Sudden unexpected death in epilepsy in lamotrigine randomized‐controlled trials

Purpose: Nonrandomized studies of the relationship of antiepileptic drugs (AEDs) with sudden unexpected death in epilepsy (SUDEP) may be susceptible to confounding by tonic–clonic seizure frequency, polypharmacy, and other potential risk factors for SUDEP. We evaluated the risk of SUDEP with lamotrigine (LTG) compared to active comparators and placebo in randomized controlled clinical trials conducted by GlaxoSmithKline (GSK) between 1984 and 2009. Methods: Among 7,774 subjects in 42 randomized clinical trials, there were 39 all‐cause deaths. Ten deaths occurred >2 weeks after discontinuation of study medication and were excluded. Narrative summaries of deaths were independently reviewed by three clinical experts (TT, LH, DF), who were blinded to randomized treatment arm. The risk of definite or probable SUDEP was compared between treatment arms for each trial type (placebo‐controlled, active‐comparator, crossover), using exact statistical methods. Key Findings: Of 29 on‐treatment deaths, eight were definite/probable SUDEP, four were possible SUDEP, and 17 were non‐SUDEP. The overall, unadjusted rate of definite/probable SUDEP for LTG was 2.2 events per 1,000‐patient years (95% confidence interval [95% CI] 0.70–5.4). The odds ratios (OR) for on‐treatment, definite/probable SUDEP in LTG arms relative to comparator arms, adjusted for length of exposure and trial, were the following: placebo‐controlled, OR 0.22 (95% CI 0.00–3.14; p = 0.26); active‐comparator, OR 2.18 (95% CI 0.17–117; p = 0.89); and placebo‐controlled cross‐over, OR 1.08 (95% CI 0.00–42.2; p = 1.0). Significance: There was no statistically significant difference in rate of SUDEP between LTG and comparator groups. However, the CIs were wide and a clinically important effect cannot be excluded.     

Does hospital ownership influence hospital referral region health rankings in the United States

Extensive evidence demonstrates that a hospital's organizational ownership structure impacts its overall performance, but little is known concerning the influence of hospital structure on the health of its community. This paper explores the association between US hospital referral region (HRR) health rankings and hospital ownership and performance. Data from the 2016 Commonwealth Fund Scorecard on Local Health System Performance, the American Hospital Association dataset, and the Hospital Value‐Based Purchasing dataset are utilized to conduct a cross‐sectional analysis of 36 quality measures across 306 HRRs. Multivariate regression analysis was used to estimate the association among hospital ownership, system performance measures—access and affordability, prevention and treatment, avoidable hospital use and cost, and healthy lives—and performance as measured by value‐based purchasing total performance scores. We found that indicators of access and affordability, as well as prevention and treatment, were significantly associated across all 3 hospitals' organizational structures. Hospital referral regions with a greater number of not‐for‐profit hospitals demonstrated greater indications of access and affordability, as well as better prevention and treatment rankings than for‐profit and government hospitals. Hospital referral regions with a greater number of government, nonfederal hospitals had worse scores for healthy lives. Furthermore, the greater the total performance scores score, the better the HRR score on prevention and treatment rankings. The greater the per capita income, the better the score across all 4 dimensions. As such, this inquiry supports the assertion that performance of a local health system is dependent on its community's resources of health care delivery entities and their structure.     

Hematopoietic growth factors for graft failure after bone marrow transplantation: a randomized trial of granulocyte-macrophage colony- stimulating factor (GM-CSF) versus sequential GM-CSF plus granulocyte- CSF

Delay in hematologic recovery after bone marrow transplantation (BMT) can extend and amplify the risks of infection and hemorrhage, compromise patients' survival, and increase the duration and cost of hospitalization. Because current studies suggest that granulocyte- macrophage (GM) colony-stimulating factor (CSF) may potentiate the sensitivity of hematopoietic progenitor cells to G-CSF, we performed a prospective, randomized trial comparing GM-CSF (250 micrograms/m2/d x 14 days) versus sequential GM-CSF x 7 days followed by G-CSF (5 micrograms/kg/d x 7 days) as treatment for primary or secondary graft failure after BMT. Eligibility criteria included failure to achieve a white blood cell (WBC) count > or = 100/microL by day +21 or > or = 300/microL by day +28, no absolute neutrophil count (ANC) > or = 200/microL by day +28, or secondary sustained neutropenia after initial engraftment. Forty-seven patients were enrolled: 23 received GM-CSF (10 unrelated, 8 related allogeneic, and 5 autologous), and 24 received GM- CSF followed by G-CSF (12 unrelated, 7 related allogeneic, and 5 autologous). For patients receiving GM-CSF alone, neutrophil recovery (ANC > or = 500/microL) occurred between 2 and 61 days (median, 8 days) after therapy, while those receiving GM-CSF+G-CSF recovered at a similar rate of 1 to 36 days (median, 6 days; P = .39). Recovery to red blood cell (RBC) transfusion independence was slow, occurring 6 to 250 days (median, 35 days) after enrollment with no significant difference between the two treatment groups (GM-CSF: median, 30 days; GM-CSF+G- CSF; median, 42 days; P = .24). Similarly, platelet transfusion independence was delayed until 4 to 249 days (median, 32 days) after enrollment, with no difference between the two treatment groups (GM- CSF: median, 28 days; GM-CSF+G-CSF: median, 42 days; P = .38). Recovery times were not different between patients with unrelated donors and those with related donors or autologous transplant recipients. Survival at 100 days after enrollment was superior after treatment with GM-CSF alone. Only 1 of 23 patients treated with GM-CSF died versus 7 of 24 treated with GM-CSF+G-CSF who died 16 to 84 days (median, 38 days) after enrollment, yielding Kaplan-Meier 100-day survival estimates of 96% +/- 8% for GM-CSF versus 71% +/- 18% for GM-CSF+G-CSF (P = .026). These data suggest that sequential growth factor therapy with GM-CSF followed by G-CSF offers no advantage over GM-CSF alone in accelerating trilineage hematopoiesis or preventing lethal complications in patients with poor graft function after BMT.(ABSTRACT TRUNCATED AT 400 WORDS)     

Hepatitis C Seroprevalence Among Prison Inmates Since 2001: Still High but Declining

Objectives

Although the hepatitis C epidemic in the United States disproportionately affects correctional populations, the last national estimates of seroprevalence and disease burden among these populations are more than a decade old. We investigated routine hepatitis C surveillance conducted in state prison systems and updated previous estimates.

Methods

We surveyed all U.S. state correctional departments to determine which state prison systems had performed routine hepatitis C screening since 2001. Using seroprevalence data for these prison systems, we estimated the national hepatitis C seroprevalence among prisoners in 2006 and the share of the epidemic borne by correctional populations.

Results

Of at least 12 states performing routine testing from 2001 to 2012, seroprevalences of hepatitis C ranged from 9.6% to 41.1%. All but one state with multiple measurements demonstrated declining seroprevalence. We estimated the national state prisoner seroprevalence at 17.4% in 2006. Based on the estimated total U.S. correctional population size, we projected that 1,857,629 people with hepatitis C antibody were incarcerated that year. We estimated that correctional populations represented 28.5%–32.8% of the total U.S. hepatitis C cases in 2006, down from 39% in 2003.

Conclusions

Our results provide an important updated estimate of hepatitis C seroprevalence and suggest that correctional populations bear a declining but still sizable share of the epidemic. Correctional facilities remain important sites for hepatitis C case finding and therapy implementation. These results may also assist future studies in projecting the societal costs and benefits of providing new treatment options in prison systems.Hepatitis C virus (HCV) is the most common chronic bloodborne pathogen in the United States, both in the general population and among prisoners. National Health and Nutrition Examination Survey (NHANES) data from 2003–2006 suggested an overall anti-HCV serum antibody prevalence (seroprevalence) of 1.3% among household-dwelling populations.¹ Others have suggested that the national seroprevalence may be closer to 2.0% after adding prisoners, homeless people, and other populations not sampled by NHANES.² However, enrollment in NHANES requires several months of housing stability,³ so people with unstable or intermittent housing at any time during a given year are unlikely to participate. Thus, the number of infected people not in households during a period of time, rather than at a single point, should be added to the national seroprevalence estimate.Unsafe injection practices, including injection drug use, are the primary risk factors for HCV infection in the general population.⁴ National HCV prevalence is greater among men than women, and among non-Hispanic black people compared with non-Hispanic white people.¹ Prevalence peaks among individuals born between 1945 and 1965.⁵HCV infection disproportionately affects those who have been in jails and prisons. Although men (compared with women) and black people (compared with white people) are disproportionately incarcerated, the most likely cause for this infection rate disparity is injection drug use, which is both a risk factor for the disease and a criminal behavior.⁶ Hammett et al. estimated that correctional populations in 1997 accounted for 29.4%–43.2% of the total U.S. hepatitis C case burden.⁷ In 2003, the Centers for Disease Control and Prevention (CDC) reported that 16%–41% of inmates had serological evidence of prior HCV exposure, based on data derived from eight states. CDC also estimated that correctional populations bore 39% of the disease burden.⁸The 1976–1980 birth cohort currently comprises the largest proportion of state prison, federal prison, and local jail populations.⁹ As the birth cohort with peak HCV prevalence (1945–1965) ages out of crime-prone years, its contact with the criminal justice system will decline. Hence, the prevalence of HCV among correctional populations should fall. Two states included in the 2003 CDC analysis have since updated their seroprevalence estimates and both demonstrated declines. In Rhode Island, a sampling of prisoners in the mid-1990s showed an HCV seroprevalence of 37%,¹⁰ but seroprevalence dropped to 23% from 1998 to 2000.¹¹ In California, seroprevalence dropped from 41% of entering inmates in 1994¹² to 34% among a small cohort of entrants tested in 2001.¹³It has been estimated that 65%–75% of people with viral hepatitis are unaware of their status.¹⁴ Inmates are likely to be at the upper end of this range.¹⁵ Correctional facilities have represented rich sources for case finding. Once identified, new cases can be directed to treatment programs either in prison or the community. The need to initiate treatment before release for each case is contingent upon multiple factors. One determinant is whether the expected duration of incarceration is longer than the time required for treatment, which is currently one year but becoming shorter.¹⁶Prison health-care planners would benefit from up-to-date information regarding the number of hepatitis C infections in their systems. Currently, the U.S. lacks data on the prevalence of HCV among prisoners and the share of the epidemic borne by incarcerated individuals since the last national estimates were derived a decade ago.^7,8 We investigated routine HCV surveillance conducted in state prison systems to update estimates of the national prison HCV seroprevalence and the share of the epidemic borne by inmates and releasees. We hypothesized that HCV prevalence was falling nationwide among prisoners and that imprisoned populations represented a reduced share of the hepatitis C epidemic.     

Left radial approach for coronary angiography: Results of a prospective study

Although radial approach has been shown to be feasible for coronary angiography, angioplasty, and even stent placement, there have been no prospective evaluations of ease and safety of left radial approach for coronary angiogram. We examined procedural duration and success as well as complications in 415 consecutive patients. Radial artery occlusion was assessed immediately post-procedure and at 2 month follow-up using echo-Doppler measurements. Procedure failure rate was 9%, mean time for sheath insertion was 4.7 ± 4.7 min, and mean procedure duration was 19.1 ± 8.2 min. No major complications occurred. Asymptomatic radial artery occlusion was noted in 71% of the first 49 patients, decreased to 24% in the next 119 receiving 2,000–3,000 units of heparin, and to 4.3% in the last 210 receiving 5000 (p < 0.05). Comparison with the femoral approach in the same laboratory suggested that the radial approach took longer, but provided similarly high-quality results without great difficulty in coronary cannulation. Hence, the left radial approach for coronary angiography (with heparin administration) allows immediate ambulation and may be especially useful for outpatients and when the femoral approach is not possible. © 1996 Wiley-Liss, Inc.     

Idiopathic acute eosinophilic pneumonia: A rare cause of hypoxic respiratory failure

Idiopathic Acute Eosinophilic Pneumonia (IAEP) is a life-threatening cause of hypoxic respiratory failure. IAEP is challenging to diagnose as it may mimic infectious pneumonia or acute respiratory distress syndrome. Distinguishing IAEP from these alternatives is important; the mainstay of treatment for IAEP is corticosteroids, a therapy which might not otherwise be indicated. Patients treated appropriately usually experience a full recovery. In this case report we describe the presentation, evaluation, and management of a 19-year old male who presented to the emergency department (ED) in respiratory failure from IAEP. The patient was a military trainee who recently moved to the United States from Saudi Arabia. He also recently began smoking cigarettes for the first time, a known risk factor for IAEP. Upon initial presentation, the patient was in respiratory distress and had an oxygen saturation of 82% on room air. His ED diagnostic workup included chest X-ray showing diffuse interstitial thickening and chest computed tomography that demonstrated diffuse nodular opacification of pulmonary parenchyma. The patient was admitted to the intensive care unit (ICU) where bronchoscopy yielded cytology with 30% eosinophilia. The patient ultimately required 3 days of extra corporeal membrane oxygenation (ECMO) due to worsening hypoxic respiratory failure. After both intravenous and outpatient oral steroid treatments, the patient went on to have a full recovery with no ongoing respiratory issues. To our knowledge, this is the first case of IAEP requiring ECMO reported in the emergency medicine literature.