On-Demand Manufacturing of Direct Compressible Tablets: Can Formulation Be Simplified?

PURPOSE: Oral direct compressible tablets are the most frequently used drug products. Manufacturing of tablets requires design and development of formulations, which need a number of excipients. The choice of excipients depends on the concentration, manufacturability, stability, and bioavailability of the active pharmaceutical ingredients (APIs). At MIT, we developed a miniature platform for on-demand manufacturing of direct compressible tablets. This study investigated how formulations could be simplified to use a small number of excipients for a number of different API's in which long term stability is not required. METHOD: Direct compressible tablets of five pharmaceutical drugs, Diazepam, Diphenhydramine HCl, Doxycycline Monohydrate, Ibuprofen, and Ciprofloxacin HCl, with different drug loadings, were made using direct compression in an automated small scale system.. The critical quality attributes (CQA) of the tablets were assessed for the quality standards set by the United States Pharmacopeia (USP). RESULTS: This miniature system can manufacture tablets - on-demand from crystalline API using the minimum number of excipients required for drug product performance. All drug tablets met USP quality standards after manufacturing and after 2 weeks of accelerated stability test, except for slightly lower drug release for Ibuprofen. CONCLUSIONS: On-demand tablets manufacturing where there is no need for long term stability using a flexible, miniature, automated (integrated) system will simplify pharmaceutical formulation design compared to traditional formulations. This advancement will offer substantial economic benefits by decreasing product time-to-market and enhancing quality.

Effect of simulated refractive error on adult visual acuity for paediatric tests.

PURPOSE: Although vanishing optotype preferential-looking tasks are commonly used to measure visual acuity (VA), the relative sensitivity of these tests to refractive error is not well understood. To address this issue, we determined the effect of spherical and astigmatic simulated refractive errors on adult VA measures obtained using vanishing optotypes, picture optotypes and Sloan letters. METHODS: VA was determined uniocularly for adults under conditions of spherical (0.0-3.0 DS; n = 23) and astigmatic (0.0-3.0 DC at 90° and 180°; n = 20) defocus using the Cardiff Acuity Test (vanishing optotypes), crowded linear Lea Symbols (picture-optotype recognition task) and the Early Treatment of Diabetic Retinopathy Study (ETDRS) letter chart. RESULTS: The Cardiff Acuity Test over-estimated VA compared with the Lea Symbols and ETDRS charts in both focused and defocused conditions. The mean difference between the Cardiff Acuity Test and the ETDRS chart was 0.31 logMAR (95% limits of agreement (LOA) 0.10-0.52 logMAR) in focused conditions and 0.64 logMAR (95% LOA 0.25-1.05 logMAR) with 3D of spherical defocus. Defocus degraded VA on all charts, however there was a significant chart-by-defocus interaction whereby the Cardiff Acuity Test was more resistant to the effects of both spherical (P < 0.0001) and cylindrical (P < 0.001) optical defocus than the recognition acuity tasks at all defocus levels. CONCLUSION: Although the Cardiff Acuity Test provides an easy method for VA measurement in infants and toddlers, there is a considerable overestimation of VA compared with recognition acuity tasks particularly in the presence of defocus. A simple correction factor (of for example three lines overestimate) cannot be applied to Cardiff acuity measures as there is increasing over-estimation of VA with increasing defocus. Infants with significant refractive error may fall within normal visual acuity ranges for the Cardiff Acuity Test.

Competence, Compassion, and Care of the Self: Family Caregiving Needs and Concerns in Heart Failure.

BACKGROUND: Family caregivers are essential to the well-being of patients with chronic heart failure (HF) because they provide care in managing complex medication regimens, dietary sodium restrictions, and symptoms. OBJECTIVE: The purpose of this qualitative study was to gain a deeper understanding of the HF caregiving experience and describe the needs and concerns expressed by caregivers. METHODS: Qualitative descriptive methodology was conducted using data from responses to open-ended questions asked as part of a larger longitudinal study. The sample was 63 patients with HF and 63 family caregivers. RESULTS: Using basic content analysis, the 3 main themes of needs and concerns that emerged were competence concerns, compassion maintenance, and care of the self. Subthemes of competence concerns were doing things right, making a serious mistake, and uncertainty. CONCLUSIONS: Family caregivers of patients with HF had many needs and concerns about their competence in performing tasks, their compassion, and caring for themselves. Data can be used to design testable interventions to improve the HF caregiving experience for patients and caregivers.

Psychometric evaluation of the ostomy complication severity index.

PURPOSE: The purpose of this study was to evaluate the psychometric properties of a new instrument to measure incidence and severity of ostomy complications early in the postoperative period. SUBJECTS AND SETTINGS: 71 participants were enrolled, most were men (52%), white (96%), and married or partnered (55%). The mean age of participants was 57 ± 15.09 years (mean ± SD). Fifty-two participants (84%) experienced at least 1 ostomy complication in the 60-day postoperative period. The research setting was 3 acute care settings within a large healthcare system in the Midwestern United States. INSTRUMENT: We developed an evidence-based conceptual model to guide development and evaluation of a new instrument, the Pittman Ostomy Complication Severity Index (OCSI). The OCSI format includes Likert-like scale with 9 individual items scored 0 to 3 and a total score computed by summing the individual items. Higher scores indicate more severe ostomy complications. METHOD: This study consisted of 2 phases: (1) an expert review, conducted to establish content validity; and (2) a prospective, longitudinal study design, to examine psychometric properties of the instrument. A convenience sample of 71 adult patients who underwent surgery to create a new fecal ostomy was recruited from 3 hospitals. Descriptive analyses, content validity indices, interrater reliability testing, and construct validity testing were employed. RESULTS: Common complications included leakage (60%), peristomal moisture-associated dermatitis (50%), stomal pain (42%), retraction (39%), and bleeding (32%). The OCSI demonstrated acceptable evidence of content validity index (CVI = 0.9) and interrater reliability for individual items (k = 0.71-1.0), as well as almost perfect agreement for total scores among raters (ICC = 0.991, P ≤ .001). Construct validity of the OCSI was supported by significant correlations among variables in the conceptual model (complications, risk factors, stoma care self-efficacy, and ostomy adjustment). CONCLUSION: OCSI demonstrated acceptable validity and reliability and can be used to assess incidence and severity of ostomy complications in the early postoperative period. We found the OCSI to be brief, easy-to-use, and clinically practical. It can be used to (a) identify priority areas for nursing intervention related to the ostomy, (b) determine appropriate interventions to prevent or treat complications, and (c) evaluate the effects of nursing interventions designed to improve outcomes for patients with ostomies.

Family caregivers of patients with heart failure: a longitudinal study.

BACKGROUND: The family caregivers of patients with heart failure (HF) report burden and poor quality of life, but little is known about changes in their perceptions over time. OBJECTIVES: The aims of this study were (1) to evaluate changes in caregiver burden (perceived time spent and difficulty with caregiving tasks), perceived control, depressive symptoms, anxiety, perceived life changes, and physical and emotional health-related quality of life; (2) to determine differences in perceptions between caregivers of patients with low HF symptoms (New York Heart Association class I and II) and caregivers of patients with high HF symptoms (New York Heart Association class III and IV); and (3) to the estimate time spent performing caregiving tasks. METHODS: Sixty-three HF patients and 63 family caregivers were enrolled; 53 caregivers completed the longitudinal study. Data were collected from medical records and interviews conducted by advanced practice nurses at baseline and 4 and 8 months later. RESULTS: Caregivers who completed the study had significant improvements in perceived time spent on and difficulty of caregiving tasks from baseline to 4 and 8 months, and depressive symptoms decreased from baseline to 8 months. Perceived life changes resulting from caregiving became more positive from baseline to 4 and 8 months. Perceived control, anxiety, and health-related quality of life did not change. Compared with caregivers of patients with low symptoms, caregivers of patients with high symptoms perceived that they spent more time on tasks and that tasks were more difficult, had higher anxiety, and had poorer physical health-related quality of life. Estimated time in hours spent providing care was high. CONCLUSIONS: In this sample, perceptions of the caregiving experience improved over 8 months. Health-related quality of life was moderately poor over the 8 months. Caregivers of patients with more severe HF symptoms may be particularly in need of interventions to reduce time and difficulty of caregiving tasks and improve physical health-related quality of life.

'Struggling to be an insider': a phenomenological design of new nurses' transition.

AIMS AND OBJECTIVES: To obtain a comprehensive understanding of the transition process of new nurses in Taiwan. Background. The transition period for new nurses can be a daunting and traumatic experience. The large number of newly graduated Taiwanese nurses who resign from their jobs within three months indicates that this process can be complicated. However, the problems associated with the experiences of new nurses have not yet been recognised. DESIGN: We adopted a phenomenological design using focus group interviews. METHODS: Sixteen new nurses (less than one year working experience) participated in eight weekly group interviews lasting two hours each to grasp their experience of 'being new'. Interview data were analysed according to Sloan's (2002) three moments, and the whole process of analysis followed the suggestions of Agar (1986), which was performed in a close collaboration between researchers until the consensus about the findings could be reached. RESULTS: The overarching pattern of the transition process of new nurses becoming experienced members of the clinical nursing team was revealed as a journey of 'struggling to be an insider'. This phenomenon was characterised by four themes, including (1) 'being new as being weak', (2) 'masking myself', (3) 'internalising the unreasonable' and (4) 'transforming myself to get a position'. CONCLUSIONS: While Western culture view abusive indoctrination of new nurses as toxic behaviour, under the Chinese traditions of yield, tolerance and self-oppression, following the power hierarchy and seeking harmony, the transition of new nurses is interpreted differently. RELEVANCE TO CLINICAL PRACTICE: Recognition of the journey of 'struggling to be an insider' helps nurse administrators to (1) gain a better understanding of what new nurses encounter in their transition process, (2) help new nurses without harm, (3) improve in-service training programmes and (4) retain future nurses.

An Insurance Value Modeling Approach That Captures the Wider Value of a Novel Antimicrobial to Health Systems, Patients, and the Population.

Background: Traditional health economic evaluations of antimicrobials currently underestimate their value to wider society. They can be supplemented by additional value elements including insurance value, which captures the value of an antimicrobial in preventing or mitigating impacts of adverse risk events. Despite being commonplace in other sectors, constituents of the impacts and approaches for estimating insurance value have not been investigated. Objectives: This study assessed the insurance value of a novel gram-negative antimicrobial from operational healthcare, wider population health, productivity, and informal care perspectives. Methods: A novel mixed-methods approach was used to model insurance value in the United Kingdom: (1) literature review and multidisciplinary expert workshops to identify risk events for 4 relevant scenarios: ward closures, unavoidable shortage of conventional antimicrobials, viral respiratory pandemics, and catastrophic antimicrobial resistance (AMR); (2) parameterizing mitigable costs and frequencies of risk events across perspectives and scenarios; (3) estimating insurance value through a Monte Carlo simulation model for extreme events and a dynamic disease transmission model. Results: The mean insurance value across all scenarios and perspectives over 10 years in the UK was £718 million, should AMR remain unchanged, where only £134 million related to operational healthcare costs. It would be 50%-70% higher if AMR steadily increased or if a more risk-averse view (1-in-10 year downside) of future events is taken. Discussion: The overall insurance value if AMR remains at current levels (a conservative projection), is over 5 times greater than insurance value from just the operational healthcare costs perspective, traditionally the sole perspective used in health budgeting. Insurance value was generally larger for nationwide or universal (catastrophic AMR, pandemic, and conventional antimicrobial shortages) rather than localized (ward closure) scenarios, across perspectives. Components of this insurance value match previously published estimates of operational costs and mortality impacts. Conclusions: Insurance value of novel antimicrobials can be systematically modeled and substantially augments their traditional health economic value in normal circumstances. These approaches are generalizable to similar health interventions and form a framework for health systems and governments to capture broader value in health technology assessments, improve healthcare access, and increase resilience by planning for adverse scenarios.

Influence of body mass on risk prediction during cardiopulmonary exercise testing in patients with chronic heart failure.

INTRODUCTION: Peak oxygen uptake (VO2) during a maximal exercise test is used to stratify patients with chronic heart failure (CHF) and is usually corrected for body mass. OBJECTIVE: To explore the influence of body mass on risk prediction during treadmill cardiopulmonary exercise testing (CPET) in patients with CHF. METHODS: A total of 411 patients with suspected CHF (mean [± SD] age 64±12 years; 81% male; mean left ventricular ejection fraction 39±6%) underwent symptom-limited, maximal CPET on a treadmill. Patients were categorized as normal weight, overweight or obese based on body mass index. RESULTS: One hundred fifteen patients died during a median follow-up period of 8.7±2.3 years in survivors. In the univariable analysis, peak VO2 adjusted for body mass (χ(2)=41.4) and unadjusted (χ(2)=40.2) were similar for predicting all-cause mortality. Peak VO2 adjusted for body mass showed marginally higher χ(2) values in normal weight, overweight and obese categories than unadjusted values. Anaerobic threshold had similar prognostic power regardless of whether it was corrected for body mass (χ(2)=22.4 and χ(2)=24.4), with no difference between the two in any of the subgroups separately. In all patients, unadjusted ventilation (VE)/carbon dioxide production (VCO2) slope (χ(2)=40.6) was a stronger predictor of all-cause mortality than body mass adjusted values (χ(2)=32.8), and unadjusted values remained stronger in normal weight, overweight and obese subgroups. CONCLUSION: Correcting peak VO2 for body mass slightly improves risk prediction, especially in obese patients with CHF. The adjustment of other CPET-derived variables including anaerobic threshold and VE/VCO2 slope for body mass appears to provide less prognostic value.

Variations in comorbidity burden in people with type 2 diabetes over disease duration: A population-based analysis of real world evidence.

Background: The prevalence of type 2 diabetes (T2DM) is increasing, but increasing longevity among persons with diagnosed diabetes may be is associated with more extensive and diverse types of morbidity. The extent and breadth of morbidity and how this varies across sub-groups is unclear and could have important clinical and public health implications. We aimed to estimate comorbidity profiles in people with T2DM and variations across sub-groups and over time. Methods: We identified approximately 224,000 people with T2DM in the Discover-NOW dataset, a real-world primary care database from 2000 to 2020 covering 2.5 million people across North-West London, England, linked to hospital records. We generated a mixed prevalence and incidence study population through repeated annual cross sections, and included a broad set of 35 comorbidities covering traditional T2DM conditions, emerging T2DM conditions and other common conditions.We estimated annual age-standardised prevalence of comorbidities, over the course of the disease in people with T2DM and several sub-groups. Findings: Multimorbidity (two or more chronic conditions) is common in people with T2DM and increasing, but the comorbidity profiles of people with T2DM vary substantially. Nearly 30% of T2DM patients had three or more comorbidities at diagnosis, increasing to 60% of patients ten years later. Two of the five commonest comorbidities at diagnosis were traditional T2DM conditions (hypertension (37%) and ischaemic heart disease (10%)) the other three were not (depression (15%), back pain (25%) and osteoarthritis (11%)). The prevalence of each increased during the course of the disease, with more than one in three patients having back pain and one in four having depression ten years post diagnosis.People with five or more comorbidities at diagnosis had higher prevalence of each of the 35 comorbidities. Hypertension (73%) was the commonest comorbidity at diagnosis in this group; followed by back pain (69%), depression (67%), asthma (45%) and osteoarthritis (36%). People with obesity at diagnosis had substantially different comorbidity profiles to those without, and the five commonest comorbidities were 50% more common in this group. Interpretation: Preventative and clinical interventions alongside care pathways for people with T2DM should transition to reflect the diverse set of causes driving persistent morbidity. This would benefit both patients and healthcare systems alike. Funding: The study was funded by the National Institute for Health and Care Excellence (NICE).

Cognitive deficits in chronic heart failure.

BACKGROUND: Patients with heart failure (HF) have been found to have cognitive deficits, but it remains unclear whether these deficits are associated with HF or with aging or comorbid conditions common in HF. OBJECTIVES: : The purpose of this study was (a) to determine the types, the frequency, and the severity of cognitive deficits among patients with chronic HF compared with age- and education-matched healthy participants and participants with major medical conditions other than HF, and (b) to evaluate the relationships between HF severity, age, and comorbidities and cognitive deficits. METHODS: A sample of 414 participants completed the study (249 HF patients, 63 healthy and 102 medical participants). The HF patients completed measures of HF severity, comorbidity (multiple comorbidity, depressive symptoms), and neuropsychological functioning. Blood pressure and oxygen saturation were assessed at interview; clinical variables were abstracted from records. Participants in the comparison groups completed the same measures as the HF patients except those specific to HF. RESULTS: Compared with the healthy and medical participants, HF patients had poorer memory, psychomotor speed, and executive function. Significantly more HF patients (24%) had deficits in three or more domains. Higher (worse) HF severity was associated with more cognitive deficits; HF severity interacted with age to explain deficits in executive function. Surprisingly, men with HF had poorer memory, psychomotor speed, and visuospatial recall ability than women. Multiple comorbidity, hypertension, depressive symptoms, and medications were not associated with cognitive deficits in this sample. DISCUSSION: HF results in losses in memory, psychomotor speed, and executive function in almost one fourth of patients. Patients with more severe HF are at risk for cognitive deficits. Older patients with more severe HF may have more problems in executive function, and men with HF may be at increased risk for cognitive deficits. Studies are urgently needed to identify the mechanisms for the cognitive deficits in HF and to test innovative interventions to prevent cognitive loss and decline.

Cognitive deficits and health-related quality of life in chronic heart failure.

BACKGROUND: Patients with chronic heart failure (HF) have cognitive deficits in memory, psychomotor speed, and executive function and poor health-related quality of life (HRQL), but the association between cognitive deficits and HRQL is unknown. OBJECTIVES: The objectives of this study were to (1) evaluate the relationship between HF severity, age, comorbidities, and cognitive deficits and HRQL among patients with chronic HF and (2) examine whether cognitive deficits mediated the relationship between HF severity and HRQL. DESIGN AND SAMPLE: This study was part of a larger explanatory study; 249 patients with HF completed face-to-face interviews. METHODS: Measures of HF severity, comorbidity (multiple comorbid conditions, hypertension, and depressive symptoms), cognitive function (domains of language, working memory, memory, psychomotor speed, and executive function), and HRQL were obtained. Clinical variables were abstracted from patients' records. Statistical analyses were conducted using descriptive statistics, Pearson correlation coefficients, and multiple linear regression analyses. RESULTS: Overall, the HRQL of patients was moderately poor. Heart failure severity, age, depressive symptoms, and total recall memory explained 55% of the variance in HRQL, but the contribution of memory was minimal (1%). Patients with more severe HF, younger age, and more depressive symptoms had poorer HRQL. Other cognitive function variables, multiple comorbidity, and hypertension were not significant explanatory variables for HRQL. Cognitive deficits did not mediate the relationship between HF severity and HRQL. CONCLUSIONS: Novel interventions targeted at improving HRQL continue to be urgently needed, particularly among younger patients and patients with depressive symptoms. Measures of HRQL are not sufficient as outcomes when investigating cognitive deficits in HF. Investigators need to include outcome measures of patients' actual abilities to perform daily activities and HF self-care.

Family caregiver outcomes in heart failure.

BACKGROUND: Family caregivers of patients with heart failure report high stress, burden, and poor emotional and physical health, but less is known about predictors of health among these caregivers. OBJECTIVES: To determine predictors of family caregiving outcomes among caregivers of patients with heart failure and to identify the tasks reported as most difficult and the most negative outcomes. METHODS: A total of 63 patients with heart failure and their 63 family caregivers were enrolled in this prospective study. Data were collected from medical records and from interviews conducted at baseline and 4 and 8 months later. RESULTS: Caregivers reported moderately poor physical and emotional health-related quality of life. Those with more depressive symptoms at baseline were more likely to report their lives had changed for the worse at 4 months (P=.03). The caregivers' medical health condition (P<.001) and perceived difficulty of caregiving tasks (P=.04) were predictors of physical health-related quality of life at 4 months; at 8 months, medical health condition was the only predictor (P=.004). At 4 and 8 months, depressive symptoms were predictors of emotional health-related quality of life (P<.001 and P=.001, respectively). The most difficult caregiving tasks were those dealing with patients' behavior problems; the most negative outcome was having less time for activities with friends. CONCLUSIONS: Studies are needed in larger samples to identify needs of vulnerable populations of caregivers of patients with heart failure and to develop and test interventions for improving caregivers' outcomes.

Cognitive deficits in heart failure: Re-cognition of vulnerability as a strange new world.

BACKGROUND: Patients with chronic heart failure (HF) have impairment in memory, psychomotor speed, and executive function. OBJECTIVE: The aim of this study was to describe how individuals with HF and cognitive deficits manage self-care in their daily lives. METHODS: Using an interpretive phenomenology method, HF patients completed unstructured face-to-face interviews about their ability to manage complex health regimens and maintain their health-related quality of life. Analysis of data was aided by use of Atlas.ti computer software. RESULTS: The sample consisted of 12 patients (10 men; aged 43-81 years) who had previously undergone neuropsychological testing and were found to have deficits in 3 or more cognitive domains. Patients confirmed that they followed the advice of healthcare providers by adherence to medication regimens, dietary sodium restrictions, and HF self-care. One overarching theme was identified: "Re-cognition of Vulnerability: A Strange New World." This theme was further differentiated into 3 components: (1) not recognizing cognitive deficits; (2) recognizing cognitive deficits, described as (a) never could remember anything, (b) just old age, (c) HF-related change, and (d) making normal accommodations; and (3) recognizing vulnerability, explained by perception of (a) cognitive, (b) physical, and (c) social vulnerabilities, as well as perception of (d) the nearness of death. DISCUSSION: Although the study was designed to focus on the cognitive changes in HF patients, it was difficult to separate cognitive, physical, and social challenges. These changes are most useful when taken as a constellation. Healthcare professionals can use the knowledge to identify problems and interventions for HF patients.

Physical function of patients with implantable cardioverter-defibrillators.

BACKGROUND: Patients with implantable cardioverter-defibrillators (ICDs) face problems in physical function, but little is known about how mastery predicts physical function over time. PURPOSE: The primary purpose of this study was to examine the influence of mastery (assessed at baseline) on physical function (observed distance walked and perceived function) over 12 months among ICD patients. Secondary purposes were to (1) examine the influence of aging, in interaction with mastery, on physical function and (2) determine predictors of 12-month physical function. METHODS: The ICD patients (N = 122; 75% men; 88% white; mean age, 65 years) completed the baseline interviews; 100 patients completed the 12-month interviews. Repeated-measures 1-way analyses of variance were used to examine the influence of mastery and the interaction of mastery and aging on physical function over 12 months. Multiple regression analyses were conducted to determine predictors of 12-month physical function. RESULTS: The ICD patients with higher mastery had better walk distances than those with lower mastery; and walk distances were improved over 12 months, but only in those with lower mastery (F = 5.40, P = .02). The ICD patients with higher mastery had better perceived physical function than those with lower mastery (F = 25.57, P < .0001), but those with both lower and higher mastery did not show significant improvement. Neither significant interaction of aging and mastery on physical function nor predictors of walk distances were found. Baseline depression significantly predicted 12-month perceived physical function (F = 8.94, P = .0042). CONCLUSIONS: The ICD patients with lower mastery had considerable impairments in physical function compared with those with higher mastery over time. Depression is more likely to predict perceived physical function. Further prospective studies are needed to validate these findings in a larger sample and develop interventions to improve physical impairment in ICD patients.

A causal model of health-related quality of life in Thai patients with heart-failure.

BACKGROUND: Heart failure is an increasing global health problem which adversely affects all aspects of a patient's health-related quality of life (HRQOL). PURPOSE: The hypothesized causal model of HRQOL in Thai heart-failure patients was based on Wilson and Cleary's HRQOL conceptual model. We examined causal relationships among bio-physiological status, symptoms, functional status, general health perception (GHP), and HRQOL shown in the model, and added an additional item-social support. METHODS: A stratified four-stage random sampling method was used to obtain 422 heart-failure patients 18 years of age and older who visited nine outpatient hospital clinics from five regions of Thailand including metropolitan Bangkok. In addition to the participants' personal medical records, research instruments consisted of a personal information questionnaire, the Enhancing Recovery in Coronary Heart Disease Social Support Instrument, Cardiac Symptom Survey, the New York Heart Association functional classification system, a 100-mm horizontal visual analogue scale of GHP, and the Minnesota Living with Heart Failure Questionnaire. Data were analyzed using SPSS and AMOS computer programs. RESULTS: The model fit well with the empirical data (chi(2)=19.87, df=13, p=0.10, GFI =0.99, and RMSEA=0.04). Symptom status was the most influential factor affecting HRQOL by both direct and indirect effects through functional status and GHP. Social support was the least influential factor affecting HRQOL. Social support had a negative direct effect on HRQOL, but had a positive indirect effect on HRQOL through symptom status and GHP. CONCLUSIONS: HRQOL was affected by each variable proposed in our causal model of HRQOL in Thai heart-failure patients. Symptom status had the strongest effect on HRQOL. CLINICAL RELEVANCE: A comprehensive symptom management and prevention program that includes the described health outcome measures could lead to improved HRQOL for Thai heart-failure patients, and perhaps others.

Perceived unsatisfactory care as a barrier to diabetes self-management for Coeur d'Alene tribal members with type 2 diabetes.

The prevalence of diabetes and related complications are disproportionally higher in Native Americans. Diabetes self-management (DSM) is instrumental in preventing complications. The results presented here are a part of a larger hermeneutic phenomenology study to explore living with diabetes for one Pacific Northwest tribe. This study identified barriers to DSM within the worldview of the tribal people. Using purposive sampling, 10 Coeur d'Alene tribal members, ages 26 to 86 years, participated in in-depth interviews. Data interpretation used a three-step method leading to integrated themes across the transcripts. Perceived unsatisfactory care emerged as the major barrier to self-management, including communication barriers (distrust, misunderstanding, and educational methods) and organizational barriers (quality of care and access issues). Findings highlight the need to improve cross-cultural communication and calls for different approaches to diabetes education. Our profession is challenged to create new DSM and diabetes educational approaches for acceptable and compassionate cross-cultural nursing care.

Development of a composite model derived from cardiopulmonary exercise tests to predict mortality risk in patients with mild-to-moderate heart failure.

OBJECTIVE: Cardiopulmonary exercise testing (CPET) is used to predict outcome in patients with mild-to-moderate heart failure (HF). Single CPET-derived variables are often used, but we wanted to see if a composite score achieved better predictive power. METHODS: Retrospective analysis of patient records at the department of cardiology, Castle Hill Hospital, Kingston-upon-Hull. 387 patients (median (25th-75th percentile)) (age 65 (56-72) years; 79% men; LVEF 34 (31-37) %) were included. Patients underwent a symptom-limited, maximal CPET on a treadmill. During a median follow-up of 8.6±2.1 years in survivors, 107 patients died. Survival models were built and validated using a hybrid approach between the bootstrap and Cox regression. Nine CPET-derived variables were included. Z-score defined each variable's predictive strength. Model coefficients were converted to a risk score. RESULTS: Four CPET-related variables were independent predictors of all-cause mortality in the survival model: the presence of exertional oscillatory ventilation (EOV), increasing slope of the relation between ventilation and carbon dioxide production (VE/VCO2 slope), decreasing oxygen uptake efficiency slope (OUES), and an increase in the lowest ventilatory equivalent for carbon dioxide (VEqCO2 nadir). Individual predictors of mortality ranged from 0.60 to 0.71 using Harrell's C-statistic, but the optimal combination of EOV+VE/VCO2 slope+OUES+VEqCO2 nadir reached 0.75. The Hull CPET risk score had a significantly higher area under the curve (0.78) when compared to the HF Survival Score (AUC=0.70; p<0.001). CONCLUSIONS: A composite risk score using variables from CPET out-performs the traditional single variable approach in predicting outcome in patients with mild-to-moderate HF.

Abnormalities of the ventilatory equivalent for carbon dioxide in patients with chronic heart failure.

Introduction. The relation between minute ventilation (VE) and carbon dioxide production (VCO(2)) can be characterised by the instantaneous ratio of ventilation to carbon dioxide production, the ventilatory equivalent for CO(2) (VEqCO(2)). We hypothesised that the time taken to achieve the lowest VEqCO(2) (time to VEqCO2 nadir) may be a prognostic marker in patients with chronic heart failure (CHF). Methods. Patients and healthy controls underwent a symptom-limited, cardiopulmonary exercise test (CPET) on a treadmill to volitional exhaustion. Results. 423 patients with CHF (mean age 63 ± 12 years; 80% males) and 78 healthy controls (62% males; age 61 ± 11 years) were recruited. Time to VEqCO2 nadir was shorter in patients than controls (327 ± 204 s versus 514 ± 187 s; P = 0.0001). Univariable predictors of all-cause mortality included peak oxygen uptake (X(2) = 53.0), VEqCO(2) nadir (X(2) = 47.9), and time to VEqCO(2) nadir (X(2) = 24.0). In an adjusted Cox multivariable proportional hazards model, peak oxygen uptake (X(2) = 16.7) and VEqCO(2) nadir (X(2) = 17.9) were the most significant independent predictors of all-cause mortality. Conclusion. The time to VEqCO(2) nadir was shorter in patients with CHF than in normal subjects and was a predictor of subsequent mortality.

Influence of step length on 6-minute walk test performance in patients with chronic heart failure.

OBJECTIVE: To investigate the influence of gait parameters including step length and walking speed during performance of the 6-minute walking test (6MWT) in patients with chronic heart failure (CHF). DESIGN: Observational study. SETTING: Specialist heart failure clinic. PARTICIPANTS: Patients with CHF and aged-matched, apparently healthy controls. INTERVENTIONS: Each patient and control performed a 6MWT following a standardised protocol in a 15m corridor. The number of steps (defined as step from left foot to right foot) taken every 15m was counted, and reported as minute-by-minute changes in 6MWT performance. In addition, minute-by-minute changes in time taken to complete 15m and mean walking speed throughout the test were calculated. MAIN OUTCOME MEASURES: Walking speed and step length. RESULTS: Thirty patients with CHF {87% males; mean age 75 [standard deviation (SD) 8] years} and 10 healthy controls [80% males; mean age 77 (SD 11) years] undertook the 6MWT. For the CHF group, the mean distance walked was 309 (SD 48)m and the peak Borg score was 12 (SD 1). For the controls, the mean distance walked was 334 (SD 138)m and the peak Borg score was 12 (SD 1). Patients with CHF showed no significant minute-by-minute changes in step length or walking speed over the course of the 6MWT. In the first 5minutes, healthy controls had a longer step length and faster walking speed than patients with CHF [step length: mean difference in the first minute was 0.03m, 95% confidence interval (CI) of the difference 0.01 to 0.05m; P=0.02; walking speed: mean difference in the first minute 0.04m/second, 95% CI of the difference 0.02 to 0.07m/second; P=0.01]. A multiple linear regression analysis demonstrated that body mass index (P=0.02) was the most important predictor of 6MWT performance. CONCLUSION: Patients with CHF have a shorter step length and walk more slowly than controls during the 6MWT. Altered gait mechanics may contribute to limited exercise capacity in patients with CHF.