The five current members of the thrombospondin (TSP) family can be divided in two subgroups according to their molecular architecture. TSP-1 and -2 (subgroup A) are trimeric matricellular proteins that do not contribute directly to tissue integrity, but influence cell function by modulating cell-matrix interactions, whereas TSP-3, -4 and -5 (subgroup B) are pentameric proteins. TSP-1 and TSP-2 are markedly induced in healing wounds and may regulate cellular responses important for tissue repair. TSP-1 is a crucial activator of TGF-beta, whereas both TSP-1 and TSP-2 inhibit angiogenesis. This manuscript reviews our current knowledge on the expression and role of the TSPs in healing myocardial infarcts. In both canine and murine infarcts, TSP-1 shows a strikingly selective localization in the infarct border zone. In the absence of injury, TSP-1 -/- mice exhibit normal cardiac morphology and show no evidence of myocardial inflammation. Infarcted TSP-1 -/- mice have an enhanced and protracted inflammatory response with subsequent expansion of granulation tissue in the non-infarcted area, resulting in myofibroblast infiltration into the viable myocardium neighboring the infarct. Infarcted TSP-1 -/- animals have enhanced left ventricular remodeling compared with their wildtype littermates. We suggest that TSP-1 is a critical component of the protective mechanisms induced in the infarct border zone in order to limit expansion of fibrosis into the non-infarcted myocardium. Localized TSP-1 expression may suppress expansion of the inflammatory process by activating TGF-beta or by inhibiting local angiogenesis. In addition, TSP-1-mediated inhibition of MMP activity may decrease adverse remodeling. TSP-2, on the other hand, appears to be a crucial regulator of the integrity of the cardiac matrix that is necessary for the myocardium to cope with increased loading. The expression and potential role of the pentameric TSPs in the infarcted heart remain unknown. Understanding the specific mechanisms responsible for the protective effects of TSP-1 and TSP-2 in healing infarcts may lead to novel therapeutic interventions aiming at attenuating adverse left ventricular remodeling.

IMPORTANCE Targeted drug delivery (TDD) has potential for cost savings compared with conventional medical management (CMM). Despite positive clinical and economic evidence, TDD remains underused to treat cancer pain. OBJECTIVE To assess the cost of TDD and CMM in treating cancer-related pain. DESIGN, SETTING, AND PARTICIPANTS This retrospective economic evaluation using propensity score-matched analysis was conducted using MarketScan commercial claims data on beneficiaries receiving TDD and CMM or CMM only for cancer pain from January 1, 2009, to September 30, 2015. Participants were matched on age, sex, cancer type, comorbidity score, and pre-enrollment characteristics. Data analysis was performed from June 1 to September 30, 2017. MAIN OUTCOMES AND MEASURES Total 2-, 6-, and 12-month costs, number of health care encounters, length of hospital stay, additional components of cost, and health care utilization. RESULTS A total of 376 TDD and CMM patients (mean [SD] age, 51.88 [9.98] years; 216 [57.5%] female) and 4839 CMM only patients (mean [SD] age, 51.52 [11.16] years; 3005 [62.1%] female) were identified for study inclusion. After matching, 536 patients were included in the study: 268 patients in the TDD and CMM group and 268 in the CMM only group.

Objective: Surgical site infections can cause negative clinical and economic outcomes. A recent international survey on Spinal Cord Stimulation (SCS) infection control practices demonstrated low compliance with evidence-based guidelines. This study defines infection rate for SCS implants and identifies infection risk factors. Results: In the logistic regression (n = 6615), 12 m device-related infection rate was 3.11%. Infection risk factors included peripheral vascular disease (OR, 1.784; 95% CI: 1.011-3.149; p = 0.0457) and infection in 12 m before implant (OR, 1.518; 95% CI: 1.022-2.254; p = 0.0386). The odds of patients experiencing an infection decreased by 3.2% with each additional year of age (OR, 0.968; 95% CI: 0.952-0.984; p < 0.0001). Survival analysis (n = 13,214) identified prior infection (HR, 1.770; 95% CI: 1.342-2.336; p < 0.0001) as a risk factor. Infection was less likely in older patients (HR, 0.974; 95% CI: 0.962-0.986; p < 0.0001). Expected risk factors including obesity, diabetes, and smoking were not identified as risk factors in this analysis. There was no significant difference between infection rate for initial and replacement implants.Conclusions: The 3.11% SCS-related infection rate within 12 m of implant emphasizes the need for improved infection control practices. Research is needed to limit SCS infections in younger patients and those with infection history.

BackgroundAlthough the role of serum procalcitonin (PCT) and high-sensitivity C-reactive protein (hs-CRP) in the diagnosis of sepsis and septic shock is well studied, it has not been investigated among oldest old patients. The aim of our study is to determine the role of PCT and hs-CRP in the assessment of sepsis and septic shock in this specific group of patients in the ICU.MethodsThis is a prospective observational study. Patients >85 years of age admitted to the ICU from May 1st, 2016 to February 1st, 2017 were evaluated. Patients were divided into a sepsis and septic shock group(sepsis/SS) and a non-sepsis group. Serum levels of PCT, hs-CRP and the WBC were measured within 12 h of admission.ResultsA total of 70 patients aged 85 years and older were enrolled in this study. Fifty patients were labelled as sepsis/SS and the other 20 were labelled non-sepsis. A ROC analysis showed that the area under the curves (AUC) of hs-CRP and PCT for the discrimination of sepsis/SS patients were 0.825 (95% confidence interval[CI]: 0.73-0.92; P < 0.001) and 0.819 (95%CI:0.72-0.92; p < 0.001), respectively. In a subgroup analysis of the sepsis/SS group, 27 patients had sepsis, while the other 23 patients had septic shock. The ROC analysis showed that the AUCs of hs-CRP and PCT for the discrimination of septic shock patients from sepsis patients were 0.751 (95% CI: 0.62-0.88; P = 0.002) and 0.719 (95% CI:0.57-0.86; p = 0.007), respectively.ConclusionFor the oldest old patients, hs-CRP is not inferior to PCT in the diagnosis of sepsis and septic shock.

cation prescriptions; reliance on pharmacotherapy in obesity treatment; the odds of a specific patient's being prescribed antiobesity medication; and consistency of prescribing with the 1998 obesity guidelines. METHODS: Data for adult patients were obtained from the National Ambulatory Medical Care Survey and the National Hospital Ambulatory Medical Care Survey, and were appropriately weighted to produce national estimates of prescribing patterns. Obesity was identified using ICD-9 codes, BMI values, and a chronic-obesity-condition variable. For obese patients, a logistic regression model was estimated to determine the odds of receiving pharmacotherapy. RESULTS: The number of outpatient visits with any mention of an antiobesity medication increased from 6.5 million from 1999-2001 to 13.0 million from 2008-2010. Only 2.0% of the 987 million obese-patient visits from 2005-2010 mentioned an antiobesity drug. Additionally, there were 6.5 million visits by nonobese patients with an antiobesity drug mention. Visits made by females (OR = 2.89; 95% CI: 2.08-4.03), by white patients (OR = 1.55; 95% CI: 1.08-2.24), by younger adults (OR = 1.71; 95% CI: 1.34-2.20), and in the South (OR = 3.39; 95% CI: 1.49-7.72) were more likely to involve an antiobesity drug prescription. CONCLUSIONS: Pharmacotherapy has been underutilized as a treatment option for obese patients. Only 1 in 50 patients is receiving a prescription for an antiobesity medication. Prescribing regulations and drug safety concerns have clearly discouraged the use of pharmacotherapy. Moreover, in contrast to what the 1998 guidelines suggested, physicians have tended to prescribe antiobesity medications to self-paying young, white, females, many of whom lived in the South, and not all of whom were obese; they have tended not to prescribe them to patients with comorbidities like hypertension. OBJECTIVES:To determine the antiobesity-drug prescribing patterns of U.S. physicians over the last decade (1999-2010) by quantifying trends in antiobesity medi-

Cancer patients are at a high risk of being infected with COVID-19 and have a poor prognosis after infection. Breast cancer is one of the most common cancers. Since vaccination is an effective measure to prevent the spread of COVID-19, we studied the vaccination rate among breast cancer survivors and analyzed their characteristics to provide evidence for boosting the vaccination rate. The researchers conducted a multicenter, cross-sectional study on 747 breast cancer survivors from six hospitals in Wuhan city between June 5, 2021, and June 12, 2021. The self-administrated questionnaires based on relevant studies were distributed. The researchers then compared differences in characteristics among vaccinated patients, hesitant patients, and non-vaccinated patients. Moreover, they performed univariable and multivariable logistic regression analyses to identify potential factors associated with vaccination hesitancy. The researchers assessed a total of 744 breast cancer survivors −94 cases in the vaccinated group, 103 in the planning group, 295 in the hesitancy group, and 252 in the refusal group. The vaccination rate was 12.63% (95% CI 10.25–15.02%) and 37.23% (95% CI 27.48–47.82%) patients reported adverse reactions. The vaccination hesitancy/refusal rate was 73.52% (95% CI 70.19–76.66%), which was independently associated with current endocrine or targeted therapy (odds ratio [OR] = 1.52, 95% CI 1.03–2.24), no notification from communities or units (OR = 2.46, 95% CI 1.69–3.59) and self-perceived feel (general vs. good, OR = 1.46, 95% CI 1.01–2.13; bad vs. good, OR = 4.75, 95% CI 1.85–12.16). In the hesitancy/refusal group, the primary reason was “I did not know who to ask whether I can get vaccinated” (46.07%), the person who would most influence decisions of patients was the doctor in charge of treatment (35.83%). Effective interaction between doctors and patients, simple and consistent practical guidelines on vaccination, and timely and positive information from authoritative media could combat misinformation and greatly reduce vaccine hesitancy among breast cancer survivors.

BackgroundGiven that the quinolones is one of the antibacterial classes most frequently used to treat patients with bacterial infections in the United States, any change in prescribing patterns of quinolones will impact Medicaid medical expenditures.ObjectivesThis study was undertaken to examine trends in utilization, reimbursement, and prices of quinolone antibacterials for the US Medicaid population.MethodsThe publicly available Medicaid State Drug Utilization outpatient pharmacy files were used for this study. Quarterly and annual prescription counts and reimbursement amounts were calculated for each of the quinolones reimbursed by Medicaid from quarter 1, 1991 through quarter 2, 2015. Average per-prescription reimbursement, as a proxy for drug price, was calculated as the drug reimbursement divided by the number of prescriptions.ResultsThe total annual number of quinolone prescriptions increased 402%, from 247,395 in the first quarter of 1991 to 1.2 million in the second quarter of 2015, peaking at 1.3 million in the first quarter of 2005. Similarly, the total reimbursement for quinolone agents increased by 245.5% over the same period. More than 80% of quinolone prescriptions reimbursed by Medicaid were for the second-generation agent, ciprofloxacin, and the third-generation agent, levofloxacin. The average payment per prescription for quinolones increased from US$43.8 in the first quarter of 1991 to US$87.6 in the second quarter of 2015.ConclusionsA substantial rise in Medicaid expenditures on quinolones was observed during the 25-year study period, which was mainly because of rising utilization. Therefore, there is a need for additional research that has access to clinically relevant data with which to measure the rate of inappropriate quinolone use among the Medicaid population and associated clinical outcomes and healthcare costs.Electronic supplementary materialThe online version of this article (doi:10.1007/s41669-016-0007-y) contains supplementary material, which is available to authorized users.

Aim The Prevention of Arrhythmia Device Infection Trial (PADIT) infection risk score, developed based on a large prospectively collected data set, identified five independent predictors of cardiac implantable electronic device (CIED) infection. We performed an independent validation of the risk score in a data set extracted from U.S. healthcare claims. Methods and results Retrospective identification of index CIED procedures among patients aged ≥18 years with at least one record of a CIED procedure between January 2011 and September 2014 in a U.S health claims database. PADIT risk factors and major CIED infections (with system removal, invasive procedure without system removal, or infection-attributable death) were identified through diagnosis and procedure codes. The data set was randomized by PADIT score into Data Set A (60%) and Data Set B (40%). A frailty model allowing multiple procedures per patient was fit using Data Set A, with PADIT score as the only predictor, excluding patients with prior CIED infection. A data set of 54 042 index procedures among 51 623 patients with 574 infections was extracted. Among patients with no history of prior CIED infection, a 1 unit increase in the PADIT score was associated with a relative 28% increase in infection risk. Prior CIED infection was associated with significant incremental predictive value (HR 5.66, P &lt; 0.0001) after adjusting for PADIT score. A Harrell’s C-statistic for the PADIT score and history of prior CIED infection was 0.76. Conclusion The PADIT risk score predicts increased CIED infection risk, identifying higher risk patients that could potentially benefit from targeted interventions to reduce the risk of CIED infection. Prior CIED infection confers incremental predictive value to the PADIT score.