Effect of pregabalin initiation on diuretic requirements in patients with chronic heart failure.

BACKGROUND: Literature on pregabalin use in patients with heart failure is largely limited to patient case reports and cohort studies. OBJECTIVE: This study aimed to evaluate the effect of pregabalin initiation on diuretic requirements in patients with heart failure. METHODS: A retrospective analysis of patients with heart failure who were started on pregabalin between January 1, 2014, and September 1, 2021, at the Veterans Affairs North Texas Health Care System was used. The primary objective was to determine the median change in loop diuretic dose, in furosemide dose equivalents, 6 months after pregabalin initiation. RESULTS: Of 58 patients analyzed, there was no statistically significant difference in the primary outcome (P = 0.162). The secondary outcomes were found to be nonstatistically significant, and there was no correlation between pregabalin dose and outcomes. CONCLUSION: This represents the largest analysis of diuretic dose requirements in patients with heart failure after initiation of pregabalin. Although there was no difference in the median change of diuretic dose prescribed, pregabalin should still be used with caution.

Metformin Use Is Associated With Lower Mortality in Veterans With Diabetes Hospitalized With Pneumonia.

BACKGROUND: Recent studies suggest that metformin use may be associated with improved infectious disease-related outcomes, whereas other papers suggest potentially worse outcomes in serious bacterial infections. Our purpose was to examine the association of prior outpatient prescription of metformin on 30- and 90-day mortality for older veterans with pre-existing diabetes hospitalized with pneumonia. METHODS: We conducted a retrospective cohort study using national Department of Veterans Affairs data of patients ≥65 years with a prior history of diabetes who were hospitalized with pneumonia over a 10-year period (fiscal years 2002-2012.) For our primary analysis, we created a propensity score and matched metformin users to nonusers 1:1. RESULTS: We identified 34 759 patients who met the inclusion criteria, 20.3% of whom were prescribed metformin. Unadjusted 30-day mortality was 9.6% for those who received metformin versus 13.9% in nonusers (P < .003), and 90-day mortality was 15.8% for those who received metformin versus 23.0% for nonusers (P < .0001). For the propensity score model, we matched 6899 metformin users to 6899 nonusers. After propensity matching, both 30-day (relative risk [RR]: .86; 95% confidence interval [CI]: .78-.95) and 90-day (RR: .85; 95% CI: .79-.92) mortality was significantly lower for metformin users. CONCLUSIONS: Prior receipt of metformin was associated with significantly lower mortality after adjusting for potential confounders. Additional research is needed to examine the safety and potential benefits of metformin use in patients with respiratory infections.

Association of medical tests use with care continuity in primary care service: evidence from the Department of Veterans Affairs.

BACKGROUND: Continuity of care (CoC) is an important component of health care delivery that can have cost implications and improve patient outcomes. We analysed data obtained from the Department of Veterans Affairs to examine the relationship between CoC and use of image-oriented diagnostic tests in patients with comorbid chronic conditions. METHODS: A longitudinal, retrospective cohort study involving participants ≥18 years old, with comorbid diabetes and chronic kidney disease. We used a multivariate linear regression model to test whether greater care continuity, measured using a care continuity index (CCI), is associated with less frequent use of diagnostic tests. RESULTS: Total of 267,442 patients and 8,142,036 tests were included. Of the diagnostic tests we chose to evaluate, the 4 most frequently ordered tests were X-ray (45.6%), electrocardiogram (EKG, 16.8%), computerized tomography (CT, 13.4%), and magnetic resonance imaging (MRI, 3.4%). Overall, greater CCI was associated with fewer use of tests (P < 0.001). A 1 standard deviation (SD, 0.27) increase in CCI was associated with 4.2% decrease (P < 0.001) in number of tests. But a mixed pattern existed. For X-ray and EKG, greater continuity was associated with less testing, 6.2% (P < 0.001) and 3.3% (P < 0.05) reductions, respectively. Whereas, for CT and MRI, greater continuity was associated with more testing, 2.3% (P < 0.001) and 1.4% increases (P < 0.01), respectively. CONCLUSION: Overall, greater CoC was associated with fewer use of tests, representing a greater presumed efficiency of care. This has implications for designing health care delivery.

Effectiveness of Beta-Lactam plus Doxycycline for Patients Hospitalized with Community-Acquired Pneumonia.

BACKGROUND: Despite clinical practice guideline recommendations to use doxycycline as part of combination therapy for some patients hospitalized with pneumonia, there is minimal evidence supporting this recommendation. Our aim was to examine the association between beta-lactam plus doxycycline and mortality for patients hospitalized with community-acquired pneumonia. METHODS: We identified patients >65 years of age admitted to any US Department of Veterans Affairs hospital in fiscal years 2002-2012 with a discharge diagnosis of pneumonia. We excluded those patients who did not receive antibiotic therapy concordant with the 2019 American Thoracic Society/Infectious Diseases Society of America (ATS/IDSA) clinical practice guidelines. Using propensity score matching, we examined the association of doxycycline with 30- and 90-day mortality. RESULTS: Our overall cohort was comprised of 70533 patients and 5282 (7.49%) received doxycycline. Unadjusted 30-day mortality was 6.4% for those who received a beta-lactam plus doxycycline versus 9.1% in those who did not (P < .0001), and 90-day mortality was 13.8% for those who received a beta-lactam + doxycycline versus 16.8% for those who did not (P < .0001). In the propensity score matched models, both 30- (odds ratio 0.72, 95% confidence interval [CI], .63-.84) and 90-day (0.83, 95% CI, .74-.92) mortality were significantly lower for those who received doxycycline. CONCLUSIONS: In this retrospective observational cohort study, we found that doxycycline use, as part of guideline-concordant antibiotic therapy, was associated with lower 30- and 90-day mortality than regimens without doxycycline. While this supports the safety and effectiveness of antibiotic regimes that include doxycycline, additional studies, especially randomized clinical trials, are needed to confirm this.

Soybean protein concentrate as a protein source for totoaba (Totoaba macdonaldi) juveniles: Effect on intermediary metabolism and liver histological organization.

This study aimed to investigate the effects of replacing fish meal (FM) with soybean protein concentrates (SPC) on the intermediary metabolism and health of Totoaba macdonaldi juveniles. Fish (initial weight 50 ± 1 g) were fed for 60 days with eight diets: a reference diet (RD) and seven experimental diets where FM was replaced gradually with 15 to 100% SPC (SPC15, SPC30, SPC45, SPC60, SPC75, SPC90, and SPC100, respectively). Hexokinase (HK), glucokinase (GK), and alanine aminotransferase (ALT) enzyme activities showed highly significant differences (p < 0.01) between fish fed RD (0% SPC) compared to fish fed the diets with 60, 75, 90, and 100% SPC. The ALT enzyme shows a highly significant (p < 0.01) decrease in activity for fish fed 75, 90, and 100% SPC inclusions compared to fish fed the RD. The aspartate aminotransferase AST/ALT ratio showed a significant increase in activity for fish fed 100% soybean compared only with fish fed the control diet. The histological organization of the liver in totoaba juveniles fed RD, SPC15, SPC30 and SPC45 diets were similar. Totoaba fed with SPC90 and SPC100 showed histological alterations in hepatic and pancreatic parenchyma. Overall, according to the findings in this study, 45% of dietary FM could be replaced by SPC without causing adverse changes in metabolism, histological organization of liver, and health of juveniles of totoaba when cultured for 60 days. However, levels greater than 60% of SPC could compromise the health status of fish.

Rates of appropriate laxative prophylaxis for opioid-induced constipation in veterans with lung cancer: a retrospective cohort study.

PURPOSE: Opioid-induced constipation (OIC) is the most common side effect in patient-prescribed opioids for cancer pain treatment. Current guidelines recommend routine prescription of a laxative for preventing OIC in all patients prescribed an opioid unless a contraindication exists. We determined patterns of prescription of laxative agents in patients with lung cancer initiating opioids. METHODS: We performed a retrospective cohort study evaluating the prescription of laxatives for OIC to adult patients with incident lung cancer seen in the Veteran's Affairs (VA) system, between January 1, 2003, and December 31, 2016. Exposure to laxative agents was categorized as follows: none, docusate monotherapy, docusate plus another laxative, and other laxatives only. Prevalence of OIC prophylaxis was analyzed using descriptive statistics. Linear regression was performed to identify time trends in the prescription of OIC prophylaxis. RESULTS: Overall, 130,990 individuals were included in the analysis. Of these, 87% of patients received inadequate prophylaxis (75% no prophylaxis and 12% docusate alone), while 5% received OIC prophylaxis with the unnecessary addition of docusate to another laxative. Through the study period, laxative prescription significantly decreased, while all other categories of OIC prophylaxis were unchanged. We noted an inverse relationship with OIC prophylaxis and likelihood of a diagnosis of constipation at 3 and 6 months. CONCLUSIONS: In this study of veterans with lung cancer, almost 90% received inadequate or inappropriate OIC prophylaxis. Efforts to educate physicians and patients to promote appropriate OIC prophylaxis in combination with systems-level changes are warranted.

Statins in survivors of traumatic brain injury: a propensity score-matched analysis.

BACKGROUND: Several in-vitro and animal studies suggest that statins may have beneficial effects on clinical outcomes of traumatic brain injury (TBI), however, clinical data are scarce. OBJECTIVES: To examine the association of statin use with TBI clinical outcomes among patients with TBI. METHODS: A retrospective cohort study of Tricare beneficiaries who had a TBI diagnosis, as defined by the Barbell injury diagnosis matrix. Outcomes were defined using ICD-9 codes and included: post-concussion syndrome, neurological disorders, substance dependence or abuse, and psychiatric disorders. Statin-users and non-users were propensity score (PS)-matched using 103 baseline characteristics. RESULTS: Out of 1187 adult patients with a TBI diagnosis (172 statin-users and 1015 nonusers), we PS-matched 70 statin-users to 70 non-users. There were no statistically significant differences in the PS-matched cohort of statin-users in comparison to nonusers for post-concussion syndrome (odds ratio [OR]: 0.24, 95% confidence interval [CI]: 0.03-2.20), neurological disorders (OR: 0.60, CI: 0.31-1.16); substance dependence or abuse (OR: 0.80, CI: 0.40-1.60), or psychiatric disorders (OR 0.80, CI: 0.41-1.55). CONCLUSION: This study did not show benefit or harm for statins among survivors of TBI. Our findings do not support the evidence from some animal studies and small randomized controlled trials. Further studies utilizing larger sample sizes are warranted.

The Transcription Factor SCX is a Potential Serum Biomarker of Fibrotic Diseases.

Fibrosing diseases are causes of morbidity and mortality around the world, and they are characterized by excessive extracellular matrix (ECM) accumulation. The bHLH transcription factor scleraxis (SCX) regulates the synthesis of ECM proteins in heart fibrosis. SCX expression was evaluated in lung fibroblasts and tissue derived from fibrotic disease patients and healthy controls. We also measured SCX in sera from 57 healthy controls, and 56 Idiopathic Pulmonary Fibrosis (IPF), 40 Hypersensitivity Pneumonitis (HP), and 100 Systemic Sclerosis (SSc) patients. We report high SCX expression in fibroblasts and tissue from IPF patients versus controls. High SCX-serum levels were observed in IPF (0.663 ± 0.559 ng/mL, p < 0.01) and SSc (0.611 ± 0.296 ng/mL, p < 0.001), versus controls (0.351 ± 0.207 ng/mL) and HP (0.323 ± 0.323 ng/mL). Serum levels of the SCX heterodimerization partner, TCF3, did not associate with fibrotic illness. IPF patients with severely affected respiratory capacities and late-stage SSc patients presenting anti-topoisomerase I antibodies and interstitial lung disease showed the highest SCX-serum levels. SCX gain-of-function induced the expression of alpha-smooth muscle actin (α-SMA/ACTA2) in fibroblasts when co-overexpressed with TCF3. As late and severe stages of the fibrotic processes correlated with high circulating SCX, we postulate it as a candidate biomarker of fibrosis and a potential therapeutic target.

α-enolase is an antigenic target in primary Sjögren's syndrome.

OBJECTIVES: Although anti-cyclic citrullinated peptides antibodies are specific markers for rheumatoid arthritis (RA), they might be present in other diseases. Our aim was to assess the native or citrullinated antigens recognised by patients with primary Sjögren's syndrome (pSS) and to evaluate their association with clinical and serological features. METHODS: In an initial screening, we assessed the serum reactivity of 12 patients with pSS against native or in vitro citrullinated antigens of HEp-2 cells by immunoblotting. We identified a 47kDa band, which was preferentially recognised and corresponded to α-enolase. Thus, levels of IgA and IgG anti-native and citrullinated α-enolase antibodies were measured in 50 pSS patients, 20 RA patients and 20 healthy subjects (HS) by ELISA. RESULTS: We identified α-enolase as a predominant antigen recognised in pSS. These patients had higher levels of anti-citrullinated α-enolase IgG antibodies compared with RA or HS (p=0.003 and p<0.0001, respectively). Furthermore, there was an increase of IgG anti-citrullinated α-enolase vs IgG anti-non-citrullinated α-enolase antibodies in pSS patients (p=0.001), by contrast no difference was found in RA. The presence of IgA and IgG anti-non-citrullinated and anti-citrullinated α-enolase antibodies were not associated with any clinical manifestation whatsoever, including non-erosive arthritis among pSS, but an association of IgA anti-citrullinated α-enolase with anti-Ro/SSA antibodies was found. CONCLUSIONS: We characterised α-enolase as a dominant antigen in lysates of HEp- 2 cells in pSS. Nevertheless, their precise role in pSS remains to be elucidated.

Polypharmacy and patterns of prescription medication use among cancer survivors.

BACKGROUND: The population of cancer survivors is rapidly growing in the United States. Long-term and late effects of cancer, combined with the ongoing management of other chronic conditions, make survivors particularly vulnerable to polypharmacy and its adverse effects. In the current study, the authors examined patterns of prescription medication use and polypharmacy in a population-based sample of cancer survivors. METHODS: Using data from the Medical Expenditure Panel Survey (MEPS), the authors matched cancer survivors (5216 survivors) with noncancer controls (19,588 controls) by age, sex, and survey year. Polypharmacy was defined as ≥5 unique medications. The authors estimated the percentage of respondents prescribed medications within therapeutic classes and total prescription expenditures. RESULTS: A higher percentage of cancer survivors were prescribed ≥5 unique medications (64.0%; 95% confidence interval [95% CI], 62.3%-65.8%) compared with noncancer controls (51.5%; 95% CI, 50.4%-52.6%), including drugs with abuse potential. Across all therapeutic classes, a higher percentage of newly (≤1 year since diagnosis) and previously (>1 years since diagnosis) diagnosed survivors were prescribed medications compared with controls, with large differences observed with regard to central nervous system agents (65.8% [95% CI, 62.3%-69.3%] vs 57.4% [95% CI, 55.3%-59.5%] vs 46.0% [95% CI, 45.0%-46.9%]). Specifically, nearly 10% of survivors were prescribed benzodiazepines and/or opioids compared with approximately 5% of controls. Survivors had more than double the prescription expenditures (median of $1633 vs $784 among controls). Findings persisted across age and comorbidity categories. CONCLUSIONS: Cancer survivors were prescribed a higher number of unique medications, including drugs with abuse potential, thereby increasing their risk of adverse drug events, financial toxicity, poor adherence, and drug-drug interactions. Cancer 2018;124:2850-2857. © 2018 American Cancer Society.

Role of Transverse Displacements in the Formation of Subaqueous Barchan Dunes.

Crescentic shape dunes, known as barchan dunes, are formed by the action of a fluid flow on a granular bed. These bedforms are common in many environments, existing under water or in air, and being formed from grains organized in different initial arrangements. Although they are frequently found in nature and industry, details about their development are still to be understood. In a recent paper [C. A. Alvarez and E. M. Franklin, Phys. Rev. E 96, 062906 (2017)PRESCM2470-004510.1103/PhysRevE.96.062906], we proposed a timescale for the development and equilibrium of single barchans based on the growth of their horns. In the present Letter, we report measurements of the growth of horns at the grain scale. In our experiments, conical heaps were placed in a closed conduit and individual grains were tracked as each heap, under the action of a water flow, evolved into a barchan dune. We identified the trajectories of the grains that migrated to the growing horns, and found that most of them came from upstream regions on the periphery of the initial heap, with an average displacement of the order of the heap size. In addition, we show that individual grains had transverse displacements by rolling and sliding that are not negligible, with many of them going around the heap. The mechanism of horns formation revealed by our experiments contrasts with the general picture that barchan horns form from the advance of the lateral dune flanks due to the scaling of migration velocity with the inverse of dune size. Our results change the way in which the growth of subaqueous barchan dunes is explained.

Association of Statin Therapy With Risk of Epilepsy in 2 Propensity Score-Matched Cohorts.

BACKGROUND: Studies have suggested that statins may have a neuroprotective effect against epilepsy. However, evidence from rat models and case reports have suggested an opposite effect. Overall data are limited. OBJECTIVE: To examine the association between statin use and epilepsy risk in a general population and in a healthy population (individuals with no severe comorbidities). METHODS: Patients were Tricare beneficiaries from October 2003 to March 2012. Based on patients' characteristics during baseline phase (fiscal year [FY] 2004-2005), 2 propensity score (PS)-matched cohorts of statin users and nonusers were formed: (1) a PS-matched general cohort and (2) a PS-matched healthy cohort. Our outcome was defined using inpatient or outpatient ICD-9 codes for epilepsy during the follow-up phase (FY 2006 to March 2012) in the cohorts of statin users and nonusers. RESULTS: The study included a total of 43 438 patients (13 626 statin users and 29 812 nonusers). The PS-matched general cohort matched 6342 statin users to 6342 nonusers; the odds ratio (OR) of epilepsy in this cohort during follow-up was 0.91; 95% CI = 0.67-1.23. The PS-matched healthy cohort matched 3351 statin users to 3351 nonusers; OR in the PS-matched healthy cohort during follow-up was 1.08; 95% CI = 0.64-1.83. CONCLUSIONS: This study did not demonstrate a significant beneficial or deleterious effect of statin use on risk of being diagnosed with epilepsy. Clinicians should not withhold statins, whenever indicated, in patients with epilepsy.

Autoimmune comorbidity in achalasia patients.

BACKGROUND AND AIM: Idiopathic achalasia is a rare esophageal motor disorder. The disease state manifests local and systemic inflammation, and it appears that an autoimmune component and specific autoantibodies participate in the pathogenesis. The study aims to determine the prevalence of autoimmune and chronic inflammatory diseases in patients with achalasia and compare the results with those from patients with gastroesophageal reflux disease (GERD). METHODS: It was a cross-sectional and included 114 patients with idiopathic achalasia and 114 age-matched and sex-matched control patients with GERD. Data on the presence of autoimmune and inflammatory diseases, the time of presentation, and any family history of autoimmune disease were obtained from the hospital's medical records. RESULTS: Seventy three (64%) were female patients (mean age: 42.3 ± 15.5; median disease duration: 12 months). We identified the presence of autoimmune disease in 19 patients with achalasia (16.7%), hypothyroidism was the main diagnosis, and it was present in 52.6% of patients compared with 4.2% in controls. Thirteen of the 19 achalasia patients (68.4%) with autoimmune disease had history of familial autoimmunity. We identified 11 achalasia (9.6%) and 5 GERD patients (4.16%) with an inflammatory condition. Compared with the GERD, the achalasia group was 3.8 times more likely to have an autoimmune disease (95% CI: 1.47-9.83), 3.0 times more likely to have thyroidopathies (95% CI: 1.00-9.03), and 3.02 times more likely to suffer from any chronic inflammatory disease (95% CI: 1.65-6.20). CONCLUSIONS: The non-negligible number of patients with autoimmune diseases identified among the patients with idiopathic achalasia supports the hypothesis that achalasia has an autoimmune component.

Low-health literacy flashcards & mobile video reinforcement to improve medication adherence in patients on oral diabetes, heart failure, and hypertension medications.

OBJECTIVE: To design and investigate a pharmacist-run intervention using low health literacy flashcards and a smartphone-activated quick response (QR) barcoded educational flashcard video to increase medication adherence and disease state understanding. DESIGN: Prospective, matched, quasi-experimental design. SETTING: County health system in Dallas, Texas. PARTICIPANTS: Sixty-eight primary care patients prescribed targeted heart failure, hypertension, and diabetes medications INTERVENTION: Low health literacy medication and disease specific flashcards, which were also available as QR-coded online videos, were designed for the intervention patients. The following validated health literacy tools were conducted: Newest Vital Sign (NVS), Rapid Estimate of Adult Literacy Medicine-Short Form, and Short Assessment of Health Literacy-50. MAIN OUTCOME MEASURES: The primary outcome was the difference in medication adherence at 180 days after pharmacist intervention compared with the control group, who were matched on the basis of comorbid conditions, targeted medications, and medication class. Medication adherence was measured using a modified Pharmacy Quality Alliance proportion of days covered (PDC) calculation. Secondary outcomes included 90-day PDC, improvement of greater than 25% in baseline PDC, and final PDC greater than 80%. Linear regression was performed to evaluate the effect of potential confounders on the primary outcome. RESULTS: Of the 34 patients receiving the intervention, a majority of patients scored a high possibility of limited health literacy on the NVS tool (91.2%). The medication with the least adherence at baseline was metformin, followed by angiotensin-converting enzyme inhibitors and beta blockers. At 180 days after intervention, patients in the intervention group had higher PDCs compared with their matched controls (71% vs. 44%; P = 0.0069). CONCLUSION: The use of flashcards and QR-coded prescription bottles for medication and disease state education is an innovative way of improving adherence to diabetes, hypertension, and heart failure medications in a low-health literacy patient population.

Impact of an Analgesia-Based Sedation Protocol on Mechanically Ventilated Patients in a Medical Intensive Care Unit.

BACKGROUND: Recent attention to adverse effects of intensive care unit (ICU) sedation has led to the use of strategies that target a "lighter" depth of sedation. Among these strategies are "analgosedation" protocols, which prioritize pain management and preferentially use IV opioids before administration of continuously infused sedatives such as propofol or midazolam. We hypothesized that using an analgosedation protocol would result in a shorter duration of mechanical ventilation than a protocol with greater emphasis on IV sedatives METHODS: : We conducted a retrospective study comparing the duration of mechanical ventilation before and after implementation of an analgosedation protocol in a 24-bed medical ICU. Patients were aged 18 years or older and required mechanical ventilation where a light level of sedation was clinically appropriate. Exclusion criteria included a clinical need for deeper levels of sedation or tracheal intubation confined to the perioperative period. RESULTS: Seventy-nine patients were included in the postimplementation group and 65 in the preimplementation group. After adjustment for baseline covariates, introduction of the 2013 analgosedation protocol was associated with a decreased duration of mechanical ventilation (-26.62 hours; 95% confidence interval, - 44.98 to -8.26, P = 0.005). Patients managed with the analgosedation protocol experienced a lighter level of sedation (median Richmond Agitation-Sedation Scale, -2.57 vs -1.25, P = 0.001) and improved pain management (median Critical-Care Pain Observation Tool score, 2.0 vs 1.5, P = 0.03). The use of continuously infused sedatives was reduced by 54.3% (92.3% vs 38.0%, P < 0.001). CONCLUSIONS: Our findings suggest that implementation of an analgosedation protocol was associated with an overall lighter level of sedation, shorter mean ventilator duration, and a reduced use of continuous infusion sedatives. Further studies are needed to assess the impact of such protocols on ICU delirium.

Impact of a Pharmacy-Led Pain Management Team on Adults in an Academic Medical Center.

Background: Pain is a major health problem affecting more than 15% of adults in the United States. In a multidisciplinary pain management team, pharmacists can optimize pharmacotherapy quality by ensuring safe and appropriate medication use. Objective: Assess the impact of a pharmacy pain medication management service on pain-related outcomes in an adult inpatient population. Methods: This retrospective study evaluated patients who were admitted from November 2009 through November 2011 and received a pharmacy pain consult. Patients were excluded if they left against medical advice, their care was assumed by palliative care, or they had no complaint of pain when seen by the pharmacist. The primary outcome was the difference between each patient's average pain score from pre-consult to post-consult. Secondary outcomes were difference between each patient's average pain score from pre-consult to pre-discharge, overall functional improvement, pharmacist interventions, and 14-day and 30-day readmissions. Results: One hundred patients were included in the final analysis. Eight hundred twenty-one interventions were made by the clinical pharmacists. Patients displayed a significant reduction in their pre- and post-consult pain intensity scores on a 0 to 10 numerical rating scale (6.15 vs 3.25; p < .001). Likewise, a significant reduction in pain intensity scores was seen from pre-consult to pre-discharge (6.15 vs 3.6; p < .001). Overall functional improvement, specifically sleep, mobility, and appetite, was seen in 86.6% of patients. Conclusions: Pain management is an area that provides opportunities for pharmacotherapy interventions. Pharmacists' involvement in pain management on an inpatient consult service had a positive impact on pain scores and improvement in functionality.

Association of skeletal muscle relaxers and antihistamines on mortality, hospitalizations, and emergency department visits in elderly patients: a nationwide retrospective cohort study.

BACKGROUND: High-risk medication exposure in the elderly is common and associated with increased mortality, hospitalizations, and emergency department (ED) visits. Skeletal muscle relaxants and antihistamines are high-risk medications commonly prescribed in elderly patients. The objective of this study was to determine the association between skeletal muscle relaxants or antihistamines and mortality, hospitalizations, and emergency department visits. METHODS: This study used a new-user, retrospective cohort design using national Veteran Affairs (VA) data from 128 hospitals. Veterans ≥65 years of age on October 1, 2005 who received VA inpatient/outpatient care at least once in each of fiscal year (FY) 2005 and FY 2006 were included. Exposure to skeletal muscle relaxants and antihistamines was defined by the National Committee for Quality Assurance Healthcare Effectiveness Data and Information Set measures for high-risk medications in the elderly. Primary outcomes identified within one year of exposure were death, ED visit, or hospitalization; ED visits or hospitalizations due to falls and fracture were also assessed. Propensity score matching (1 to 1 match) was used to balance covariates between exposed patients and non-exposed patients. RESULTS: In this cohort of 1,807,404 patients 55,566 patients were included in the propensity-matched cohort for skeletal muscle relaxants and 60,058 patients were included in the propensity-matched cohort for anti-histamines. Mortality was lower in skeletal muscle relaxants-exposed patients (adjusted odds ratio [AOR] 0.87, 95% CI 0.81-0.94), but risk of emergency care (AOR 2.25, 95% CI 2.16-2.33) and hospitalization (AOR 1.56, 95% CI 1.48-1.65) was higher for patients prescribed skeletal muscle relaxants. Similar findings were observed for emergency and hospital care for falls or fractures. Mortality (AOR 1.93, 95% CI 1.82-2.04), ED visits (AOR 2.35, 95% CI 2.27-2.43), and hospitalizations (AOR 2.21, 95% CI 2.11-2.32) were higher in the antihistamine-exposed group, with similar findings for falls and fractures outcomes. CONCLUSION: Skeletal muscle relaxants and antihistamines are associated with an increased risk of ED visits and hospitalizations in elderly patients. Antihistamines were also associated with an increased risk of death, further validating the classification of these drug classes as "high risk".

The role of ß2-glycoprotein I (ß2GPI) carbohydrate chains in the reactivity of anti-ß2GPI antibodies from patients with primary antiphospholipid syndrome and in the activation and differentiation of U937 cells.

Several studies have shown that conformational changes of ß(2)-glycoprotein I (ß(2)GPI) when bound to negatively charged components expose cryptic epitopes and subsequent binding of anti-ß(2)GPI from patients with antiphospholipid syndrome (APS). However, the role of the carbohydrate chains of ß(2)GPI in this anti-ß(2)GPI reactivity is poorly understood. We therefore studied the reactivity and inhibition of anti-ß(2)GPI antibodies from APS patients with native, partially glycosylated ß(2)GPI (pdß(2)GPI; without sialic acid) and completely deglycosylated ß(2)GPI (cdß(2)GPI). To determine the potential biologic importance of these glycoforms and their interaction with anti-ß(2)GPI in vitro, stimulation assays were performed with the U937 cell line. Circular dichroism (CD) and fluorescence analysis of the three ß(2)GPI forms were also studied. We found an increased reactivity of anti-ß(2)GPI against pdß(2)GPI and cdß(2)GPI compared to native ß(2)GPI. Both deglycosylated ß(2)GPI isoforms showed higher inhibition of the anti-ß(2)GPI reactivity than the native protein in soluble-phase. Likewise, the antibody/ß(2)GPI/glycoform complexes increased the synthesis of IL-6, IFNγ and TNFα and the expression of HLA-DR, CD14 and CD11c in U937 cells. CD and fluorescence studies of the glycoforms yielded considerable changes in the fluorescence signals. Our work suggests that the partial or complete removal of the carbohydrate chains uncover cryptic epitopes present in ß(2)GPI. The differentiation and increased synthesis of pro-inflammatory cytokines by U937 cells in vitro may have pathogenetic implications.

Association of azithromycin with mortality and cardiovascular events among older patients hospitalized with pneumonia.

IMPORTANCE: Although clinical practice guidelines recommend combination therapy with macrolides, including azithromycin, as first-line therapy for patients hospitalized with pneumonia, recent research suggests that azithromycin may be associated with increased cardiovascular events. OBJECTIVE: To examine the association of azithromycin use with all-cause mortality and cardiovascular events for patients hospitalized with pneumonia. DESIGN: Retrospective cohort study comparing older patients hospitalized with pneumonia from fiscal years 2002 through 2012 prescribed azithromycin therapy and patients receiving other guideline-concordant antibiotic therapy. SETTING: This study was conducted using national Department of Veterans Affairs administrative data of patients hospitalized at any Veterans Administration acute care hospital. PARTICIPANTS: Patients were included if they were aged 65 years or older, were hospitalized with pneumonia, and received antibiotic therapy concordant with national clinical practice guidelines. MAIN OUTCOMES AND MEASURES: Outcomes included 30- and 90-day all-cause mortality and 90-day cardiac arrhythmias, heart failure, myocardial infarction, and any cardiac event. Propensity score matching was used to control for the possible effects of known confounders with conditional logistic regression. RESULTS: Of 73,690 patients from 118 hospitals identified, propensity-matched groups were composed of 31,863 patients exposed to azithromycin and 31,863 matched patients who were not exposed. There were no significant differences in potential confounders between groups after matching. Ninety-day mortality was significantly lower in those who received azithromycin (exposed, 17.4%, vs unexposed, 22.3%; odds ratio [OR], 0.73; 95% CI, 0.70-0.76). However, we found significantly increased odds of myocardial infarction (5.1% vs 4.4%; OR, 1.17; 95% CI, 1.08-1.25) but not any cardiac event (43.0% vs 42.7%; OR, 1.01; 95% CI, 0.98-1.05), cardiac arrhythmias (25.8% vs 26.0%; OR, 0.99; 95% CI, 0.95-1.02), or heart failure (26.3% vs 26.2%; OR, 1.01; 95% CI, 0.97-1.04). CONCLUSIONS AND RELEVANCE: Among older patients hospitalized with pneumonia, treatment that included azithromycin compared with other antibiotics was associated with a lower risk of 90-day mortality and a smaller increased risk of myocardial infarction. These findings are consistent with a net benefit associated with azithromycin use.

Compliance with recommended pneumococcal vaccination schedule in patients treated for rheumatoid arthritis: A retrospective cohort study in the Veterans Affairs population.

INTRODUCTION: Invasive pneumococcal disease (IPD) is a leading cause of death. Rheumatoid arthritis (RA) patients are at risk of IPD due to immunosuppressant medications. Up until 2022, two pneumococcal vaccines, the 13-valent Pneumococcal conjugate vaccine (PCV13) and pneumococcal polysaccharide vaccine (PPSV23), were recommended. Despite the recommendation change to give a single 20-valent PCV vaccine (PCV20), some still require multiple vaccinations. There is a need to identify barriers to vaccine uptake. METHODS: We conducted a retrospective cohort study to assess the on-time vaccination rates for PCV13 and PPSV23 in treated RA patients between 2010 and 2018 using national Veterans Affairs data. Patients > 18 years of age diagnosed with RA and newly initiated on RA treatment were included. Pneumococcal vaccine compliance was assessed by measuring on-time receipt of PCV13 and PPSV23 vaccinations. We identified factors using multivariate logistic regression and described the occurrence of these factors using descriptive statistics. RESULTS: A total of 39,243 patients were included in the study. Most patients were white (75.8 %), male (85.4 %), on methotrexate therapy (41.4 %). The average age was 62.3 years. The proportion of patients considered vaccine compliant is 43.9 %. The primary independent risk factors for vaccine non-compliance were black/African American race (Odds Ratio [OR] 1.26, 95 % Confidence Interval [CI] 1.19-1.34) or missing/unknown race (OR 1.45, 95 % CI 1.31-1.61), missing/unknown ethnicity (OR 1.21, 1.02-1.43), never married (OR 1.10, 95 % CI 1.02-1.19) or widowed (OR 1.23, 95 % CI 1.12-1.34), diagnosed with congestive heart failure (OR 1.10, 95 % CI 1.00-1.22), or dementia (OR 1.48, 95 % CI 1.16-1.91). The proportion of patients who were non-compliant in patients who were vaccine naïve was 32.1 % and the non-compliance rate for non-naïve patients was 65.3 %. CONCLUSIONS: Providers should identify barriers to pneumococcal vaccination in RA patients to improve compliance. Efforts to increase vaccination should be tailored to specific high-risk groups.