Ingestion of monosodium glutamate (MSG) causes headache, nausea, and craniofacial tenderness in healthy individuals. The present study explored whether MSG produces behavioural signs of headache, nausea, and changes in craniofacial sensitivity in rats. The behavior of male and female Sprague-Dawley rats was video recorded before and after intraperitoneal (i.p.) injections of MSG (1-1000 mg/kg), nitroglycerin (GTN, 10 mg/kg), or normal saline. Behaviors (grimace score, head-flicks, rearing, head scratches, facial grooming, lying-on-belly, and temporalis muscle region mechanical withdrawal threshold) were evaluated. Facial cutaneous temperature of the nose and forehead was measured before and after i.p. injections via infrared thermography. Plasma glutamate and calcitonin gene-related peptide concentrations after administration of 1000 mg/kg MSG were measured in anesthetized rats. Monosodium glutamate induced nocifensive, headache-like, and nausea-like behaviors in a dose-related manner but had no effect on me behavior in females but a longer duration of nausea-like behavior in males. Monosodium glutamate produced a prolonged increase in plasma glutamate and calcitonin gene-related peptide concentrations. Co-administration of the median effective dose of MSG (350 mg/kg) with GTN (10 mg/kg) amplified headache-like behaviors, induced significant craniofacial sensitivity, and produced increased nausea-like behaviour. Co-administration of sumatriptan or naproxen with MSG (1000 mg/kg) significantly attenuated MSG-induced nocifensive and headache-like behaviors. Our data suggest that systemic administration of MSG to rats induces behavioral correlates of headache and nausea. This model may offer another avenue for research on the mechanism and treatment of primary headache disorders such as migraine.
To summarize published literature on the incidence of adverse drug effects (ADEs) associated with guideline-directed medical therapy (GDMT) for patients with heart failure with reduced ejection fraction (HFrEF).

Systematic literature review.

A systematic literature review was conducted in PubMed, Ovid MEDLINE, and Clinical Key covering January 1990 to December 2018. Key search terms were ADEs for β-blockers (BBs), ACE inhibitors (ACEis), angiotensin receptor blockers (ARBs), mineralocorticoid receptor antagonists (MRAs), and/or angiotensin receptor-neprilysin inhibitors (ARNis) in adult patients (≥ 18 years) withHFrEF.

A total of 279 eligible articles were identified, of which 29 reported drug-related adverse effects and were included in this review. Of the 29 studies, 11 examined BBs; 9, MRAs; 6, ARNis; 2, ACEis; and 1, ARBs. The most common reported ADEs across these therapeutic classes included bradycardia, dizziness, hypotension, hyperkalemia, cough, and renal impairment. The incidence of BB-induced bradycardia was 1% to 52% based on 9 studies, and 6 studies described dizziness as a result of BBs and ARNis (15%-43%). Fourteen studies reported induced hypotension (1.4%-63%); 13 studies, hyperkalemia (0.6%-30.2%); 3 studies, cough (37%-50%); and 4 studies, renal impairment (0.6%-7.6%).

Findings show that drug-related adverse effects are commonly reported in clinical trials and highlight the sizable burden of ADEs with medical therapy across patients with HFrEF. Additional real-world evidence and studies aiming to improve the tolerability of GDMT for patients with HFrEF are warranted.
Findings show that drug-related adverse effects are commonly reported in clinical trials and highlight the sizable burden of ADEs with medical therapy across patients with HFrEF. Additional real-world evidence and studies aiming to improve the tolerability of GDMT for patients with HFrEF are warranted.
To determine associations between a large-scale primary care redesign-the Comprehensive Primary Care Plus (CPC+) Initiative-and the extent of continuity or fragmentation of ambulatory care for Medicare fee-for-service beneficiaries during the first 3 years of CPC+.

We used a difference-in-differences framework with a comparison group of practices that were similar to CPC+ practices at baseline (eg, practice size, demographics, Medicare spending). Regressions controlled for clustering, baseline patient characteristics, and practice fixed effects. Our study covered January 2016 through December 2019 and included 1,085,707 beneficiaries attributed to 2883 CPC+ practices and 2,274,068 beneficiaries attributed to 6912 comparison practices.

We focused on beneficiaries with highly fragmented care at baseline because they may have changed the most in response to CPC+. Key outcome measures were the numbers of ambulatory visits and unique practitioners, reported by specialty category; the percentage of visits with the usual provider of care (measuring continuity); and the reversed Bice-Boxerman Index (rBBI; measuringfragmentation).

Medicare beneficiaries with high fragmentation (rBBI ≥ 0.85) at baseline (40% of the sample) had a mean of 13 ambulatory visits across 7 practitioners; the most frequent provider of care accounted for only 28% of visits. By contrast, the remaining beneficiaries had a mean of 10visits across 4 practitioners, with the most frequent provider accounting for 54% of visits. https://www.selleckchem.com/products/lf3.html There were no differences in continuity or fragmentation of care for CPC+ vs comparisonbeneficiaries.

We find no evidence that CPC+ increased continuity or decreased fragmentation of care.
We find no evidence that CPC+ increased continuity or decreased fragmentation of care.
To study the association between Medicare's wage index adjustment and the differential use of labor-intensive surgical procedures and medical device-intensive minimally invasive clinical procedures across the UnitedStates.

We combine a conceptual model and an empirical investigation of its predictions, applied to aortic valve replacement, to study the relationship between variation in Medicare wage index payment adjustment across hospital referral regions (HRRs) and the utilization of transcatheter aortic valve replacement (TAVR) and surgical aortic valve replacement (SAVR) in these areas.

Using detailed individual Medicare claims data for 2013-2018 and a novel geographical crosswalk to nest information on Medicare's wage index and utilization of TAVR and SAVR, we estimate a mixed effects Poisson regression model across HRRs to test our hypotheses.

We find regional variation in Medicare wage index adjustment levels to be correlated with differential TAVR and SAVR utilization and growth over time. In particular, in HRRs where the wage index is half the national mean there is a 35% decline in the rate of TAVR use and in HRRs where the wage index is 50% higher than the national mean there is a 52% increase in the rate of TAVR use.

Consistent with our framework and hypothesis, our results highlight the importance of adjusting Medicare hospital inpatient payments for device-intensive procedures. Absent such adjustment, access to appropriate interventions may be reduced in areas with low wage index, and lower reimbursement, when driven by wage index adjustment, may influence the treatment approach selected.
Consistent with our framework and hypothesis, our results highlight the importance of adjusting Medicare hospital inpatient payments for device-intensive procedures. Absent such adjustment, access to appropriate interventions may be reduced in areas with low wage index, and lower reimbursement, when driven by wage index adjustment, may influence the treatment approach selected.
To determine whether baloxavir use is associated with lower health care resource utilization (HCRU) and costs for secondary influenza complications post treatment compared with oseltamivir.

Retrospective cohort study.

Patients filling a prescription for baloxavir or oseltamivir within 48 hours following an influenza-related outpatient visit were identified in the 2018-2019 influenza season from the US Truven MarketScan Research Databases and propensity matched 12 (baloxaviroseltamivir). Outcomes were assessed 15 and 30 days after antiviral treatment and included all-cause, all respiratory-related, and select respiratory-related (influenza, asthma, chronic obstructive pulmonary disease, or infection) HCRU and costs.

The study included 5080 baloxavir-treated and 10,160 matched oseltamivir-treated patients. All-cause emergency department (ED) visits and inpatient hospitalizations were lower in baloxavir-treated patients, with a statistically significant difference in the percentage hospitalized at 30 dayth oseltamivir, particularly in high-risk patients.
The COVID-19 pandemic has caused hospitals around the world to quickly develop not only strategies to treat patients but also methods to protect health care and frontline workers.

Descriptive study.

We outlined the steps and processes that we took to respond to the challenges presented by the COVID-19 pandemic while continuing to provide our routine acute care services to our community.

These steps and processes included establishing teams focused on maintaining an adequate supply of personal protection equipment, cross-training staff, developing disaster-based triage for the emergency department, creating quality improvement teams geared toward updating care based on the most current literature, developing COVID-19-based units, creating COVID-19-specific teams of providers, maximizing use of our electronic health record system to allocate beds, and providing adequate practitioner coverage by creating a computer-based dashboard that indicated the need for health care practitioners. These processes led to seamless and integrated care for all patients with COVID-19 across our health system and resulted in a reduction in mortality from a high of 20% during the first peak (March and April 2020) to 6% during the plateau period (June-October 2020) to 12% during the second peak (November and December 2020).

The detailed processes put in place will help hospital systems meet the continuing challenges not only of COVID-19 but also beyond COVID-19 when other unique public health crises may present themselves.
The detailed processes put in place will help hospital systems meet the continuing challenges not only of COVID-19 but also beyond COVID-19 when other unique public health crises may present themselves.In response to study findings showing the risk of cardiovascular adverse events associated with testosterone therapy, the FDA issued safety warnings in 2014 and modified testosterone labeling in March 2015 to indicate the increased risk of stroke and heart attack. It is unknown whether there were changes in testosterone marketing practices by pharmaceutical companies following the FDA label warning. Both primary care physicians (PCPs) and non-PCPs prescribe testosterone and are targeted by pharmaceutical marketing representatives to encourage testosterone prescribing. Likewise, pharmaceutical marketing occurs in both urban and rural areas. Our study is the first to examine testosterone marketing practices around the period of the testosterone label warning by physician specialty and rural vs urban primary care service area. In this study, we found that testosterone marketing efforts such as marketing spending per encounter, quarterly marketing spending per physician, and quarterly number of encounters per physician increased among non-PCPs and urban physicians for 4 quarters following an FDA boxed warning in 2015 on testosterone prescriptions.