Clinical Practice Guidelines by the Infectious Diseases Society of America (IDSA), American Academy of Neurology (AAN), and American College of Rheumatology (ACR): 2020 Guidelines for the Prevention, Diagnosis and Treatment of Lyme Disease.

This evidence-based clinical practice guideline for the prevention, diagnosis, and treatment of Lyme disease was developed by a multidisciplinary panel representing the Infectious Diseases Society of America (IDSA), the American Academy of Neurology (AAN), and the American College of Rheumatology (ACR). The scope of this guideline includes prevention of Lyme disease, and the diagnosis and treatment of Lyme disease presenting as erythema migrans, Lyme disease complicated by neurologic, cardiac, and rheumatologic manifestations, Eurasian manifestations of Lyme disease, and Lyme disease complicated by coinfection with other tick-borne pathogens. This guideline does not include comprehensive recommendations for babesiosis and tick-borne rickettsial infections, which are published in separate guidelines. The target audience for this guideline includes primary care physicians and specialists caring for this condition such as infectious diseases specialists, emergency physicians, internists, pediatricians, family physicians, neurologists, rheumatologists, cardiologists and dermatologists in North America.

Clinical Practice Guidelines by the Infectious Diseases Society of America (IDSA), American Academy of Neurology (AAN), and American College of Rheumatology (ACR): 2020 Guidelines for the Prevention, Diagnosis and Treatment of Lyme Disease.

This evidence-based clinical practice guideline for the prevention, diagnosis, and treatment of Lyme disease was developed by a multidisciplinary panel representing the Infectious Diseases Society of America (IDSA), the American Academy of Neurology (AAN), and the American College of Rheumatology (ACR). The scope of this guideline includes prevention of Lyme disease, and the diagnosis and treatment of Lyme disease presenting as erythema migrans, Lyme disease complicated by neurologic, cardiac, and rheumatologic manifestations, Eurasian manifestations of Lyme disease, and Lyme disease complicated by coinfection with other tick-borne pathogens. This guideline does not include comprehensive recommendations for babesiosis and tick-borne rickettsial infections, which are published in separate guidelines. The target audience for this guideline includes primary care physicians and specialists caring for this condition such as infectious diseases specialists, emergency physicians, internists, pediatricians, family physicians, neurologists, rheumatologists, cardiologists and dermatologists in North America.

2017 European League Against Rheumatism/American College of Rheumatology classification criteria for adult and juvenile idiopathic inflammatory myopathies and their major subgroups.

OBJECTIVE: To develop and validate new classification criteria for adult and juvenile idiopathic inflammatory myopathies (IIM) and their major subgroups. METHODS: Candidate variables were assembled from published criteria and expert opinion using consensus methodology. Data were collected from 47 rheumatology, dermatology, neurology and paediatric clinics worldwide. Several statistical methods were used to derive the classification criteria. RESULTS: Based on data from 976 IIM patients (74% adults; 26% children) and 624 non-IIM patients with mimicking conditions (82% adults; 18% children), new criteria were derived. Each item is assigned a weighted score. The total score corresponds to a probability of having IIM. Subclassification is performed using a classification tree. A probability cut-off of 55%, corresponding to a score of 5.5 (6.7 with muscle biopsy) 'probable IIM', had best sensitivity/specificity (87%/82% without biopsies, 93%/88% with biopsies) and is recommended as a minimum to classify a patient as having IIM. A probability of ≥90%, corresponding to a score of ≥7.5 (≥8.7 with muscle biopsy), corresponds to 'definite IIM'. A probability of <50%, corresponding to a score of <5.3 (<6.5 with muscle biopsy), rules out IIM, leaving a probability of ≥50 to <55% as 'possible IIM'. CONCLUSIONS: The European League Against Rheumatism/American College of Rheumatology (EULAR/ACR) classification criteria for IIM have been endorsed by international rheumatology, dermatology, neurology and paediatric groups. They employ easily accessible and operationally defined elements, and have been partially validated. They allow classification of 'definite', 'probable' and 'possible' IIM, in addition to the major subgroups of IIM, including juvenile IIM. They generally perform better than existing criteria.

Associations of Weight Gain From Early to Middle Adulthood With Major Health Outcomes Later in Life.

IMPORTANCE: Data describing the effects of weight gain across adulthood on overall health are important for weight control. OBJECTIVE: To examine the association of weight gain from early to middle adulthood with health outcomes later in life. DESIGN, SETTING, AND PARTICIPANTS: Cohort analysis of US women from the Nurses' Health Study (1976-June 30, 2012) and US men from the Health Professionals Follow-Up Study (1986-January 31, 2012) who recalled weight during early adulthood (at age of 18 years in women; 21 years in men), and reported current weight during middle adulthood (at age of 55 years). EXPOSURES: Weight change from early to middle adulthood (age of 18 or 21 years to age of 55 years). MAIN OUTCOMES AND MEASURES: Beginning at the age of 55 years, participants were followed up to the incident disease outcomes. Cardiovascular disease, cancer, and death were confirmed by medical records or the National Death Index. A composite healthy aging outcome was defined as being free of 11 chronic diseases and major cognitive or physical impairment. RESULTS: A total of 92 837 women (97% white; mean [SD] weight gain: 12.6 kg [12.3 kg] over 37 years) and 25 303 men (97% white; mean [SD] weight gain: 9.7 kg [9.7 kg] over 34 years) were included in the analysis. For type 2 diabetes, the adjusted incidence per 100 000 person-years was 207 among women who gained a moderate amount of weight (≥2.5 kg to <10 kg) vs 110 among women who maintained a stable weight (weight loss ≤2.5 kg or gain <2.5 kg) (absolute rate difference [ARD] per 100 000 person-years, 98; 95% CI, 72 to 127) and 258 vs 147, respectively, among men (ARD, 111; 95% CI, 58 to 179); hypertension: 3415 vs 2754 among women (ARD, 662; 95% CI, 545 to 782) and 2861 vs 2366 among men (ARD, 495; 95% CI, 281 to 726); cardiovascular disease: 309 vs 248 among women (ARD, 61; 95% CI, 38 to 87) and 383 vs 340 among men (ARD, 43; 95% CI, -14 to 109); obesity-related cancer: 452 vs 415 among women (ARD, 37; 95% CI, 4 to 73) and 208 vs 165 among men (ARD, 42; 95% CI, 0.5 to 94). Among those who gained a moderate amount of weight, 3651 women (24%) and 2405 men (37%) achieved the composite healthy aging outcome. Among those who maintained a stable weight, 1528 women (27%) and 989 men (39%) achieved the composite healthy aging outcome. The multivariable-adjusted odds ratio for the composite healthy aging outcome associated with moderate weight gain was 0.78 (95% CI, 0.72 to 0.84) in women and 0.88 (95% CI, 0.79 to 0.97) in men. Higher amounts of weight gain were associated with greater risks of major chronic diseases and lower likelihood of healthy aging. CONCLUSIONS AND RELEVANCE: In these cohorts of health professionals, weight gain during adulthood was associated with significantly increased risk of major chronic diseases and decreased odds of healthy aging. These findings may help counsel patients regarding the risks of weight gain.

Preventive Treatments for Rheumatoid Arthritis: Issues Regarding Patient Preferences.

The detection of biomarkers in the preclinical phase of rheumatoid arthritis (RA) and recent therapeutic advances suggest that it may be possible to identify and treat persons at high risk and to prevent the development of RA. Several trials are ongoing to test the efficacy of a therapeutic intervention in primary prevention. This paper reviews potential populations that might be considered for preventative medication. Further, we review the medications that are being explored to treat individuals considered at high risk of developing RA. Finally, in a group of asymptomatic individuals at high risk of developing RA, we assessed which factors mattered most when considering a preventive therapeutic intervention and what type of preventive treatment would be most acceptable to them. Understanding subjects' perceptions of risks and benefits and willingness to undergo preventive therapy will be important in designing and implementing screening and preventive strategies.

Long-acting risperidone and oral antipsychotics in unstable schizophrenia.

BACKGROUND: Long-acting injectable risperidone, a second-generation antipsychotic agent, may improve adherence to treatment and outcomes in schizophrenia, but it has not been tested in a long-term randomized trial involving patients with unstable disease. METHODS: We randomly assigned patients in the Veterans Affairs (VA) system who had schizophrenia or schizoaffective disorder and who had been hospitalized within the previous 2 years or were at imminent risk for hospitalization to 25 to 50 mg of long-acting injectable risperidone every two weeks or to a psychiatrist's choice of an oral antipsychotic. All patients were followed for up to 2 years. The primary end point was hospitalization in a VA or non-VA psychiatric hospital. Symptoms, quality of life, and functioning were assessed in blinded videoconference interviews. RESULTS: Of 369 participants, 40% were hospitalized at randomization, 55% were hospitalized within the previous 2 years, and 5% were at risk for hospitalization. The rate of hospitalization after randomization was not significantly lower among patients who received long-acting injectable risperidone than among those who received oral antipsychotics (39% after 10.8 months vs. 45% after 11.3 months; hazard ratio, 0.87; 95% confidence interval, 0.63 to 1.20). Psychiatric symptoms, quality of life, scores on the Personal and Social Performance scale of global functioning, and neurologic side effects were not significantly improved with long-acting injectable risperidone as compared with control treatments. Patients who received long-acting injectable risperidone reported more adverse events at the injection site and more extrapyramidal symptoms. CONCLUSIONS: Long-acting injectable risperidone was not superior to a psychiatrist's choice of oral treatment in patients with schizophrenia and schizoaffective disorder who were hospitalized or at high risk for hospitalization, and it was associated with more local injection-site and extrapyramidal adverse effects. (Supported by the VA Cooperative Studies Program and Ortho-McNeil Janssen Scientific Affairs; ClinicalTrials.gov number, NCT00132314.).

Differences in treatment effect among clinical subgroups in a randomized clinical trial of long-acting injectable risperidone and oral antipsychotics in unstable chronic schizophrenia.

A long-term randomized trial of unstable patients with schizophrenia found no benefit of long-acting injectable (LAI) risperidone over oral treatment in preventing or delaying time to psychiatric hospitalizations or on clinical outcomes. The initial analyses did not examine whether benefits of LAI emerged in selected subgroups.Patients with schizophrenia or schizoaffective disorder who had been hospitalized within the past 2 years or judged to be at risk for hospitalization because of increasing psychiatric service use were randomly assigned to LAI risperidone 12.5 to 50 mg per injection biweekly or to the psychiatrist's choice of oral antipsychotics and followed for up to 2 years. The primary endpoint was psychiatric rehospitalization. Symptoms, quality of life, and global functioning were assessed through blinded videoconference interviews. Cox's regression and mixed effects models were used to assess difference in treatment effect within 12 subgroups defined by hospitalization at study entry, substance abuse, race, symptom severity, quality of life, body mass index, age, race or sex, or reported medication compliance.Mixed models and Cox's regression using up to 24 months of follow-up data showed no significant differences in treatment effect in 10 of 12 subgroups on psychiatric symptoms, quality of life, or time to hospitalization. With adjustment for multiple comparisons, treatment effect differed by race on substance use outcomes, with white participants showing more benefit from LAI than other groups.LAI risperidone showed no superiority to psychiatrist's choice of oral treatment in most clinically defined subgroups, although the white patients benefited more than the other groups on substance abuse outcomes.

Hal Holman of Stanford.

Before age 35, Holman hit over 0.500 at the University of California Los Angeles (UCLA); was recruited by professional baseball; led the Association of Interns and Medical Students and the International Union of Students in Denmark; had his passport confiscated; was stripped of a prestigious internship; shadowed by the Federal Bureau of Investigation ; grilled before a Senate committee on subversive activities; made a major medical discovery; and was recruited to be the new Chief of Medicine at Stanford. Holman was involved in building a leading academic institution. He expanded what medical students and graduates learned and what they researched. Holman saw the collision course between the technological capacity to do more and the growing expectations of the public. Moreover, he anticipated the monetization of health care and how it would widen the gap between what we know and what we practice in health care. He reinvented himself in population health. In contrast to reductionist laboratory-based research, his work embraced complexity and made action researchable and research action-oriented. Some innovations did not survive as originally conceived, but their ethos became mainstream. These included evidence-based management, shared physician-patient decision-making, self-management, critical evaluation of medical technology and diagnostics, and chronic disease management. Through the rise of the twentieth century American biomedical medicine, medical education, and slow-motion health care delivery crises that still occur, Holman changed the debate in a time when the funding, the people, the technology, and the need made all things seem possible.

Choosing to End African American Health Disparities in Patients With Systemic Lupus Erythematosus.

Systemic lupus erythematosus (SLE) is three times more common and its manifestations are more severe in African American women compared to women of other races. It is not clear whether this is due to genetic differences or factors related to the physical or social environments, differences in health care, or a combination of these factors. Health disparities in patients with SLE between African American patients and persons of other races have been reported since the 1960s and are correlated with measures of lower socioeconomic status. Risk factors for these disparities have been demonstrated, but whether their mitigation improves outcomes for African American patients has not been tested except in self-efficacy. In 2002, the first true US population-based study of patients with SLE with death certificate records was conducted, which demonstrated a wide disparity between the number of African American women and White women dying from SLE. Five years ago, another study showed that SLE mortality rates in the United States had improved but that the African American patient mortality disparity persisted. Between 2014 and 2021, one study demonstrated racism's deleterious effects in patients with SLE. Racism may have been the unmeasured confounder, the proverbial "elephant in the room"-unnamed and unstudied. The etymology of "risk factor" has evolved from environmental risk factors to social determinants to now include structural injustice/structural racism. Racism in the United States has a centuries-long existence and is deeply ingrained in US society, making its detection and resolution difficult. However, racism being man made means Man can choose to change the it. Health disparities in patients with SLE should be addressed by viewing health care as a basic human right. We offer a conceptual framework and goals for both individual and national actions.

A comprehensive care management program to prevent chronic obstructive pulmonary disease hospitalizations: a randomized, controlled trial.

BACKGROUND: Improving a patient's ability to self-monitor and manage changes in chronic obstructive pulmonary disease (COPD) symptoms may improve outcomes. OBJECTIVE: To determine the efficacy of a comprehensive care management program (CCMP) in reducing the risk for COPD hospitalization. DESIGN: A randomized, controlled trial comparing CCMP with guideline-based usual care. (ClinicalTrials.gov registration number: NCT00395083) SETTING: 20 Veterans Affairs hospital-based outpatient clinics. PARTICIPANTS: Patients hospitalized for COPD in the past year. INTERVENTION: The CCMP included COPD education during 4 individual sessions and 1 group session, an action plan for identification and treatment of exacerbations, and scheduled proactive telephone calls for case management. Patients in both the intervention and usual care groups received a COPD informational booklet; their primary care providers received a copy of COPD guidelines and were advised to manage their patients according to these guidelines. Patients were randomly assigned, stratifying by site based on random, permuted blocks of variable size. MEASUREMENTS: The primary outcome was time to first COPD hospitalization. Staff blinded to study group performed telephone-based assessment of COPD exacerbations and hospitalizations, and all hospitalizations were blindly adjudicated. Secondary outcomes included non-COPD health care use, all-cause mortality, health-related quality of life, patient satisfaction, disease knowledge, and self-efficacy. RESULTS: Of the eligible patients, 209 were randomly assigned to the intervention group and 217 to the usual care group. Citing serious safety concerns, the data monitoring committee terminated the intervention before the trial's planned completion after 426 (44%) of the planned total of 960 patients were enrolled. Mean follow-up was 250 days. When the study was stopped, the 1-year cumulative incidence of COPD-related hospitalization was 27% in the intervention group and 24% in the usual care group (hazard ratio, 1.13 [95% CI, 0.70 to 1.80]; P= 0.62). There were 28 deaths from all causes in the intervention group versus 10 in the usual care group (hazard ratio, 3.00 [CI, 1.46 to 6.17]; P= 0.003). Cause could be assigned in 27 (71%) deaths. Deaths due to COPD accounted for the largest difference: 10 in the intervention group versus 3 in the usual care group (hazard ratio, 3.60 [CI, 0.99 to 13.08]; P= 0.053). LIMITATIONS: Available data could not fully explain the excess mortality in the intervention group. Ability to assess the quality of the educational sessions provided by the case managers was limited. CONCLUSION: A CCMP in patients with severe COPD had not decreased COPD-related hospitalizations when the trial was stopped prematurely. The CCMP was associated with unanticipated excess mortality, results that differ markedly from similar previous trials. A data monitoring committee should be considered in the design of clinical trials involving behavioral interventions.

Estimating the per-protocol effect of lithium on suicidality in a randomized trial of individuals with depression or bipolar disorder.

BACKGROUND: The CSP590 randomized trial was designed to estimate the effect of lithium on suicidality. After a third of the intended number of participants were enrolled, the hazard ratio of suicidality was 1.10 (95% CI: 0.77, 1.55). Based on this, the trial was stopped for futility. However, only 17% of patients adhered to the specified protocol. AIMS: The objective was to estimate the per-protocol effect of lithium on suicidality, that is, the effect of adhering to the treatment strategies as specified in the protocol. METHODS: We stopped individuals' follow-up if/when they showed evidence of nonadherence. We then conducted the analysis in the restricted sample, adjusting for prognostic factors that predict adherence via inverse probability weighting. The primary outcome was the 12-month risk of suicidality (including death from suicide, suicide attempt, interrupted attempt, hospitalization specifically to prevent suicide). RESULTS: The estimated 12-month risk of suicidality was 18.8% for lithium, and 24.3% for placebo. The risk ratio was 0.78 (95% CI: 0.43, 1.37) and the risk difference -5.5 percentage points (95% CI: -17.5, 5.5). Results were consistent across sensitivity analyses. CONCLUSIONS: With one-third of the targeted sample size, lithium effects (compared with placebo) ranging between a 17.5% reduction and a 5.5% increase in the risk of suicidality were highly compatible with the data. Thus, a protective effect of lithium on suicidality among patients with bipolar disorder or major depressive disorder cannot be ruled out. Trials should incorporate adequate per-protocol analyses into the decision-making processes for stopping trials for futility.

Alcohol Consumption and Risk of Total Hip Replacement Due to Hip Osteoarthritis in Women.

OBJECTIVE: This study was undertaken to examine the relationship between alcohol consumption and hip osteoarthritis in women. Alcohol has been associated with both adverse and beneficial health effects generally; however, the relationship between alcohol consumption and hip osteoarthritis has been minimally studied. METHODS: Among women in the Nurses' Health Study cohort in the US, alcohol consumption was assessed every 4 years, starting in 1980. Intake was computed as cumulative averages and simple updates with latency periods of 0-4 through 20-24 years. We followed 83,383 women without diagnosed osteoarthritis in 1988 to June 2012. We identified 1,796 cases of total hip replacement due to hip osteoarthritis defined by self-report of osteoarthritis with hip replacement. RESULTS: Alcohol consumption was positively associated with hip osteoarthritis risk. Compared with nondrinkers, multivariable hazard ratios (HRs) and 95% confidence intervals (95% CIs) were HR 1.04 (95% CI 0.90, 1.19) for drinkers of >0 to <5 grams/day, HR 1.12 (95% CI 0.94, 1.33) for 5 to <10 grams/day, HR 1.31 (95% CI 1.10, 1.56) for 10 to <20 grams/day, and HR 1.34 (95% CI 1.09, 1.64) for ≥20 grams/day (P for trend < 0.0001). This association held in latency analyses of up to 16-20 years, and for alcohol consumption between 35-40 years of age. Independent of other alcoholic beverages, the multivariable HRs (per 10 grams of alcohol) were similar for individual types of alcohol intake (wine, liquor, and beer; P = 0.57 for heterogeneity among alcohol types). CONCLUSION: Higher alcohol consumption was associated with greater incidence of total hip replacement due to hip osteoarthritis in a dose-dependent manner in women.

Lithium Treatment in the Prevention of Repeat Suicide-Related Outcomes in Veterans With Major Depression or Bipolar Disorder: A Randomized Clinical Trial.

Importance: Suicide and suicide attempts are persistent and increasing public health problems. Observational studies and meta-analyses of randomized clinical trials have suggested that lithium may prevent suicide in patients with bipolar disorder or depression. Objective: To assess whether lithium augmentation of usual care reduces the rate of repeated episodes of suicide-related events (repeated suicide attempts, interrupted attempts, hospitalizations to prevent suicide, and deaths from suicide) in participants with bipolar disorder or depression who have survived a recent event. Design, Setting, and Participants: This double-blind, placebo-controlled randomized clinical trial assessed lithium vs placebo augmentation of usual care in veterans with bipolar disorder or depression who had survived a recent suicide-related event. Veterans at 29 VA medical centers who had an episode of suicidal behavior or an inpatient admission to prevent suicide within 6 months were screened between July 1, 2015, and March 31, 2019. Interventions: Participants were randomized to receive extended-release lithium carbonate beginning at 600 mg/d or placebo. Main Outcomes and Measures: Time to the first repeated suicide-related event, including suicide attempts, interrupted attempts, hospitalizations specifically to prevent suicide, and deaths from suicide. Results: The trial was stopped for futility after 519 veterans (mean [SD] age, 42.8 [12.4] years; 437 [84.2%] male) were randomized: 255 to lithium and 264 to placebo. Mean lithium concentrations at 3 months were 0.54 mEq/L for patients with bipolar disorder and 0.46 mEq/L for patients with major depressive disorder. No overall difference in repeated suicide-related events between treatments was found (hazard ratio, 1.10; 95% CI, 0.77-1.55). No unanticipated safety concerns were observed. A total of 127 participants (24.5%) had suicide-related outcomes: 65 in the lithium group and 62 in the placebo group. One death occurred in the lithium group and 3 in the placebo group. Conclusions and Relevance: In this randomized clinical trial, the addition of lithium to usual Veterans Affairs mental health care did not reduce the incidence of suicide-related events in veterans with major depression or bipolar disorders who experienced a recent suicide event. Therefore, simply adding lithium to existing medication regimens is unlikely to be effective for preventing a broad range of suicide-related events in patients who are actively being treated for mood disorders and substantial comorbidities. Trial Registration: ClinicalTrials.gov Identifier: NCT01928446.

Challenges in the design and conduct of controlled clinical effectiveness trials in schizophrenia.

BACKGROUND: The introduction of antipsychotic medication has been a major advance in the treatment of schizophrenia and allows millions of people to live outside of institutions. It is generally believed that long-acting intramuscular antipsychotic medication is the most effective approach to increasing medication adherence and thereby reduce relapse in high-risk patients with schizophrenia, but the data are scant. PURPOSE: To report the design of a study to assess the effect of long-acting injectable risperidone in unstable patients and under more realistic conditions than previously studied and to evaluate the effect of this medication on psychiatric inpatient hospitalization, schizophrenia symptoms, quality of life, medication adherence, side effects, and health care costs. METHODS: The trial was an open randomized clinical comparative effectiveness trial in patients with schizophrenia or schizo-affective disorders in which parenteral risperidone was compared to an oral antipsychotic regimen selected by each control patient's psychiatrist. Participants had unstable psychiatric disease defined by recent hospitalization or exhibition of unusual need for psychiatric services. The primary endpoint was hospitalization for psychiatric indications; the secondary endpoint was psychiatric symptoms. RESULTS: Overall, 382 patients were randomized. Determination of a persons' competency to understand the elements of informed consent was addressed. The use of a closed-circuit TV interview for psychosocial measures provided an economical, high quality, reliable means of collecting data. A unique method for insuring that usual care was optimal was incorporated in the follow-up of all subjects. LIMITATIONS: Patients with schizophrenia or schizo-affective disorders and with the common co-morbid illnesses seen in the VA are a challenging group of subjects to study in long-term trials. Some techniques unique in the VA and found useful may not be generalizable or applicable in other research or treatment settings. CONCLUSIONS: The trial tested a new antipsychotic medication early in its adoption in the Veterans Health Administration. The VA has a unique electronic medical record and database which can be used to identify the endpoint, that is, first hospitalization due to a psychiatric problem, with complete ascertainment. Several methodologic solutions addressed competency to understand elements of consent, the costs and reliability of collecting interview data gathering, and insuring usual care.

A point-of-care clinical trial comparing insulin administered using a sliding scale versus a weight-based regimen.

BACKGROUND: Clinical trials are widely considered the gold standard in comparative effectiveness research (CER) but the high cost and complexity of traditional trials and concerns about generalizability to broad patient populations and general clinical practice limit their appeal. Unsuccessful implementation of CER results limits the value of even the highest quality trials. Planning for a trial comparing two standard strategies of insulin administration for hospitalized patients led us to develop a new method for a clinical trial designed to be embedded directly into the clinical care setting thereby lowering the cost, increasing the pragmatic nature of the overall trial, strengthening implementation, and creating an integrated environment of research-based care. PURPOSE: We describe a novel randomized clinical trial that uses the informatics and statistics infrastructure of the Veterans Affairs Healthcare System (VA) to illustrate one key component (called the point-of-care clinical trial - POC-CT) of a 'learning healthcare system,' and settles a clinical question of interest to the VA. METHODS: This study is an open-label, randomized trial comparing sliding scale regular insulin to a weight-based regimen for control of hyperglycemia, using the primary outcome length of stay, in non-ICU inpatients within the northeast region of the VA. All non-ICU patients who require in-hospital insulin therapy are eligible for the trial, and the VA's automated systems will be used to assess eligibility and present the possibility of randomization to the clinician at the point of care. Clinicians will indicate their approval for informed consent to be obtained by study staff. Adaptive randomization will assign up to 3000 patients, preferentially to the currently 'winning' strategy, and all care will proceed according to usual practices. Based on a Bayesian stopping rule, the study has acceptable frequentist operating characteristics (Type I error 6%, power 86%) against a 12% reduction of median length of stay from 5 to 4.4 days. The adaptive stopping rule promotes implementation of a successful treatment strategy. LIMITATIONS: Despite clinical equipoise, individual healthcare providers may have strong treatment preferences that jeopardize the success and implementation of the trial design, leading to low rates of randomization. Unblinded treatment assignment may bias results. In addition, generalization of clinical results to other healthcare systems may be limited by differences in patient population. Generalizability of the POC-CT method depends on the level of informatics and statistics infrastructure available to a healthcare system. CONCLUSIONS: The methods proposed will demonstrate outcome-based evaluation of control of hyperglycemia in hospitalized veterans. By institutionalizing a process of statistically sound and efficient learning, and by integrating that learning with automatic implementation of best practice, the participating VA Healthcare Systems will accelerate improvements in the effectiveness of care.

What are the topics you care about making trials in lupus more effective? Results of an Open Space meeting of international lupus experts.

Despite promising candidates for new therapeutic options in the treatment of systemic lupus erythematosus (SLE), many clinical trials have failed in the past few years. The disappointing results have been at least partly be attributed to trial designs. With the aim of stimulating new developments in SLE trial design, an international open space meeting was held on occasion of the European Lupus Meeting 2018 in Duesseldorf, Germany about 'What are the topics you care about for making trials in lupus more effective?'. The Open Space is a participant-driven technology, where the discussion topics and schedule are selected during the meeting by all participants and discussion rounds are led by the people attending encouraging active contributions. Eleven topics were selected for further discussion, of which 6 were voted to be more intensively discussed in two consecutive rounds. Major topics were the optimal handling of glucocorticoids in clinical trials, the improvement of outcome measures, reducing or controlling the placebo response and the identification of biomarkers and stratification parameters. Further, the importance of local and international networks was emphasised. By networking, collaborations are facilitated, patient recruitment is more efficient and treatment can be harmonised thus lead to more successful SLE trials. Further discussions are needed to substantiate the results and develop new trial designs.

Clinical Practice Guidelines by the Infectious Diseases Society of America, American Academy of Neurology, and American College of Rheumatology: 2020 Guidelines for the Prevention, Diagnosis, and Treatment of Lyme Disease.

This evidence-based clinical practice guideline for the prevention, diagnosis, and treatment of Lyme disease was developed by a multidisciplinary panel representing the Infectious Diseases Society of America (IDSA), the American Academy of Neurology (AAN), and the American College of Rheumatology (ACR). The scope of this guideline includes prevention of Lyme disease, and the diagnosis and treatment of Lyme disease presenting as erythema migrans, Lyme disease complicated by neurologic, cardiac, and rheumatologic manifestations, Eurasian manifestations of Lyme disease, and Lyme disease complicated by coinfection with other tick-borne pathogens. This guideline does not include comprehensive recommendations for babesiosis and tick-borne rickettsial infections, which are published in separate guidelines. The target audience for this guideline includes primary care physicians and specialists caring for this condition such as infectious diseases specialists, emergency physicians, internists, pediatricians, family physicians, neurologists, rheumatologists, cardiologists and dermatologists in North America.

Treatment of very early rheumatoid arthritis with symptomatic therapy, disease-modifying antirheumatic drugs, or biologic agents: a cost-effectiveness analysis.

BACKGROUND: Long-term control or remission of rheumatoid arthritis (RA) may be possible with very early treatment. However, no optimal first therapeutic strategy has been determined. OBJECTIVE: To assess the potential cost-effectiveness of major therapeutic strategies for very early RA. DESIGN: Decision analytic model with probabilistic sensitivity analyses. DATA SOURCES: Published data, the National Data Bank for Rheumatic Diseases, and actual 2007 hospital costs. TARGET POPULATION: U.S. adults with very early RA (symptom duration

The effect of cash lottery on response rates to an online health survey among members of the Canadian Association of Retired Persons: a randomized experiment.

OBJECTIVES: The objectives of the study were 1) to assess the effect of cash lottery on participation rates in a web-based study of physical activity and joint health and 2) to compare recruitment via direct e-mail versus advertisement in an online newsletter. METHODS: A sample of 1,150 individuals, randomly selected from a database of members of the Canadian Association of Retired Persons (CARP), was e-mailed a request to participate in an online survey, with follow-up e-mails after 1 and 2 weeks. The sample was randomly split into two groups. Half the sample was offered entry into a cash draw with a $500 grand prize and five $100 prizes, whereas the other half was not offered any incentive. In addition, a brief advertisement about the survey (without an incentive) was placed in an online newsletter that was circulated to 14,000 randomly selected CARP members. RESULTS: In the incentive group, 305 (53.0%) clicked on the hyperlink and visited the website and 84 (14.6%) completed the survey. In the group who received no incentive, 280 (48.7%) clicked on the link and 59 (10.3%) completed the survey. Of those who received the online newsletter, 492 (3.5%) visited the website and 106 (0.76%) completed the survey. CONCLUSION: A relatively modest financial incentive in the form of a cash lottery significantly increased participation rates in an online health survey. Recruitment through a newsletter advertisement had a very low yield compared to direct e-mail.

Evaluation of the internet for finding persons with undiagnosed rheumatoid arthritis and systemic lupus erythematosus.

BACKGROUND: The internet is used by many new rheumatology patients before visiting a health care provider, and is also used for health education, for recruiting study participants, administering surveys, conducting clinical trials, data entry and management of multicenter trials, and providing a forum for patients to share experiences in chat rooms. The internet has not been used for nor evaluated for public health applications. OBJECTIVES: We evaluated the internet for early detection and referral of individuals with "typical" early symptoms of undiagnosed rheumatoid arthritis (RA) and systemic lupus erythematosus (SLE). METHODS: The websites and selected links identified by search terms of typical symptoms were evaluated for health information quality, readability, and whether or not the sites prioritized possibilities and suggested actions. RESULTS: None of the websites examined were completely suitable for finding undiagnosed persons with early RA or SLE. Although the websites had accurate information, their reading levels were too high for the average reader, and were generally poor in terms of giving a differential diagnosis, prioritizing the possibilities and none provided an algorithm for action. CONCLUSIONS: Internet sites could be enhanced for early detection and referral. The internet has become an important factor in clinical practice and physicians are increasingly explaining or responding to the information that their patients find on the internet. Our study shows that the information available to individuals with undiagnosed RA and SLE is likely to be of little help to them and could delay their seeking appropriate attention.