboratory measurement of HbA1c. Methods: Four clinical sites recruited 240 participants (aged 4-80 years, HbA1c 5.1%-13.5%). Capillary blood samples were obtained by the participant or parent using collection kits from two laboratories (University of Minnesota Advanced Research and Diagnostic Laboratory (ARDL) and Children's Mercy Hospital Laboratory (CMH)) and mailed under varying shipping conditions by United States Postal Service to the laboratories. Comparisons were made between HbA1c measurements from capillary samples and contemporaneously obtained venous samples. The primary outcome was percentage of capillary HbA1c values within 5% of the corresponding venous values. Results: HbA1c values were within 5% of venous values for 96% of ARDL kit specimens shipped with a cold pack and 98% without a cold pack and 99% and 99%, respectively, for the CMH kits. R2 values were 0.98, 0.99, 0.99, and 0.99, respectively. Results appeared similar across HbA1c levels and for pediatric and adult participants. Usability survey scores were high. Conclusions: Capillary blood collection kits, suitable for home use, from two academic laboratories, were demonstrated to be easy to use and provided results that are comparable with those obtained from venous specimens. Based on these results, there is strong evidence that HbA1c measurements from capillary specimens obtained with these specific kits can be used interchangeably with HbA1c measurements from venous specimens for clinical research and clinical care.

Evaluating Glucose Control With a Novel Composite Continuous Glucose Monitoring Index.

OBJECTIVE: The objective was to describe a novel composite continuous glucose monitoring index (COGI) and to evaluate its utility, in adults with type 1 diabetes, during hybrid closed-loop (HCL) therapy and multiple daily injections (MDI) therapy combined with real-time continuous glucose monitoring (CGM). METHODS: COGI consists of three key components of glucose control as assessed by CGM: Time in range (TIR), time below range (TBR), and glucose variability (GV) (weighted by 50%, 35% and 15%). COGI ranges from 0 to 100, where 1% increase of time <3.9 mmol/L (<70 mg/dl) is equivalent to 4.7% reduction of TIR between 3.9-10 mmol/L (70-180 mg/dl), and 0.5 mmol/L (9 mg/dl) increase in standard deviation is equivalent to 3% reduction in TIR. RESULTS: Continuous subcutaneous insulin infusion (CSII) users with HbA1c >7.5-10%, had significantly higher COGI during 12 weeks of HCL compared to sensor-augmented pump therapy, mean (SD), 60.3 (8.6) versus 69.5 (6.9), P < .001. Similarly, in CSII users with HbA1c <7.5%, HCL improved COGI from 59.9 (11.2) to 74.8 (6.6), P < .001. In MDI users with HbA1c >7.5% to 9.9%, use of real-time CGM led to improved COGI, 49.8 (14.2) versus 58.2 (9.1), P < .0001. In MDI users with impaired awareness of hypoglycemia, use of real-time CGM led to improved COGI, 53.4 (12.2) versus 66.7 (11.1), P < .001. CONCLUSIONS: COGI summarizes three key aspects of CGM data into a concise metric that could be utilized to evaluate the quality of glucose control and to demonstrate the incremental benefit of a wide range of treatment modalities.

Accuracy, Utilization, and Effectiveness Comparisons of Different Continuous Glucose Monitoring Systems.

BACKGROUND: Accuracy and feature sets of continuous glucose monitoring (CGM) systems may influence device utilization and outcomes. We compared clinical trial accuracy and real-world utilization and effectiveness of two different CGM systems. MATERIALS AND METHODS: Separately conducted accuracy studies of a fifth-generation and a sixth-generation CGM system involved 50 and 159 adults, respectively. For between-system performance comparisons, propensity score methods were utilized to balance cohort characteristics. Real-world outcomes were assessed in 10,000 anonymized patients who had switched from the fifth-generation to the sixth-generation system and had used connected mobile devices to upload data from both systems, allowing pairwise comparisons of device utilization and glucose concentration distributions. RESULTS: Propensity score-adjusted mean absolute relative differences for the fifth- and sixth-generation systems were 9.0% and 9.9%, and the percentages of values within ±20%/20 mg/dL were 93.1% and 92.5%, respectively. The sixth-generation system, but not the fifth-generation system, met accuracy criteria for interoperable CGM systems. Both systems had high real-world utilization rates (93.8% and 95.3% in the fifth- and sixth-generation systems, respectively). Use of the sixth-generation system was associated with fewer glucose values <55 mg/dL (<3.1 mmol/L) (0.7% vs. 1.1%, P < 0.001) and more values 70-180 mg/dL (3.9-10.0 mmol/L) (57.3% vs. 56.0%, P < 0.001) than the fifth-generation system. CONCLUSIONS: CGM performance outcomes can be compared through the propensity score analysis of clinical trial data and pairwise comparisons of real-world data. The systems compared here had nearly equivalent accuracy and utilization rates. Longer term biochemical and psychosocial benefits observed with the fifth-generation system are also expected with the sixth-generation system.

Performance of a Factory-Calibrated, Real-Time Continuous Glucose Monitoring System in Pediatric Participants With Type 1 Diabetes.

BACKGROUND: The perceived value and consistent use of continuous glucose monitoring (CGM) systems depends in part on their accuracy. We assessed the performance of a sixth-generation CGM system (Dexcom G6) in children and adolescents. METHODS: Forty-nine participants (6-17 years of age, mean ± SD of 13.5 ± 3.3 years), all with type 1 diabetes, enrolled and data were available from 37. Each participant wore 1 sensor for up to 10 days and was asked to undergo an in-clinic visit lasting 6-12 hours for frequent blood glucose (BG) sample testing on one of the sensor wear days. Estimated glucose values (EGVs) from the G6 system were compared with venous BG values measured with a laboratory reference instrument (YSI). RESULTS: The overall mean absolute relative difference (MARD) for 1387 EGV-YSI pairs was 7.7%, and the overall percentage of EGVs within 20% or 20 mg/dL of the YSI reference value (for YSI > or ⩽100 mg/dL, respectively, the "%20/20") was 96.2%. The %20/20 was 92.1% on Day 1 and 91.0% on Day 10 of sensor wear. For EGVs <70 mg/dL, 92.6% of the YSI values were within 20 mg/dL and for EGVs >250 mg/dL, 100% of the YSI values were within 20%. Differences between EGVs and YSI values in over 99.9% of the pairs posed no or only slight clinical risk as evaluated by surveillance error grid analysis. CONCLUSIONS: The accuracy of the G6 CGM system in pediatrics may encourage consistent use of the system and contribute to improved glycemic outcomes in this population.

Resistance to Acetaminophen Interference in a Novel Continuous Glucose Monitoring System.

Acetaminophen (APAP) can cause erroneously high readings in real-time continuous glucose monitoring (rtCGM) systems. APAP-associated bias in an investigational rtCGM system (G6) was evaluated by taking the difference in glucose measurements between rtCGM and YSI from 1 hour before to 6 hours after a 1-g oral APAP dose in 66 subjects with type 1 or type 2 diabetes. The interference effect was defined as the average post-dose (30-90 minutes) bias minus the average baseline bias for each subject. The clinically meaningful interference effect was defined as 10 mg/dL. The G6 system's overall mean (±SD) interference effect was 3.1 ± 4.8 mg/dL (one-sided upper 95% CI = 4.1 mg/dL), significantly lower than 10 mg/dL. The G6 system's resistance to APAP interference should provide reassurance to those using the drug.

Assessment of occupational exposure to heat stress and solar ultraviolet radiation among groundskeepers in an eastern North Carolina university setting.

Groundskeepers spend most of the year working outdoors, exposing them to heat and solar ultraviolet (UV) radiation and increasing their risk to related adverse health effects. Various studies on heat and UV exposures in different occupations have been published, but those on groundskeepers are rare. The purpose of this study was to assess the exposure to heat stress and solar UV radiation among groundskeepers in an eastern North Carolina university setting. Wet bulb globe temperature (WBGT) index using a heat stress monitor and UV effective irradiance (UVeff) index using a digital UV meter were recorded in various work areas three times a day (morning, noon, afternoon) and during three seasons (spring, summer, fall). Data analysis was conducted using descriptive statistics, analysis of variance (ANOVA), Tukey Honestly Significant Difference (HSD), and Pearson Correlation tests. The mean (±SD) WBGT index was the highest in the afternoon (25.4 ± 5.0°C), summer (27.8 ± 3.1°C), and July (29.0 ± 2.6°C); the mean UVeff index was the highest at noon, summer and June (0.0116 ± 0.0061, 0.0101 ± 0.0081, and 0.0114 ± 0.0089 mW/cm2, respectively). Differences in the mean WBGT and UVeff indices within the time periods of day, seasons and months were significant (P < 0.01). The overall correlation between WBGT and UV indices was moderate (r = 0.42, P < 0.01) but lack of correlation was found during different times of the day during the fall and summer seasons. The largest percentages of WBGT indices exceeding the American Conference of Governmental Industrial Hygienists (ACGIH) threshold limit values (TLVs) for different workloads were found in the afternoon (11.3-40.7%), summer (14.6-56%), and July (28.8-76.3%). The mean UVeff for noon (0.0116 mW/cm2) and afternoon (0.0100 mW/cm2) exceeded the TLV for 30-min exposure. This study shows that groundskeepers are potentially exposed to excessive heat stress and UV radiation, and are at risk to developing heat- and UV-related illnesses. The study findings will be beneficial in implementing recommended control measures to prevent heat stress and UV exposure among groundskeepers and other similar outdoor workers.

Computed tomography correlates with improvement with ivacaftor in cystic fibrosis patients with G551D mutation.

BACKGROUND: Ivacaftor corrects the cystic fibrosis transmembrane conductance regulator (CFTR) gating defect associated with G551D mutation and is quickly becoming an important treatment in patients with cystic fibrosis (CF) due to this genetic mutation. METHODS: A single-center study was performed in CF patients receiving ivacaftor to evaluate the usefulness of high resolution computed tomography (HRCT) of the chest as a way to gauge response to ivacaftor therapy. RESULTS: Ten patients with CF were enrolled for at least one year before and after starting ivacaftor. At time of enrollment, mean age was 20.9 ± 10.8 (range 10-44) years. There were significant improvements from baseline to 6 months in mean %FVC (93 ± 16 to 99 ± 16) and %FEV1 (79 ± 26 to 87 ± 28) but reverted to baseline at one year. Mean sweat chloride levels decreased significantly from baseline to one year. Mean weight and BMI improved at 6 months. Weight continued to improve with stabilization of BMI at one year. Chest HRCT showed significant improvement at one year in mean modified Brody scores for bronchiectasis, mucous plugging, airway wall thickness, and total Brody scores. Elevated bronchiectasis and airway wall thickness scores correlated significantly with lower %FEV1, while higher airway wall thickness and mucus plugging scores correlated with more pulmonary exacerbations requiring IV and oral antibiotics respectively. CONCLUSIONS: Based on our findings, HRCT imaging is a useful tool in monitoring response to ivacaftor therapy that corrects the gating defect associated with the G551D-CFTR mutation.

Wilcoxon's signed-rank statistic: what null hypothesis and why it matters.

In statistical literature, the term 'signed-rank test' (or 'Wilcoxon signed-rank test') has been used to refer to two distinct tests: a test for symmetry of distribution and a test for the median of a symmetric distribution, sharing a common test statistic. To avoid potential ambiguity, we propose to refer to those two tests by different names, as 'test for symmetry based on signed-rank statistic' and 'test for median based on signed-rank statistic', respectively. The utility of such terminological differentiation should become evident through our discussion of how those tests connect and contrast with sign test and one-sample t-test. Published 2014. This article is a U.S. Government work and is in the public domain in the USA.

Trends in the treatment of localized prostate cancer using supplemented cancer registry data.

OBJECTIVE: To conduct an analysis of localized prostate cancer treatment in the USA between 1998 and 2002. PATIENTS AND METHODS: Results from the National Cancer Institute's Patterns of Care study from 10 regional cancer registries in 1998 and 14 registries in 2002 were compared using univariate and multivariate statistical methods. RESULTS: Patients with localized prostate cancer in 2002 were younger, had lower prostate-specific antigen values, and higher Gleason scores compared with those diagnosed in 1998. Little change occurred in age-adjusted percentages of men who were treated with a radical prostatectomy (45-46%) or by external beam radiation (EBRT) alone (19-20%). The proportion receiving brachytherapy (BT), alone or with EBRT, increased from 14.9 to 17.7%, while the proportion receiving watchful waiting declined from 12.6 to 9.0%. Younger African-American men with intermediate/high-risk disease were less likely to receive any type of aggressive therapy in comparison with Non-Hispanic White men. Over 70% of men who were ≥ 75 years of age, with low-risk disease, were treated with EBRT or BT. CONCLUSIONS: Older men with low-risk disease might be overtreated with aggressive therapy, while younger intermediate/high-risk African-American men appear less likely to receive indicated aggressive therapy.

Racial/Ethnic differences in functional outcomes in the 5 years after diagnosis of localized prostate cancer.

PURPOSE: We investigated racial/ethnic differences in functional outcomes up to 5 years after diagnosis among men with aggressively treated localized prostate cancer. PATIENTS AND METHODS: Patients were from the Prostate Cancer Outcomes Study, a population-based cohort study that surveyed patients at 6, 12, 24, and 60 months after diagnosis. Analyses were stratified by primary treatment. Racial/ethnic differences at each time point were assessed using Generalized Estimating Equations, adjusting for pretreatment function, age at diagnosis, secondary treatment, and other confounders. An adjusted summary score for each functional domain was calculated for each time period. RESULTS: Patients included 1,475 non-Hispanic white, 321 African-American, and 279 Hispanic prostate cancer patients. After 60 months, among prostatectomy patients, African-Americans had significantly higher sexual function scores than non-Hispanic whites (43.9 v 36.1; P = .02), but were more likely to have a moderate to big problem with sexual function (50.6% v 44.4%; P = .04). African-Americans also had higher urinary function scores at 5 years than non-Hispanic whites (78.5 v 72.4; P = .04) and were less likely to have problems with incontinence. Changes in sexual and bowel function after radiotherapy showed no significant racial/ethnic differences. CONCLUSION: This long-term cohort study found that, among prostatectomy patients, African-Americans had better recovery of sexual and urinary function at 60 months after diagnosis that was likely to be of mild clinical significance, despite reporting more problems with sexual function than non-Hispanic whites. More study is necessary to understand reasons for these differences. In contrast, no racial/ethnic differences in recovery from radiotherapy were found.

Developing and implementing lifestyle management programs© with people with multiple sclerosis.

SUMMARY This paper describes the development and use of Lifestyle Management Programs© (LMPs) by occupational therapists at the Multiple Sclerosis Society of New South Wales, Australia. A case study is used to demonstrate how the program is applied in an individual situation. LMPs are used with people with MS, or their support people, to enable management of the impact of fluctuating and interactive physical, sensory and cognitive symptoms. LMPs are flexible and adaptable systems, allowing integration of information and strategies for managing symptoms. LMPs assist clients to sustain meaningful activities and life roles. Subjective client feedback supports the effectiveness of the programs in meeting specific individual goals. Formal outcome measures are being explored.