Dulaglutide and Glomerular Hyperfiltration, Proteinuria, and Albuminuria in Youth With Type 2 Diabetes: Post Hoc Analysis of the AWARD-PEDS Study.

OBJECTIVE: To examine changes in glomerular hyperfiltration and other measures of kidney function in youth with type 2 diabetes treated with dulaglutide or placebo. RESEARCH DESIGN AND METHODS: Post hoc analysis was performed on kidney laboratory data from 154 youths (age 10-18 years) with type 2 diabetes enrolled in a completed placebo-controlled glycemic control trial of dulaglutide. RESULTS: Mean estimated glomerular filtration rate (eGFR) decreased from baseline to 26 weeks in participants treated with dulaglutide versus placebo (-5.8 vs. -0.1 mL/min/1.73 m2; P = 0.016). Decreases in eGFR were observed primarily in participants with baseline glomerular hyperfiltration. At 26 weeks, the prevalence of both glomerular hyperfiltration and proteinuria increased with placebo but decreased with dulaglutide (P = 0.014 and 0.004 vs. placebo, respectively). CONCLUSIONS: Dulaglutide was associated with attenuated glomerular hyperfiltration and proteinuria in youth with type 2 diabetes. The impact of these changes on the risk of diabetic kidney disease is unclear.

Feasibility of Telehealth Occupational Therapy for Behavioral Symptoms of Adults With Dementia: Randomized Controlled Trial.

IMPORTANCE: Supporting community residency of adults with Alzheimer's disease (AD) is a critical public health initiative. Occupational therapy can contribute to this goal. OBJECTIVE: To assess the feasibility of a novel telehealth intervention to support occupational engagement in community-residing people with AD. DESIGN: Single-blind, three-arm, parallel, randomized controlled trial. SETTING: Occupational therapy delivered through telehealth in participants' homes. PARTICIPANTS: People with AD who reside in the community with behavioral symptoms and their care partners (dyads). INTERVENTIONS: (1) HARMONY (Helping older Adults cReate & Manage OccupatioNs successfully), a telehealth intervention that applies principles of individualized guided discovery with environmental cueing for caregivers of persons with AD to promote activity participation and manage behavioral symptoms; (2) standardized training regarding the use of a sensory-based approach in dementia care; and (3) a control, including home safety education and weekly monitoring of behaviors. OUTCOMES AND MEASURES: Feasibility was assessed as the primary outcome measured by completion of at least 75% of the telehealth sessions. Secondary outcomes included change in functional activity performance and neuropsychiatric behavioral symptoms. RESULTS: Twenty-eight dyads participated. The intervention was feasible, with high adherence to weekly visits (M number of visits = 5.4 for HARMONY, 4.9 for standardized training, and 4.6 for control), with high participant retention in the intervention arms. HARMONY demonstrated promise in improving patient performance and behavioral symptoms. CONCLUSIONS AND RELEVANCE: HARMONY is feasibly delivered through telehealth service and has a positive effect on occupational performance and behavioral symptoms of AD. Additional studies are needed to explore effectiveness in a broader population. What This Article Adds: Use of HARMONY for community-residing adults with AD is feasible and has promise for improving functional activity performance and behavioral symptoms, as well as caregiver satisfaction.

Trajectories of body weight change and survival among patients with mCRC treated with systemic therapy: Pooled analysis from the ARCAD database.

BACKGROUND: Higher body mass index is associated with a higher incidence of colorectal cancer (CRC) but also with improved survival in metastatic CRC (mCRC). Whether weight change after mCRC diagnosis is associated with survival remains largely unknown. METHODS: We analysed individual patient data for previously untreated patients enrolled in five phase 3 randomised trials conducted between 1998 and 2006. Weight measurements were prospectively collected at baseline and up to 59.4 months after diagnosis. We used stratified multivariable Cox models to assess the prognostic associations of weight loss with overall and progression-free survival, adjusting for other factors. The primary end-point was a difference in overall survival (OS) between populations with weight loss and stable or increasing weight. FINDINGS: Data were available for 3504 patients. The median weight change at 3 months was -0.54% (IQR -3.9 … +1.5%). We identified a linear trend of increasing risk of death associated with progressive weight loss. Unstratified median OS was 20.5, 18.0, and 11.9 months (p < 0.001) for stable weight or gain, <5% weight loss, and ≥5% weight loss at 3 months, respectively. Weight loss was associated with a higher risk of death (<5% loss: aHR 1.18 [1.06-1.30], p < 0.002; ≥5% loss: aHR 1.87 [1.67-2.1], p < 0.001) as compared to stable or increasing weight at 3 months post-baseline (reference), while adjusting for age, sex, performance, and a number of metastatic sites. INTERPRETATION: Patients losing weight during systemic therapy for metastatic colorectal cancer have significantly shorter OS. The degree of weight loss is proportional to the observed increased risk of death and remains evident among underweight, normal weight, and obese individuals. On-treatment weight change could be used as an intermediate end-point. FUNDING: The creation and management of the database containing the individual patient data from the original randomised trials is supported by the Aide et Recherche en Cancérologie Digestive Foundation.

Impact of Using A Mixed Data Collection Modality on Statistical Inferences in Decentralized Clinical Trials.

BACKGROUND: Decentralized clinical trials offer the promise of reduced patient burden, faster and more diverse recruitment, and have received regulatory support during the COVID-19 pandemic. However, lack of data accuracy or data validation poses a challenge for fully decentralized trials. A mixed data collection modality where onsite measurements are collected at key time points and decentralized measurements are taken at intermediate time points is attractive operationally. To date, the impact of decentralized measurements (which could presumably be less accurate) taken at intermediate time points on statistical inference on the primary or other key time points has not been evaluated. METHODS: In this article we evaluate the estimation and statistical inference for three scenarios: (1) all onsite measurements, (2) a mixture of onsite and decentralized measurements, and (3) all decentralized measurements, in the setting of a chronic weight management trial. We consider scenarios where decentralized measurements have additional within- and between-subject variabilities and/or bias. RESULTS: In the mixed modality setting, simulation studies showed that the estimation and inference for the key time points with onsite measurements have good properties and are not impacted by the additional variability and bias from intermediate decentralized measurements. However, estimates for intermediate decentralized time points for the mixed modality and estimates for the all decentralized modality measurements have increased variability and bias. CONCLUSION: Mixed modality trials can help achieve the benefits of decentralized clinical trials by reducing the number of onsite visits with little impact on statistical inferences for various estimands, compared to traditional (all onsite) clinical trials.

Subgroup-specific dose finding for phase I-II trials using Bayesian clustering.

In most models and algorithms for dose-finding clinical trials, it is assumed that the trial participants are homogeneous-the optimal dose is the same for all those who qualify for the trial. However, if there are heterogeneous populations who may benefit from the same treatment, it is inefficient to conduct dose-finding separately for each group, and assuming homogeneity across all subpopulations may lead to identification of the incorrect dose for some (or all) subgroups. To accommodate heterogeneity in dose-finding trials when both efficacy and toxicity outcomes must be used to identify the optimal dose (as in immunotherapeutic oncology treatments), we utilize an adaptive Bayesian clustering method which borrows strength among similar subgroups and clusters truly homogeneous subgroups. Unlike methodology already described in the literature, our proposed methodology does not require the assumption of exchangeability between subgroups or a priori ordering of subgroups, but does allow for specification of different subgroup-specific priors if prior information is available. We provide a comparison of operating characteristics between our method and Bayesian hierarchical models for subgroups in a variety of relevant scenarios. After simulation studies with four a priori subgroups, we observed that our method and the hierarchical models both outperform separate subgroup-specific models when all subgroups have the same dose-efficacy and dose-toxicity curves. However, our method outperforms hierarchical models when one subgroup has a different dose-efficacy or dose-toxicity curve from the other three subgroups.

Associations between body mass index and body composition measures in a birth cohort.

BACKGROUND: Associations among body composition measures have been limited to cross-sectional analyses of different subjects. We identified cross-sectional relationships between body mass index (BMI) and other body composition measures and predicted body composition measures from BMI throughout childhood and adolescence. METHODS: BMI was calculated and % body fat (%BF), fat mass index (FMI), and fat-free mass index (FFMI) were measured using dual-energy x-ray absorptiometry at ages 5, 9, 11, 13, 15, and 17 years in a birth cohort (n = 629). Sex-specific body composition measures were calculated for BMI-for-age percentiles; associations between BMI and body composition measures were characterized; and body composition measures were predicted from BMI. RESULTS: %BF, FMI, and FFMI generally increased with BMI-for-age percentiles at each age. Correlations between BMI and %BF or FMI were generally higher at BMI-for-age percentiles ≥95% than for lower BMI-for-age percentiles. Correlations between BMI and FFMI were generally higher for participants at very low and very high BMI-for-age percentiles than at moderate BMI-for-age percentiles. Age- and sex-specific predictions from BMI are provided for %BF, FM, and FFMI. CONCLUSIONS: Sex-specific body composition measures throughout childhood and adolescence are presented. BMI is a better indicator of adiposity at higher than at lower BMI values. IMPACT: Sex-specific body composition measures throughout childhood and adolescence are described. % BF, FMI, and FFMI generally increased with BMI-for-age percentiles for both sexes throughout childhood and adolescence. BMI is a better indicator of adiposity at higher BMI levels than at lower BMI values throughout childhood and adolescence.

Beverage Intakes and Toothbrushing During Childhood Are Associated With Caries at Age 17 Years.

BACKGROUND: Sugar-sweetened beverages (SSBs) have been associated with childhood caries; however, associations among lifelong beverage intakes and adolescent caries have received less attention. OBJECTIVE: To investigate associations between beverage intakes during childhood and adolescence and caries experience at 17 years of age, while adjusting for fluoride intakes and toothbrushing. DESIGN: Descriptive model analyses were conducted on data collected from a longitudinal birth cohort study. PARTICIPANTS/SETTING: Participants included Iowa Fluoride Study members (n = 318) recruited at birth between 1992 and 1995 with at least 6 beverage questionnaires completed from ages 1 to 17 years and a caries examination at age 17. EXPOSURE: Predictors included mean daily milk, juice (100% juice and juice drinks before age 9), SSB (including juice drinks after age 9), and water/sugar-free beverage (SFB) intakes; daily fluoride intakes; and daily toothbrushing frequencies for ages 1 to 17. MAIN OUTCOME MEASURES: The outcome was dental caries count at age 17, adjusted for the number of scored tooth surfaces (decayed and filled surfaces attack rate [DFSAR]). STATISTICAL ANALYSES PERFORMED: Univariable generalized linear models were fit for each predictor and the outcome DFSAR. Multivariable models assessed combined effects of beverage types, fluoride variables, toothbrushing, sex, and baseline socioeconomic status. RESULTS: Based on multivariable models, each 8 oz of additional daily juice and water/SFB decreased expected DFSAR by 53% (95% confidence interval [CI]: 17%-73%) and 29% (95% CI: 7%-46%), respectively, and 8 additional oz SSBs increased expected DFSAR by 42% (95% CI: 5%-92%), after adjustment for other beverage intakes, toothbrushing, total fluoride intake excluding SSB fluoride (non-SSB total fluoride), sex, and baseline socioeconomic status. Each additional daily toothbrushing event decreased expected DFSAR by 43% (95% CI: 14%-62%) after adjustment for beverage intakes, non-SSB total fluoride intake, sex, and baseline SES. CONCLUSIONS: Higher juice and water/SFB intakes and more toothbrushing were associated with lower caries at age 17, while higher SSB intakes were associated with higher caries.

The value of a post-polio syndrome self-management programme.

BACKGROUND: Post-polio syndrome is characterised by symptoms of fatigue, pain and new-onset neuromuscular weakness, and emerges decades after the initial poliovirus infection. We sought to evaluate the only post-polio syndrome specific self-management programme in the United Kingdom. METHODS: This was a retrospective study of patients who had completed a residential self-management programme led by a multi-disciplinary clinical team. Following a confirmed diagnosis of post-polio syndrome by rehabilitation and neurology specialists, patients were offered to participate in the programme. Although group-based, patients also received individually tailored support on physical exercise and fatigue management. Physical effects, physical function, psychosocial well-being measures were assessed at baseline and 6 months follow-up. Knowledge was tested at baseline and immediately following the programme. Statistical comparisons were made using paired t-test and Wilcoxon signed rank test according to the data distribution. RESULTS: Over a period of 17 years, 214 participants (median age 61.3 years old, 63% female) attended 31 programmes. At 6 months the following post-polio syndrome specific symptoms improved significantly: fatigue, as measured by the Multidimensional Assessment of Fatigue scale [37.6 (7.1) vs. 34.2 (9.3), P=0.005]; and pain [15.0 (6.1) vs. 13.1 (6.7), P=0.001], atrophy [10.0 (8.0-12.0) vs. 9.0 (7.0-11.0), P=0.002] and bulbar symptoms [3.0 (1.0-5.0) vs. 2.0 (0-4.0), P=0.003] as measured by the Index of Post-polio Sequelae scale. Knowledge related to post-polio syndrome also significantly increased [14.0 (11.0-16.0) vs. 17.0 (16.0-19.0), P=0.001]. Participants were able to walk at a faster speed over 10 meters [0.77 (0.59-1.00) vs. 0.83 (0.67-1.10) m/s, P=0.003] and walked longer distances during the 2-minute walk test [76.9 (31.7) vs. 82.0 (38.4) m, P=0.029]. Depression and anxiety scores did not change over time [PHQ-9, 2.0 (0.3-10.8) vs. 2.0 (0.3-6.8), P=0.450; GAD-7, 2.0 (0-7.0) vs. 1.0 (0-3.0), P=0.460] nor was there change in self-reported quality of life {60 [50-70] vs. 60 [55-70], P=0.200}. CONCLUSIONS: This study suggests that a post-polio syndrome self-management programme led to improvement in symptoms, knowledge and walking speed, but not quality of life. Anxiety and depression scores remained low.

Identification of and Associations among Low, Middle, and High Body Composition Trajectories from Age 5- to 17-Years.

Our objective was to identify sex-specific age 5- to 17-year body composition (body mass index (BMI), % body fat, fat mass index, fat-free mass index) trajectories, compare trajectories assigned using age 5 (AGE5) data to those assigned using all available (ALL) data, and compare BMI assignments to other body composition assignments. Cluster analysis was used to identify low, medium, and high trajectories from body composition measures obtained from dual energy x-ray absorptiometry (DXA) scans at 5, 9, 11, 13, 15, and 17 years in a birth cohort followed longitudinally (n = 469). Moderate agreement was observed for comparisons between AGE5 data and ALL data cluster assignments for each body composition measure. Agreement between cluster assignments for BMI and other body composition measures was stronger using ALL data than using AGE5 data. Our results suggest that BMI, % body fat, fat mass index, and fat free mass index trajectories are established during early childhood, and that BMI is a reasonable predictor of body composition appropriate to track obesity in public health and clinical settings.

Child and Adolescent Sugar-Sweetened Beverage Intakes Are Longitudinally Associated with Higher Body Mass Index z Scores in a Birth Cohort Followed 17 Years.

BACKGROUND: Sugar-sweetened beverages (SSB) are considered a risk factor for obesity. OBJECTIVE: The objective of the current study was to investigate associations between the predictors of beverage and energy intakes and mean adequacy ratios (MARs), and the outcome of body mass index (BMI) z scores, in a birth cohort using longitudinal models. DESIGN: This was a longitudinal analysis of secondary data. PARTICIPANTS/SETTING: Participants in the Iowa Fluoride and Iowa Bone Development Studies with two beverage intake questionnaires completed between ages 2 and 4.7 years or 5 and 8.5 years or one questionnaire between ages 9 and 10.5, 11 and 12.5, 13 and 14.5, or 15 and 17 years (n=720); two food and beverage diaries completed between ages 2 and 4.7 years or 5 and 8.5 years or completion of the Block's Kids' Food Frequency Questionnaires at age 11, 13, 15, or 17 years (n=623); and anthropometric measures at the corresponding age 5-, 9-, 11-, 13-, 15-, or 17-year examination(s). PREDICTORS: Mean daily 100% juice, milk, SSB, water/sugar-free beverage, and energy intakes and MARs averaged over ages 2 to 4.7, 5 to 8.5, 9 to 10.5, 11 to 12.5, 13 to 14.5, or 15 to 17 years were predictors. OUTCOME: BMI z score was the outcome. STATISTICAL ANALYSES: Linear mixed models were fit for each beverage, energy, and MAR variable, with the beverage, energy, or MAR variable as the predictor and BMI z score as the outcome. Beverage models were adjusted for energy and MAR and baseline socioeconomic status. RESULTS: SSB intake adjusted for energy intake, MAR, and baseline socioeconomic status was associated with BMI z score; each additional 8 oz SSB consumed/day throughout childhood and adolescence increased the BMI z score an average 0.050 units (95% CI 0.022 to 0.079; P=0.001). Adjusted water/sugar-free beverage intake (0.026 units; 95% CI 0.006 to 0.046; P=0.013) was modestly associated with BMI z score, while 100% juice (-0.001 units; 95% CI -0.059 to 0.057; P=0.97) and milk (0.022 units; 95% CI -0.007 to 0.052; P=0.13) intakes were not associated with BMI z scores. CONCLUSIONS: Higher SSB intakes were associated with increased BMI z scores throughout childhood and adolescence in Iowa Fluoride Study participants. Public health initiatives targeting SSB consumption during childhood and adolescence remain relevant.

Description of Child and Adolescent Beverage and Anthropometric Measures According to Adolescent Beverage Patterns.

Our objective is to retrospectively describe longitudinal beverage intakes and anthropometric measures according to adolescent beverage patterns. Data were collected from Iowa Fluoride Study participants (n = 369) using beverage questionnaires at ages 2⁻17 years. Weight and height were measured at ages 5, 9, 13 and 17 years. Cluster analyses were used to identify age 13- to 17-year beverage patterns. Treating age and beverage cluster as explanatory factors, sex-specific generalized linear mixed models were used to identify when differences in beverage intakes and anthropometric measures began. Predominant beverage intakes were higher in each of the corresponding clusters by 9⁻12.5 years; females with high milk intakes during adolescence and males with high 100% juice or sugar-sweetened beverage intakes during adolescence reported higher intakes of that beverage beginning at 2⁻4.7 years. Females and males in the 100% juice cluster had lower weights than other clusters beginning at 13 years, while females and males in the neutral cluster were shorter beginning at 13 years. Females in the water/sugar-free beverage cluster had higher body mass indices (BMIs) beginning at 9 years. Females and males in the 100% juice cluster had lower BMIs beginning at 5 and 9 years, respectively. Childhood beverage intakes and growth patterns differ according to adolescent beverage patterns.

Higher Longitudinal Milk Intakes Are Associated with Increased Height in a Birth Cohort Followed for 17 Years.

Background: Height is an indicator of nutritional status; linear growth faltering has recognized consequences for cognitive, emotional, and chronic disease risk. Although height is routinely studied in developing countries, less attention is given to height in the United States. Objective: The objective of this study was to identify longitudinal associations between childhood and adolescent beverage intakes, nutrient adequacy, or energy intake and height in a birth cohort. Methods: Data for participants through ages 2-17 y (n = 717; 353 males, 364 females) recruited at birth for the longitudinal Iowa Fluoride Study (IFS) were used in the current cohort analyses. Beverage intakes (n = 708) were collected by beverage-frequency questionnaires at 3- to 6-mo intervals, whereas nutrient data (n = 652) were obtained from 3-d food diaries completed at 3- to 6-mo intervals through age 8.5 y and from Block Kids' food-frequency questionnaires at 2-y intervals after age 8.5 y. Nutrient adequacy ratios were calculated with the use of age- and sex-specific Estimated Average Requirements. Height was measured at clinic visits when the participants were approximately ages 5, 9, 11, 13, 15, and 17 y. Linear mixed models were used to identify longitudinal associations between dietary variables and height. A baseline model that adjusted for changing growth patterns during adolescence was established. Dietary and potential confounding variables were added to this baseline model. Results: Milk intake adjusted for mean adequacy ratio, energy intake, and baseline socioeconomic status was associated with height; for each additional 8 ounces (236 mL) of milk consumed per day throughout childhood and adolescence, height increased, on average, by 0.39 cm (95% CI: 0.18, 0.60 cm; P < 0.001). Conclusions: IFS participants' height increased by 0.39 cm for each additional 8 ounces (236 mL) of milk consumed throughout childhood and adolescence. The clinical implications of the mild linear growth faltering observed in healthy youth are unknown. This trial was registered at www.clinicaltrials.gov as 199112665.

Longitudinal associations between dental caries increment and risk factors in late childhood and adolescence.

OBJECTIVES: To assess longitudinal associations between permanent tooth caries increment and both modifiable and non-modifiable risk factors, using best subsets model selection. METHODS: The Iowa Fluoride Study has followed a birth cohort with standardized caries exams without radiographs of the permanent dentition conducted at about ages 9, 13, and 17 years. Questionnaires were sent semi-annually to assess fluoride exposures and intakes, select food and beverage intakes, and tooth brushing frequency. Exposure variables were averaged over ages 7-9, 11-13, and 15-17, reflecting exposure 2 years prior to the caries exam. Longitudinal models were used to relate period-specific averaged exposures and demographic variables to adjusted decayed and filled surface increments (ADJCI) (n = 392). The Akaike Information Criterion (AIC) was used to assess optimal explanatory variable combinations. RESULTS: From birth to age 9, 9-13, and 13-17 years, 24, 30, and 55 percent of subjects had positive permanent ADJCI, respectively. Ten models had AIC values within two units of the lowest AIC model and were deemed optimal based on AIC. Younger age, being male, higher mother's education, and higher brushing frequency were associated with lower caries increment in all 10 models, while milk intake was included in 3 of 10 models. Higher milk intakes were slightly associated with lower ADJCI. CONCLUSIONS: With the exception of brushing frequency, modifiable risk factors under study were not significantly associated with ADJCI. When possible, researchers should consider presenting multiple models if fit criteria cannot discern among a group of optimal models.

The relationships between fluoride intake levels and fluorosis of late-erupting permanent teeth.

OBJECTIVES: To examine the relationships between fluoride intake levels and fluorosis of late-erupting permanent teeth. METHODS: The current study used information collected from 437 children in the longitudinal Iowa Fluoride Study. Participants' fluoride intake information was collected using questionnaires from birth to age 10 years. Estimated mean daily fluoride intake was categorized into low, moderate, and high intake tertiles for each age interval (2-5, 5-8, and 2-8 years). Bivariate analyses were performed to study the relationships between self-reported fluoride intake levels during three age intervals and dental fluorosis. RESULTS: For canines and second molars, the prevalence of mostly mild fluorosis was less than 10% in the lowest fluoride intake tertile and more than 25% in the highest intake tertile. For both first and second premolars, the prevalence in the low and high intake tertiles was approximately 10-15% and 25-40%, respectively. When estimated total daily fluoride intake was 0.04 mg/kg BW during ages 2-8 years, the predicted probability of fluorosis was 16.0%, 20.5%, 21.8%, and 15.4% for canines, 1st and 2nd and premolars and 2nd molars, respectively. We found that an incremental increase in fluoride intake during the age 5- to 8-year interval led to greater odds for development of mostly mild dental fluorosis in late-erupting teeth compared to increases in fluoride intake during other age intervals. CONCLUSIONS: Our results clearly show that dental fluorosis prevalence is closely related to fluoride intake levels and that teeth have greater susceptibility to fluoride intake during certain age intervals.

Dental caries clusters among adolescents.

OBJECTIVES: There have been very few longitudinal studies of dental caries in adolescents, and little study of the caries risk factors in this age group. The purpose of this study was to describe different caries trajectories and associated risk factors among members of the Iowa Fluoride Study (IFS) cohort. METHODS: The IFS recruited a birth cohort from 1992 to 1995, and has gathered dietary, fluoride and behavioural data at least twice yearly since recruitment. Examinations for dental caries were completed when participants were ages 5, 9, 13 and 17 years. For this study, only participants with decayed and filled surface (DFS) caries data at ages 9, 13 and 17 were included (N=396). The individual DFS counts at age 13 and the DFS increment from 13 to 17 were used to identify distinct caries trajectories using Ward's hierarchical clustering algorithm. A number of multinomial logistic regression models were developed to predict trajectory membership, using longitudinal dietary, fluoride and demographic/behavioural data from 9 to 17 years. Model selection was based on the akaike information criterion (AIC). RESULTS: Several different trajectory schemes were considered, and a three-trajectory scheme-no DFS at age 17 (n=142), low DFS (n=145) and high DFS (n=109)-was chosen to balance sample sizes and interpretability. The model selection process resulted in use of an arithmetic average for dietary variables across the period from 9 to 17 years. The multinomial logistic regression model with the best fit included the variables maternal education level, 100% juice consumption, brushing frequency and sex. Other favoured models also included water and milk consumption and home water fluoride concentration. The high caries cluster was most consistently associated with lower maternal education level, lower 100% juice consumption, lower brushing frequency and being female. CONCLUSIONS: The use of a clustering algorithm and use of Akaike's Information Criterion (AIC) to determine the best representation of the data were useful means in presenting longitudinal caries data. Findings suggest that high caries incidence in adolescence is associated with lower maternal educational level, less frequent tooth brushing, lower 100% juice consumption and being female.

Tobacco use and outcome in radical prostatectomy patients.

Cigarette smoking has been consistently associated with increased risk of overall mortality, but the importance of smoking for patients with prostate cancer (CaP) who are candidates for curative radical prostatectomy (RP) has received less attention. This retrospectively designed cohort study investigated the association of smoking history at RP with subsequent CaP treatment outcomes and overall mortality. A total of 1981 patients who underwent RP at Roswell Park Cancer Institute (RPCI) between 1993 and 2014 were studied. Smoking history was considered as a risk factor for overall mortality as well as for currently accepted CaP treatment outcomes (biochemical failure, treatment failure, distant metastasis, and disease-specific mortality). The associations of smoking status with these outcomes were tested by Cox proportional hazard analyses. A total of 153 (8%) patients died during follow-up. Current smoking at diagnosis was a statistically significant predictor of overall mortality after RP (current smokers vs. former and never smokers, hazards ratio 2.07, 95% confidence interval [CI]: 1.36-3.14). This association persisted for overall mortality at 3, 5, and 10 years (odds ratios 2.07 [95% CI: 1.36-3.15], 2.05 [95% CI: 1.35-3.12], and 1.8 [95% CI: 1.18-2.74], respectively). Smoking was not associated with biochemical failure, treatment failure, distant metastasis, or CaP-specific mortality, and the association of smoking with overall mortality did not appear to be functionally related to treatment or biochemical failure, or to distant metastasis. Smoking is a non-negligible risk factor for death among CaP patients who undergo RP; patients who smoke are far more likely to die of causes other than CaP.

Are Established Methods of Physiotherapeutic Management for Long-term Neurological Conditions Applicable to 'Orphan' Conditions such as Syringomyelia?

BACKGROUND AND PURPOSE: Syringomyelia is a rare or 'orphan' condition with the potential to cause significant disability and detrimental effects to quality of life. Syringomyelia shares similar symptoms to those common in other long-term neurological conditions, including spinal cord injury and multiple sclerosis. In these more prevalent conditions, physiotherapy is utilized widely and is effective in optimizing physical, psychological and social parameters. Therefore, we theorized that physiotherapy might be transferable to, and beneficial to syringomyelia patients. As a paucity of literature exists in this area, we aimed to evaluate the existing uptake and perceived efficacy of physiotherapy. METHODS: An exploratory, mixed methodology was selected to derive sufficient qualitative data for analysis. Specifically designed questionnaires and semi-structured interviews yielded data on uptake and perceived physiotherapy efficacy. One hundred patients from a National Health Service tertiary syringomyelia service were invited to participate. RESULTS: The questionnaire and interviews were completed by 49 and 20 patients, respectively. Of the small number of patients receiving physiotherapy, the majority reported beneficial effects on pain modulation and quality of life. Stretching and hydrotherapy were deemed effective for relief of pain and stiffness. Additionally, physiotherapy was reported to provide similar benefits to surgical intervention. DISCUSSION: Syringomyelia patients report physiotherapy to provide benefits for symptom management and quality of life. Such findings suggest that established rehabilitation techniques in more common conditions may be transferable to those less prevalent. Uptake of physiotherapy was limited, seemingly because of inadequate information, knowledge and resources. To address these deficiencies, further studies should be planned investigating the effectiveness of physiotherapy modalities, such as hydrotherapy, in parallel or in conjunction with surgery and/or pharmacology. Additionally, syringomyelia could be represented alongside similar pathologies in research trials to initiate further research questions and drivers for funding.

Feasibility of using MIRA with adult patients presenting with upper limb motor dysfunction post neurological damage.

Computer-based technology is an emerging modality to facilitate upper limb rehabilitation post neurological damage. A feasibility project using MIRA technology in an adult outpatient neurophysiotherapy service was conducted. Ten patients trialled nine MIRA games that promoted discrete and continuous unilateral and bilateral upper limb movements. The effect of MIRA use on usual service operation as well as any adverse events was noted. Patient views of using MIRA were explored through self-reported questionnaires. For six patients, comparison of amount and frequency of active upper limb exercises using MIRA and typical prescribed upper limb exercises was made. Use of MIRA did not negatively affect service operation and was not associated with any adverse event reporting. The majority of patients enjoyed using MIRA and felt that it was a useful modality to supplement existing prescribed upper limb exercises. Those with previous experience of technology expressed the most positive feedback. There is evidence that MIRA tasks may facilitate intensive repetitive upper limb movements, although some patients reported in-exercise discomfort. In conclusion, it was feasible to use MIRA with adult patients post neurological damage presenting with upper limb motor dysfunction, particularly those patients with proximal upper limb motor dysfunction previously familiar with computer use or gaming experience.

Clinical predictive value of manual muscle strength testing during critical illness: an observational cohort study.

INTRODUCTION: Impaired skeletal muscle function has important clinical outcome implications for survivors of critical illness. Previous studies employing volitional manual muscle testing for diagnosing intensive care unit-acquired weakness (ICU-AW) during the early stages of critical illness have only provided limited data on outcome. This study aimed to determine inter-observer agreement and clinical predictive value of the Medical Research Council sum score (MRC-SS) test in critically ill patients. METHODS: Study 1: Inter-observer agreement for ICU-AW between two clinicians in critically ill patients within ICU (n = 20) was compared with simulated presentations (n = 20). Study 2: MRC-SS at awakening in an unselected sequential ICU cohort was used to determine the clinical predictive value (n = 94) for outcomes of ICU and hospital mortality and length of stay. RESULTS: Although the intra-class correlation coefficient (ICC) for MRC-SS in the ICU was 0.94 (95% CI 0.85-0.98), κ statistic for diagnosis of ICU-AW (MRC-SS <48/60) was only 0.60 (95% CI 0.25-0.95). Agreement for simulated weakness presentations was almost complete (ICC 1.0 (95% CI 0.99-1.0), with a κ statistic of 1.0 (95% CI 1.0-1.0)). There was no association observed between ability to perform the MRC-SS and clinical outcome and no association between ICU-AW and mortality. Although ICU-AW demonstrated limited positive predictive value for ICU (54.2%; 95% CI 39.2-68.6) and hospital (66.7%; 95% CI 51.6-79.6) length of stay, the negative predictive value for ICU length of stay was clinically acceptable (88.2%; 95% CI 63.6-98.5). CONCLUSIONS: These data highlight the limited clinical applicability of volitional muscle strength testing in critically ill patients. Alternative non-volitional strategies are required for assessment and monitoring of muscle function in the early stages of critical illness.