Longitudinal Regression Models Research Articles

Changes in neighborhood environments and the increasing socioeconomic gap in child obesity risks: Evidence from Singapore.

Most empirical research studying the link between neighborhood environments and child obesity risks are conducted in contexts such as the U.S., with pronounced patterns of residential segregation, making it difficult to extrapolate how far built environment characteristics contribute to socioeconomic disparities in obesity risks in less segregated contexts. Using a large national dataset of almost 625,000 students' height and weight data collected at ages 7, 11 and 14, between 2004 and 2015, this paper explores whether differences in eight neighborhood characteristics measuring access to different type of food outlets, parks and other active spaces, and public transport infrastructure might be responsible for socioeconomic differences in child obesity risks in Singapore, a city-state with relatively low levels of residential segregation. Through descriptive analyses we find that socioeconomic disparities in child BMIz in Singapore widened from 2004 onwards. However, while longitudinal regression models with individual and time fixed effects suggest that family socioeconomic status modified the relationship between environmental exposures and BMIz, there does not seem to be a clear, unequivocal relationship between built environment changes and the observed widening of the socioeconomic obesity gap.

The Effect of Topical Aminophylline on Hyposmia and Anosmia.

Introduction:Olfactory training is accounted as a significantly beneficial therapy for hyposmia or anosmia. There is some evidence about methylxanthine usage for this issue. In the present study, we have investigated the effects of topical aminophylline in hyposmic and anosmic patients.Materials and Methods:In this clinical trial study, patients were randomly divided into two groups (n= 20/each), the case group was given aminophylline drops over a three-month period (using the contents of the vial aminophylline in the form of nasal drops, 250 micrograms daily) with olfactory training and the control group was given normal saline drops with olfactory training over a three-month period. The olfactory capacities were assessed before the start and after the completion of treatments using a valid and reliable smell identification test.Results:In the saline and aminophylline groups, the mean ± SD relative changes in SIT score were 0.55±0.31 and 0.85±0.56, respectively. As a result, the SIT score in the saline group climbed by 55 percent but increased by 85 percent in the aminophylline group. The difference in SIT score between pre- and post-test was meaningful in both groups (P< 0.001). The aminophylline group scored significantly higher according to the marginal longitudinal regression model, adjusting baseline parameters.Conclusions:Intranasal aminophylline plus olfactory training significantly improved SIT scores in severe hyposmia or anosmia. Hypothetically, these effects are mediated through changes in cAMP and cGMP.

Patient-reported outcome measure clustering after surgery for adult symptomatic lumbar scoliosis.

Adult symptomatic lumbar scoliosis (ASLS) is a widespread and debilitating subset of adult spinal deformity. Although many patients benefit from operative treatment, surgery entails substantial cost and risk for adverse events. Patient-reported outcome measures (PROMs) are patient-centered tools used to evaluate the appropriateness of surgery and to assist in the shared decision-making process. Framing realistic patient expectations should include the possible functional limitation to improvement inherent in surgical intervention, such as multilevel fusion to the sacrum. The authors' objective was to predict postoperative ASLS PROMs by using clustering analysis, generalized longitudinal regression models, percentile analysis, and clinical improvement analysis of preoperative health-related quality-of-life scores for use in surgical counseling. Operative results from the combined ASLS cohorts were examined. PROM score clustering after surgery investigated limits of surgical improvement. Patients were categorized by baseline disability (mild, moderate, moderate to severe, or severe) according to preoperative Scoliosis Research Society (SRS)-22 and Oswestry Disability Index (ODI) scores. Responder analysis for patients achieving improvement meeting the minimum clinically important difference (MCID) and substantial clinical benefit (SCB) standards was performed using both fixed-threshold and patient-specific values (MCID = 30% of remaining scale, SCB = 50%). Best (top 5%), worst (bottom 5%), and median scores were calculated across disability categories. A total of 171/187 (91%) of patients with ASLS achieved 2-year follow-up. Patients rarely achieved a PROM ceiling for any measure, with 33%-43% of individuals clustering near 4.0 for SRS domains. Patients with severe baseline disability (< 2.0) SRS-pain and SRS-function scores were often left with moderate to severe disability (2.0-2.9), unlike patients with higher (≥ 3.0) initial PROM values. Patients with mild disability according to baseline SRS-function score were unlikely to improve. Crippling baseline ODI disability (> 60) commonly left patients with moderate disability (median ODI = 32). As baseline ODI disability increased, patients were more likely to achieve MCID and SCB (p < 0.001). Compared to fixed threshold values for MCID and SCB, patient-specific values were more sensitive to change for patients with minimal ODI baseline disability (p = 0.008) and less sensitive to change for patients with moderate to severe SRS subscore disability (p = 0.01). These findings suggest that ASLS surgeries have a limit to possible improvement, probably due to both baseline disability and the effects of surgery. The most disabled patients often had moderate to severe disability (SRS < 3, ODI > 30) at 2 years, emphasizing the importance of patient counseling and expectation management.

Outsourcing health-care services to the private sector and treatable mortality rates in England, 2013–20: an observational study of NHS privatisation

The effects of outsourcing health services to for-profit providers are contested, with some arguing that introducing such providers will improve performance through additional competition while others worry that this will lead to cost cutting and poorer outcomes for patients. We aimed to examine this debate by empirically evaluating the impact of outsourced spending to private providers, following the 2012 Health and Social Care Act, on treatable mortality rates and the quality of health-care services in England. For this observational study, we used a novel database composed of parsable procurement contracts between April 1, 2013, and Feb 29, 2020 (n=645 674, value >£25 000, total value £204·1 billion), across 173 clinical commissioning groups (CCGs; regional health boards) in England. Data were compiled from 12 709 heterogenous expenditure files primarily scraped from commissioner websites with supplier names matched to registers identifying them as National Health Service (NHS) organisations, for-profit companies, or charities. We supplemented these data with rates of local mortality from causes that should be treatable by medical intervention, indicating the quality of health-care services. We used multivariate longitudinal regression models with fixed effects at the CCG level to analyse the association of for-profit outsourcing on treatable mortality rates in the following year. We used the average marginal effects to estimate total additional deaths attributable to changes in for-profit outsourcing. We provided alternative model specifications to test the robustness of our findings, match on background characteristics, examine the potential impact of measurement error, and adjust for possible confounding factors such as population demographics, total CCG expenditure, and local authority expenditure. We found that an annual increase of one percentage point of outsourcing to the private for-profit sector corresponded with an annual increase in treatable mortality of 0·38% (95% CI 0·22-0·55; p=0·0016) or 0·29 (95% CI 0·09-0·49; p=0·0041) deaths per 100 000 population in the following year. This finding was robust to matching on background characteristics, adjusting for possible confounding factors, and measurement error in our dataset. Changes to for-profit outsourcing since 2014 were associated with an additional 557 (95% CI 153-961) treatable deaths across the 173 CCGs. The privatisation of the NHS in England, through the outsourcing of services to for-profit companies, consistently increased in 2013-20. Private sector outsourcing corresponded with significantly increased rates of treatable mortality, potentially as a result of a decline in the quality of health-care services. Wellcome Trust.

MSR30 Modelling Monthly Migraine Day Distribution: A Case Study of Fremanezumab Japanese-Korean Clinical Trials for Migraine Prevention

A cost-effectiveness model (CEM) for fremanezumab in migraine prevention has been developed from a Japanese public healthcare payer perspective. Our objective of this study was to assess the performance of three longitudinal regression models in fitting the monthly migraine days (MMD) distribution and to inform health-state distributions based on data from Japanese-Korean trials.

Salivary Biomarkers as Predictors of Obesity and Intermediate Hyperglycemia in Adolescents.

IntroductionChildhood obesity presents a major risk for metabolic diseases in adulthood. Noninvasive methods are needed for predicting the course of obesity in children and its complications. Using blood for longitudinal analyses of biomarkers to predict disease in children is not a convenient method. Saliva presents a noninvasive platform to detect inflammatory changes in biomarkers as possible predictive measures of future pathological events.ObjectivesThe aim of this study was to evaluate the relationship between specific salivary biomarkers, obesity, and intermediate hyperglycemia in children. We also investigated the longitudinal association between the salivary biomarkers and change in Body Mass Index-for-age percentile scores (BMIz).MethodsData on 353 adolescents were collected from the individuals recruited for seven years in an ongoing Kuwait Healthy Life Study cohort. BMIz was measured at 10, 12, and 17 years of age. Interleukin (IL)-6, IL-8, IL-10, Leptin, C-Reactive Protein (CRP), Insulin, Vascular Endothelial Growth Factor (VEGF), and Monocyte Chemoattractant Protein-1 (MCP-1) were measured in saliva and serum. Additionally, fasting blood plasma glucose levels were recorded. Multilevel longitudinal regression modeling, mediation analyses, and logistic regression were used to determine the predictive value of salivary biomarkers in obesity and hyperglycemia.ResultsLongitudinal analyses showed that with each one-unit increase of salivary CRP and insulin, there was a 3.5 kg/m2 and 3.2 kg/m2 increase in BMIz, respectively. Comparable to serum CRP and insulin, higher salivary CRP and insulin OR 4.94 [95%CI: 1.66,14., OR 2.64 [95%CI: 1.09, 6.38], respectively) were predictive of hyperglycemia and obesity (OR 4.53 [95%CI: 2.40,8.50], OR 3.29 [95%CI: 1.82,5.97], respectively). Insulin was a strong mediator in the relationship between obesity and hyperglycemia.ConclusionOur findings demonstrated that salivary CRP and insulin were associated with hyperglycemia, obesity, and possibly diabetes in adolescents. Salivary biomarkers are a noninvasive approach with significant value for disease risk assessment and prevention.

Potential Explanatory Factors for the Concurrent Experience of Dyspnea and Pain in Patients with COPD

Previous research has identified unexpectedly strong associations between dyspnea and pain, but the reasons remain unclear. Ascertaining the underlying biological and psychological mechanisms might enhance the understanding of the experience of both conditions, and suggest novel treatments. We sought to elucidate whether demographic factors, disease severity, psychological symptoms and biomarkers might account for the association between pain and dyspnea in individuals with COPD. We analyzed data from 301 patients with COPD who were followed in a prospective longitudinal observational study over 2 years. Measures included self-reported dyspnea and pain, pulmonary function tests, serum levels of inflammatory cytokines, measures of physical deconditioning, and scales for depression and anxiety. Analyses involved cross-sectional and longitudinal linear regression models. Pain and dyspnea were strongly correlated cross-sectionally (r = 0.77, 95% CI 0.72–0.82) and simultaneously across time (r = 0.42, 95% CI 0.28–0.56). Accounting for any of the other health factors only slightly mitigated the associations. Symptoms of pain and dyspnea thus may be fundamentally linked in COPD, rather than being mediated by common biological, psychological, or functional factors. From the patient’s perspective, pain and dyspnea may be part of the same essential experience. It is possible that treatments for one condition would improve the other.

Using customized PRO profiles to evaluate expected patient quality-of-life outcomes.

e18607 Background: Patient Reported Outcomes (PROs) are routinely employed in patient-focused drug development programs. However, PRO data are often under-utilized. Better approaches could employ trial data to describe expected patient outcomes. The objective of this work was to present a method for leveraging PRO-based patient profiles to project and thereby anticipate expected patient outcomes. Methods: A model-based approach to analyzing PRO scores allows for a more tailored approach to evaluating outcomes of interest. To demonstrate this approach, we analyzed PRO data from a Phase 3 trial of patients with prostate cancer randomized to either Hypofractionated 3D-CRT/MRT (experimental arm) or Conventionally Fractionated 3D-CRT/MRT (comparator arm). The outcome of interest was the difference between treatment arms on the Expanded Prostate cancer Index Composite (EPIC) urinary domain scores, defined on the sum of responses to 12 items. A longitudinal regression model was fit to EPIC scores at 6, 12, 24, and 60 months post-baseline. Patient profile variables (baseline EPIC urinary scores, treatment arm, age, race, clinical T-stage, and Gleason score) were included as predictors. For a particular patient profile of interest, expected EPIC urinary score at 6 months was estimated, as well as associated 95% confidence intervals, which allowed for an understanding of the range of likely outcomes for that particular patient profile. Results: n = 550 patients in the experimental arm and n = 542 patients in the comparator were analyzed. The difference in EPIC urinary scores between treatment arms at 6 and 12 months were computed, with higher scores reflecting greater symptom severity. The model estimated a difference of 2.12 points (p = 0.009) at 6 months and 2.16 points (p = 0.013) at 12 months, favoring the experimental arm. To illustrate how customized patient profiles can be used to better understand patient outcomes, a single profile is presented. At baseline, a patient receiving the experimental treatment, EPIC urinary score 98.0, age 57, white, clinical T-stage T2, Gleason score 6, could be expected to report an EPIC urinary score of 94.3 (92.06, 96.00) at 6 months based on the statistical model. In the observed trial data, one patient with this profile reported an EPIC urinary score of 93.8 at 6 months. The expected EPIC urinary score overestimated the observed score by only 0.53%, indicating the accuracy of the expected EPIC urinary scores. This corresponds to approximately one category decrease on two of the 12 domain items (i.e., a decrease in symptom severity). Conclusions: Well-established statistical methods can lead to improved clinician understanding of expected outcomes specific to a given patient profile. This would facilitate communication between clinician and patient regarding anticipated oncology treatment outcomes. Recommendations to support the use of these methods should be considered.

Awareness of Age-Related Changes Among Middle-Aged and Older Adults: Longitudinal Trajectories, and the Role of Age Stereotypes and Personality Traits.

Awareness of Age-Related Change (AARC) describes to what extent people become aware of changes which they attribute to getting older. So far little is known regarding how different AARC dimensions change over time, to what extent these changes in different domains of AARC gains and losses are interrelated, and which predictors account for inter-individual differences in within-person longitudinal trajectories. Specifically, the extent to which individuals perceive age-related gains and losses might be shaped by their chronological age, their personality as well as by their general views on aging (i.e., their age stereotypes). We investigated changes in global and domain-specific AARC gains and losses over about five years in a sample of originally N = 423 participants aged 40 to 98 years at baseline. We analyzed the role of personality traits and age stereotypes for levels and changes of AARC, taking into account participants' age at baseline and controlling for gender, education, and subjective health. Based on longitudinal multilevel regression models, we observed mean-level declines in most AARC gain domains. In contrast, perceived general AARC losses, as well as AARC losses in health and physical functioning, in cognitive functioning and in social-cognitive/socio-emotional functioning remained, on average, stable over time. Baseline scores on AARC gains (global scale) were higher among individuals with higher neuroticism, openness, conscientiousness and more positive age stereotypes. Additionally, the association of higher neuroticism with higher AARC gain scores was stronger among individuals with more positive age stereotypes. Higher neuroticism and more negative age stereotypes also predicted higher baseline scores on AARC losses (global scale). At the same time, higher neuroticism was associated with a steeper decrease in AARC loss perceptions over time. Most of the intercorrelations within the intercepts and within the intra-individual trajectories of the different AARC domains were positive, but small in size. Our findings show the importance of considering trajectories of age-related gains and losses in parallel and across multiple developmental domains when investigating the subjective perception of the aging process. They also suggest that personality traits and general age stereotypes are related with individual experiences of aging.

An observational study of centrally facilitated pain in individuals with chronic low back pain.

Central pain facilitation can hinder recovery in people with chronic low back pain (CLBP). The objective of this observational study was to investigate whether indices of centrally facilitated pain are associated with pain outcomes in a hospital-based cohort of individuals with CLBP undertaking a pain management programme. Participants provided self-report and pain sensitivity data at baseline (n = 97) and again 3 months (n = 87) after a cognitive behavioural therapy-based group intervention including physiotherapy. Indices of centrally facilitated pain were pressure pain detection threshold, temporal summation and conditioned pain modulation at the forearm, Widespread Pain Index (WPI) classified using a body manikin, and a Central Mechanisms Trait (CMT) factor derived from 8 self-reported characteristics of anxiety, depression, neuropathic pain, fatigue, cognitive dysfunction, pain distribution, catastrophizing, and sleep. Pain severity was a composite factor derived from Numerical Rating Scales. Cross-sectional and longitudinal regression models were adjusted for age and sex. Baseline CMT and WPI each was associated with higher pain severity (CMT: r = 0.50, P < 0.001; WPI: r = 0.21, P = 0.04) at baseline and at 3 months (CMT: r = 0.38, P < 0.001; WPI: r = 0.24, P = 0.02). High baseline CMT remained significantly associated with pain at 3 months after additional adjustment for baseline pain (β = 2.45, P = 0.04, R 2 = 0.25, P < 0.0001). Quantitative sensory testing indices of pain hypersensitivity were not significantly associated with pain outcomes at baseline or at 3 months. Central mechanisms beyond those captured by quantitative sensory testing are associated with poor CLBP outcome and might be targets for improved therapy.

Immigrant Organizations and Neighborhood Crime

We examine the impact of immigrant-serving organizations on neighborhood crime in the Los Angeles Metropolitan area, while accounting for other community correlates of crime as well as potential endogeneity. We estimate longitudinal negative binomial regression models that test for the main, mediating, and moderating effects of immigrant-serving organizations. We found that immigrant-serving organizations generally have crime-reducing effects for all types of crime. We also find that high immigrant concentration is associated with lower levels of crime in general, and this effect is moderated by the number of organizations, which underlines the importance of accounting for these organizations when studying the nexus of immigrant concentration and neighborhood crime.

Resistance training for Black men with depressive symptoms: a pilot randomized controlled trial to assess acceptability, feasibility, and preliminary efficacy

BackgroundDepression is under-recognized in Black men, who are less likely to seek or have access to psychiatric treatment. Resistance training (RT; i.e., weight lifting) can improve depressive symptoms and may be more acceptable to Black men, but its effects have not been examined for Black men with depressive symptoms.MethodsFifty Black men with depressive symptoms were randomized to either (a) 12 weeks of RT (coupled with Behavioral Activation techniques to promote adherence) or (b) an attention-control group (Health, Wellness, and Education; HWE). Both groups met twice/week for 12 weeks, and follow-up assessments were done at end-of-treatment (EOT) and 6 months after enrollment. Changes in physical activity and muscular strength were collected as a manipulation check. The primary outcome was interviewer assessed symptoms of depression using the Quick Inventory of Depression Symptomology (QIDS). Secondary outcomes included self-reported depressive symptoms, anxiety, and stress. The association between change in QIDS from baseline to EOT and concurrent changes in physical activity and muscular strength in the RT group were explored as an initial assessment of mechanism. Longitudinal mixed effects regression models with subject-specific intercepts were used to examine intervention effects.ResultsA sample with high rates of medical comorbidities (e.g., 44% HIV positive), substance use (e.g., 34% smoking), and negative social determinates of health (e.g., 50% unemployed) was enrolled. Recruitment, engagement, and retention data indicate that the intervention and design were feasible. The RT group showed greater gains in self-reported exercise (b = 270.94, SE = 105.69, p = .01) and muscular strength (b = 11.71, SE = 4.23, p = .01 for upper body and b = 4.24, SE = 2.02, p = .04 for lower body) than the HWE group. The RT group had greater reductions in QIDS scores at both EOT (b = -3.00, SE = 1.34, p = .01) and 6 months (b = -2.63, SE = 1.81, p = .04). The RT group showed a greater reduction in anxiety at EOT (b = -2.67, SE = 1.06, p = .02). Findings regarding self-reported depressive symptoms and stress were non-significant, but in the expected direction with effect sizes in the small to medium range. In the RT group, improvement on the QIDS between baseline and EOT was associated with concurrent improvements in physical activity (b = 21.03, SE = 11.16, p = .02) and muscular strength (b = 1.27, SE = .44, p = .03 for upper body and b = .75, SE = .14, p = .03 for lower body). ConclusionsResults suggest that RT is feasible and may be efficacious for reducing depressive symptoms among underserved urban Black men.Trial RegistrationClinicalTrial.gov #: NCT03107039 (Registered 11/04/2017).

Methamphetamine/amphetamine use over time among persons with opioid use disorders treated with buprenorphine/naloxone versus extended-release naltrexone

BackgroundMethamphetamine use is increasing among persons with opioid use disorder (OUD). The study aims were to describe methamphetamine/amphetamine (MA/A) use among patients treated for OUD with buprenorphine/naloxone (BUP-NX) or extended-release naltrexone (XR-NTX), and to explore associations between treatment arm and MA/A use. MethodsSecondary analysis of data from a multi-site, open-label, randomized controlled trial of XR-NTX versus BUP-NX for 24 weeks. The outcome variable was MA/A use defined by either positive urine drug toxicology or self-report. The main predictor was treatment assignment (BUP-NX v. XR-NTX). Longitudinal mixed-effects logistic regression models were fit to model the odds of MA/A use during the study. Additional predictors included study visit and baseline MA/A use. ResultsAmong the sample of 570 participants with OUD, baseline use of MA/A was observed in 105 (18.4%). There was no significant treatment effect over the study period, though BUP-NX subjects, on average, had about half the odds of MA/A use compared to XR-NTX subjects (OR=0.50; p = 0.051). In the same model, baseline MA/A use and study visit were both significantly associated with MA/A use over time. ConclusionIn this sample of treated OUD patients, nearly a fifth of participants had MA/A use at baseline and the frequency of use did not decline over time: in fact, the odds of use slightly increased for each later visit. These secondary analyses found no significant difference in MA/A use between BUP-NX and XR-NTX treatment arms, however, the observation of less MA/A in the buprenorphine arm merits further investigation. Clinical trial registrationClinicalTrials.gov (NCT02032433)

Optimizing evaluation in pediatric and young adult patients with Marfan syndrome: Novel longitudinal metrics to track growth of aortic structures

ObjectiveSurveillance metrics in pediatric and young adult Marfan syndrome (pMFS) are challenging. We evaluated the utility of aortic root cross-sectional area/height index (CSA/Ht) on echocardiogram among pMFS patients as a risk stratification and surgical triage metric. MethodsGenotype or phenotype positive pMFS patients aged 25 years or younger seen at our center from 2001 to 2020 were identified. Time-related transition to surgery was modeled using parametric methods. Predictive utility of CSA/Ht compared with aortic root diameter (ARd) and root Z score (ARz) were modeled using nonlinear multivariable parametric and nonparametric longitudinal regression models. ResultsSeventy-nine patients (43% female) presented at median age of 5.8 years (15th-85th percentile, 0.75-17 years) with median follow-up of 4.4 years (range, 0-18.5 years). Baseline echocardiography data were: CSA/Ht, 3.9 ± 1.4 cm2/m; ARd, 2.4 ± 0.89 cm; and ARz, 2.4 ± 1.7. CSA/Ht tracked ARd better compared with ARz (r = 0.91 vs 0.24). Eighteen patients underwent surgery. Surgical procedures included at least 2 components in 17 (aortic, mitral, tricuspid, aortic root, and arch procedures) and isolated mitral valve procedures in 1 patient. Time-related transition to surgery showed a prominent early phase to 1 year post presentation, followed by a slowly increasing late phase. CSA/Ht had a more linear correlation versus ARz during periods of rapid somatic growth in surgical patients. Surgical repair occurred at CSA/Ht between 5 and 7 cm2/m. ConclusionsCSA/Ht tracked ARd well over time. CSA/Ht between 5 and 7 cm2/m might be a promising metric for surgical triage in pMFS patients. CSA/Ht surgical threshold values in pMFS patients occurred at lower than current accepted “surgical” threshold values for CSA/Ht in adult Marfan syndrome patients.

What's in the Sauce? The Specific Benefits of Palliative Care for Parkinson's Disease

ContextIncreasing evidence demonstrates the benefits of palliative care among individuals with Parkinson's disease and related disorders (PDRD), but the critical components that contribute to therapeutic effects are not well understood. ObjectivesTo determine the specific items most responsive to a palliative care intervention in PDRD and identify key correlates of improvement in patient and care partner outcomes. MethodsThe main trial was a pragmatic comparative effectiveness trial of outpatient integrated palliative care compared to standard care among participants with PDRD (NCT02533921), showing significantly higher patient QOL at six months and lower care partner burden at 12 months. We used longitudinal regression models to analyze changes in subdomains of patient QOL and care partner burden and Spearman correlations to evaluate key correlates of change scores in patient and care partner outcomes. We performed a secondary analysis of data from 210 patients and 175 care partners. ResultsCompared to controls, patients in the intervention reported greater improvement in perceptions of the “self as a whole” at six months (coeff = 0.22, P < 0.05) and care partners reported greater reduction in stress, anger, and loss of control at 12 months (coeff = -.40, -0.25, -0.31, P < 0.05). Positive change in numerous patient non-motor symptoms and grief correlated with improved patient QOL, reduced patient anxiety, and increased care partner spirituality. Alleviation of care partner anxiety and depression correlated with reduced care partner burden. ConclusionSpecific benefits of an integrated palliative approach in PDRD include improvement in patient holistic self-impressions, care partner self-efficacy, and non-motor symptoms.

The use of podcasts as a tool to teach clinical reasoning: a pseudorandomized and controlled study.

Podcasts have emerged as an efficient method for widespread delivery of educational clinical reasoning (CR) content. However, the impact of such podcasts on CR skills has not been established. We set out to determine whether exposure to expert reasoning in a podcast format leads to enhanced CR skills. This is a pseudo-randomized study of third-year medical students (MS3) to either a control group (n=22) of pre-established online CR modules, or intervention group (n=26) with both the online modules and novel CR podcasts. The podcasts were developed from four "clinical unknown" cases presented to expert clinician educators. After completing these assignments in weeks 1-2, weekly history and physical (H&P) notes were collected and graded according to the validated IDEA rubric between weeks 3-7. A longitudinal regression model was used to compare the H&P IDEA scores over time. Usage and perception of the podcasts was also assessed via survey data. Ninety control and 128 intervention H&Ps were scored. There was no statistical difference in the change of average IDEA scores between intervention (0.92, p=0.35) and control groups (-0.33, p=0.83). Intervention participants positively received the podcasts and noted increased discussion of CR principles from both their ward (3.1 vs. 2.4, p=0.08) and teaching (3.2 vs. 2.5, p=0.05) attendings. This is the first objective, pseudo-randomized assessment of CR podcasts in undergraduate medical education. While we did not demonstrate significant improvement in IDEA scores, our data show that podcasts are a well-received tool that can prime learners to recognize CR principles.

Analytic approaches to assess the impact of local spending on sexually transmitted diseases.

To compare the estimated associations between annual sexually transmitted diseases (STD) expenditures per capita and STD incidence rates among Florida and Washington local health departments (LHDs) from 2001 to 2017, using two approaches-a longitudinal regression model with lagged STD spending and a regression model with the Arellano-Bond panel estimator. Secondary data for LHDs were obtained from Florida and Washington state government offices and combined with county sociodemographic and health system data from the federal government. We examined LHDs in Florida and Washington using a longitudinal panel study design to estimate ecological relationships between annual STD expenditures per capita and annual STD incidence rates from 2001 to 2017, with LHDs as the unit of analysis. We compared two regression models: generalized estimating equations (GEE) and the Arellano-Bond panel estimator (an instrumental variable approach). The secondary data were combined to build a longitudinal panel database for LHDs in Florida and Washington from 2001 to 2017. In the GEE model with both states, greater STD spending in a prior year was associated unexpectedly with greater STD incidence rates in succeeding years. The Arellano-Bond models for both states had the expected inverse associations but were not significant. In the Arellano-Bond models for Florida, a $1 increase in STD spending in previous years was followed by decreases in STD incidence rates ranging between 29 and 58 points in succeeding years (0.09 ≥ p ≥ 0.04). In longitudinal panel data for LHDs in two states, the Arellano-Bond estimator, or other instrumental variable approach, is preferred over conventional regression models to obtain unbiased estimates of the relationship between annual STD spending rates and annual STD rates. Future studies will require accurate, standardized, and detailed longitudinal data and rigorous analytic approaches, such as those illustrated in our study.

Examining Consequences Related to Unmet Care Needs Across the Long-Term Care Continuum.

To examine how different care arrangements across the long-term care continuum are associated with experiencing unmet care need consequences (UCNCs), such as skipping meals, going without clean clothes, or taking the wrong medication. We include older adults receiving assistance with at least one self-care, mobility, or household activity (for health/functioning reasons) in the 2015 National Health and Aging Trends Study (N = 2,388). We examine the likelihood of experiencing a UCNC across the long-term care continuum: those receiving unpaid community care only, paid community care, and residential care. Cross-sectional logistic and longitudinal multinomial logistic regression models examine if type of care arrangement in 2015 is associated with UCNCs in 2015 and change in UCNCs by 2017. In adjusted cross-sectional models, paid community care recipients had roughly 2 times greater odds of experiencing a UCNC in 2015 compared to those living in residential care or receiving only unpaid care. In adjusted longitudinal models, the risk of experiencing persistent UCNCs (compared to having needs met in both years) was 4.81 times higher for those receiving paid community care compared to those in residential care and 2.17 times that of those receiving unpaid care only. Older adults receiving paid care face significant and consequential gaps in care, particularly in comparison to those in other care arrangements. More attention is needed to determine how paid care arrangements can be improved and/or expanded to meet the needs of the growing number of older adults receiving paid care in the community.

Opioid Taper is Associated with Improved Experimental Pain Tolerance in Patients with Chronic Pain: An Observational Study.

IntroductionThe degree to which opioid-induced hyperalgesia contributes to the pain experience of patients with chronic pain remains relatively undescribed. The objective of this pilot study was to determine if experimental pain responses improve in patients with chronic pain as they undergo a planned opioid taper.MethodsThis was a prospective observational study. Seven patients with chronic neuropathic pain on at least 120 mg morphine equivalents/day were enrolled. The participants were followed over the course of an individualized opioid taper to a lower dose. Measures of experimental pain sensitivity, including indicators of central pain modulation, were collected on a biweekly basis; in addition, measures of function and quality of life were collected monthly. The effect of opioid taper on pain responses and functional outcomes over time were examined using longitudinal mixed-effects regression modeling and general linear regression modeling with regularization as a function of baseline dose, end dose, and taper rate.ResultsIn this small sample of patients undergoing highly individualized and variable opioid taper, the opioid taper was significantly associated with improved pain responses to the cold-pressor test, with the pain threshold on average increasing by 1.14 s every 6 weeks (p = 0.0084, 95% confidence interval [CI] for 6-week change 0.3039–2.0178) and pain tolerance on average increasing by 2.87 s every 6 weeks (p = 0.0026, 95% CI for 6-week change 1.02–4.7277). Taper-related changes in central pain modulation were not observed, although conditioned modulation trended toward improvement by the completion of opioid taper. Similarly, no declines in function and quality of life were observed with the opioid taper, suggesting stability despite decreased opioid dose.ConclusionsOpioid taper was associated with improvements in experimental pain responses without a decline in function and quality of life, suggestive of diminished opioid-induced hyperalgesia in this clinical sample.Trial RegistrationClinicalTrials.gov identifier, NCT03912298.Supplementary InformationThe online version contains supplementary material available at 10.1007/s40122-021-00348-8.

Quantitative assessment of the exposure-efficacy relationship of glucocerebrosidase using Markovian elements in Gaucher patients treated with enzyme replacement therapy.

The aims of this study are (i) to develop a population pharmacokinetic model of enzyme activity in Gaucher-type 1 (GD1) patients after intravenous administration of enzyme replacement therapy (ERT), and (ii) to establish an exposure-efficacy relationship for bone marrow infiltration to propose dose adjustments according to patient covariate values. A prospective follow-up, semi-experimental multi-centre study was conducted in four hospitals to evaluate the pharmacokinetics, efficacy and safety of ERT in GD1 patients. Twenty-five individuals with 266 glucocerebrosidase (GCase) observations in plasma and leukocytes and 14 individuals with 68 Spanish magnetic resonance imaging (S-MRI) observations were enrolled. A two concatenated compartment model with zero-order endogenous production and first-order distribution (CL1 = 3.85 × 10-1 L/d) and elimination (CL2 = 1.25 L/d) allowed GCase observations in plasma and leukocytes to be described, respectively. An exponential time dependency (kT = 6.14 × 10-1 d-1 ) effect on CL1 was incorporated. The final exposure-efficacy model was a longitudinal logistic regression model with a first-order Markov element. An Emax function (EC50 = 15.73 U/L and Emax = 2.33) linked steady-state concentrations of GCase in leukocytes to the probability of transition across the different S-MRI stages. A population pharmacokinetic model successfully characterized the leukocyte activity-time profiles of GCase following intravenous administration of ERT in GD1 patients together with an exposure-efficacy relationship in bone marrow using Markovian elements. The information obtained from this study could be of high clinical relevance in individualization of ERT in GD1 patients, as this could lead to anticipative decision-making regarding clinical response in bone and optimal dosing strategy.