Changes In Clinical Outcome Measures Research Articles

Five-year follow-up study on quantitative muscle magnetic resonance imaging in facioscapulohumeral muscular dystrophy: The link to clinical outcome.

It is unclear how changes in quantitative muscle magnetic resonance imaging (MRI) relate to changes in clinical outcome in facioscapulohumeral muscular dystrophy (FSHD), although this information is crucial for optimal use of MRI as imaging biomarker in trials. We therefore assessed muscle MRI and clinical outcome measures in a large longitudinal prospective cohort study. All patients were assessed by MRI at baseline and at 5-year follow-up, employing 2pt-Dixon and turbo inversion recovery magnitude (TIRM) sequences, after which fat fraction and TIRM positivity of 19 leg muscles were determined bilaterally. The MRI compound score (CoS) was defined as the mean fat fraction of all muscles weighted for cross-sectional area. Clinical outcome measures included the Ricci-score, FSHD clinical score (FSHD-CS), MRC sumscore (MRC-SS), and motor-function-measure (MFM). We included 105 FSHD patients [mean age 54±14years, median Ricci-score 7 (range 0-10)]. The median change over 5years' time in the MRI-CoS was 2.0% (range -4.6 to +12.1; P<0.001). The median change over 5years' time in clinical outcome measures was small in all measures, with z-scores ranging from 5.0 to 7.2 (P<0.001). The change in MRI-CoS correlated with change in FSHD-CS and Ricci-score (ρ=0.25, respectively; ρ=0.23, P<0.05). The largest median increase in MRI-CoS was seen in baseline subgroups with an MRI-CoS 20-40% (6.1%), with ≥2 TIRM positive muscles (3.5%) or with an FSHD-CS 5-10 (3.1%). This 5-year study showed significant changes in MRI and clinical outcome measures and a significant correlation between changes in MRI-CoS and changes in clinical outcome measures. In addition, we identified subgroups of patients that are most prone to radiological disease progression. This knowledge further establishes quantitative MRI parameters as prognostic biomarkers in FSHD and as efficacy biomarkers in upcoming clinical trials.

Current understanding of AD pathophysiology and impact of amyloid beta-targeted treatments on biomarkers and clinical endpoints.

Alzheimer's disease (AD) is a fatal, neurodegenerative disease whose pathogenesis includes the buildup of amyloid beta (Aß; one of the defining brain changes of AD) years before clinical symptoms appear. Anti-Aß therapeutics that target the complex underlying AD pathophysiology have been the focus of many recent clinical trials, representing a viable option that may ultimately slow cognitive decline in some patients. Evidence has been accumulating within the science community that plaque-removing monoclonal antibodies can impact Aß, tau, and neurodegeneration, the hallmarks of AD. The spring 2022 Alzheimer's Association's Research Roundtable (AARR) convened leaders from industry and academia, as well as patients, clinicians, and government scientists and regulatory agencies, to discuss the topic, “Current Understanding of AD Pathophysiology & Impact of Amyloid Beta–Targeted Treatments on Biomarkers and Clinical Endpoints.” The meeting addressed two fundamental questions: (1) What is the evidence regarding the relationship between Aß and tau? and (2) What does the evidence show about how anti-Aß therapies alter clinical function? The meeting opened with a series of presentations to lay the groundwork on what we know about the biology of AD, including a primer on various species of Aß and how animal models may inform our understanding of disease progression. The meeting continued with representatives from active, observational studies sharing how biomarker and clinical data contribute to our understanding of Aß, tau, and other pathologies, and subject matter experts who presented modeling data to advance AD treatment strategies. Several major pharmaceutical companies that are AARR members also presented current evidence from multiple phase 2 and 3 clinical trials that manipulation (or removal) of Aß has a clear downstream impact on tau, neurodegeneration, and cognitive/functional measures. At the conclusion of the 2-day meeting, presenters, panelists, and the AARR membership in attendance came to several conclusions based on the scientific evidence presented, discussed and debated. The totality of scientific evidence (clinical trials, animal data, modeling, and observational studies) on Aß is helping our understanding of the downstream effects and overall importance of lowering Aß. Based on data from multiple phase 2 and 3 clinical trials of monoclonal antibodies, there is evidence to support that a change in Aß is associated with a change in tau and clinical endpoints. And finally, biomarker changes in Aß are reasonably likely to predict changes in clinical outcome measures, and should be considered meaningful to all patients who may potentially benefit from these treatments. The spring 2022 AARR meeting not only furthered our understanding of the pathophysiology of AD, but also brought to light the strength of the evidence supporting the hypothesis that a change in Aß can produce meaningful change in biomarkers and clinical endpoints. There is much work to be done, and the scientific community needs to stay focused on defining those tools most appropriate to capture these changes, the populations best suited to enroll in clinical trials, and defining our expectations of what changes can be expected over a particular interval of time. A more detailed report of this meeting will appear in a future issue of Alzheimer's & Dementia.

Resource Management & Healthy Purchasing Behaviors Show Direct Effects on Diet Change in Pathway Analysis Exploring Mechanisms of Action for a Produce Prescription Program

ObjectivesInvestigate the mechanisms of action in a produce prescription program through pathway analysis. MethodsThe Georgia Food for Health program is a produce prescription program that provides cooking classes, nutrition education, and vouchers redeemable for produce over a six-month intervention period. Program data collected between 2018 and 2019 were used to fit a pathway model estimating the relationships in the program. Measures included the number of program visits attended, per-person total produce voucher redemption (in US dollars), change in food security, diet score (based on a modified food frequency questionnaire), purchase score (a measure of healthy purchasing behaviors), resource score (a measure of resource management behaviors), as well as blood pressure, waist circumference, and BMI. The model controlled for sex and age of participant as well as site and year of program participation. Model fit was interpreted based on the following indices: Root Mean Squared Error of Approximation (RMSEA), Comparative Fit Index (CFI), Tucker-Lewis Index (TLI), and Standardized Root Mean Squared Residual (SRMR). The lavaan package version 0.6–3 in R software was used for the pathway analysis component. ResultsNeither number of visits attended nor per-person total redemption had direct effects on change in resource score or change in purchase score from baseline to endline of the program. Change in resource score had a moderate direct effect on change in diet score (β = 0.185, P < 0.05). Change in purchase score also had a moderate direct effect on change in diet score (β = 0.149, P < 0.05). No factors had significant effects on change in food security. Diet score did not have significant effects on change in clinical outcome measures. Model fit was good with RMSEA <0.001, CFI is >0.95, TLI >0.95, and SRMR <0.08. ConclusionsProduce prescription programs show promise of improving diet scores through improving healthy purchasing and resource management behaviors. Additional research is needed to determine factors that influence changes in these behaviors and how to maximize their effects for similar programs. Funding SourcesSupported partially by the National Center for Advancing Translational Sciences of the National Institutes of Health under Award Number UL1TR002378. Additional funding provided by Open Hand Atlanta.

Associations Between Variant Repeat Interruptions and Clinical Outcomes in Myotonic Dystrophy Type 1

ObjectiveTo assess the association between variant repeat (VR) interruptions in patients with myotonic dystrophy type 1 (DM1) and clinical symptoms and outcome measures after cognitive behavioral therapy (CBT) intervention.MethodsAdult patients with DM1 were recruited within the OPTIMISTIC trial (NCT02118779). Disease-related history, current clinical symptoms and comorbidities, functional assessments, and disease- and health-related questionnaires were obtained at baseline and after 5 and 10 months. After genetic analysis, we assessed the association between the presence of VR interruptions and clinical symptoms' long-term outcomes and compared the effects of CBT in patients with and without VR interruptions. Core trial outcome measures analyzed were: 6-minute walking test, DM1-Activ-C, Checklist Individual Strength Fatigue Score, Myotonic Dystrophy Health Index, McGill-Pain questionnaire, and Beck Depression inventory—fast screen. Blood samples for DNA testing were obtained at the baseline visit for determining CTG length and detection of VR interruptions.ResultsVR interruptions were detectable in 21/250 patients (8.4%)—12 were assigned to the standard-of-care group (control group) and 9 to the CBT group. Patients with VR interruptions were significantly older when the first medical problem occurred and had a significantly shorter disease duration at baseline. We found a tendency toward a milder disease severity in patients with VR interruptions, especially in ventilation status, mobility, and cardiac symptoms. Changes in clinical outcome measures after CBT were not associated with the presence of VR interruptions.ConclusionsThe presence of VR interruptions is associated with a later onset of the disease and a milder phenotype. However, based on the OPTIMISTIC trial data, the presence of VR interruptions was not associated with significant changes on outcome measures after CBT intervention.Trial Registration InformationClinicalTrials.gov NCT02118779.

Combining Accelerometer and GPS Features to Evaluate Community Mobility in Knee Ankle Foot Orthoses (KAFO) Users.

Orthotic and assistive devices such as knee ankle foot orthoses (KAFO), come in a variety of forms and fits, with several levels of available features that could help users perform daily activities more naturally. However, objective data on the actual use of these devices outside of the research lab is usually not obtained. Such data could enhance traditional lab-based outcome measures and inform clinical decision-making when prescribing new orthotic and assistive technology. Here, we link data from a GPS unit and an accelerometer mounted on the orthotic device to quantify its usage in the community and examine the correlations with clinical metrics. We collected data from 14 individuals over a period of 2 months as they used their personal KAFO first, and then a novel research KAFO; for each device we quantified number of steps, cadence, time spent at community locations and time wearing the KAFO at those locations. Sensor-derived metrics showed that mobility patterns differed widely between participants (mean steps: 591.3, SD =704.2). The novel KAFO generally enabled participants to walk faster during clinical tests (Δ6Minute-Walk-Test=71.5m, p=0.006). However, some participants wore the novel device less often despite improved performance on these clinical measures, leading to poor correlation between changes in clinical outcome measures and changes in community mobility (Δ6Minute-Walk-Test – ΔCommunity Steps: r=0.09, p=0.76). Our results suggest that some traditional clinical outcome measures may not be associated with the actual wear time of an assistive device in the community, and obtaining personalized data from real-world use through wearable technology is valuable.

Can kinematic parameters of 3D reach-to-target movements be used as a proxy for clinical outcome measures in chronic stroke rehabilitation? An exploratory study

BackgroundDespite numerous trials investigating robot-assisted therapy (RT) effects on upper-extremity (UE) function after stroke, few have explored the relationship between three-dimensional (3D) reach-to-target kinematics and clinical outcomes. The objectives of this study were to 1) investigate the correlation between kinematic parameters of 3D reach-to-target movements and UE clinical outcome measures, and 2) examine the degree to which differences in kinematic parameters across individuals can account for differences in clinical outcomes in response to RT.MethodsTen chronic stroke survivors participated in a pilot RT intervention (eighteen 1-h sessions) integrating cognitive skills training and a home-action program. Clinical outcome measures and kinematic parameters of 3D reach-to-target movements were collected pre- and post-intervention. The correlation between clinical outcomes and kinematic parameters was investigated both cross-sectionally and longitudinally (i.e., changes in response to the intervention). Changes in clinical outcomes and kinematic parameters were tested for significance in both group and subject-by-subject analyses. Potential associations between individual differences in kinematic parameters and differences in clinical outcomes were examined.ResultsModerate-to-strong correlation was found between clinical measures and specific kinematic parameters when examined cross-sectionally. Weaker correlation coefficients were found longitudinally. Group analyses revealed significant changes in clinical outcome measures in response to the intervention; no significant group changes were observed in kinematic parameters. Subject-by-subject analyses revealed changes with moderate-to-large effect size in the kinematics of 3D reach-to-target movements pre- vs. post-intervention. Changes in clinical outcomes and kinematic parameters varied widely across participants.ConclusionsLarge variability was observed across subjects in response to the intervention. The correlation between changes in kinematic parameters and clinical outcomes in response to the intervention was variable and not strong across parameters, suggesting no consistent change in UE motor strategies across participants. These results highlight the need to investigate the response to interventions at the individual level. This would enable the identification of clusters of individuals with common patterns of change in response to an intervention, providing an opportunity to use cluster-specific kinematic parameters as a proxy of clinical outcomes.Trial registrationClinicalTrials.gov, NCT02747433. Registered on April 21st, 2016

The effect of community pharmacist–led health coaching on clinical outcomes

ObjectiveTo evaluate the impact of a community pharmacist–driven health coaching program on clinical outcomes from baseline to 1 year. SettingIndependent community pharmacy in western North Carolina. Practice descriptionSona Pharmacy + Clinic is an independent community pharmacy offering enhanced clinical services such as medication synchronization, adherence packaging, and free delivery. Sona Benefits offers pharmacy benefit manager (PBM) services to self-funded plans in western North Carolina. Practice innovationSona Health Management Program is a disease management program offered to Sona Benefits PBM clients; the services began in October 2016. Evaluation: Change in clinical outcome measures (total number of medications, blood pressure, hemoglobin A1c, weight, low-density lipoprotein cholesterol [LDL-C], high-density lipoprotein cholesterol [HDL-C], triglycerides [TG], patient health questionnaire [PHQ-9] scores, and asthma control test [ACT] scores) were assessed for members who participated in the program for a minimum of 12 months for at least 2 of the following conditions: hypertension, hyperlipidemia, diabetes, depression, and asthma. ResultsHealth coaching was provided to 42 members (mean age of 55.9 years and 2.7 qualifying disease states). The mean number of medications per patient significantly decreased from 7.2 to 6.2 (P = 0.02). Systolic and diastolic blood pressures were significantly reduced from 130.8 mm Hg to 125.7 mm Hg (P = 0.04) and 76.9 mm Hg to 73.7 mm Hg (P = 0.04), respectively. Other clinical outcome measures evaluated, such as hemoglobin A1c, weight, LDL-C, HDL-C, TG, and PHQ-9 and ACT scores, were improved but did not reach significance. ConclusionThese results suggest that community pharmacists can have a positive impact on patients with multiple chronic conditions through health coaching services. This project suggests a potential model of pharmacist health coaching through pharmacist-run PBM services.

Longitudinal changes in clinical outcome measures in COL6-related dystrophies and LAMA2-related dystrophies.

To identify the rate of change of clinical outcome measures in children with 2 types of congenital muscular dystrophy (CMD), COL6-related dystrophies (COL6-RDs) and LAMA2-related dystrophies (LAMA2-RDs). Over the course of 4 years, 47 individuals (23 with COL6-RD and 24 with LAMA2-RD) 4 to 22 years of age were evaluated. Assessments included the Motor Function Measure 32 (MFM32), myometry (knee flexors and extensors, elbow flexors and extensors), goniometry (knee and elbow extension), pulmonary function tests, and quality-of-life measures. Separate linear mixed-effects models were fitted for each outcome measurement, with subject-specific random intercepts. Total MFM32 scores for COL6-RDs and LAMA2-RDs decreased at a rate of 4.01 and 2.60 points, respectively, each year (p < 0.01). All muscle groups except elbow flexors for individuals with COL6-RDs decreased in strength between 1.70% (p < 0.05) and 2.55% (p < 0.01). Range-of-motion measurements decreased by 3.21° (p < 0.05) at the left elbow each year in individuals with LAMA2-RDs and 2.35° (p < 0.01) in right knee extension each year in individuals with COL6-RDs. Pulmonary function demonstrated a yearly decline in sitting forced vital capacity percent predicted of 3.03% (p < 0.01) in individuals with COL6-RDs. There was no significant change in quality-of-life measures analyzed. Results of this study describe the rate of change of motor function as measured by the MFM32, muscle strength, range of motion, and pulmonary function in individuals with COL6-RDs and LAMA2-RDs.

Changes in metabolites in the brain of patients with fibromyalgia after treatment with an NMDA receptor antagonist

The aims of this work were to evaluate whether the treatment of patients with fibromyalgia with memantine is associated with significant changes in metabolite concentrations in the brain, and to explore any changes in clinical outcome measures. Magnetic resonance spectroscopy was performed of the right anterior and posterior insula, both hippocampi and the posterior cingulate cortex. Questionnaires on pain, anxiety, depression, global function, quality of life and cognitive impairment were used. Ten patients were studied at baseline and after three months of treatment with memantine. Significant increases were observed in the following areas: N-acetylaspartate (4.47 at baseline vs. 4.71 at three months, p = 0.02) and N-acetylaspartate+N-acetylaspartate glutamate in the left hippocampus (5.89 vs. 5.98; p = 0.007); N-acetylaspartate+N-acetylaspartate glutamate in the right hippocampus (5.31 vs 5.79; p = 0.01) and the anterior insula (7.56 vs. 7.70; p = 0.033); glutamate+glutamine/creatine ratio in the anterior insula (2.03 vs. 2.17; p = 0.022) and the posterior insula (1.77 vs. 2.00; p = 0.004); choline/creatine ratio in the posterior cingulate (0.18 vs. 0.19; p = 0.023); and creatine in the right hippocampus (3.60 vs. 3.85; p = 0.007). At the three-month follow-up, memantine improved cognitive function assessed by the Cognition Mini-Exam (31.50, SD = 2.95 vs. 34.40, SD = 0.6; p = 0.005), depression measured by the Hamilton Depression Scale (7.70, SD = 0.81 vs. 7.56, SD = 0.68; p = 0.042) and severity of illness measured by the Clinical Global Impression severity scale (5.79, SD = 0.96 vs. 5.31, SD = 1.12; p = 0.007). Depression, clinical global impression and cognitive function showed improvement with memantine. Magnetic resonance spectroscopy could be useful in monitoring response to the pharmacological treatment of fibromyalgia.

Evaluation of the economic and clinical impact of community pharmacist-driven pharmacy benefit management services

ObjectiveTo evaluate the economic and clinical impact of community pharmacist–led pharmacy benefit management (PBM) services. SettingIndependent community pharmacy in western North Carolina. Practice descriptionSona Benefits is a PBM partner to self-funded plans in western North Carolina. The services provided by Sona Benefits are led by pharmacists at its affiliate company, Sona Pharmacy + Clinic. Practice innovationIn October 2016, Sona Benefits began providing PBM services to members employed by a local continuing care retirement community. EvaluationEconomic outcome measures included change in total medical and prescription costs per member per year (PMPY) and change in cost per prescription from baseline. Change in clinical outcome measures (hemoglobin A1C, weight, blood pressure) was assessed for members who participated in 2 or more quarterly health coaching sessions. ResultsPrescription costs were reduced from $1219.72 to $858.57 PMPY and medical health care costs were reduced from $5910.76 to $4290.30 PMPY from baseline. This represented a total decrease of $1981.61 PMPY in health care costs. A reduction in the average cost per prescription from $95.10 to $61.88 was observed. For patients enrolled and active in health coaching, we observed reductions in weight, hemoglobin A1C, and blood pressure. Between the initial and final health coaching visits, average weight decreased from 204.6 lb (92.8 kg) to 203.6 lb (92.4 kg), the percentage of patients at hemoglobin A1C goal increased from 47% to 53%, and percentage of patients at goal for blood pressure increased from 58% to 78%. ConclusionInclusion of community pharmacists in PBM service delivery produced economic benefits for plan sponsors. Preliminary clinical data suggested benefits of pharmacist-led health coaching services, but further evaluation is needed to determine the long-term impact.

Predictors of Return to Work 6 Months After the End of Treatment in Patients with Common Mental Disorders: A Cohort Study

Purpose Common mental disorders (CMDs) account for a large portion of sickness absence. Even after attending return to work (RTW) interventions, many patients with a CMD remain on sick leave. To identify people at risk of long-term work disability, more needs to be known about factors that predict RTW after treatment. Methods This was a prospective cohort study that followed 106 former patients at an RTW outpatient clinic for CMDs for 6 months after the end of treatment. Changes in work participation and mental health status between the end of treatment and the 6-month follow-up were analysed. Changes in work participation were used to identify patients with successful RTW. Patient characteristics and end-of-treatment measures of mental health status, work ability, generalized self-efficacy and expectations of future work ability, and changes in clinical outcome measures during treatment were included in logistic regression analyses to identify predictors of RTW at the 6-month follow-up. Results In the final model, high occupational status and higher work ability at the end of treatment predicted successful RTW at the 6-month follow-up. Further analyses showed that if the expectancy of future work ability improved or remained positive from before to the end of treatment, this was also strongly associated with RTW at the 6-month follow-up. Conclusions Among patients treated for CMDs, those with a low occupational status and who report lower work ability at the end of treatment are at risk of long-term disability.

\u2018Work it out\u2019: evaluation of a chronic condition self-management program for urban Aboriginal and Torres Strait Islander people, with or at risk of cardiovascular disease

BackgroundChronic diseases disproportionately burden Aboriginal and Torres Strait Islander people in Australia, with cardiovascular (CV) diseases being the greatest contributor. To improve quality of life and life expectancy for people living with CV disease, secondary prevention strategies such as rehabilitation and self-management programs are critical. However, there is no published evidence examining the effect of chronic condition self-management (CCSM) group programs for Aboriginal and Torres Strait Islander people who have, or are at risk of, CV disease specifically. This study evaluates the Work It Out program for its effect on clinical outcome measures in urban Aboriginal and Torres Strait Islander participants with or at risk of CV disease.MethodsThis study was underpinned by a conceptual framework based on Aboriginal and Torres Strait Islander community control. Participants had at least one diagnosed CV disease, or at least one CV disease risk factor. Short-term changes in clinical outcome measures over (approximately) 12 weeks were evaluated with a quasi-experimental, pre-post test design, using paired t-tests. Factors contributing to positive changes were tested using general linear models. The outcome measures included blood pressure (mmHg), weight (kg), body mass index (kg/m2), waist and hip circumference (cm), waist to hip ratio (waist cm/hip cm) and six minute walk test (6MWT).ResultsChanges in several clinical outcome measures were detected, either within the entire group (n = 85) or within specific participant sub-groups. Participant’s 6MWT distance improved by an average 0.053 km (95% CI: 0.01–0.07 km). The change in distance travelled was influenced by number of social and emotional wellbeing conditions participants presented with. The weight of participants classified with extreme obesity decreased on average by 1.6 kg (95% CI: 0.1–3.0 kg). Participants with high baseline systolic blood pressure demonstrated a mean decrease of 11 mmHg (95% CI: 3.2–18.8 mmHg). Change in blood pressure was influenced by the number of cardiovascular conditions participants experienced.ConclusionsShort-term improvements seen in some measures could indicate a trend for improvement in other indicators over the longer term. These results suggest the Work It Out program could be a useful model for cardiovascular rehabilitation and prevention for other urban Aboriginal and Torres Strait Islander populations.

Serum phosphorylated neurofilament-heavy chain levels in multiple sclerosis patients

ObjectivesWe evaluated whether the measurement of serum phosphorylated neurofilament heavy chain (pNF-H) titre is likely to be a valid biomarker of axonal injury in multiple sclerosis (MS).MethodsSerum pNF-H concentrations were...

Answer to the Editorial of J. O’Dowd and A. Casey

We would like to thank the authors of this editorial for their very thorough and balanced editorial. One of the concerns highlighted by the authors of the editorial is the hype in the media, and I can assure you that it was a great surprise to the authors of these papers as well. The study was published in e-pub in February 2013, and the interest from the press and the scientific society was non-existent. We then became worried that the science related to chronic back pain caused by Modic changes would be ignored, as was the discovery of Helicobacter in peptic ulceration. Following that discovery there was a shockingly slow decline in gastric surgery. It took more than a decade before the news that you could treat stomach ulcers with antibiotics as opposed to removing the stomach surgically was widely spread. Therefore, in conjunction with the studies being presented for the medical community at the Royal Society of Medicine in London, the press was invited to attend; six journalists attended, and the researchers were rather disappointed about this apparent lack of interest. However, these six journalists started an avalanche, which got completely out of our control. I have no idea how we could have been able to control this and I am certain that no one else has figured out how to do this either in today’s communication age and almighty presence of social media. We do agree with the authors regarding most of their comments. It is indeed necessary that the surgical and scientific communities should have a more tempered and objective response to our studies and that much remains to be done. The clinical trial needs to be replicated in a different clinical and scientific setting, and we are aware of several groups in Europe, which are far along in the planning stages of additional trials. The study was not underpowered when comparing antibiotics and placebo, but when comparing single and double-dose regimes a larger population is necessary. We also think that other antibiotics or combinations of antibiotics should be studied. The follow-up study on our paper [1], where MIC are being explored, indicates that possibly other antibiotics should be used instead of amoxicillin (study in press). The lack of spontaneous change in clinical outcome measures in this study in the controlled group with untreated Modic changes has been seen before [2]. We agree that it would also be interesting to see if the results could be replicated in back pain sufferers who have Modic type 1 changes, but have not had a documented disc herniation. We do not agree that it should be common practice to perform a biopsy and culture of the disc before treatment with antibiotics. We have carried out several attempts to do this and not found any surgical tools, in which you could safely, surely and efficiently extrude a sufficient amount of disc material. The procedure has to be performed in three-dimensional X-ray on a semi-sedated patient, and it exposes the patient to another risk infection. Furthermore, it is far from pain free in a number of patients. Additionally, the culture techniques are difficult and only mastered by a few laboratories. As we point out in our own paper, we do agree with the authors of the editorial that at the moment the only patients that should be considered for a course of antibiotics outside the environment of a clinical trial are those with: low back pain of more than 6 months’ duration that has not responded to exercise therapy; a symptomatic disc herniation within the previous 2 years; Modic type 1 changes at the same level as the disc herniation. The time since herniation in the authors’ response is 1 year, but in our study it was 2 years and we do believe that this is more correct.

Rasagiline, Parkinson neuroprotection, and delayed-start trials

Rasagiline has been studied as a Parkinson disease (PD) neuroprotective agent in 2 major clinical trials, utilizing the delayed-start design in an attempt to separate symptomatic drug benefits from a disease-modifying effect. The ostensibly positive outcomes of these studies, however, are obscured by potential confounding factors that seem intrinsic to this trial design, including 1) very small changes in clinical outcome measures that could easily be overshadowed by other influences; 2) probable incomplete blinding to study end; 3) subjective components of the Unified Parkinson's Disease Rating Scale (UPDRS) scoring system; and 4) practice influences from repeated scoring. Interpretation of the recent Attenuation of Disease Progression with Azilect Given Once-daily (ADAGIO) trials is especially problematic given 1) divergent results with the 2 symptomatically beneficial doses and 2) variability in UPDRS scores with active rasagiline, which was twice the magnitude of the major finding of the study. These studies further illustrate the difficulty in documenting a disease-modifying effect when considering a PD drug with symptomatic benefit.

The Effects of Redesigning the IDEATel Architecture on Glucose Uploads

The objective of this evaluation was to determine the effect of redesigning the Informatics for Diabetes Education and Telemedicine (IDEATel) telemedicine architecture on the average upload delay and on the average number of glucose uploads to a central database. These two measures positively influence our ability to deliver timely and accurate patient care to the study population. The redesign was also undertaken to improve the patients' experience in using the system and thereby increase the frequency and timeliness of their self-monitoring behavior. Using the total number of glucose uploads, we compared the delay in glucose upload times according to the type of home telemedicine unit the study participants used and the region where the participants lived. The participants were Medicare beneficiaries with diabetes living in medically underserved neighborhoods in New York City and rural Upstate New York. The populations in these two regions differed considerably in terms of ethnicity, language spoken (Spanish, English), and education level. Participants who had Generation 2 (Gen 2) (mean = 10.75, SD +/- 7.96) home telemedicine units had significantly shorter upload delay times (p < 0.001) as measured in days than those participants with Generation 1 (Gen 1) (mean = 22.44, SD +/- 11.18) and those who were upgraded from Gen 1 (mean = 20.67, SD +/- 8.85) to Gen 2 (mean = 14.93, SD +/- 9.37). Additionally, the delay was significantly shorter for participants living upstate (mean = 24.14 days, SD +/- 11.95 days) than downstate (mean = 15.30 days, SD +/- 7.87 days), t (975) = 13.98, p < 0.01. The system redesign made a significant impact in reducing glucose upload delays of IDEATel participants. However, upload delays were significantly impacted by the region where the participants resided.

The Regression Effect as a Neglected Source of Bias in Nonrandomized Intervention Trials and Systematic Reviews of Observational Studies

Health care providers depend on the findings of observational intervention studies and systematic reviews of those studies to make evidence-based decisions about their clients' care. The nonrandom methods of group formation in observational studies necessitate carefully assessing threats to the validity of conclusions. Regression to the mean is a source of change in clinical outcome measures that has escaped widespread notice as a potential threat to the accuracy of conclusions from observational studies and systematic reviews thereof. Failure to assess the degree to which regression confounds study results elevates the risk of making clinical decisions using biased estimates of intervention effectiveness. Because the change in average outcome scores due to regression can be quantified, it is a type of bias whose direct influence can be known. Yet determining and reporting change due to regression is uncommon in observational studies or systematic reviews thereof. The means to quantify change due to regression in average outcome scores is illustrated by example in this article.

Advancing Diabetes Self-Management in the Mexican American Population

The purpose of this study was to pilot test the effectiveness of health promoters trained in the transtheoretical model of change to provide diabetes management education and support to Mexican Americans in a primary care setting. The study site was an urban community health center in Oakland, California. This study reports on 142 patients who were enrolled for at least 1 year in the program. Community health workers acted as extenders of the medical staff to facilitate behavior change, using patient-centered counseling. This was a 1-group pretest/posttest pilot study. Descriptive statistics and the paired-sample t test were used to compare the change in clinical outcome measures from baseline to 6 months and 1 year. Statistically significant changes were correlated with frequency of community health worker contact. The paired-sample t test showed significant reduction in glycosylated hemoglobin (HbA1c) from baseline to 1 year (P < .004). Reductions were also seen in low-density lipoprotein cholesterol and blood pressure, but they were not statistically significant. When stratified by gender, women showed a greater reduction in HbA1c than men at 1 year. Patients with a higher frequency of community health worker contact showed a greater decline in HbA1c level. The pilot study demonstrates that community health workers, as an integral part of the health care team, are effective agents in providing self-management support to persons with diabetes.

Are internal derangement and osteoarthrosis linked to changes in clinical outcome measures of arthrocentesis of the temporomandibular joint?

Purpose: Arthrocentesis and hydraulic distention of the temporomandibular joint (TMJ) have been described as an effective modality in the treatment of patients with clinical findings consistent with the diagnosis of disc displacement without reduction. The purpose of this study was to investigate whether the magnetic resonance (MR) imaging variables of internal derangement (ID) and osteoarthrosis (OA) and the presence of capsulitis/synovitis (C/S) may be linked to changes in TMJ signs and symptoms associated with the performance of arthrocentesis and hydraulic distention. Patients and Methods: The study consisted of 27 TMJ pain patients, who were assigned a clinical unilateral TMJ diagnosis of ID type III (disc displacement without reduction). Bilateral sagittal and coronal MR images were obtained immediately preoperatively and at a 2-month follow-up to establish the presence or absence of ID and OA. TMJ pain level of function and mandibular range of motion were assessed preoperatively and compared with the respective 2-month follow-up findings. Results: The pretreatment data revealed a significant relationship between the clinical finding of TMJ pain and the MR imaging findings of ID ( P < .001), ID type ( P < .001), and OA ( P < .05). At 2-month follow-up, clinical evaluation showed a significant reduction in TMJ pain during function ( P < .001), a significant reduction in the clinical diagnoses of ID type III ( P < .05), and a significant increase in mandibular range of motion ( P < .05). There was no change in the prevalence rates of associated MR imaging diagnoses of TMJ ID and/or OA. Conclusion: The study findings suggest that clinical pain is related to TMJ-related MR imaging findings of ID and OA. These diagnoses proved not to be linked to changes in therapeutic outcome measures of TMJ pain and mandibular range of motion.

Long-Term Outcomes of Pelvic Floor Exercise and Biofeedback Treatment for Patients With Fecal Incontinence

The aim of this study was to assess the long-term clinical and quality of life outcomes for patients after referral to a four-month treatment program for fecal incontinence based on pelvic floor exercises and biofeedback. Secondary objectives were to document patients' subsequent treatment activities and their perception of the biofeedback training; to establish the long-term outcomes and initial predictors for the subset of patients who did not complete the treatment, or who failed to improve during the program; and to correlate changes in clinical outcome measures and quality of life over time. Patients were contacted by telephone to determine their perception of progress subsequent to the treatment program, any subsequent treatment or activities relating to their fecal incontinence, and which aspect of the treatment program they believed was most helpful. St. Mark's and Pescatori fecal incontinence scores were also recorded, along with patients' self-assessments of their incontinence severity and quality of life. Eighty-three (69 percent) patients were contacted for interviews at a median of 42 (range, 26-56) months after program completion. At the time of follow-up, patients who completed the program continued to enjoy strongly significant improvements in all outcome measures, with 75 percent perceiving a symptomatic improvement and 83 percent reporting improved quality of life. For many patients, improvement continued subsequent to program completion. Patients whose incontinence scores became worse during treatment still reported improvement in their quality of life and perceived incontinence severity during the same time period; many experienced some degree of "catch-up" in their continence scores during the follow-up period. Fourteen patients (17 percent) went on to have surgery for fecal incontinence; of these, 6 (7 percent) had a stoma. Twenty (24 percent) regularly took antidiarrheal medication. Thirty program completers (41 percent) were continuing pelvic floor exercises. This study confirms the long-term improvement in fecal incontinence achieved through treatment with biofeedback and pelvic floor exercises. In this study, patients also continued to improve after treatment completion, possibly because of the strong emphasis placed on patients during treatment to continue the pelvic floor exercises on their own. The poor correlation between quality of life and quantitative scores of fecal incontinence suggests that there are important aspects of continence that are not being appropriately recognized.