Descriptive, real-world treatment patterns, resource use, and total cost of care among eculizumab- and ravulizumab-treated members with paroxysmal nocturnal hemoglobinuria.

BACKGROUND: Paroxysmal nocturnal hemoglobinuria (PNH) is a rare, genetic, chronic, and life-threatening blood disease with an estimated prevalence of 13 per 1,000,000 persons reported in the United States. Available at analysis, PNH treatment included the use of C5 inhibitors (C5is), which prevent formation of membrane attack complex and consequently intravascular hemolysis. Limited real-world evidence suggests some individuals with PNH continue to experience anemia and breakthrough hemolysis (BTH) after C5i treatment, indicating unmet needs. OBJECTIVE: To describe real-world treatment patterns and outcomes among individuals treated with C5is, eculizumab (ECU), and ravulizumab (RAV), focusing on affordability challenges and therapy unmet needs from a US payer perspective. METHODS: This retrospective cohort study was conducted using deidentified data from Prime Therapeutics' approximately 15 million commercially insured US members with integrated medical and pharmacy claims data. Members were identified between January 1, 2018, and December 31, 2020. Inclusion criteria for cohort identification were adults aged 18 years or older at ECU or RAV index date requiring 2 or more claims for ECU or 1 or more claims for RAV. ECU and RAV users were excluded if they had a claim indicating treatment for a US Food and Drug Administration (FDA)-approved non-PNH indication. Members were required to be continuously enrolled 6 months before and 12 months after their index ECU or RAV claim. Real-world C5i claims-based treatment dosage and frequency patterns were compared with FDA-labeled dosing. Clinical outcomes, including transfusions and BTH events, were identified in the pre-index and post-index periods. Health care resource use and costs were calculated after network discounts, including member share. RESULTS: A total of 86 commercial members met analysis criteria: 34 in the ECU cohort and 52 in the RAV cohort. The mean age was 42.6 years, and 54.6% were female. Estimated higher-than-label PNH-recommended dosage occurred in 38.2% of ECU and 9.6% of RAV members. In total, 29.4% of ECU and 17.3% of RAV members had 4 or more transfusions in the post-index period. Additionally, 29.4% of ECU and 13.5% of RAV members had 1 or more BTH episodes. Post-index period mean per member total health care costs were $711,785 among ECU members and $624,911 among RAV members, and C5i costs accounted for 79.7% and 85.6% of total health care costs, respectively. CONCLUSIONS: Although all members received at minimum FDA-approved dosages, transfusions and BTH events continue to occur for some members. These findings indicate potentially inadequate therapy responses in a substantial subset of C5i users, adding additional therapy costs to an already extremely expensive therapy. DISCLOSURES: This study was funded by Apellis Pharmaceuticals. Drs Broderick and Fishman report employment by Apellis Pharmaceuticals and own stock options. Dr Burke reports employment by Prime Therapeutics, LLC, which has received research funding from Apellis Pharmaceuticals. Dr Gleason reports employment by Prime Therapeutics, LLC, which has received research funding from Apellis Pharmaceuticals; serves on the advisory committee at the Institute for Clinical and Economic Review; and has served on the Board of Directors at the Academy of Managed Care Pharmacy.

Health care costs in patients with painful diabetic peripheral neuropathy prescribed pregabalin or duloxetine.

BACKGROUND: Pregabalin and duloxetine are two FDA-approved medications for the treatment of pain associated with diabetic peripheral neuropathy (pDPN). The objective of this study was to compare changes in all-cause and pDPN-related health care costs in patients with pDPN initiated on pregabalin or duloxetine. METHODS: Patients at least 18 years of age initiating pregabalin or duloxetine between March 1, 2006 and December 31, 2008 were identified from a large U.S. managed care plan database. The date of the first pregabalin or duloxetine prescription was defined as the index date. Patients with claims-based evidence of pDPN and who had continuous enrollment for 6-month pre- and post-index periods were selected for study inclusion. Duloxetine patients with depression or generalized anxiety disorder (GAD) were excluded. All-cause and pDPN-related total health care costs (over 6 month pre-index and post-index periods) were analyzed with difference-in-differences (DiD) models. RESULTS: A total of 2,136 patients (1,785 pregabalin and 351 duloxetine) were identified. No significant differences in gender, age, or pre-index Quan-Charlson comorbidity score were observed between the two cohorts. No significant differences (pregabalin vs. duloxetine) in pre-index to post-index change in mean all-cause health care costs ($1,411 vs. $1,560, P = 0.93) or mean pDPN-related health care costs ($704 vs. -$240, P = 0.22) were found. The DiD models showed no significant difference in all-cause (mean) costs attributable to pregabalin vs. duloxetine therapy between pre-index and post-index periods (mean cost ratio = 0.97, 95% CI: 0.75 to 1.26), but showed that patients receiving pregabalin had a significantly higher increase in pDPN-related costs compared with patients receiving duloxetine (mean cost ratio = 2.35, 95% CI: 1.01 to 5.46). However, the difference (pre- to post-index) in pDPN-related costs attributable to pregabalin vs. duloxetine therapy was nonsignificant (mean cost ratio = 2.30, 95% CI: 0.93 to 5.68) in a sensitivity analysis in which patients with depression and GAD were excluded from both cohorts. CONCLUSION: No differences were noted in all-cause costs attributable to pregabalin or duloxetine. Although patients receiving pregabalin had a significantly greater pre- to post-index increase in pDPN-related health care costs compared with patients receiving duloxetine, this may have been due to an imbalance in patient exclusion criteria between cohorts.

Health care costs in patients with fibromyalgia on pregabalin vs. duloxetine.

BACKGROUND: The economic burden associated with fibromyalgia in the U.S. is substantial. The objective of this study was to compare changes in health care costs in fibromyalgia patients initiated on pregabalin and duloxetine in real-world settings. METHODS: Patients (≥ 18 years old) initiating pregabalin or duloxetine between June 1, 2007 and December 31, 2008 were identified using a U.S. managed care database. Patients were selected if they had ≥ 2 medical claims for fibromyalgia (ICD-9-CM, 729.1) at least 90 days apart or ≥ 1 claim for fibromyalgia followed within 30 days by a pharmacy claim for pregabalin. The date of the first pregabalin or duloxetine prescription was defined as the index date, and continuous enrollment for 6-month pre- and postindex periods was required. RESULTS: A total of 1,616 pregabalin and 207 duloxetine patients were identified. Treatment differences between pregabalin and duloxetine in the pre-/postindex change in mean [SD] all-cause total health care costs ($1,307 [16,747] vs. -$158 [17,337]; P = 0.24) or fibromyalgia-related total health care costs ($584 [3,834] vs. $759 [2,133]; P = 0.32) were not significant. Multivariate analysis using difference-in-differences models showed no significant difference in all-cause costs (mean cost ratio = 1.05, 95% CI: 0.84 to 1.31) or fibromyalgia-related costs (0.85, 95% CI: 0.61 to 1.18) between treatments during the postindex period. CONCLUSION: No significant differences were found between pregabalin and duloxetine in the pre- to postindex change in mean all-cause or fibromyalgia-related total health care costs.

The incidence of central serous chorioretinopathy in Olmsted County, Minnesota, 1980-2002.

PURPOSE: To determine the incidence of central serous chorioretinopathy (CSC) in Olmsted County, Minnesota from 1980 to 2002, determine the associated risk factors for CSC based on previously reported risk factors, investigate for any new risk factors not previously reported, and determine a population-based recurrence rate. DESIGN: Population-based retrospective cohort and case-control study. PARTICIPANTS: Cases were all patients with newly diagnosed CSC in Olmsted County Minnesota, from January 1, 1980 through December 31, 2002. Controls were selected from the same general population. Control group 1 patients were matched for age, gender, length of medical follow-up, and index date (corresponding with date of diagnosis for cases). Control group 2 patients were matched for all the same criteria as control group 1, and they had documented normal eye examination results. METHODS: Using the Rochester Epidemiology Project medical records linkage system, which captures virtually all medical care provided to residents of Olmsted County, Minnesota, we identified all cases of CSC in county residents between 1980 and 2002. We reviewed the entire medical record of cases and applied standardized criteria for CSC. The medical records of cases and controls were reviewed for the presence of risk factors as well. MAIN OUTCOME MEASURE: Incidence of CSC. Secondary outcomes were also evaluated. RESULTS: There were 74 cases (63 men, 11 women) of CSC. Mean annual age-adjusted incidences per 100 000 were 9.9 (95% confidence interval [CI], 7.4-12.4) for men and 1.7 (95% CI, 0.7-2.7) for women. The incidence of CSC was approximately 6 times higher in men than in women (P<0.001). There were no significant risk factors identified for CSC. Twenty-three (31%) of the 74 patients with CSC had recurrences. The mean number of recurrences was 1.5 (range, 1-4). Median time from diagnosis to recurrence was 1.3 years (range, 0.4-18.2). CONCLUSION: The incidence of CSC has not previously been reported in a population-based study. In accordance with previous studies, we found that CSC occurs more frequently in men than in women.

Incidence and types of childhood esotropia: a population-based study.

OBJECTIVE: To describe the incidence and types of childhood esotropia in a defined population. DESIGN: Retrospective population-based cohort. PARTICIPANTS: All pediatric (<19 years of age) residents of Olmsted County, Minnesota, diagnosed with an esodeviation (> or =10 prism diopters) from January 1, 1985, through December 31, 1994. METHODS: The medical records of all potential patients identified by the resources of the Rochester Epidemiology Project were reviewed. MAIN OUTCOME MEASURES: Incidence and types of childhood esotropia. RESULTS: Three hundred eighty-five cases of childhood esotropia were identified during the 10-year period, yielding an annual age- and gender-adjusted incidence of 111.0 (95% confidence interval, 99.9-122.1) per 100,000 patients younger than 19 years of age. This rate corresponds to a cumulative prevalence of approximately 2.0% of all children younger than 6 years, with a significant decrease in older ages (P<0.0001). Of the 385 study children, the specific forms and percentages of esotropia diagnosed were as follows: fully accommodative, 140 (36.4%); acquired nonaccommodative, 64 (16.6%); esotropia associated with an abnormal central nervous system, 44 (11.4%); partially accommodative, 39 (10.1%); congenital, 31 (8.1%); sensory, 25 (6.5%); paralytic, 25 (6.5%); undetermined, 13 (3.4%); and other, 4 (1.0%). CONCLUSIONS: The incidence of childhood esotropia from this self-referred population-based study is comparable with prevalence rates reported among Western populations. Esotropia is most common during the first decade of life, with the accommodative and acquired nonaccommodative forms occurring most frequently. The congenital, sensory, and paralytic forms of childhood esotropia were less common in this population.

Incidence of cataract surgery from 1980 through 2004: 25-year population-based study.

PURPOSE: To estimate sex- and age-specific incidence rates of cataract surgery in a defined United States population and evaluate the change in incidence over time. SETTING: Department of Ophthalmology, Mayo Clinic College of Medicine, Rochester, Minnesota, USA. METHODS: Rochester Epidemiology Project databases were used to identify all incident cataract surgeries in Olmsted County, Minnesota, residents during the 25-year period from January 1, 1980, through December 31, 2004. Annual incidence rates for each sex and 10-year age group were calculated and adjusted to the 2000 U.S. white population. Change in incidence over time was assessed by fitting generalized linear models assuming a Poisson error structure. RESULTS: During the study period, 10 245 cataract extractions were performed in 7141 residents of all ages. Overall, the age-adjusted cataract surgery incident rate per 100000 residents was 548 (95% confidence interval [CI], 534-561) for women, 462 (95% CI, 447-478) for men, and 511 (95% CI, 501-521) for all residents. The incidence of cataract surgery increased 500% among women and 467% among men during the study period (P<.001). Overall, the incidence of cataract surgery was highest in residents 70 years and older (3538 surgeries [95% CI, 3322-3764] per 100,000 residents). CONCLUSIONS: This population-based study found a substantial increase in incident cataract surgery among Olmsted County residents during the 25-year study period. The rate of cataract surgery increased in a nearly linear fashion during a period when phacoemulsification replaced extracapsular cataract extraction in the community.

The risk of glaucoma in pseudoexfoliation syndrome.

PURPOSE: To determine the conversion rate of pseudoexfoliation syndrome (PEX) to pseudoexfoliative glaucoma or treated ocular hypertension. METHODS: Retrospective community-based study of newly diagnosed cases of PEX syndrome in all residents of Olmsted County, Minnesota between 1976 and 1991. The end point was considered the initiation of therapy, which included patients with glaucoma (optic disc damage or visual field defects), or with elevated intraocular pressure (IOP) >21 mm Hg in the presence of risk factors; the subsequent development of damage in the latter group was also determined. RESULTS: Two hundred fifty-five patients (318 eyes) had newly diagnosed PEX over the 15-year interval. Mean age was 73+/-10 years; 78% (199/255) were female. Of all PEX patients, 16% were placed on therapy at the time of initial diagnosis of PEX. In the remaining PEX patients, the probability of being placed on therapy was 44% at 15 years. Bilateral PEX was present in 25% at initial diagnosis and developed in another 29% by 15 years. Of those not placed on therapy, 16% (23/142) had IOP increase 5+ mm Hg during follow-up, with 11% (16/142) reaching 22 mm Hg or more. The strongest risk factors for converting to therapy were IOP at initial diagnosis of PEX and bilateral involvement. CONCLUSIONS: In a geographically defined population of PEX patients, 16% required treatment upon presentation. Of the remaining PEX patients, 44% received therapy over the next 15 years.

In vivo evaluation of biomechanical anterior cervical plate failure.

Anterior cervical plate (ACP) failure is rarely addressed in the literature. In this retrospective, observational, longitudinal, cohort study, the objectives were to (1) identify incidences of in vivo biomechanical failure in commercially available, US Food and Drug Administration-approved ACP systems, (2) describe modes of failure, (3) suggest structural explanations for system failure, and (4) discuss complications and treatment of patients with failed ACP systems. Investigators retrospectively identified patients who underwent anterior cervical procedures followed by use of ACP as a fusion adjunct and showed evidence of ACP failure on plain radiographs. Components of the ACP system that led to failure were identified and examined. A total of 240 patients received ACP supplementation of anterior cervical fusion constructs during the 9.5-y study period. Evidence of ACP failure was noted in 7 patients (3.3%), and an eighth patient was referred for evaluation after ACP failure. Screw-plate interface failure occurred in all 8 cases. The biomechanical method by which the bone screw head was secured into the vertebral body, or against the ACP, the use of hybrid systems, the surgical technique selected, and host factors were used to determine the rate of failure. Concern for esophageal or other tissue injury often necessitated ACP removal. Screw-plate interface failure, which was found to be the most common mode of biomechanical ACP failure, may occur in hybrid constructs and in systems that do not create a rigid interface between the screw head and the ACP. Surgical technique and patient host factors may also influence the rate of biomechanical construct failure.

Incidence and types of childhood hypertropia: a population-based study.

OBJECTIVE: To determine the incidence and types of childhood hypertropia in a defined population. DESIGN: Retrospective population-based cohort. PARTICIPANTS: All pediatric (<19 years of age) residents of Olmsted County, Minnesota, diagnosed with vertical strabismus from January 1, 1985, through December 31, 1994. METHODS: The medical records of all potential patients identified by the resources of the Rochester Epidemiology Project were reviewed. MAIN OUTCOME MEASURES: Incidence and types of childhood hypertropia. RESULTS: Forty-two cases of childhood hypertropia were identified during the 10-year period, yielding an annual age- and gender-adjusted incidence of 12.9 (95% confidence interval, 9.0-16.9) per 100000 patients younger than 19 years of age. This rate corresponds to a prevalence of approximately 0.26%, or 1 in 391, of all children younger than 19 years of age. Nearly three fourths (71.4%) of the children had a IVth cranial nerve palsy, primary inferior oblique overaction, Brown syndrome, or a vertical tropia in the setting of an abnormal central nervous system. CONCLUSIONS: The incidence rates for childhood hypertropia in this population-based study are higher than published reports of prevalence. Fourth cranial nerve palsy and primary dysfunction of the inferior oblique muscle were the most common forms of vertical strabismus in this population.

Risk of retinal detachment after cataract extraction, 1980-2004: a population-based study.

PURPOSE: To estimate the long-term cumulative risk of retinal detachment (RD) after cataract extraction (CE). DESIGN: Retrospective cohort study and nested case-control study. PARTICIPANTS: All residents of Olmsted County, Minnesota who had CE from 1980 through 2004 (10 256 CEs in 7137 residents) and were diagnosed subsequently with RD in the same period. Two controls chosen from the primary cataract surgery cohort were matched to each RD case by age, gender, and duration of follow-up. METHODS: Cases were identified through the Rochester Epidemiology Project databases. Records were reviewed to confirm case status and ascertain risk factor information. The observed probability of RD after CE was estimated using the Kaplan-Meier method. A cumulative probability ratio of RD after CE was determined by comparing the observed probability of RD and the expected probability of RD in residents without CE. Logistic regression models assessed differences between cases and controls. MAIN OUTCOME MEASURES: Probability of and risk factors associated with RD after CE. RESULTS: Eighty-two cases of RD were identified. The cumulative probability of RD increased in a nearly linear manner over the 25-year study period. At 1, 5, 10, 15, and 20 years after extracapsular CE (ECCE) and phacoemulsification, cumulative probabilities of RD were 0.27%, 0.71%, 1.23%, 1.58%, and 1.79%, respectively. There was no significant difference in the probability of RD after ECCE when compared with phacoemulsification (P = 0.13). The cumulative probability ratio of RD at 20 years after ECCE and phacoemulsification remained 4.0-fold (95% confidence interval, 2.6-5.4) higher than would be expected in a similar group of residents not undergoing CE (P<0.001). Male gender, younger age, myopia, increased axial length, and posterior capsular tear were associated significantly with RD (P<0.01). CONCLUSIONS: The cumulative risk of RD after ECCE and phacoemulsification is increased for up to 20 years after surgery.

Relative risk of mortality associated with diabetes as a function of birth weight.

OBJECTIVE: Birth weight is a risk factor for both diabetes and mortality. Diabetes is a risk factor for mortality. Whether the excess mortality observed for diabetes varies with birth weight is unclear. RESEARCH DESIGN AND METHODS: Among all 2,508 Rochester, Minnesota, residents who first met research criteria for adult-onset diabetes in 1960-1995, 171 were born locally in-hospital after 1922 (i.e., birth weights available) as singleton, term infants. Each case subject and two age- and sex-matched nondiabetic control subjects (born locally, residing locally when the case subject met the criteria for diabetes) were followed through 31 December 2000 for vital status. RESULTS: Of the diabetic case subjects, 16% (27 of 171) died vs. 7% (25 of 342) of control subjects (P = 0.004). The difference was less for normal-birth-weight (NBW) (2,948-<3,856 g) individuals (12% [12 of 102] vs. 8% [20 of 246], P = 0.31) than for abnormal-birth-weight individuals (low birth weight [LBW] 20% [8 of 39] vs. 2% [1 of 46], P = 0.01; high birth weight [HBW] 23% [7 of 30] vs. 8% [4 of 50], P = 0.16), as confirmed with age- and sex-adjusted Cox proportional hazards (diabetes-associated hazard ratio 1.4 [95% CI 0.69-2.90] for NBW vs. 4.8 [1.7-13.3] for abnormal birth weight, test for interaction P = 0.056). The observed diabetes deaths were greater than expected, based on mortality for the general population (27 vs. 13.3, P < 0.001), with 70% of excess deaths occurring among LBW (8 vs. 2.2, P < 0.001) and HBW (7 vs. 3.1, P = 0.03) individuals. CONCLUSIONS: The excess mortality observed for diabetes appears disproportionately concentrated among abnormal-birth-weight individuals, thus identifying a subset of at-risk diabetic individuals and reinforcing the importance of NBW deliveries.

From Value Assessment to Value Cocreation: Informing Clinical Decision-Making with Medical Claims Data.

Big data and advances in analytical processes represent an opportunity for the healthcare industry to make better evidence-based decisions on the value generated by various tests, procedures, and interventions. Value-based reimbursement is the process of identifying and compensating healthcare providers based on whether their services improve quality of care without increasing cost of care or maintain quality of care while decreasing costs. In this article, we motivate and illustrate the potential opportunities for payers and providers to collaborate and evaluate the clinical and economic efficacy of different healthcare services. We conduct a case study of a firm that offers advanced biomarker and disease state management services for cardiovascular and cardiometabolic conditions. A value-based analysis that comprised a retrospective case/control cohort design was conducted, and claims data for over 7000 subjects who received these services were compared to a matched control cohort. Study subjects were commercial and Medicare Advantage enrollees with evidence of CHD, diabetes, or a related condition. Analysis of medical claims data showed a lower proportion of patients who received biomarker testing and disease state management services experienced a MI (p < 0.01) or diabetic complications (p < 0.001). No significant increase in cost of care was found between the two cohorts. Our results illustrate the opportunity healthcare payers such as Medicare and commercial insurance companies have in terms of identifying value-creating healthcare interventions. However, payers and providers also need to pursue system integration efforts to further automate the identification and dissemination of clinically and economically efficacious treatment plans to ensure at-risk patients receive the treatments and interventions that will benefit them the most.

Longitudinal treatment patterns among US patients with atherosclerotic cardiovascular disease or familial hypercholesterolemia initiating lipid-lowering pharmacotherapy.

BACKGROUND: The most recent American College of Cardiology-American Heart Association guidelines recommend high-dose statin therapy for most patients with confirmed atherosclerotic cardiovascular disease (ASCVD) and patients with high cardiovascular risk. There is limited information regarding long-term treatment patterns among these patients. OBJECTIVE: To examine longitudinal treatment modifications in patients with ASCVD or familial hypercholesterolemia (FH). METHODS: This retrospective analysis of administrative claims data identified patients initiating statin or ezetimibe therapy between January 1, 2007, and December 31, 2012, who had evidence of ASCVD or FH. Patients were followed for up to 3 years and up to 4 treatment episodes. After initial treatment, subsequent treatment episodes began on the date of a treatment modification, which included discontinuation, statin dose change, switching, and augmentation. RESULTS: A total of 92,621 patients (mean age 64.7 years, 57.3% male) were identified; 91,740 had ASCVD, 937 had FH (56 had both). Most ASCVD (89.6%) and FH (85.8%) patients initiated on statin monotherapy. The most common treatment modification in the first treatment episode was discontinuation (ASCVD: 42.0%; FH: 58.4%); among patients who discontinued, most reinitiated therapy (70.5% of ASCVD, 76.8% of FH). Most ASCVD (68.2%) and FH (71.1%) patients initiated on moderate-dose statins; statin dose increase occurred in 10.3% of ASCVD and 18.5% of FH patients in the first episode. CONCLUSION: Among patients with high cardiovascular risk, most initiated on moderate-dose statins with infrequent uptitration. In light of the recent American College of Cardiology-American Heart Association guidelines, statin initiation practices will need to change to ensure appropriate therapy for high-risk patients.

Thrombomodulin gene polymorphisms or haplotypes as potential risk factors for venous thromboembolism: a population-based case-control study.

Dysfunction of the protein C anticoagulant system is associated with venous thromboembolism (VTE) and thrombomodulin (TM) is a critical cofactor within the protein C system. The aim of this study was to test the hypotheses that polymorphisms or haplotypes within the TM gene are common risk factors for VTE. We screened the TM putative promoter, exon and 3'-untranslated region for sequence variations in a random sample (n = 266) of consecutive idiopathic, objectively confirmed non-Olmsted County VTE patients referred to the Mayo Clinic. We then genotyped a sample of Olmsted County, MN residents with a first lifetime, objectively confirmed VTE in the 25-year period, 1966-90 (n = 223), and a sample of Olmsted County residents without VTE (n = 237) for polymorphisms either discovered in the screening population or previously published, and tested for an association of VTE with TM genotype or haplotypes using unconditional logistic regression and generalized linear models, respectively. We also genotyped these Olmsted County cases and controls at 20 'null' genetic maker loci and tested for population admixture. Nine novel and three previously described mutations were identified in the screening population. Mutations within the TM promoter, EGF(1-5), serine/threonine-rich, transmembrane, and cytoplasm regions were absent or uncommon. TM845G-->A (Ala25Thr; lectin region), TM2136T-->C (Ala455Val; EGF(6) region), TM2470C deletion (3'-untranslated region), and 4363A-->G (3'-flanking region) were more common, but were not associated with VTE by genotype or haplotype. Null genetic marker allele frequencies did not differ significantly among cases and controls. We conclude that polymorphisms or haplotypes within the TM gene are not common risk factors for incident VTE.

Incidence and types of childhood exotropia: a population-based study.

OBJECTIVE: To determine the incidence and types of childhood exotropia in a defined population. DESIGN: Retrospective, population-based cohort. PARTICIPANTS: All pediatric (<19 years old) residents of Olmsted County, Minnesota diagnosed with an exodeviation (>or=10 prism diopters) from January 1, 1985 through December 31, 1994. METHODS: The medical records of all potential patients identified by the resources of the Rochester Epidemiology Project were reviewed. MAIN OUTCOME MEASURES: Incidence and types of childhood exotropia. RESULTS: Two hundred five cases of childhood exotropia were identified during the 10-year period, yielding an annual age- and gender-adjusted incidence of 64.1 (95% confidence interval: 55.2-72.9)/100,000 patients younger than 19 years. This rate corresponds to a prevalence of approximately 1.0% of all children younger than 11 years, with a significant decrease in the incidence during the second decade of life (P<0.001). Eighty-six percent of the children had intermittent exotropia, convergence insufficiency, or an exotropia in the setting of an abnormal central nervous system. CONCLUSIONS: The incidence of childhood exotropia from this population-based study is comparable to the prevalence rates in prior reports. Exotropia is most prevalent during the first decade of life, with intermittent exotropia and convergence insufficiency occurring most frequently.

Diabetes and hypertension in isolated sixth nerve palsy: a population-based study.

PURPOSE: Diabetes mellitus and systemic hypertension are frequently reported as ischemic causes of sixth nerve palsy/paresis, but there are few rigorous studies to support these associations. We conducted a population-based case-control study to determine the presence and magnitude of any association of preexisting diabetes mellitus and systemic hypertension with isolated sixth nerve palsy. DESIGN: Retrospective population-based case-control study. PARTICIPANTS AND CONTROLS: Participants were patients with new onset of neurologically isolated sixth nerve palsy or paresis (n = 76) in Olmsted County, Minnesota, from January 1, 1978, to December 31, 1992. Controls (n = 76) were selected from the same general population and were matched for age, gender, and length of medical follow-up. METHODS: Using the Rochester Epidemiology Project medical records linkage system, which captures virtually all medical care provided to residents of Olmsted County, Minnesota, we identified all incident cases of neurologically isolated sixth nerve palsy/paresis (n = 76) among county residents between the given dates. An equal number (n = 76) of controls were randomly selected from the general population. We reviewed the entire medical record of each case and control, using stringent predetermined criteria to define the presence of diabetes mellitus and systemic hypertension. We compared the prevalence of diabetes and systemic hypertension between cases and controls by use of chi-square tests, and we calculated odds ratios (OR) with 95% confidence intervals (CI). MAIN OUTCOME MEASURES: Presence or absence of diabetes mellitus and systemic hypertension. RESULTS: Diabetes mellitus occurred more frequently in cases (23.7%) than in controls (5.3%; P = 0.001; OR, 5.59; 95% CI, 1.79-17.42). Systemic hypertension occurred with similar frequency in cases (51.3%) and controls (39.5%; P = 0.14; OR, 1.62; 95% CI, 0.85-3.08). Coexistent diabetes mellitus and hypertension were more common in cases (18.4%) than in controls (2.6%; P = 0.002; OR, 8.36; 95% CI, 1.83-38.18). CONCLUSIONS: We conclude that there is a 6-fold increase in odds of having diabetes in cases of sixth nerve palsy over controls, whereas systemic hypertension does not seem to be associated with increased odds. In contrast, there is an 8-fold increased odds of having coexistent diabetes and hypertension in cases of sixth nerve palsy over controls. The much-cited association of systemic hypertension alone with sixth nerve palsy may be coincidental.

Long-term trends in thyroid carcinoma: a population-based study in Olmsted County, Minnesota, 1935-1999.

OBJECTIVE: To determine whether there was a significant increase in the incidence of thyroid carcinoma in Olmsted County, Minnesota, that may be attributed to the widespread use of therapeutic head and neck irradiation between 1920 and the 1950s or to exposure to atomic fallout at the Nevada Test Site in the 1960s. METHODS: Rochester Epidemiology Project resources were used to identify potential cases of thyroid carcinoma among residents of Olmsted County between 1935 and 1984. We extended this earlier study through 1999. RESULTS: During the study period, thyroid carcinoma was newly diagnosed in 263 residents. In women, the age-adjusted incidence increased from 2.7 per 100,000 person-years (p-y) in 1935-1949 to 9.2 per 100,000 p-y in 1990-1999 (P = .001); In men, the rate increased from 0.8 to 5.0 per 100,000 p-y (P = .007). However, most of the increase occurred before 1965 and remained relatively stable thereafter. Similar trends were observed for papillary carcinoma alone. CONCLUSION: Although the Incidence of thyroid carcinoma increased significantly between 1935 and 1964, no significant Increases have been seen since 1965, suggesting that neither atmospheric atomic fallout from the Nevada Test Site nor use of ionizing radiation to treat conditions of the head and neck significantly affected the incidence of thyroid carcinoma in Olmsted County.

Iatrogenic vertebral artery injury during anterior cervical spine surgery.

BACKGROUND CONTEXT: Iatrogenic injury to the vertebral artery during an anterior cervical decompression is a rarely mentioned but potentially catastrophic complication. PURPOSE: This study was designed to examine the incidence and management of iatrogenic vertebral artery injury (IVAI) in a large database. STUDY DESIGN/SETTING: This was a retrospective study performed at a large teaching institution over a 7-year period (1994-2001). PATIENT SAMPLE: All anterior cervical spinal procedures performed for herniated or degenerative disc disease, or cervical spondylosis were identified, as were incidences of IVAI. Anterior cervical procedures performed for trauma, neoplasia, or infection were excluded from this study. OUTCOME MEASURES: Neurological and associated morbidity as well as mortality were recorded. METHODS: Data were accessed through an institution-wide electronic medical record search through the operative reports of 10 spine surgeons. Hospital and clinical charts of IVAI cases were subsequently reviewed. Demographic data and intraoperative strategies for repair were recorded. RESULTS: A total of 1,976 patients underwent anterior cervical spinal procedures in the review period. Six cases of IVAI were identified. In three of the six patients, arterial bleeding was controlled with hemostatic agents. Of these three, two suffered complications. The initial management of controlling arterial bleeding is by hemostatic agents; however, one must also consider repair or ligation. The remaining three patients were treated with primary repair or ligation, and no complications were noted. CONCLUSIONS: IVAI is a rare complication (0.3%) of anterior cervical procedures. The arterial bleeding can usually be controlled with topical hemostatic agents, but mortality may occur in instances where it cannot be adequately addressed in a timely fashion.

A population perspective on diabetes prevention: whom should we target for preventing weight gain?

OBJECTIVE: To examine the influence of obesity and prevention of weight gain on the incidence of type 2 diabetes. RESEARCH DESIGN AND METHODS: We examined participants in the San Antonio Heart Study, a prospective population-based study of Mexican Americans and non-Hispanic whites residing in San Antonio, Texas. BMI was stratified into four categories: normal (<25 kg/m(2)), overweight (> or =25 kg/m(2) and <30 kg/m(2)), obese (> or =30 kg/m(2) and <35 kg/m(2)), and very obese (> or =35 kg/m(2)). The number and proportion of incident cases prevented by targeting each BMI category were estimated. In addition, we calculated the decrease in risk of developing type 2 diabetes associated with weight gain prevention across both the BMI and age spectra. RESULTS: Preventing normal individuals from becoming overweight would result in the greatest reduction in incidence of type 2 diabetes. This would result in a 62 and 74% reduction in the incidence of type 2 diabetes in Mexican Americans and non-Hispanic whites, respectively. Preventing the entire population from gaining, on average, 1 BMI unit would result in a reduction in incidence of type 2 diabetes of 12.4 and 13.0% in Mexican Americans and non-Hispanic whites, respectively. CONCLUSIONS: The majority of cases of type 2 diabetes were in individuals who were overweight or mildly obese with a family history of type 2 diabetes. Public health resources should be directed toward the prevention of weight gain among normal and overweight individuals in order to prevent the maximum number of cases of type 2 diabetes.

Characterizing pulmonary hypertension-related hospitalization costs among Medicare Advantage or commercially insured patients with pulmonary arterial hypertension: a retrospective database study.

OBJECTIVES: This study assessed pulmonary hypertension (PH)-related hospitalizations, including readmissions, among US patients with pulmonary arterial hypertension (PAH), a rare disease characterized by high morbidity and premature mortality. STUDY DESIGN: Analysis of claims data (January 1, 2007-April 30, 2011) from adult enrollees with commercial or Medicare Advantage with Part D coverage from a large US health plan. METHODS: Patients with PAH were identified based on ≥ 1 medical claim with a PH-related diagnostic code (International Classification of Diseases, Ninth Edition, Clinical Modification code 416.0 for primary pulmonary hypertension or 416.8 for other chronic pulmonary heart disease) and ≥ 1 pharmacy claim for a medication indicated for PAH or frequently used in PAH. Data were analyzed for patients with ≥ 1 hospitalization with a primary or secondary diagnostic code of PH. PH-related hospitalizations were defined as those with ≥ 1 PH-related diagnostic code. The principal diagnosis was defined as the diagnosis most frequently in the first-listed position on a hospitalization's facility claims. Total hospitalization costs (inflated to 2011 US$) and length of stay (LOS) were analyzed. A subgroup analysis evaluated readmissions. RESULTS: Of 4009 enrollees meeting inclusion criteria, 2275 had ≥ 1 PH-related hospitalization during follow-up: 56.9% were female, 59.4% were < 65 years old, and 67.8% had commercial insurance. Mean (SD) costs across all hospitalizations were $46,118 ($135,137) for commercially insured and $16,319 ($30,046) for Medicare Advantage enrollees; LOS was 10.9 (20.4) and 12.8 (21.2) days, respectively. Costs and LOS were higher for admissions with a principal diagnosis of PH compared with other principal diagnoses: $61,922 ($213,596) versus $42,455 ($108,925) and 14.2 (32.3) versus 10.2 (16.4) days, respectively, for the commercially insured, and $19,584 ($29,501) versus $15,904 ($30,097) and 16.7 (25.7) versus 12.3 (20.5) days, respectively, for Medicare Advantage enrollees. Of the 954 patients who experienced ≥ 1 PH-related readmission within the first year after discharge from the initial hospitalization, 483 (50.6%), 246 (25.8%), and 225 (23.6%) patients had 1, 2, and ≥ 3 readmissions, respectively. CONCLUSIONS: PH-related hospitalizations incur substantial healthcare costs and require long hospital stays for patients with PAH; many are readmitted within 1 year. Improved treatment approaches are needed to reduce PAH disease progression leading to costly and burdensome inpatient stays.