Experiences of patients with poststroke spasticity throughout a botulinum toxin treatment cycle: Results from a prospective ethnographic study.

This study was conducted to capture the experience of patients with poststroke spasticity (PSS) throughout one botulinum neurotoxin A (BoNT-A) treatment cycle. The REBOT study (NCT03995524) was a prospective, observational ethnographic study conducted in France, Italy, the UK, and the USA. It combined a mixed-method ethnography (including semi-structured qualitative interviews within a week of a BoNT-A injection) with completion of a longitudinal quantitative patient-reported outcome questionnaire and sharing of video and images, both reported weekly over a 12-14-week period throughout the BoNT-A treatment cycle. The study recruited 30 adult patients with PSS who were receiving BoNT-A treatment. The most commonly used BoNT-A product was onabotulinumtoxinA (Botox®), which was administered to 21 patients (70%), whereas two patients (6.7%) received abobotulinumtoxinA (Dysport®) and seven patients (23.3%) did not specify the BoNT-A medication that they received. Patients reported a high, continuous burden of PSS, with spasms, sleeping difficulties, stiffness, and pain being the most commonly reported symptoms. In line with an observed waning effect of BoNT-A injections, spasticity symptoms initially were improved at Weeks 4-6 after injection but reemerged after 9-11 weeks. Treatment satisfaction levels decreased over the BoNT-A treatment cycle, as reflected by the worsening of symptoms and the need to self-medicate and consult a physician. The psychological impact of PSS was high. Patients acknowledged the benefits of BoNT-A treatment but wished for more individualized treatment plans with flexible dosing and injection intervals. Additionally, only 10% of patients reported that they had a trusting relationship with their physician and believed that their needs were considered by those managing their PSS. To our knowledge, this was the first ethnographic study in patients with PSS who were treated with BoNT-A. This ethnographic approach to patient surveys complements traditional research methods and allows improved identification of patients' unmet needs by capturing their weekly experience of treatment. The findings of this study confirm previous observations of the diminishing effectiveness of BoNT-A injections between treatment sessions, highlighting the need for agents with a longer duration of action and/or a more flexible treatment pattern that allows for more frequent injections.

The spasticity-related quality of life 6-dimensions instrument in upper-limb spasticity: Part I Development and responsiveness.

OBJECTIVE: To describe the development of the Spasticity-related Quality of Life 6-Dimensions instrument (SQoL-6D) and its sensitivity to clinical change (responsiveness). DESIGN: Multicentre, prospective, longitudinal cohort study at 8 UK sites (NCT03442660). PATIENTS: Adults (n = 104) undergoing focal treatment of upper limb spasticity. METHODS: No condition-specific health-related quality of life tool is available for upper-limb spasticity of any aetiology. The SQoL-6D was developed to fulfil this need, designed to complement the Upper Limb Spasticity Index (which incorporates the Goal Attainment Scaling evaluation of upper limb spasticity [GASeous] tool) with targeted standardised measures. The 6 dimensions of the SQoL-6D (score range 0-4) map onto common treatment goal areas identified in upper-limb spasticity studies. A Total score (0-100) provides overall spasticity-related health status. To assess responsiveness, the SQoL-6D, Global Assessment of Benefit scale and "GASeous" were administered at enrolment and 8 weeks. RESULTS: Significant differences in mean SQoL-6D Total score change and effect sizes across patients rating "some benefit" (0.51) and "great benefit" (0.88) supported responsiveness. CONCLUSION: The SQoL-6D is a promising new measure of health status in upper limb spasticity, that enables systematic assessment of the impact of this condition in relation to patients' priority treatment goals. A psychometric evaluation of SQoL-6D is presented separately.

The spasticity-related quality of life 6-dimensions instrument in upper-limb spasticity: Part II A first psychometric evaluation.

OBJECTIVE: Psychometric evaluation of the Spasticity-related Quality of Life 6-Dimensions instrument (SQoL-6D). DESIGN: A clinimetric evaluation conducted in a multicentre, prospective, longitudinal cohort study at 8 UK sites. PATIENTS: Adult patients (n=104) undergoing focal treatment of upper-limb spasticity. METHODS: The SQoL-6D was administered in the clinic at enrolment and at 8 weeks, then 1-4 days later at home to assess test-retest reliability. RESULTS: The SQoL-6D demonstrated adequate construct validity and unidimensionality of the scale, allowing the calculation of a Total score. Cronbach's alpha (0.74) supported the internal consistency reliability, while the intraclass correlation coefficient supported test-retest reliability (0.82). Correlation coefficients with established instruments supported convergent validity, while significant differences between known-groups (of differing clinical severity) in SQoL-6D Total score confirmed its sensitivity to both cross-sectional and longitudinal differences. CONCLUSION: The SQoL-6D is a promising new measure to assess health status for patients with upper-limb spasticity of any aetiology. Further investigation and exploration of the allocation of weights to convert the SQoL-6D to a health-related quality of life utility index, are required.

Clinical correlates of hypoglycaemia over 4 years in people with type 2 diabetes starting insulin: An analysis from the CREDIT study.

AIM: To identify factors associated with documented symptomatic and severe hypoglycaemia over 4 years in people with type 2 diabetes starting insulin therapy. MATERIALS AND METHODS: CREDIT, a prospective international observational study, collected data over 4 years on people starting any insulin in 314 centres; 2729 and 2271 people had hypoglycaemia data during the last 6 months of years 1 and 4, respectively. Multivariable logistic regression was used to select the characteristics associated with documented symptomatic hypoglycaemia, and the model was tested against severe hypoglycaemia. RESULTS: The proportions of participants reporting ≥1 non-severe event were 18.5% and 16.6% in years 1 and 4; the corresponding proportions of those achieving a glycated haemoglobin (HbA1c) concentration <7.0% (<53 mmol/mol) were 24.6% and 18.3%, and 16.5% and 16.2% of those who did not. For severe hypoglycaemia, the proportions were 3.0% and 4.6% of people reaching target vs 1.5% and 1.1% of those not reaching target. Multivariable analysis showed that, for documented symptomatic hypoglycaemia at both years 1 and 4, baseline lower body mass index and more physical activity were predictors, and lower HbA1c was an explanatory variable in the respective year. Models for documented symptomatic hypoglycaemia predicted severe hypoglycaemia. Insulin regimen was a univariate explanatory variable, and was not retained in the multivariable analysis. CONCLUSIONS: Hypoglycaemia occurred at significant rates, but was stable over 4 years despite increased insulin doses. The association with insulin regimen and with oral agent use declined over that time. Associated predictors and explanatory variables for documented symptomatic hypoglycaemia conformed to clinical impressions and could be extended to severe hypoglycaemia. Better achieved HbA1c was associated with a higher risk of hypoglycaemia.

Factors Associated With Diabetes-Specific Health-Related Quality of Life in Youth With Type 1 Diabetes: The Global TEENs Study.

OBJECTIVE: Our objective was to characterize diabetes-specific health-related quality of life (D-HRQOL) in a global sample of youth and young adults with type 1 diabetes (T1D) and to identify the main factors associated with quality of life. RESEARCH DESIGN AND METHODS: The TEENs study was an international, cross-sectional study of youth, 8-25 years of age, with T1D. Participants (N = 5,887) were seen in clinical sites in 20 countries across 5 continents enrolled for 3 predetermined age groups: 8-12, 13-18, and 19-25 years of age. To assess D-HRQOL, participants completed the PedsQL Diabetes Module 3.0 and were interviewed about family-related factors. Specifics about treatment regimen and self-management behaviors were collected from medical records. RESULTS: Across all age groups, females reported significantly lower D-HRQOL than did males. The 19-25-year age group reported the lowest D-HRQOL. Multivariate linear regression analyses revealed that D-HRQOL was significantly related to HbA1c; the lower the HbA1c, the better the D-HRQOL. Three diabetes-management behaviors were significantly related to better D-HRQOL: advanced methods used to measure food intake; more frequent daily blood glucose monitoring; and more days per week that youth had ≥30 min of physical activity. CONCLUSIONS: In all three age groups, the lower the HbA1c, the better the D-HRQOL, underscoring the strong association between better D-HRQOL and optimal glycemic control in a global sample of youth and young adults. Three diabetes-management behaviors were also related to optimal glycemic control, which represent potentially modifiable factors for clinical interventions to improve D-HRQOL as well as glycemic control.

Predictors of HbA1c over 4 years in people with type 2 diabetes starting insulin therapies: The CREDIT study.

AIMS: To identify factors associated with glucose control, as measured by HbA1c over 4 years, in people with type 2 diabetes starting insulin therapy. METHODS: CREDIT, an observational cohort study, collected data semi-annually over 4 years, on people with type 2 diabetes starting any insulin, in 311 centres in 12 countries; 2803 people had data on HbA1c during follow-up. Multivariable backward regression analysis selected characteristics associated with glycaemic control from a limited number of candidate variables. RESULTS: Before starting insulin therapy, HbA1c was 9.3% (78 mmol/mol) and decreased to 7.6% (60 mmol/mol) after 1 year, and changed little after that. Insulin dose increased from 0.21 U/kg to 0.36 U/kg at 1 year, and then by 0.10 U/kg over the next 3 years. Body weight increased by 2.0 kg in the first year and increased little thereafter. Poorer glycaemic control over the 4 years was mainly determined by the HbA1c before starting therapy, after accounting for the other statistically significant associated variables in multivariable analysis: higher BMI, younger age, longer diabetes duration, more glucose-lowering drugs, using basal insulin alone, higher insulin dose and female sex. At 4 years, a higher current insulin dose was the characteristic most strongly associated with a higher concurrent HbA1c. CONCLUSIONS: HbA1c at the start of insulin therapy was the characteristic most predictive of later HbA1c, after accounting for other variables associated with HbA1c. This may provide some justification for earlier insulin introduction to improve glucose control to target.

Effects of food on the pharmacokinetics of levodopa in a dual-release formulation.

The objective was to assess the effect of food on the pharmacokinetics of levodopa and 3-O-methyldopa after administration of a new levodopa/benserazide formulation with a dual-release drug delivery profile (Madopar DR). In an open-label, two-way cross-over study, 19 healthy volunteers who had fasted overnight were randomized to receive a single oral dose of levodopa/benserazide (200/50 mg) in the absence or presence of a standardized, high-fat breakfast, administered 30 min before drug administration. The treatment periods (fasting, non-fasting) were preceded by a baseline regimen of levodopa/benserazide (100/25 mg t.i.d. for 6 or 7 days). Blood samples were taken at specific times over a 12-hour period. Plasma concentrations of levodopa and 3-O-methyldopa were determined by high-performance liquid chromatography for pharmacokinetic evaluation. The parameter C(max) of levodopa was significantly lower and t(max) longer under postprandial conditions than under fasting conditions (mean C(max) 1.41 vs. 2.09 mg l(-1); mean t(max) 3.1 vs. 1.0 h). With food, the area under the curve (AUC) of levodopa was equivalent to that following an overnight fast. Compared with volunteers who had fasted, food did not alter t(1/2). Estimates of C(max), t(max) and AUC of 3-O-methyldopa under non-fasting conditions were not significantly different from those under fasting conditions. In conclusion, food decreases the rate of levodopa absorption, but had no effect on the systemic exposure to levodopa and the degree of 3-O-methyldopa formation. Standardization of levodopa/benserazide administration with respect to meal times is recommended.