The potential economic value of sputum culture use in patients with community-acquired pneumonia and healthcare-associated pneumonia.

OBJECTIVE: Despite numerous studies, the clinical value of sputum cultures in the management of pneumonia remains controversial; therefore, understanding the economic value of sputum cultures may help decision makers determine their appropriate use in patient management. METHODS: We developed a decision model to determine the economic and clinical value of using sputum cultures in the treatment of community-acquired pneumonia (CAP) and healthcare-associated pneumonia (HCAP) from the hospital perspective under various conditions. RESULTS: For both CAP and HCAP patients, obtaining sputum cultures resulted in similar costs compared to no culture, even if cultures cost $0. Given current clinical practices, obtaining cultures cost $539-631 more per CAP patient and $13-170 per HCAP patient compared to no culture use. However, cultures saved $8-202 per HCAP patient with a 40% probability the pathogen was the true cause (75% reduction in adverse outcomes, greater length of hospital stay (LOS) increase) to a 70% probability the pathogen was the true cause (25% reduction in outcomes and greater LOS increase and a 75% reduction in outcomes and all LOS increases). Additionally, obtaining sputum cultures had no impact on the number of adverse outcomes (i.e., adverse drug events, Clostridium difficile infection, pneumonia readmissions, additional hospitalization days). When all patients were treated with antibiotics empirically, obtaining cultures saved $4-342. CONCLUSIONS: Overall, obtaining sputum cultures does not provide significant clinical or economic benefits for CAP or HCAP patients; however, it can reduce costs and shorten overall LOS under some circumstances. Clinicians should consider their local conditions when making decisions about sputum culture use.

Newer glycopeptide antibiotics for treatment of complicated skin and soft tissue infections: systematic review, network meta-analysis and cost analysis.

OBJECTIVES: Skin and soft tissue infections (SSTIs) carry significant economic burden, as well as morbidity and mortality, especially when caused by methicillin-resistant Staphylococcus aureus (MRSA). Several new MRSA-active antibiotics have been developed, including semisynthetic glycopeptides (telavancin, dalbavancin and oritavancin). Of these, dalbavancin and oritavancin offer extended dosing intervals. METHODS: We performed a systematic review, network meta-analysis and cost analysis to compare the newer glycopeptides to standard care and to each other for the treatment of complicated SSTIs (cSSTI). A search for randomized controlled trials (RCTs) was conducted in Medline, Embase and the Cochrane Central Register of Controlled Trials. We also developed a model to evaluate the costs associated with dalbavancin and oritavancin from the third-party payer perspective. RESULTS: Seven RCTs met the inclusion criteria. Network meta-analyses suggested that the clinical response to telavancin, dalbavancin and oritavancin was similar to standard care (odds ratio (OR) 1.09, 95% confidence interval (CI) 0.90-1.33; OR 0.78, 95% CI 0.52-1.18; and OR 1.06, 95% CI 0.85-1.33, respectively). Head-to-head comparisons showed no difference in clinical response between oritavancin and dalbavancin (OR 1.36; 95% CI 0.85-2.18), oritavancin and telavancin (OR 0.98; 95% CI 0.72-1.31) or dalbavancin and telavancin (OR 0.72; 95% CI 0.45-1.13). Telavancin had a higher incidence of overall adverse events compared to standard care (OR 1.33; 95% CI 1.10-1.61). Compared to telavancin, there were fewer overall adverse events with dalbavancin (OR 0.58; 95% CI 0.45-0.76) and oritavancin (OR 0.71; 95% CI 0.55-0.92). Studies were of high quality overall. Our cost analyses demonstrated that dalbavancin and oritavancin were less costly compared to standard care under baseline assumptions and many scenarios evaluated. The use of dalbavancin could save third-party payers $1442 to $4803 per cSSTI, while the use of oritavancin could save $3571 to $6932 per cSSTI. CONCLUSIONS: Dalbavancin and oritavancin demonstrate efficacy and safety comparable to standard care in well-designed RCTs and result in cost savings when standard care is treatment that covers MRSA.

Centers for disease control and prevention guideline for the prevention of surgical site infection, 2017

IMPORTANCE: The human and financial costs of treating surgical site infections (SSIs) are increasing. The number of surgical procedures performed in the United States continues to rise, and surgical patients are initially seen with increasingly complex comorbidities. It is estimated that approximately half of SSIs are deemed preventable using evidence-based strategies. OBJECTIVE: To provide new and updated evidence-based recommendations for the prevention of SSI. EVIDENCE REVIEW: A targeted systematic review of the literature was conducted in MEDLINE, EMBASE, CINAHL, and the Cochrane Library from 1998 through April 2014. A modified Grading of Recommendations, Assessment, Development, and Evaluation (GRADE) approach was used to assess the quality of evidence and the strength of the resulting recommendation and to provide explicit links between them. Of 5759 titles and abstracts screened, 896 underwent full-text review by 2 independent reviewers. After exclusions, 170 studies were extracted into evidence tables, appraised, and synthesized. FINDINGS: Before surgery, patients should shower or bathe (full body) with soap (antimicrobial or nonantimicrobial) or an antiseptic agent on at least the night before the operative day. Antimicrobial prophylaxis should be administered only when indicated based on published clinical practice guidelines and timed such that a bactericidal concentration of the agents is established in the serum and tissues when the incision is made. In cesarean section procedures, antimicrobial prophylaxis should be administered before skin incision. Skin preparation in the operating room should be performed using an alcohol-based agent unless contraindicated. For clean and clean-contaminated procedures, additional prophylactic antimicrobial agent doses should not be administered after the surgical incision is closed in the operating room, even in the presence of a drain. Topical antimicrobial agents should not be applied to the surgical incision. During surgery, glycemic control should be implemented using blood glucose target levels less than 200 mg/dL, and normothermia should be maintained in all patients. Increased fraction of inspired oxygen should be administered during surgery and after extubation in the immediate postoperative period for patients with normal pulmonary function undergoing general anesthesia with endotracheal intubation. Transfusion of blood products should not be withheld from surgical patients as a means to prevent SSI. CONCLUSIONS AND RELEVANCE: This guideline is intended to provide new and updated evidence-based recommendations for the prevention of SSI and should be incorporated into comprehensive surgical quality improvement programs to improve patient safety.

Alginate therapy is effective treatment for GERD symptoms: a systematic review and meta-analysis.

In patients with gastroesophageal reflux disease (GERD) and erosive esophagitis, treatment with proton pump inhibitors (PPIs) is highly effective. However, in some patients, especially those with nonerosive reflux disease or atypical GERD symptoms, acid-suppressive therapy with PPIs is not as successful. Alginates are medications that work through an alternative mechanism by displacing the postprandial gastric acid pocket. This study performed a systematic review and meta-analysis to examine the benefit of alginate-containing compounds in the treatment of patients with symptoms of GERD. PubMed/MEDLINE, Embase, and the Cochrane library electronic databases were searched through October 2015 for randomized controlled trials comparing alginate-containing compounds to placebo, antacids, histamine-2 receptor antagonists (H2RAs), or PPIs for the treatment of GERD symptoms. Additional studies were identified through a bibliography review. Non-English studies and those with pediatric patients were excluded. Meta-analyses were performed using random-effect models to calculate odds ratios (OR). Heterogeneity between studies was estimated using the I2 statistic. Analyses were stratified by type of comparator. The search strategy yielded 665 studies and 15 (2.3%) met inclusion criteria. Fourteen were included in the meta-analysis (N = 2095 subjects). Alginate-based therapies increased the odds of resolution of GERD symptoms when compared to placebo or antacids (OR: 4.42; 95% CI 2.45-7.97) with a moderate degree of heterogeneity between studies (I2 = 71%, P = .001). Compared to PPIs or H2RAs, alginates appear less effective but the pooled estimate was not statistically significant (OR: 0.58; 95% CI 0.27-1.22). Alginates are more effective than placebo or antacids for treating GERD symptoms.

Alginate therapy is effective treatment for gastroesophageal reflux disease symptoms: a systematic review and meta-analysis.

In patients with gastroesophageal reflux disease (GERD) and erosive esophagitis, treatment with proton pump inhibitors (PPIs) is highly effective. However, in some patients, especially those with non-erosive reflux disease or atypical GERD symptoms, acid suppressive therapy with PPIs is not as successful. Alginates are medications that work through an alternative mechanism by displacing the post-prandial gastric acid pocket. We performed a systematic review and meta-analysis to examine the benefit of alginate-containing compounds in the treatment of patients with symptoms of GERD.PubMed/MEDLINE, Embase and the Cochrane library electronic databases were searched through October 2015 for randomized controlled trials comparing alginate-containing compounds to placebo, antacids, histamine-2 receptor antagonists (H2RAs) or PPIs for the treatment of GERD symptoms. Additional studies were identified through bibliography review. Non-English studies and those with pediatric patients were excluded. Meta-analyses were performed using random-effects models to calculate odds ratios (OR). Heterogeneity between studies was estimated using the I2 statistic. Analyses were stratified by type of comparator. The search strategy yielded 665 studies and 15 (2.3%) met inclusion criteria. Fourteen were included in the meta-analysis (N = 2095 subjects). Alginate-based therapies increased the odds of resolution of GERD symptoms when compared to placebo or antacids (OR: 4.42; 95% CI 2.45-7.97) with a moderate degree of heterogeneity between studies (I2 = 71%, P = .001). Compared to PPIs or H2RAs, alginates appear less effective but the pooled estimate was not statistically significant (OR: 0.58; 95% CI 0.27-1.22). Alginates are more effective than placebo or antacids for treating GERD symptoms.

Calcineurin Inhibitor Minimization, Conversion, Withdrawal, and Avoidance Strategies in Renal Transplantation: A Systematic Review and Meta-Analysis.

Despite their clinical efficacy, concerns about calcineurin inhibitor (CNI) toxicity make alternative regimens that reduce CNI exposure attractive for renal transplant recipients. In this systematic review and meta-analysis, we assessed four CNI immunosuppression strategies (minimization, conversion, withdrawal, and avoidance) designed to reduce CNI exposure and assessed the impact of each on patient and allograft survival, acute rejection and renal function. We evaluated 92 comparisons from 88 randomized controlled trials and found moderate- to high-strength evidence suggesting that minimization strategies result in better clinical outcomes compared with standard-dose regimens; moderate-strength evidence indicating that conversion to a mammalian target of rapamycin inhibitor or belatacept was associated with improved renal function but increased rejection risk; and moderate- to high-strength evidence suggesting planned CNI withdrawal could result in improved renal function despite an association with increased rejection risk. The evidence base for avoidance studies was insufficient to draw meaningful conclusions. The applicability of the review is limited by the large number of studies examining cyclosporine-based strategies and low-risk populations. Additional research is needed with tacrolimus-based regimens and higher risk populations. Moreover, research is necessary to clarify the effect of induction and adjunctive agents in alternative immunosuppression strategies and should include more comprehensive and consistent reporting of patient-centered outcomes.

Excerpt from PHS guideline for reducing HIV, HBV and HCV transmission through organ transplantation.

The intent of the PHS guideline is to improve organ transplant recipient outcomes by reducing the risk of unexpected HIV, HBV and HCV transmission, while preserving the availability of high-quality organs. An evidence-based approach was used to identify the most relevant studies and reports on which to formulate the recommendations. This excerpt from the guideline comprises (1) the executive summary; (2) 12 criteria for assessment of risk factors for recent HIV, HBV and HCV infection; (3) 34 recommendations on risk assessment (screening) of living and deceased donors; testing of living and deceased donors; informed consent discussion with transplant candidates; testing of recipients pre- and posttransplant; collection and/or storage of donor and recipient specimens; and tracking and reporting of HIV, HBV and HCV; and (4) 20 recommendations for further study. For the PHS guideline in its entirety, including the background, methodology and primary evidence underlying the recommendations, refer to the source document in Public Health Reports, accessible at http://www.publichealthreports.org/issuecontents.cfm?Volume=128&Issue=4. For more in-depth information on the evidence base, including tables of all study-level data, refer to Solid Organ Transplantation and the Probability of Transmitting HIV, HBV or HCV: A Systematic Review to Support an Evidence-Based Guideline, accessible at http://stacks.cdc.gov/view/cdc/12164/.

Economic value of norovirus outbreak control measures in healthcare settings.

Although norovirus is a significant cause of nosocomial viral gastroenteritis, the economic value of hospital outbreak containment measures following identification of a norovirus case is currently unknown. We developed computer simulation models to determine the potential cost-savings from the hospital perspective of implementing the following norovirus outbreak control interventions: (i) increased hand hygiene measures, (ii) enhanced disinfection practices, (iii) patient isolation, (iv) use of protective apparel, (v) staff exclusion policies, and (vi) ward closure. Sensitivity analyses explored the impact of varying intervention efficacy, number of initial norovirus cases, the norovirus reproductive rate (R(0)), and room, ward size, and occupancy. Implementing increased hand hygiene, using protective apparel, staff exclusion policies or increased disinfection separately or in bundles provided net cost-savings, even when the intervention was only 10% effective in preventing further norovirus transmission. Patient isolation or ward closure was cost-saving only when transmission prevention efficacy was very high (≥ 90%), and their economic value decreased as the number of beds per room and the number of empty beds per ward increased. Increased hand hygiene, using protective apparel or increased disinfection practices separately or in bundles are the most cost-saving interventions for the control and containment of a norovirus outbreak.

Maximizing the clinical utility of comparative effectiveness research.

Providers, consumers, payers, and policy makers are awash in choices when it comes to medical decision making and need better evidence to inform their decisions. Large federal investments in comparative effectiveness research (CER) aim to fill this need. But how do we ensure the clinical utility of CER? Here, I define comparative effectiveness and clinical utility, outline metrics to evaluate clinical utility, and suggest methods for maximizing the clinical utility of CER for the various stakeholders.

Up-regulation of oxytocin receptor messenger ribonucleic acid and protein by estradiol in the cervix of ovariectomized rat.

Oxytocin receptor (OTR) regulation has been extensively studied in uterine myometrium and endometrium. However, studies in the cervix are limited. The present studies utilized in situ hybridization and immunocytochemistry to localize OTR mRNA and protein distribution in cervices of nonpregnant ovariectomized (OVX) rats and examined the effect of combined and independent treatments with estradiol and progesterone on cervical OTR. Thirteen nonpregnant rats were bilaterally OVX under general anesthesia. At least 7 days later, the rats were exposed to one of four different treatments 24 h prior to necropsy: 1) estradiol (50 microg, n = 4); 2) progesterone (10 mg, n = 3); 3) both estradiol (50 microg) and progesterone (10 mg) (n = 3); 4) corn oil vehicle (n = 3). After 24-h estradiol treatment, OTR mRNA increased significantly (p < 0.05) in smooth muscle cells of the rat cervix as a result of increased copy numbers of OTR mRNA per cell as well as an increased population of OTR mRNA-positive cells. Progesterone alone had no effect on OTR mRNA expression; however, progesterone combined with estradiol significantly inhibited the up-regulation of OTR mRNA by estradiol alone. The increase of OTR mRNA in cervical epithelial cells was minimal in all situations. Intensity of cervical OTR immunostaining in both the epithelial cells and cervical smooth muscle cells was also elevated after estradiol treatment. The anti-rat OTR antiserum used for immunocytochemistry was validated by Western blot analysis. In conclusion, OTR and OTR mRNA were localized in smooth muscle cells and in epithelial cells of rat cervix. Estradiol-dependent activation of OTR gene expression and active OTR synthesis in smooth muscle cells account for the increased OTR level in rat cervix in vivo, in which progesterone acted as an antagonist of estradiol on OTR gene expression.