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Background: When second-generation antipsychotics (SGAs), also called atypical antipsychotics, were introduced in the 1990s, early research suggested that these drugs offered better tolerability and adherence than first-generation antipsychotics (FGAs), or typical antipsychotics. This presumably would reduce the need for hospital services. However, health research to test this hypothesis has focused mostly on psychiatric readmissions. Objective: The objective of this study was to compare rates of all-cause hospitalization among patients receiving different classes of antipsychotics (SGAs, FGAs, both, or neither) in a large, all-ages sample of both institutionalized and noninstitutionalized Medicare beneficiaries. Methods: We examined the 2005 Medicare Current Beneficiary Survey Cost and Use file for 11,236 survey participants. Antipsychotic utilization was characterized in terms of class: FGA (ie, chlorpromazine, fluphenazine, haloperidol, loxapine, perphenazine, thiothixene, thioridazine, or trifluoperazine) or SGA (ie, aripiprazole, clozapine, olanzapine, quetiapine, risperidone, or ziprasidone). Hospitalization was defined in terms of whether a Medicare beneficiary was admitted to the hospital for any reason in 2005, and was measured in terms of the number of hospital visits. In our final model, we included the following confounding variables: disability status (greater than or equal to 1 limitation in activities of daily living), Rosow-Breslau impairment score (difficulty with walking, stooping, crouching, kneeling, or doing heavy housework), cognitive impairment (diagnosis of Alzheimer's disease or memory loss that interfered with daily activity), and health behavior variables (body mass index and smoking status). Results: A total of 3.5% of Medicare beneficiaries (1.3 million) filled greater than or equal to 1 prescription for an antipsychotic medication in 2005. Controlling for demographic, socioeconomic, health, and disability variables, SGA-only users were more than twice as likely (odds ratio [OR] = 2.2 [95% CI, 1.7DS2.9]) and combination users were more than 6 times as likely (OR = 6.3 [95% CI, 2.4-16.2]) as nonusers to be hospitalized. The odds of FGA users being hospitalized were not significantly different from nonusers (OR = 1.4 [95% CI, 0.7-2.8]). Conclusions: This analysis yielded provocative, but by no means conclusive, evidence that SGAs as a class are not necessarily superior to FGAs in mitigating patient's use of hospital services under real-world conditions. Systematic analysis of this relationship with a large, multiple-year sample of Medicare beneficiaries is warranted. [ABSTRACT FROM AUTHOR]

One of the greatest achievements of the last century is the development of vaccines against viral diseases. Vaccines are essential for battling infectious diseases and many different formulations are available, including live attenuated vaccines. However, the use of live attenuated vaccines has the potential for adverse effects, including reversion of pathogenicity, recombination, and functional complementation in the host. Marek's disease is a serious disease in poultry controlled by live attenuated vaccines that has resulted in increased virulence over the decades. Recombination between circulating field viruses or vaccines is a proposed mechanism for the increase in virulence, however, complementation between vaccines and field strains has not been demonstrated in chickens. Here, we describe functional complementation of vaccines with virulent virus to functionally complement transmission and spread in the host. Using the natural virus-host model of Marek's disease in chickens, our results show dual infection of target cells in chickens with vaccine and virulent virus providing the opportunity for recombination or complementation to transpire. Interestingly, our controlled results showed no evidence of recombination between vaccine and virulent virus, but functional complementation occurred in two independent experiments providing proof for complementation during natural infection in vaccinated individuals. These results suggest complementation as a potential mechanism for vaccine-mediated viral evolution and the potential for complementation should be taken into consideration when developing novel vaccines.

Purpose: Hyperuricemia is associated with increased cardiovascular risk. Because patients with asymptomatic hyperuricemia (AH) experience no immediate discomfort and there are possible side effects of urate-lowering drugs, treatment for AH is controversial. We aimed to perform a network meta-analysis (NMA) to investigate the effects of different urate-lowering therapies (ULTs) on serum uric acid level, renal function, blood pressure (BP), and safety in AH patients., Methods: This NMA focused on AH patients. The intervention group (patients receiving urate-lowering drugs) was compared with others using other types of drugs, placebo, or usual care. We undertook a NMA under the frequentist framework by R., Results: Thirteen eligible trials were identified. The interventions included allopurinol, febuxostat, and benzbromarone, which are not approved in the United States. Benzbromarone and allopurinol had the best efficacy on lowering serum uric acid level in short-term and long-term follow-up (mean difference [MD] = -3.05; 95% CI, -5.19 to -0.91 vs MD = -3.17; 95% CI, -5.19 to -1.15). Patients using allopurinol had significantly higher eGFR than using placebo in both short-term and long-term follow-up (MD = 3.07; 95% CI, 0.18 to 5.95 vs MD = 4.10; 95% CI, 2.66 to 5.54). No difference in BP was found between groups, except for febuxostat to diastolic BP after long-term treatment (MD = -1.47; 95% CI, -2.91 to -0.04). No statistically increased odds of safety events were found with the use of ULT., Conclusions: Our result showed that in AH patients, allopurinol has a renoprotective effect. Febuxostat has a significant impact in lowering diastolic BP. ULT does not result in a higher risk of safety events., Competing Interests: Conflict of interest: None., (© Copyright 2022 by the American Board of Family Medicine.)

Background: Patients with coronary artery disease (CAD) are at high risk of atherosclerotic events. The aim of this meta-analysis is to evaluate the cardiovascular protective effect of colchicine on patients with CAD., Methods: In this systematic review and meta-analysis, we searched PubMed and Embase for studies published until April 28, 2020. We included studies that reported the incidence of myocardial infarction (MI), restenosis after percutaneous coronary intervention (PCI), and mortality for CAD patients within colchicine and control (placebo or usual care) groups. A random-effects meta-analysis model was then applied., Results: Ten eligible trials were identified, including 6398 patients (3248 received colchicine while 3150 were controls). The risk of composite events of MI and restenosis after PCI was significantly decreased with colchicine treatment [odds ratio (OR) 0.48, 95% confidence interval (CI) 0.28-0.79]. We found a similar trend of lowered risk of MI in the colchicine group, although without statistical significance (OR 0.41, 95% CI 0.16-1.08). The risk of restenosis after PCI also decreased significantly with colchicine treatment (OR 0.46, 95% CI 0.23-0.92). There was no significant difference in all-cause mortality between the two groups (OR 0.80, 95% CI 0.56-1.15). The included patients had significantly higher risks of gastrointestinal (GI) events with colchicine treatment., Conclusions: This meta-analysis shows that there is a decreased composite risk of MI and restenosis after PCI with the use of colchicine in patients with CAD. However, colchicine did not appear beneficial for all-cause mortality, and it led to a higher risk of GI events., (Copyright © 2020. Published by Elsevier Ltd.)

Background: Increasingly, women are undergoing contralateral prophylactic mastectomy for the treatment of unilateral breast cancer. The relationship between contralateral prophylactic mastectomy and breast reconstruction, postsurgical complications, additional breast-related procedures, and cost has not received the attention it deserves., Methods: Data from the New York comprehensive, all-age, all-payer, Statewide Planning and Research Cooperative System were queried to identify patients undergoing unilateral mastectomy or contralateral prophylactic mastectomy from 2008 to 2010. We identified the complications and breast-related procedures within a 2-y follow-up period. Costs of the index operation and subsequent follow-up were estimated. Univariate and multivariate analyses were conducted., Results: Of 12,959 women identified, 10.7% underwent contralateral prophylactic mastectomy. On univariate analysis, contralateral prophylactic mastectomy was positively associated with breast reconstruction, complications, and additional breast-related procedures. Rates of complications were greater for women who had contralateral prophylactic mastectomy (29.5% vs 20.8% for unilateral mastectomy group; P < .001), but not after stratifying by breast reconstruction. Additional breast-related procedures were more common in the contralateral prophylactic mastectomy group than in the unilateral mastectomy group, but only for those who underwent breast reconstruction (82.8% vs 72.1%; P < .001). Unadjusted costs were greater for women with contralateral prophylactic mastectomy than with unilateral mastectomy but did not differ between the groups after adjusting for breast reconstruction and additional breast-related procedures., Conclusion: Women who elected contralateral prophylactic mastectomy in this population-based study were more likely to have both breast reconstruction and additional breast-related procedures than women with unilateral mastectomy. The greater rates of complications and costs associated with contralateral prophylactic mastectomy were explained by breast reconstruction and additional breast-related procedures. Surgeons should counsel patients regarding the increased cost and likelihood of undergoing additional, non-complication-related procedures after contralateral prophylactic mastectomy with breast reconstruction., (Copyright © 2020 Elsevier Inc. All rights reserved.)

Background: The optimal surgery for resectable pulmonary typical carcinoid (TC), e.g., lobar resection (L-R) vs. sub-lobar resection (SL-R), is controversial. This is further explored in this population-based study., Methods: The Surveillance, Epidemiology, and End Results (SEER) Program was used to select patients ≥66 years old, and diagnosed between 2000 and 2012 with pulmonary TC. A similar cohort was developed using the SEER-Medicare database (diagnosed from 2000-2007) to identify chemotherapy (CTX) use and co-morbidity. Five-year survival was calculated using univariate and multivariate analysis., Results: A total of 1,506 and 512 patients were identified from SEER and SEER-Medicare, respectively. In the SEER cohort, 49%, 29% and 21% received L-R, SL-R, and no surgery (NS), respectively. Those who received NS were older (P<0.001), had a higher stage (P<0.001), greater comorbidity (P<0.001), and were more likely to receive radiotherapy (XRT) (P<0.001) and CTX (P<0.001). Relative survival was nearly 100% for those who received L-R or SL-R as opposed to 72% for those who received NS (P<0.001). Cox models showed no survival difference for L-R vs. SL-R (HR 1.1, P=0.663), but worse survival for those who received NS vs. L-R or SL-R (HR 3.6, P<0.001). XRT in NS cohort was associated with increased risk of death (HR 2.3, P=0.017)., Conclusions: SL-R was better than NS, and similar to L-R in terms of survival. SL-R should be considered over NS if L-R is unfeasible. Role of adjuvant CTX and XRT is unclear as these did not improve survival in this study., Competing Interests: Conflicts of Interest: The authors have no conflicts of interest to declare.

Prescription drug abuse is a growing problem nationally. In an effort to curb this problem, emergency physicians might rely on subjective cues such as race-ethnicity, often unknowingly, when prescribing opioids for pain-related complaints, especially for conditions that are often associated with drug-seeking behavior. Previous studies that examined racial-ethnic disparities in opioid dispensing at emergency departments (EDs) did not differentiate between prescriptions at discharge and drug administration in the ED. We examined racial-ethnic disparities in opioid prescription at ED visits for pain-related complaints often associated with drug-seeking behavior and contrasted them with conditions objectively associated with pain. We hypothesized a priori that racial-ethnic disparities will be present among opioid prescriptions for conditions associated with non-medical use, but not for objective pain-related conditions. Using data from the National Hospital Ambulatory Medical Care Survey for 5 years (2007-2011), the odds of opioid prescription during ED visits made by non-elderly adults aged 18-65 for 'non-definitive' conditions (toothache, back pain and abdominal pain) or 'definitive' conditions (long-bone fracture and kidney stones) were modeled. Opioid prescription at discharge and opioid administration at the ED were the primary outcomes. We found significant racial-ethnic disparities, with non-Hispanic Blacks being less likely (adjusted odds ratio ranging from 0.56-0.67, p-value < 0.05) to receive opioid prescription at discharge during ED visits for back pain and abdominal pain, but not for toothache, fractures and kidney stones, compared to non-Hispanic whites after adjusting for other covariates. Differential prescription of opioids by race-ethnicity could lead to widening of existing disparities in health, and may have implications for disproportionate burden of opioid abuse among whites. The findings have important implications for medical provider education to include sensitization exercises towards their inherent biases, to enable them to consciously avoid these biases from defining their practice behavior.

Background: An aging population, with its associated rise in cancer incidence and strain on the oncology workforce, will continue to motivate patients, healthcare providers and policy makers to better understand the existing and growing challenges of access to chemotherapy. Administrative data, and SEER-Medicare data in particular, have been used to assess patterns of healthcare utilization because of its rich information regarding patients, their treatments, and their providers. To create measures of geographic access to chemotherapy, patients and oncologists must first be identified. Others have noted that identifying chemotherapy providers from Medicare claims is not always straightforward, as providers may report multiple or incorrect specialties and/or practice in multiple locations. Although previous studies have found that specialty codes alone fail to identify all oncologists, none have assessed whether various methods of identifying chemotherapy providers and their locations affect estimates of geographic access to care., Methods: SEER-Medicare data was used to identify patients, physicians, and chemotherapy use in this population-based observational study. We compared two measures of geographic access to chemotherapy, local area density and distance to nearest provider, across two definitions of chemotherapy provider (identified by specialty codes or billing codes) and two definitions of chemotherapy service location (where chemotherapy services were proven to be or possibly available) using descriptive statistics. Access measures were mapped for three representative registries., Results: In our sample, 57.2 % of physicians who submitted chemotherapy claims reported a specialty of hematology/oncology or medical oncology. These physicians were associated with 91.0 % of the chemotherapy claims. When providers were identified through billing codes instead of specialty codes, an additional 50.0 % of beneficiaries (from 23.8 % to 35.7 %) resided in the same ZIP code as a chemotherapy provider. Beneficiaries were also 1.3 times closer to a provider, in terms of driving time. Our access measures did not differ significantly across definitions of service location., Conclusions: Measures of geographic access to care were sensitive to definitions of chemotherapy providers; far more providers were identified through billing codes than specialty codes. They were not sensitive to definitions of service locations, as providers, regardless of how they are identified, generally provided chemotherapy at each of their practice locations.

Objectives: The purpose of this study was to assess to what extent geographic variation in adjuvant treatment for non-small cell lung cancer (NSCLC) patients would remain, after controlling for patient and area-level characteristics., Materials and Methods: A retrospective cohort of 18,410 Medicare beneficiaries with resected, stage I-IIIA NSCLC was identified from the Surveillance, Epidemiology, and End Results (SEER)-Medicare linked database. Adjuvant therapies were classified as adjuvant chemotherapy (ACT), postoperative radiation therapy (PORT), or no adjuvant therapy. Predicted treatment probabilities were estimated for each patient given their clinical, demographic, and area-level characteristics with multivariate logistic regression. Area Treatment Ratios were used to estimate the propensity of patients in a local area to receive an adjuvant treatment, controlling for characteristics of patients in the area. Areas were categorized as low-, mid- and high-use and mapped for two representative SEER registries., Results: Overall, 10%, 12%, and 78% of patients received ACT, PORT and no adjuvant therapy, respectively. Age, sex, stage, type and year of surgery, and comorbidity were associated with adjuvant treatment use. Even after adjusting for patient characteristics, substantial geographic treatment variation remained. High- and low-use areas were tightly juxtaposed within and across SEER registries, often within the same county. In some local areas, patients were up to eight times more likely to receive adjuvant therapy than expected, given their characteristics. On the other hand, almost a quarter of patients lived in local areas in which patients were more than three times less likely to receive ACT than would be predicted., Conclusion: Controlling for patient and area-level covariates did not remove geographic variation in adjuvant therapies for resected NSCLC patients. A greater proportion of patients were treated less than expected, rather than more than expected. Further research is needed to better understand its causes and potential impact on outcomes., (Copyright © 2016 Elsevier Ireland Ltd. All rights reserved.)

Anthracycline-containing regimens (ACRs) are recommended for patients with diffuse large B-cell lymphoma (DLBCL). However, over 40% of elderly patients do not receive ACRs, possibly due to expected toxicities. We characterized treatment choices and compared the 3-year overall survival (OS) rates of 8262 Medicare beneficiaries diagnosed with DLBCL in 2000-2006 identified from the Surveillance, Epidemiology, and End Results (SEER)-Medicare linked database. Of the cohort, 45% had ACR with rituximab (ACR-R), 13% had ACR without R, 6% had non-ACR with R (non-ACR-R), 4% had R monotherapy, 3% had non-ACR and 29% had no systemic therapy. Patients not receiving ACR were older and/or had more comorbidities. The unadjusted OS was highest in ACR-R (65%), followed by ACR without R (55%) and non-ACR-R (44%). After adjusting patient covariates, ACR-R showed the best survival (63%). However, OS was comparable between non-ACR-R (52%) and ACR without R (52%). Non-ACR-R could be considered for patients who are poor candidates for ACR.

We evaluated 11 variable number tandem repeat (VNTR) markers for the epidemiological investigation of Salmonella enterica serovar Typhi (S. Typhi) infection and compared the results to those obtained by PFGE. PFGE, using one or two restriction enzymes (XbaI and BlnI), was insufficient to differentiate between some isolates that were epidemiologically unlinked. Multilocus variable-number tandem repeat analysis (MLVA)-8, based on analysis of the eight most variable VNTRs, displayed a high level of discrimination when distinguishing between epidemiologically unlinked isolates that could not be discerned by PFGE with two enzymes. An MLVA-8 typing scheme could be implemented as a routine subtyping tool for the epidemiological investigation of S. Typhi infections. Because seven of the 11 VNTRs are highly variable, the VNTR markers may only be useful in determining genetic relationships among very closely related isolates in short-term epidemiological studies and not for discerning S. Typhi clones.

Salmonella enterica serotype Paratyphi A is a highly clonal organism; pulsed-field gel electrophoresis (PFGE) is insufficient in discriminating isolates. A multilocus variable-number tandem repeat analysis (MLVA) was developed, and its usefulness in discriminating isolates was compared. PFGE analysis with XbaI and BlnI discriminated 55 isolates into 14 types, with a discriminatory index (DI) of 0.741 (confidence interval [CI], 0.635-0.847). MLVA divided the isolates into 23 types, with a DI of 0.937 (CI, 0.909-0.964), which was significantly higher than that for PFGE. Clustering analysis of PFGE and MLVA patterns indicated that S. Paratyphi A isolates recovered from 2000 to 2010 in South and Southeast Asia were highly clonal. Although MLVA is not sufficiently powerful in discriminating epidemiologically unrelated isolates, it can complement PFGE for epidemiologic investigation of S. Paratyphi A infections., (Copyright © 2011 Elsevier Inc. All rights reserved.)