2 Minute Medicine Rewind August 5, 2019

Hospital volume and outcomes for acute pulmonary embolism: multinational population-based cohort study

Patients with pulmonary embolism (PE) can present with a myriad of symptoms, and without prompt recognition and treatment, are at risk of developing life-threatening complications. The authors of this multinational population-based cohort study (n=39,257) aimed to evaluate whether an association exists between experience in the management of acute PE, based on hospital case volume, and mortality. Confirmatory testing for PE consisted of high probability ventilation-perfusion scintigraphy, positive computed tomography (CT) pulmonary angiography, or venous compression ultrasonography of the lower limb positive for proximal deep vein thrombosis (DVT) in patients presenting with chest symptoms. In comparing patients that were admitted to higher versus lower volume hospitals with acute PE, patients differed with respect to pre-existing medical conditions, physiological and laboratory measures. Patients admitted to higher volume centers were typically older and with more comorbid conditions. These patients also exhibited increased signs of clinical severity based on the simplified Pulmonary Embolism Severity Index (sPESI), tachycardia, hypoxemia and hypotension. Researchers found that patients admitted to hospitals in the highest quarter (>40 PEs per year) had a decreased odds of PE-related mortality at 30 days when compared to hospitals in the lowest volume quarter (<15 PEs per year) (OR 0.56, 95% CI 0.33 to 0.95, p=0.03). All-cause mortality at 30 days of follow-up, however, did not significantly differ (OR 0.78, 95% CI 0.50 to 1.22). There was also no significant difference in the odds of recurrent venous thromboembolism or major bleeding. This study therefore shows that in patients with acute PE, admission to a high volume center is associated with significant reductions in PE-related mortality at 30 days. The findings of this study may have important implications for the triage and transfer of high-risk patient subgroups.

Association with hospitalization and all-cause discontinuation among patients with schizophrenia on clozapine vs. other oral second-generation antipsychotics: a systematic review and meta-analysis of cohort studies

Patients with schizophrenia that do not respond to 2 or more antipsychotics are considered to have treatment-resistant disease. In these settings, clozapine, an atypical antipsychotic, is typically used. However, a number of randomized clinical trials comparing clozapine with other non-clozapine second generation antipsychotics (NC-SGAs), have recently put into question the superior effectiveness of clozapine in the management of treatment-resistant schizophrenia (TRS). In this systematic review and meta-analysis of cohort studies, researchers compared rates of hospitalization and all-cause discontinuation of clozapine versus oral NC-SGAs in patients with schizophrenia or schizoaffective disorder. On the basis of 63 individual cohort studies (n=109,341), researchers found that compared to NC-SGAs, clozapine was associated with significantly lower hospitalization risk (n=49,453, RR 0.817, 95% CI 0.725 to 0.920, p=0.001) and all-cause discontinuation (RR 0.732, 95% CI 0.639 to 0.838, p<0.001). Clozapine was also associated with better outcomes with respect to overall symptoms and Clinical Global Impressions scale severity (p =0.03). Of note, however, clozapine was significantly associated with increases in body weight (p=0.02), body mass index (p= 0.009), and type 2 diabetes (p=0.002). This study therefore shows that while clozapine is associated with a greater risk of cardiometabolic effects, it is associated with improved key efficacy outcomes when compared to NC-SGAs.

Association of hearing loss with dementia

With an increasing prevalence of dementia in the elderly population and treatment strategies limited to improving symptoms, there is a need to identify at-risk patients. Hearing loss (HL) has been identified as a risk factor for dementia, contributing to social isolation, depression and lower quality of life. In this population-based cohort study (n=16,270), researchers used data from the National Health Insurance Research Database of Taiwan to investigate the association between HL and incident dementia. Patients with newly diagnosed HL constituted the exposed group. Researchers found that the incidence rate of dementia was significantly greater in the HL group (19.38 per 1000 person-years, 95% CI 18.25 to 20.57) when compared to the non-HL group (13.98 per 1000 person-years, 95% CI 13.01 to 15.00). Based on an adjusted Cox proportional hazards regression, researchers also found that patients had a significant risk of incident dementia (HR 1.17, 95% CI 1.07 to 1.29). The findings of this study support prior evidence that HL is positively associated with a risk of dementia. This has important implications in modifying the risk of dementia in the elderly by way of hearing protection, screening and treatment of incident HL.

Ursodeoxycholic acid versus placebo in women with intrahepatic cholestasis of pregnancy (PITCHES): a randomised controlled trial

Studies have shown that intrahepatic cholestasis of pregnancy is associated with poor birth outcomes and neonatal unit admission. Ursodeoxycholic acid, which increases bile acid excretion, forms the mainstay of treatment, however, the evidence for its use is limited. In this double-blind, multicentre, randomized controlled trial, 605 women with intrahepatic cholestasis of pregnancy were randomized to receive ursodeoxycholic acid or placebo to evaluate whether ursodeoxycholic acid reduces adverse perinatal outcomes in this patient population. The primary outcome was a composite of perinatal death (in-utero fetal death after randomization or death up to 7 days after birth), preterm delivery, or neonatal unit admission for at least 4 hours after birth up to hospital discharge. Researchers found that the primary outcome occurred in 23% of infants in the intervention group as compared to 27% in the placebo group (RR 0.85, 95% CI 0.62 to 1.15). This study therefore shows that treatment with ursodeoxycholic acid does not reduce adverse perinatal outcomes in the setting of cholestasis of pregnancy. While some subgroups of women may respond to ursodeoxycholic acid, the lack definitive evidence regarding its efficacy should preclude its routine clinical use.

Oral antihypertensive regimens (nifedipine retard, labetalol, and methyldopa) for management of severe hypertension in pregnancy: an open-label, randomised controlled trial

Hypertension commonly affects women in pregnancy, and is associated with adverse effects for both mother and baby. Currently, there is a lack of consensus on the relative efficacy and safety of oral medications used in treating severe hypertension in pregnancy, defined as systolic blood pressure of at least 160 mm Hg or diastolic blood pressure of at least 110 mm Hg. In this multicentre randomized controlled trial, 894 women were randomized to receive one of three oral antihypertensives (labetalol, nifedipine retard, methyldopa) to compare the efficacy and safety of these oral agents in the management of severe hypertension in pregnancy. The primary outcome was blood pressure control, defined as 120-150 mm Hg systolic blood pressure and 70-100 mm Hg diastolic blood pressure, within 6 hours with no adverse outcomes. Researchers found that the primary outcome occurred more often in the nifedipine group (84%) compared to the methyldopa group (76%) (p=0.03). The proportion of women achieving the primary outcome in the nifedipine and labetalol groups, however, was comparable (p=0.05). The labetalol and methyldopa groups were also similar in this regard (p=0.80). The findings of this study therefore support the use of oral nifedipine as a single agent in the management of severe hypertension in pregnancy, though all of the studied oral antihypertensives demonstrate efficacy in this patient population.

Image: PD

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