Designing an Effective, Small-Scope Practice-based Study.

OBJECTIVE: Present a methodology to promote good practices in designing small-scale, practice-based studies. STUDY DESIGN: We propose the following methods to assist clinicians and other practice-based researchers in designing and conducting good quality, small-scale studies in a clinical setting. METHODS: Research projects applied to a limited, practice-based study may require modification to increase the consistency of patient research. RESULTS: Although common requests to collaborative methodologists mirror methods for experimental design, clinic-based studies may face different limitations. Each participant enrolled consumes resources, including time, and personnel. If practice-based studies have a different goal, to learn about the health outcomes of patients in a medical practice with limited intent for generalization, should the same methods be used? CONCLUSIONS: When limitations are clearly stated and the findings are described within the study context, these limitations may not be so severe to discourage the research. We propose a systematic method to conduct practice-based research intended for small-scale study use. Relying heavily on existing research from similar areas, the incorporation of data from the practice, and the a priori defined timelines and resources, we set forth some guiding principles to assist clinic-based investigators. Individualized focus and small-scale studies are growing in use and acceptance especially given the focus on personalized health.

Smartphone assessment of knee flexion compared to radiographic standards.

BACKGROUND: Measuring knee range of motion (ROM) is an important assessment for the outcomes of total knee arthroplasty. Recent technological advances have led to the development and use of accelerometer-based smartphone applications to measure knee ROM. The purpose of this study was to develop, standardize, and validate methods of utilizing smartphone accelerometer technology compared to radiographic standards, visual estimation, and goniometric evaluation. METHODS: Participants used visual estimation, a long-arm goniometer, and a smartphone accelerometer to determine range of motion of a cadaveric lower extremity; these results were compared to radiographs taken at the same angles. RESULTS: The optimal smartphone position was determined to be on top of the leg at the distal femur and proximal tibia location. Between methods, it was found that the smartphone and goniometer were comparably reliable in measuring knee flexion (ICC=0.94; 95% CI: 0.91-0.96). Visual estimation was found to be the least reliable method of measurement. CONCLUSIONS: The results suggested that the smartphone accelerometer was non-inferior when compared to the other measurement techniques, demonstrated similar deviations from radiographic standards, and did not appear to be influenced by the person performing the measurements or the girth of the extremity.

The Orthogonally Partitioned EM Algorithm: Extending the EM Algorithm for Algorithmic Stability and Bias Correction Due to Imperfect Data.

We propose an extension of the EM algorithm that exploits the common assumption of unique parameterization, corrects for biases due to missing data and measurement error, converges for the specified model when standard implementation of the EM algorithm has a low probability of convergence, and reduces a potentially complex algorithm into a sequence of smaller, simpler, self-contained EM algorithms. We use the theory surrounding the EM algorithm to derive the theoretical results of our proposal, showing that an optimal solution over the parameter space is obtained. A simulation study is used to explore the finite sample properties of the proposed extension when there is missing data and measurement error. We observe that partitioning the EM algorithm into simpler steps may provide better bias reduction in the estimation of model parameters. The ability to breakdown a complicated problem in to a series of simpler, more accessible problems will permit a broader implementation of the EM algorithm, permit the use of software packages that now implement and/or automate the EM algorithm, and make the EM algorithm more accessible to a wider and more general audience.

Long-term pharmacotherapy for elevated low density lipoprotein levels in children: A retrospective analysis.

BACKGROUND: There is limited research detailing low-density lipoprotein cholesterol (LDL-C) trends over the long term in children on various lipid-lowering medications. OBJECTIVES: This study sought to assess factors associated with stability of LDL-C levels in children on long-term pharmacotherapy and their ability to reach the LDL-C goal of ≤130 mg/dL while on pharmacotherapy. METHODS: Medical records of children seen in a university pediatric cholesterol clinic between 1998 and 2012 treated with a statin, ezetimibe, or both were reviewed. Aggregate data were obtained to determine the number of children able to reach an LDL-C level of ≤130 mg/dL while on pharmacotherapy. Kaplan-Meier curve and proportional hazard regression analysis were used to examine the propensity for LDL-C levels to stabilize over time while on pharmacotherapy as well as factors affecting this propensity. RESULTS: Overall, 76 patients who contributed 864 total visits were included. Of the 76 patients, 56 developed a stable LDL-C with median time to stability of 28 months on pharmacotherapy. Younger age at first visit and higher medication potencies/doses were associated with an increased propensity to stabilize. Only 36 patients were able to reach an LDL-C of ≤130 mg/dL, with only 11 of 38 patients with probable familial hypercholesterolemia reaching this goal. CONCLUSIONS: Most children reached LDL-C stability on pharmacotherapy after a median 28-month interval. However, most children had difficulty in reaching the LDL-C goal of ≤130 mg/dL even with aggressive medication titration. This was specifically true for those with probable familial hypercholesterolemia.

The Role of Arginase 1 in Post-Stroke Immunosuppression and Ischemic Stroke Severity.

A balanced immune system response plays an important role in acute ischemic stroke (AIS) recovery. Our laboratory has previously identified several immune-related genes, including arginase 1 (ARG1), with altered expression in human AIS patients. The neutrophil-lymphocyte ratio (NLR) may be a marker of the degree of immune dysregulation following AIS; however, the molecular mechanisms that may mediate the NLR are unknown. The purpose of this study was to (1) examine the relationship between ARG1, NLR, and AIS severity and (2) to utilize principal component analysis (PCA) to statistically model multiple gene expression changes following AIS. AIS patients and stroke-free control subjects were recruited, and blood samples were collected from AIS patients within 24 h of stroke symptom onset. White blood cell differentials were obtained at this time to calculate the NLR. Gene expression was measured using real-time PCR. PCA with varimax rotation was used to develop composite variables consisting of a five-gene profile. ARG1 was positively correlated with NLR (r = 0.57, p = 0.003), neutrophil count (r = 0.526, p = 0.007), NIHSS (r = 0.607, p = 0.001), and infarct volume (r = 0.27, p = 0.051). PCA identified three principal components that explain 84.4 % of variation in the original patient gene dataset comprised of ARG1, LY96, MMP9, s100a12, and PC1 was a significant explanatory variable for NIHSS (p < 0.001) and NLR (p = 0.005). Our study suggests a novel relationship between ARG1, NLR, and stroke severity, and the NLR is an underutilized clinically available biomarker to monitor the post-stroke immune response.

Reported contraceptive use, risk behaviours and STIs among military conscripts in Estonian defence forces.

Limited research exists on sexually transmitted infection (STI) and risk behaviour among military personnel. Published research on condom use and types of contraceptives used yield mixed results, yet, the perception that military members are at higher risk for STIs remains. The objectives of this cross-sectional study were to measure factors such as condom use, contraceptive methods, and risky behaviours (i.e. drug use and sex with commercial sex workers) and investigate differences between ethnic groups, where culture could influence behaviour. Data were collected from a recruited population of 584 male, military conscripts in northeastern Europe. Using multinomial logistic regression models, statistically significant findings include an interaction between the use of contraceptive methods of Russians with casual partners and ethnicity, with higher odds of effective methods used among Estonians with regular partners (OR = 8.13) or casual partners (OR = 11.58) and Russians with regular partners (OR = 4.98). Effective contraceptive methods used less frequently with casual partners by ethnic Russians is important in providing education and risk reduction services to young, male conscripts. These findings may be used as a baseline to inform health education and STI prevention programmes tailored to military members in Eastern Europe in the absence of other published studies.

The effect of error-in-confounders on the estimation of the causal parameter when using marginal structural models and inverse probability-of-treatment weights: a simulation study.

We performed an empirical study to evaluate the effect of mismeasured continuous confounders on the estimation of the causal parameter when using marginal structural models and inverse probability-of-treatment weighting. By executing an extensive simulation using 500 randomly generated parameter value combinations within a defined space, we observed the well-understood effects of attenuation and augmentation, and two unanticipated effects: null effects and sign reversals. We implemented a secondary empirical study to further investigate the sign reversal effect. We use the results of our study to identify conceptual similarities between the analytic and empirical results for multivariable linear and logistic regression, and our empirical results. Through this synthesis, we have been able to suggest feasible directions of research as well as outline the form of expected results.

Lithium in the public water supply and suicide mortality in Texas.

There is increasing evidence from ecological studies that lithium levels in drinking water are inversely associated with suicide mortality. Previous studies of this association were criticized for using inadequate statistical methods and neglecting socioeconomic confounders. This study evaluated the association between lithium levels in the public water supply and county-based suicide rates in Texas. A state-wide sample of 3123 lithium measurements in the public water supply was examined relative to suicide rates in 226 Texas counties. Linear and Poisson regression models were adjusted for socioeconomic factors in estimating the association. Lithium levels in the public water supply were negatively associated with suicide rates in most statistical analyses. The findings provide confirmatory evidence that higher lithium levels in the public drinking water are associated with lower suicide rates. This association needs clarification through examination of possible neurobiological effects of low natural lithium doses.

Leading causes of unintentional and intentional injury mortality: United States, 2000-2009.

OBJECTIVES: We have described national trends for the 5 leading external causes of injury mortality. METHODS: We used negative binomial regression and annual underlying cause-of-death data for US residents for 2000 through 2009. RESULTS: Mortality rates for unintentional poisoning, unintentional falls, and suicide increased by 128%, 71%, and 15%, respectively. The unintentional motor vehicle traffic crash mortality rate declined 25%. Suicide ranked first as a cause of injury mortality, followed by motor vehicle traffic crashes, poisoning, falls, and homicide. Females had a lower injury mortality rate than did males. The adjusted fall mortality rate displayed a positive age gradient. Blacks and Hispanics had lower adjusted motor vehicle traffic crash and suicide mortality rates and higher adjusted homicide rates than did Whites, and a lower unadjusted total injury mortality rate. CONCLUSIONS: Mortality rates for suicide, poisoning, and falls rose substantially over the past decade. Suicide has surpassed motor vehicle traffic crashes as the leading cause of injury mortality. Comprehensive traffic safety measures have successfully reduced the national motor vehicle traffic crash mortality rate. Similar efforts will be required to diminish the burden of other injury.

Ethnic differences in survival for female cancers of the breast, cervix and colorectum in British Columbia, Canada.

BACKGROUND: Chinese and South Asians are among the fastest growing minority populations in Canada; however little is known about the burden of cancer in these populations. OBJECTIVE: The objective is to examine survival rates for breast, cervical and colorectal cancers in women within these two ethnic populations, as compared to the BC general population. METHODS: Survival rates were calculated for three time periods in the Chinese, South Asian and BC general populations, using the BC cancer registry. Ethnicity within the registry was determined using surnames. RESULTS: Survival rates for female breast, cervical and colorectal cancers have improved over time in all three population groups, however general differences were found among the groups. Chinese women had higher survival rates than both South Asians and all BC women for breast and cervical cancer, and intermediate survival rates between South Asians and all BC women for colorectal cancer. South Asian women had the highest survival rates for colorectal cancer, similar survival rates to all BC women for breast cancer, and lower survival rates for cervical cancer. INTERPRETATION: Differences in the observed survival rates may be explained by variations in screening and early detection, treatment practices, and cancer biology. This is discussed more fully for each cancer site.