The Impact of an Electronic Health Record Intervention on Spirometry Completion in Patients with Chronic Obstructive Pulmonary Disease.

Spirometry is necessary to diagnose chronic obstructive pulmonary disease (COPD), yet a large proportion of patients are diagnosed and treated without having received testing. This study explored whether the effects of interventions using the electronic health record (EHR) to target patients diagnosed with COPD without confirmatory spirometry impacted the incidence rates of spirometry referrals and completions. This retrospective before and after study assessed the impact of provider-facing clinical decision support that identified patients who had a diagnosis of COPD but had not received spirometry. Spirometry referrals, completions, and results were ascertained 1.5 years prior to and 1.5 years after the interventions were initiated. Inhaler prescriptions by class were also tallied. There were 10,949 unique patients with a diagnosis of COPD who were eligible for inclusion. 4,895 patients (44.7%) were excluded because they had completed spirometry prior to the cohort start dates. The pre-intervention cohort consisted of 2,622 patients, while the post-intervention cohort had 3,392. Spirometry referral rates pre-intervention were 20.2% compared to 31.6% post-intervention (p < 0.001). Spirometry completion rates rose from 13.2% pre-intervention to 19.3% afterwards (p < 0.001). 61.7% (585 of 948) had no evidence of airflow obstruction. After excluding patients with a diagnosis of asthma, 25.8% (126 of 488) patients who had no evidence of airflow obstruction had prescriptions for long-acting bronchodilators or inhaled steroids. A concerted EHR intervention modestly increased spirometry referral and completion rates in patients with a diagnosis of COPD without prior spirometry and decreased misclassification of disease.

Use of Big Data to Aid Patient Recruitment for Clinical Trials Involving Biosimilars and Rare Diseases.

Patient recruitment and retention are arguably the greatest challenges to the timely execution of clinical trials. This is particularly true in the case of trials involving biosimilars and those focused on rare diseases. For biosimilars, recruitment success typically hinges on difficulty of access to reimbursement for the originator product and may be hindered by competition from studies with other biosimilars and those with new chemical entities. For rare diseases, recruitment success depends not only on finding enough patients but also on retaining them for the duration of the trial. Historical success with patient recruitment-in addition to site qualifications-needs to be considered in parallel with current market competition and results in an ever-changing patient recruitment environment. Multiple companies supporting the biopharmaceutical industry, such as Contract Research Organizations, have begun to leverage sophisticated data modeling tools and techniques to find additional patients for biosimilar and rare disease trials and/or to find patients more quickly. In addition, these companies seek to better understand the population of interest and refine their statistical assumptions when conducting clinical trials or real-world analyses. The largest and most well-established companies that support the biopharmaceutical industry now have unparalleled access to big data from clinical trials, electronic health records, medical claims, laboratory tests, and prescriptions. This paper will discuss how big data can be harnessed to aid patient recruitment with a focus on clinical trials for biosimilars and orphan rare diseases.

When Context Is Hard to Come By: External Comparators and How to Use Them.

External comparators, also referred to as historical or synthetic controls, present transformational opportunities for broad context and insights alongside clinical research results. The recent confluence of access to quality real-world data (RWD), advanced epidemiologic methods, and legislative directives to regulators for expanded use of RWD is increasing interest in real-world external comparators, opening the door to achieve broader generalizability and learn more, faster. In this less standardized area of research, tailored scientific methodology must be applied for external comparators to accomplish clinical development objectives. Here, we describe methodological considerations for design and illustrate how RWD comparators have been used for regulatory and reimbursement decisions.

When Context Is Hard to Come By: External Comparators and How to Use Them.

External comparators, also referred to as historical or synthetic controls, present transformational opportunities for broad context and insights alongside clinical research results. The recent confluence of access to quality real-world data (RWD), advanced epidemiologic methods, and legislative directives to regulators for expanded use of RWD is increasing interest in real-world external comparators, opening the door to achieve broader generalizability and learn more, faster. In this less standardized area of research, tailored scientific methodology must be applied for external comparators to accomplish clinical development objectives. Here, we describe methodological considerations for design and illustrate how RWD comparators have been used for regulatory and reimbursement decisions.

Anti-CD20 inhibits T cell-mediated pathology and microgliosis in the rat brain.

OBJECTIVE: The mechanism of action of anti-B cell therapy in multiple sclerosis (MS) is not fully understood. Here, we compared the effect of anti-CD20 therapy on microglial activation in two distinct focal rat models of MS. METHODS: The effect of anti-CD20 therapy on lesion formation and extralesional microglial activation was evaluated in the fDTH-EAE (experimental allergic encephalomyelitis) model, which is a focal demyelinating type-IV delayed-type hypersensitivity lesion. For comparison, effects were also assessed in the focal humoral MOG model induced by intracerebral injection of cytokine in myelin oligodendrocyte glycoprotein immunized rats. Microglial activation was assessed in situ and in vivo using the TSPO SPECT ligand [(125)I]DPA-713, and by immunostaining for MHCII. The effect of treatment on demyelination and lymphocyte recruitment to the brain were evaluated. RESULTS: Anti-CD20 therapy reduced microglial activation, and lesion formation in the humoral model, but it was most effective in the antibody-independent fDTH-EAE. Immunohistochemistry for MHCII also demonstrated a reduced volume of microglial activation in the brains of anti-CD20-treated fDTH-EAE animals, which was accompanied by a reduction in T-cell recruitment and demyelination. The effect anti-CD20 therapy in the latter model was similarly strong as compared to the T-cell targeting MS compound FTY720. INTERPRETATION: The suppression of lesion development by anti-CD20 treatment in an antibody-independent model suggests that B-cells play an important role in lesion development, independent of auto-antibody production. Thus, CD20-positive B-cell depletion has the potential to be effective in a wider population of individuals with MS than might have been predicted from our knowledge of the underlying histopathology.

Continuity of care in intensive care units: a cluster-randomized trial of intensivist staffing.

RATIONALE: Little is known about the consequences of intensivists' work schedules, or intensivist continuity of care. OBJECTIVES: To assess the impact of weekend respite for intensivists, with consequent reduction in continuity of care, on them and their patients. METHODS: In five medical intensive care units (ICUs) in four academic hospitals we performed a prospective, cluster-randomized, alternating trial of two intensivist staffing schedules. Daily coverage by a single intensivist in half-month rotations (continuous schedule) was compared with weekday coverage by a single intensivist, with weekend cross-coverage by colleagues (interrupted schedule). We studied consecutive patients admitted to study units, and the intensivists working in four of the participating units. MEASUREMENTS AND MAIN RESULTS: The primary patient outcome was ICU length of stay (LOS);we also assessed hospital LOS and mortality rates. The primary intensivist outcome was physician burnout. Analysis was by multivariable regression. A total of 45 intensivists and 1,900 patients participated in the study. Continuity of care differed between schedules (patients with multiple intensivists = 28% under continuous schedule vs. 62% under interrupted scheduling; P < 0.0001). LOS and mortality were nonsignificantly higher under continuous scheduling (ΔICU LOS 0.36 d, P = 0.20; Δhospital LOS 0.34 d, P = 0.71; ICU mortality, odds ratio = 1.43, P = 0.12; hospital mortality, odds ratio = 1.17,P = 0.41). Intensivists experienced significantly higher burnout, work­home life imbalance, and job distress working under the continuous schedule. CONCLUSIONS: Work schedules where intensivists received weekend breaks were better for the physicians and, despite lower continuity of intensivist care, did not worsen outcomes for medical ICU patients.

Primary cardiac paraganglioma.

A primary cardiac paraganglioma was identified in a 59-year-old Caucasian male who complained of palpitations and chest pain. The neoplasm (4.7 cm in diameter) was surgically excised from the left posterior atrium. Adriamycin-based adjuvant chemotherapy was administered. The patient returned to his normal activities. There is no evidence of recurrence or metastasis after two years and nine months.