Publications

P

Mandl, Olson, Mines, Liu, Tian. Provider Collaboration: Cohesion, Constellations, and Shared Patients. J Gen Intern Med. 2014.

BACKGROUND: There is a natural assumption that quality and efficiency are optimized when providers consistently work together and share patients. Diversity in composition and recurrence of groups that provide face-to-face care to the same patients has not previously been studied. OBJECTIVE: Claims data enable identification of the constellation of providers caring for a single patient. To indirectly measure teamwork and provider collaboration, we measure recurrence of provider constellations and cohesion among providers. DESIGN: Retrospective analysis of commercial healthcare claims from a single insurer. PARTICIPANTS: Patients with claims for office visits and their outpatient providers. To maximize capture of provider panels, the cohort was drawn from the four regions with the highest plan coverage. Regional outpatient provider networks were constructed with providers as nodes and number of shared patients as links. MAIN MEASURES: Measures of cohesion and stability of provider constellations derived from the networks of providers to quantify patient sharing. RESULTS: For 10,325 providers and their 521,145 patients, there were 2,641,933 collaborative provider pairs sharing at least one patient. Fifty-four percent only shared a single patient, and 19 % shared two. Of 15,449,835 unique collaborative triads, 92 % shared one patient, 5 % shared two, and 0.2 % shared ten or more. Patient constellations had a median of four providers. Any precise constellation recurred rarely-89 % with exactly two providers shared just one patient and only 4 % shared over two; 97 % of constellations with exactly three providers shared just one patient. Four percent of constellations with 2+ providers were not at all cohesive, sharing only the hub patient. In the remaining constellations, a median of 93 % of provider pairs shared at least one additional patient beyond the hub patient. CONCLUSION: Stunning variability in the constellations of providers caring for patients may challenge underlying assumptions about the current state of teamwork in healthcare.

OBJECTIVES: In a prior uncontrolled study, 23% of children with fever and petechiae without bacteremia or sepsis had a prolonged partial thromboplastin time (PTT). We attempted to validate this finding by comparing the PTTs of children with fever and petechiae who were neither septic nor bacteremic with those of children without fever and petechiae. METHODS: Design. Secondary analysis of a prospective cohort with a newly identified retrospective control cohort. Setting. Emergency department of an urban pediatric teaching hospital from December 1993 to June 1995. Study group. All patients 1 month to 18 years old from a previously identified cohort with (1) fever (temperature >or=38.0); (2) petechiae; (3) prothrombin time and partial thromboplastin time performed in the emergency department (n = 273). Control group. Age-matched patients 1 month to 18 years old who presented to the emergency department during the same time period as the study patients with (1) an injury or other potentially surgical diagnosis; (2) neither fever nor petechiae; (3) prothrombin time and partial thromboplastin time performed in the emergency department. Main outcome measures. partial thromboplastin time and prothrombin time. RESULTS: 117 control patients were identified. Partial thromboplastin time was prolonged in 23% of study patients, but in only 6% of control patients (P 0.001). Prothrombin time was prolonged in 9% of patients with fever and petechiae compared with only 4% of control patients (P = 0.09). CONCLUSION: Children with fever and petechiae without bacteremia or sepsis are more likely than controls to have prolonged partial thromboplastin time.
Olson, Grannis, Mandl. Privacy protection versus cluster detection in spatial epidemiology. Am J Public Health. 2006;96:2002–8.
OBJECTIVES: Patient data that includes precise locations can reveal patients' identities, whereas data aggregated into administrative regions may preserve privacy and confidentiality. We investigated the effect of varying degrees of address precision (exact latitude and longitude vs the center points of zip code or census tracts) on detection of spatial clusters of cases. METHODS: We simulated disease outbreaks by adding supplementary spatially clustered emergency department visits to authentic hospital emergency department syndromic surveillance data. We identified clusters with a spatial scan statistic and evaluated detection rate and accuracy. RESULTS: More clusters were identified, and clusters were more accurately detected, when exact locations were used. That is, these clusters contained at least half of the simulated points and involved few additional emergency department visits. These results were especially apparent when the synthetic clustered points crossed administrative boundaries and fell into multiple zip code or census tracts. CONCLUSIONS: The spatial cluster detection algorithm performed better when addresses were analyzed as exact locations than when they were analyzed as center points of zip code or census tracts, particularly when the clustered points crossed administrative boundaries. Use of precise addresses offers improved performance, but this practice must be weighed against privacy concerns in the establishment of public health data exchange policies.
Bourgeois, Kim, Mandl. Premarket safety and efficacy studies for ADHD medications in children. PLoS One. 2014;9:e102249.

BACKGROUND: Attention-deficit hyperactivity disorder (ADHD) is a chronic condition and pharmacotherapy is the mainstay of treatment, with a variety of ADHD medications available to patients. However, it is unclear to what extent the long-term safety and efficacy of ADHD drugs have been evaluated prior to their market authorization. We aimed to quantify the number of participants studied and their length of exposure in ADHD drug trials prior to marketing. METHODS: We identified all ADHD medications approved by the Food and Drug Administration (FDA) and extracted data on clinical trials performed by the sponsor and used by the FDA to evaluate the drug's clinical efficacy and safety. For each ADHD medication, we measured the total number of participants studied and the length of participant exposure and identified any FDA requests for post-marketing trials. RESULTS: A total of 32 clinical trials were conducted for the approval of 20 ADHD drugs. The median number of participants studied per drug was 75 (IQR 0, 419). Eleven drugs (55%) were approved after <100 participants were studied and 14 (70%) after <300 participants. The median trial length prior to approval was 4 weeks (IQR 2, 9), with 5 (38%) drugs approved after participants were studied <4 weeks and 10 (77%) after <6 months. Six drugs were approved with requests for specific additional post-marketing trials, of which 2 were performed. CONCLUSIONS: Clinical trials conducted for the approval of many ADHD drugs have not been designed to assess rare adverse events or long-term safety and efficacy. While post-marketing studies can fill in some of the gaps, better assurance is needed that the proper trials are conducted either before or after a new medication is approved.

Ong, Kohane, Cai, Gorman, Mandl. Population-Level Evidence for an Autoimmune Etiology of Epilepsy. JAMA Neurol. 2014.
IMPORTANCE Epilepsy is a debilitating condition, often with neither a known etiology nor an effective treatment. Autoimmune mechanisms have been increasingly identified. OBJECTIVE To conduct a population-level study investigating the relationship between epilepsy and several common autoimmune diseases. DESIGN, SETTING, AND PARTICIPANTS A retrospective population-based study using claims from a nationwide employer-provided health insurance plan in the United States. Participants were beneficiaries enrolled between 1999 and 2006 (N = 2 518 034). MAIN OUTCOMES AND MEASURES We examined the relationship between epilepsy and 12 autoimmune diseases: type 1 diabetes mellitus, psoriasis, rheumatoid arthritis, Graves disease, Hashimoto thyroiditis, Crohn disease, ulcerative colitis, systemic lupus erythematosus, antiphospholipid syndrome, Sjogren syndrome, myasthenia gravis, and celiac disease. RESULTS The risk of epilepsy was significantly heightened among patients with autoimmune diseases (odds ratio, 3.8; 95% CI, 3.6-4.0; P < .001) and was especially pronounced in children (5.2; 4.1-6.5; P < .001). Elevated risk was consistently observed across all 12 autoimmune diseases. CONCLUSIONS AND RELEVANCE Epilepsy and autoimmune disease frequently co-occur; patients with either condition should undergo surveillance for the other. The potential role of autoimmunity must be given due consideration in epilepsy so that we are not overlooking a treatable cause.
Bourgeois, Murthy, Pinto, Olson, Ioannidis, Mandl. Pediatric versus adult drug trials for conditions with high pediatric disease burden. Pediatrics. 2012;130:285–92.
BACKGROUND AND OBJECTIVE: Optimal treatment decisions in children require sufficient evidence on the safety and efficacy of pharmaceuticals in pediatric patients. However, there is concern that not enough trials are conducted in children and that pediatric trials differ from those performed in adults. Our objective was to measure the prevalence of pediatric studies among clinical drug trials and compare trial characteristics and quality indicators between pediatric and adult drug trials. METHODS: For conditions representing a high burden of pediatric disease, we identified all drug trials registered in ClinicalTrials.gov with start dates between 2006 and 2011 and tracked the resulting publications. We measured the proportion of pediatric trials and subjects for each condition and compared pediatric and adult trial characteristics and quality indicators. RESULTS: For the conditions selected, 59.9% of the disease burden was attributable to children, but only 12.0% (292/2440) of trials were pediatric (P .001). Among pediatric trials, 58.6% were conducted without industry funding compared with 35.0% of adult trials (P .001). Fewer pediatric compared with adult randomized trials examined safety outcomes (10.1% vs 16.9%, P = .008). Pediatric randomized trials were slightly more likely to be appropriately registered before study start (46.9% vs 39.3%, P = .04) and had a modestly higher probability of publication in the examined time frame (32.8% vs 23.2%, P = .04). CONCLUSIONS: There is substantial discrepancy between pediatric burden of disease and the amount of clinical trial research devoted to pediatric populations. This may be related in part to trial funding, with pediatric trials relying primarily on government and nonprofit organizations.
STUDY OBJECTIVES: We measure the association between proportion of children and specific pediatric age groups in a local population with the timing and rate of adult emergency department (ED) utilization for influenza and other acute respiratory infections. METHODS: We performed an ecologic study on a time-series of adult patients presenting to Massachusetts EDs and residing in the greater Boston area from October 1, 2001, to September 30, 2005. Patients presenting with acute respiratory infection, used as a marker for influenza, were aggregated by home address ZIP code. We measured geographic patterns of timing and rate of adult respiratory infection-related ED utilization. We performed correlation analysis of rates and peaks identified in this analysis with pediatric population data from the US census (including specific pediatric age groups) by Poisson regression. RESULTS: One hundred fifty seven thousand five hundred forty two adult respiratory infection-related ED visits (30 visits per 1,000 adults per year) were analyzed. Visits were distributed across 55 of ZIP codes, in which proportions of children (aged 0 to 18 years) ranged from 2.7% to 34.9% in these communities. Proportion of children in a ZIP code was directly associated with timing of seasonal onset of acute respiratory infections among adults (univariate Poisson regression rate ratio [RR] 0.985; 95% confidence interval [CI] 0.977 to 0.993). The proportion of children also explained the patterns of adult acute respiratory infection-related ED utilization rates (RR 1.035; 95% CI 1.024 to 1.047). Three- to 4-year-olds were found to be the most significant predictors of adult illness rate (RR 1.380; 95% CI 1.238 to 1.539) and timing of onset (RR 0.881; 95% CI 0.816 to 0.952). CONCLUSION: We demonstrate a positive correlation between the timing and rate of ED utilization by adults and the proportion of children in the population. These findings add to a growing body of evidence supporting a critical role played by children in community-wide transmission of acute respiratory infections.
Bourgeois, Mandl, Valim, Shannon. Pediatric adverse drug events in the outpatient setting: an 11-year national analysis. PediatricsPediatricsPediatrics. 2009;124:e744–50.
OBJECTIVE: Adverse drug events (ADEs) are a common complication of medical care, but few pediatric data are available describing the frequency or epidemiology of these events. We estimated the national incidence of pediatric ADEs requiring medical treatment, described the pediatric population seeking care for ADEs, and characterized the events in terms of patient symptoms and medications implicated. METHODS: Data were obtained from the National Center for Health Statistics, which collects information on patient visits to outpatient clinics and emergency departments throughout the United States. We analyzed data for children 0 to 18 years of age seeking medical treatment for an ADE between 1995 and 2005. RESULTS: The mean annual number of ADE-related visits was 585922 (95% confidence interval [CI]: 503687-668156) of which 78% occurred in outpatient clinics and 12% occurred in emergency departments. Children 0 to 4 years of age had the highest incidence of ADE-related visits, accounting for 43.2% (95% CI: 35.6%-51.2%) of visits. The most common symptom manifestations were dermatologic conditions (45.4% [95% CI: 36.9%-54.1%]) and gastrointestinal symptoms (16.5% [95% CI: 11.1%-23.8%]). The medication classes most frequently implicated in an ADE were antimicrobial agents (27.5% [95% CI: 21.5%-34.5%]), central nervous system agents (6.5% [95% CI: 4.0%-10.5%]), and hormones (6.1% [95% CI: 3.1%-11.6%]). While ADEs related to antimicrobial agents were most common among children 0 to 4 years old and decreased in frequency among older children, ADEs resulting from central nervous system agents and hormones increased in frequency among children 5 to 11 and 12 to 18 years old. CONCLUSIONS: ADEs result in a substantial number of health care visits, particularly in outpatient clinics. The incidence of ADEs and medications implicated vary by age, indicating that age-specific approaches for monitoring and preventing ADEs may be most effective.
BACKGROUND: Fragmentation of medical information places patients at risk for medical errors, adverse events, duplication of tests, and increased costs. We sought to quantify, at the population level, the burden of fragmentation in the acute care setting across the state of Massachusetts by measuring the rates at which individuals seek care across multiple sites. METHODS: A retrospective observational study of all adult patients with at least 2 visits or hospitalizations to the emergency departments, inpatient units, and observation units in Massachusetts from October 1, 2002, to September 30, 2007. RESULTS: The 3,692,178 adult patients who visited an acute care site during our study period accounted for 12,758,498 acute care visits. A total of 1,130,124 adult patients (31%) visited 2 or more hospitals during the study period, accounting for 56.5% of all acute care visits, while a subgroup of 43,794 patients (1%) visited 5 or more hospitals, contributing to almost one-tenth of all acute visits. Patients who visited multiple sites were younger (P .001), more likely to be male (P .001), more likely to have a primary psychiatric diagnosis (P .001), and more frequently hospitalized (P .001) and incurred higher charges than patients who used only a single site of care (P .001). CONCLUSIONS: A large number of patients seek care at multiple acute care sites. These findings provide one basis for assessing the value of an integrated electronic health information system for clinicians caring for patients across sites of care and therefore the return on investment in health information technology.