Baricitinib: The Second FDA-Approved JAK Inhibitor for the Treatment of Rheumatoid Arthritis.

Objective: To review the pharmacology, pharmacokinetics, safety, and efficacy of baricitinib, a recently approved selective Janus Kinase (JAK) inhibitor for the treatment of rheumatoid arthritis (RA), and explore its potential role in therapy. Data Sources: Articles were identified using a PubMed search from inception through January 2019 using the terms rheumatoid arthritis, Olumiant, baricitinib, and LY3009104, its molecular name. Study Selection and Data Extraction: Articles relating to randomized clinical trials, pharmacology, pharmacokinetics, efficacy, and safety of baricitinib were evaluated. Data Synthesis: Baricitinib exerts its effects by inhibiting JAK1 and JAK2 enzymes, targeting cytokine and growth factor receptor stimulation, thus reducing downstream immune cell function. Four trials have demonstrated the efficacy of baricitinib with or without methotrexate in patients naïve to disease-modifying antirheumatic drugs (DMARDs) and those who had an inadequate response to or intolerance to both conventional and biological DMARDs. Furthermore, baricitinib was associated with delayed radiographic progression. Despite baricitinib 4 mg often demonstrating greater efficacy compared with the 2 mg dose, only the 2 mg dose is Food and Drug Administration approved because of safety concerns with the 4 mg dose, primarily thromboembolism. Relevance to Patient Care and Clinical Practice: Baricitinib provides an oral treatment option for patients failing tumor necrosis factor inhibitors (TNFis). Safety, cost, and comparative effectiveness to tofacitinib should be considered prior to prescribing baricitinib. Conclusion: Baricitinib is the second medication in its class and has been proven efficacious for the treatment of RA. Given concerns for adverse effects associated with baricitinib, it should be reserved for patients who have failed one or more TNFis.

Provider beliefs about the ideal design of an opioid deprescribing and substitution intervention for older adults.

PURPOSE: Opportunities exist to meaningfully reduce suboptimal prescription opioid use among older adults. Deprescribing is one possible approach to reducing suboptimal use. Appropriate interventions should outline how to carefully taper opioids, closely monitor adverse events, substitute viable alternative and affordable nonopioid pain treatments, and initiate medications for opioid use disorder to properly manage use disorders, as needed. We sought to document and understand provider perceptions to begin developing effective and safe opioid deprescribing interventions. METHODS: We conducted 3 semistructured focus groups that covered topics such as participant perspectives on opioid deprescribing in older adults, how to design an ideal intervention, and how to identify potential barriers or facilitators in implementing an intervention. Focus group transcripts were double coded and qualitatively analyzed to identify overarching themes. RESULTS: Healthcare providers (n = 17), including physicians, pharmacists, nurses, social workers, and administrative staff, participated in 3 focus groups. We identified 4 key themes: (1) involve pharmacists in deprescribing and empower them as leaders of an opioid deprescribing service; (2) ensure tight integration and close collaboration throughout the deprescribing process from the inpatient to outpatient settings; (3) more expansive inclusion criteria than age alone; and (4) provision of access to alternative pharmacological and nonpharmacological pain management modalities to patients. CONCLUSION: Our findings, which highlight various healthcare provider beliefs about opioid deprescribing interventions, are expected to serve as a framework for other organizations to develop and implement interventions. Future studies should incorporate patients' and family caregivers' perspectives.

Development and validation of the Tool for Pharmacists to Predict 30-day hospital readmission in patients with Heart Failure (ToPP-HF).

PURPOSE: Pharmacists are well positioned to provide transitions of care (TOC) services to patients with heart failure (HF); however, hospitalizations for patients with HF likely exceed the capacity of a TOC pharmacist. We developed and validated a tool to help pharmacists efficiently identify high-risk patients with HF and maximize their potential impact by intervening on patients at the highest risk for 30-day all-cause readmission. METHODS: We conducted a retrospective cohort study including adults with HF admitted to a health system between October 1, 2016, and October 31, 2019. We randomly divided the cohort into development (n = 2,114) and validation (n = 1,089) subcohorts. Nine models were applied to select the most important predictors of 30-day readmission. The final tool, called the Tool for Pharmacists to Predict 30-day hospital readmission in patients with Heart Failure (ToPP-HF) relied upon multivariable logistic regression. We assessed discriminative ability using the C statistic and calibration using the Hosmer-Lemeshow goodness-of-fit test. RESULTS: The risk of 30-day all-cause readmission was 15.7% (n = 331) and 18.8% (n = 205) in the development and validation subcohorts, respectively. The ToPP-HF tool included 13 variables: number of hospital admissions in previous 6 months; admission diagnosis of HF; number of scheduled medications; chronic obstructive pulmonary disease diagnosis; number of comorbidities; estimated glomerular filtration rate; hospital length of stay; left ventricular ejection fraction; critical care requirement; renin-angiotensin-aldosterone system inhibitor use; antiarrhythmic use; hypokalemia; and serum sodium. Discriminatory performance (C statistic of 0.69; 95% confidence interval [CI], 0.65-0.73) and calibration (Hosmer-Lemeshow P = 0.28) were good. CONCLUSIONS: The ToPP-HF performs well and can help pharmacists identify high-risk patients with HF most likely to benefit from TOC services.

Impact of antibiotic choice on readmission in adults experiencing an acute COPD exacerbation.

PURPOSE: The impact of antibiotic therapy in managing acute chronic obstructive pulmonary disease (COPD) exacerbations requiring hospitalization remains unclear. We conducted a study to assess the impact of antibiotic therapy on the rate of 30-day readmission after discharge from a hospital stay for an acute COPD exacerbation. Additional study outcomes analyzed included the effects of antibiotic therapy on hospital length of stay, in-hospital mortality, 90-day and 12-month readmission rates, and time to next COPD exacerbation. METHODS: The study was an institutional review board-approved, retrospective, observational review of adult patients at a tertiary academic medical center. The medical records of patients 18 years of age or older who were hospitalized for an acute COPD exacerbation between January 2008 and December 2014 were evaluated. Included patients were stratified by receipt of guideline-appropriate, guideline-inappropriate, or no antibiotic therapy. Nonparametric data were analyzed using the Kruskal-Wallis test (nonparametric) and categorical data via χ 2 test, respectively. RESULTS: Three hundred twenty-five subjects were included; there were no significant differences in baseline characteristics in the 3 study groups. Sixty-eight percent of patients (n = 223) received antibiotics. The percentage of patients readmitted within 30 days did not differ between cohorts: 11.9% (appropriate therapy) vs 13.2% (nonappropriate therapy) vs 12.2% (no antibiotics) (P = 0.95 for all comparisons). Additionally, no detectable differences in 90-day or 12-month readmission rate, length of hospital day, or in-hospital mortality were found. However, a trend toward increased time to next COPD exacerbation was noted in those receiving antibiotics vs no antibiotics (352 days vs 192 days, P = 0.07). CONCLUSION: Treatment of COPD exacerbations with antibiotics did not impact readmission rates, length of hospital stay, in-hospital mortality, or time to next exacerbation. More investigation is warranted to assess the effect of antibiotics on time to next exacerbation, as well as comparative effectiveness between antibiotic classes.

Strain typing of Mycoplasma cynos isolates from dogs with respiratory disease.

The association of Mycoplasma cynos with canine infectious respiratory disease is increasingly being recognised. This study describes the strain typing of 14 M. cynos isolates cultured from trachea and bronchoalveolar lavage samples of six dogs with respiratory disease, from two separate kennels in the United Kingdom. The genetic similarity of the isolates was investigated using pulsed-field gel electrophoresis (PFGE) and random amplified polymorphic DNA (RAPD). Most of the isolates from four dogs housed at a re-homing kennel were genetically similar and some isolates from different dogs were indistinguishable by both PFGE and RAPD. These isolates were cultured from dogs with non-overlapping stays in the kennel, which may indicate maintenance of some strains within kennels. A small number of isolates showed much greater genetic heterogeneity and were genetically distinct from the main group of M. cynos strains. There was also a high degree of similarity of the M. cynos type strain (isolated from a dog with respiratory disease in Denmark in 1971) to at least one of the United Kingdom isolates using PFGE analysis, which may suggest possible conservation of pathogenic strains of M. cynos.

RNase P RNA gene (rnpB) phylogeny of Hemoplasmas and other Mycoplasma species.

Partial sequences of the RNase P RNA gene (rnpB) were obtained from a number of hemoplasmas and other Mycoplasma species. Phylogenetic analysis of these sequences showed that all hemoplasmas were present within a single clade and were most closely related to Mycoplasma fastidiosum, similar to the results found with 16S rRNA gene phylogeny.

VNTR analysis reveals unexpected genetic diversity within Mycoplasma agalactiae, the main causative agent of contagious agalactia.

BACKGROUND: Mycoplasma agalactiae is the main cause of contagious agalactia, a serious disease of sheep and goats, which has major clinical and economic impacts. Previous studies of M. agalactiae have shown it to be unusually homogeneous and there are currently no available epidemiological techniques which enable a high degree of strain differentiation. RESULTS: We have developed variable number tandem repeat (VNTR) analysis using the sequenced genome of the M. agalactiae type strain PG2. The PG2 genome was found to be replete with tandem repeat sequences and 4 were chosen for further analysis. VNTR 5 was located within the hypothetical protein MAG6170 a predicted lipoprotein. VNTR 14 was intergenic between the hypothetical protein MAG3350 and the hypothetical protein MAG3340. VNTR 17 was intergenic between the hypothetical protein MAG4060 and the hypothetical protein MAG4070 and VNTR 19 spanned the 5' end of the pseudogene for a lipoprotein MAG4310 and the 3' end of the hypothetical lipoprotein MAG4320. We have investigated the genetic diversity of 88 M. agalactiae isolates of wide geographic origin using VNTR analysis and compared it with pulsed field gel electrophoresis (PFGE) and random amplified polymorphic DNA (RAPD) analysis. Simpson's index of diversity was calculated to be 0.324 for PFGE and 0.574 for VNTR analysis. VNTR analysis revealed unexpected diversity within M. agalactiae with 9 different VNTR types discovered. Some correlation was found between geographical origin and the VNTR type of the isolates. CONCLUSION: VNTR analysis represents a useful, rapid first-line test for use in molecular epidemiological analysis of M. agalactiae for outbreak tracing and control.

UK epidemic strains of meticillin-resistant Staphylococcus aureus in clinical samples from Malta.

Since 1999, the European Antimicrobial Resistance Surveillance System (EARSS) has monitored the rise in infection due to a number of organisms, including meticillin-resistant Staphylococcus aureus (MRSA). The EARSS reported that MRSA infections within intensive care units account for 25-50 % of infections in many central and southern European countries, these included France, Spain, Great Britain, Malta, Greece and Italy. Each country has defined epidemic MRSA (EMRSA) strains; however, the method of spread of these strains from one country to another is unknown. In this current study, DNA profiles of 473 isolates of MRSA collected from the UK and Malta were determined by PFGE. Analysis of the data showed that two countries separated by a large geographical distance had a similar DNA profile pattern. Additionally it was demonstrated that strains of EMRSA normally found in the UK were also found in the Maltese cohort (EMRSA 15 and 16). A distinct DNA profile was found in the Maltese cohort, which may be a local EMRSA, and accounted for 14.4 % of all Maltese isolates. The appearance of the same MRSA and EMRSA profiles in two separate countries suggests that MRSA can be transferred out of their country of origin and potentially establish in a new locality or country.

Isolation of Mycoplasma bovis from broiler chickens in Turkey.

Mycoplasma bovis normally affects cattle, in which it causes pneumonia in calves, mastitis, arthritis and other diseases. In the present article we report the isolation of this bovine pathogen from the tracheas of broiler chickens with no clinical signs. The most probable source of infection was the cattle herd sharing the farm with the chickens.

Biofilm-grown Mycoplasma mycoides subsp. mycoides SC exhibit both phenotypic and genotypic variation compared with planktonic cells.

Biofilm formation where bacterial cells adhere to a surface and surround themselves in a polysaccharide matrix is thought to be an important factor in disease initiation and persistence for many bacterial species. We have examined biofilm formation by Mycoplasma mycoides subsp. mycoides small colony using a simple model without an air/liquid interface and have found that adherent Mmm SC was more resistant to many stresses, including heat, osmotic shock and oxidative stress. Biofilms of Mmm SC also exhibited remarkable persistence and were able to survive for up to 20 weeks in stationary phase. Significant variation was seen between Mmm SC strains in their ability to form a biofilm and the morphology of the biofilm produced with some strains unable to produce microcolonies. Proteomic analysis found that a number of proteins linked to adherence were over-expressed in biofilms compared with planktonic cells.

Development and validation of a transitions-of-care pharmacist tool to predict potentially avoidable 30-day readmissions.

PURPOSE: A practical tool for predicting the risk of 30-day readmissions using data readily available to pharmacists before hospital discharge is described. METHODS: A retrospective cohort study to identify predictors of potentially avoidable 30-day readmissions was conducted using transitions-of-care pharmacy notes and electronic medical record data from a large health system. Through univariate and multivariable logistic regression analyses of factors associated with unplanned readmissions in the study cohort (n = 690) over a 22-month period, a risk prediction tool was developed. The tool's discriminative ability was assessed using the C statistic; its calibration was assessed using the Hosmer-Lemeshow goodness-of-fit test. RESULTS: Three factors predictive of readmission risk were identified; these variables-medication count, comobidity count, and health insurance status at discharge-form the 3-predictor MEDCOINS score. Among patients identified as being at high risk for readmission using the MEDCOINS tool, the estimated readmission risk was 22.5%, as compared with an observed readmission rate of 21.9%. The discriminatory performance of MEDCOINS scoring was fair (C statistic = 0.65 [95% confidence interval, 0.60-0.70]), with good calibration (Hosmer-Lemeshow p = 0.99). CONCLUSION: Among a cohort of patients who were seen by a transitions-of-care pharmacist during an inpatient hospitalization, comorbidity burden, number of medications, and health insurance coverage were most predictive of 30-day readmission. The MEDCOINS tool was found to have fair discriminative ability and good calibration.

Identification and characterization of variable-number tandem-repeat markers for the molecular epidemiological analysis of Mycoplasma mycoides subspecies mycoides SC.

Variable-number tandem-repeat (VNTR) analysis has been developed for the causative agent of contagious bovine pleuropneumonia using the genome of Mycoplasma mycoides subspecies mycoides small colony (M.m.m. SC) PG1. Genome analysis identified 60 VNTRs within the M.m.m. SC genome; however, screening of these VNTRs with a panel of strains identified only three VNTRs that gave allelic variation. Testing of three VNTRs against 39 strains of diverse geographical origin gave 12 different VNTR profiles groups. VNTR analysis may represent a new rapid tool for subtyping M.m.m. SC isolates.

The detection of Mycoplasma (formerly Eperythrozoon) wenyonii by 16S rDNA PCR and denaturing gradient gel electrophoresis.

Although the role of Mycoplasma wenyonii in disease is still subject to some debate, infections have been reported to result in parasitaemia, anaemia, scrotal and hind limb oedema, tachycardia, pyrexia, infertility, swollen teats, prefemoral lymphadenopathy and decreased milk production. Previously, diagnosis of M. wenyonii has been based on blood smears but is not specific for M. wenyonii and can be difficult to interpret. We have previously described the use of PCR and denaturing gradient gel electrophoresis (DGGE) for the detection and differentiation of Mycoplasma species. DGGE enables the rapid and specific identification of Mycoplasma species and is ideally suited to detecting both mixed infections and new and unusual species. In this study, we have used DGGE with universal primers to detect M. wenyonii DNA from blood samples. DGGE can be used on blood samples as a rapid and specific test for M. wenyonii and can also be used as a screening test for other blood borne pathogens.

Identification and differentiation of European and African/Australian strains of Mycoplasma mycoides subspecies mycoides small-colony type using polymerase chain reaction analysis.

Mycoplasma mycoides subspecies mycoides small-colony type (M. m. m. SC) is the cause of the economically important contagious bovine pleuropneumonia. Isolates from Africa and Australia have previously been documented to have a fragment of approximately 8.84 kb, which is absent in European strains. A set of polymerase chain reaction (PCR) primers over this region was designed to identify M. m. m. SC isolates and separate European strains from those of Africa/Australia. Specificity of the PCR assay was achieved through the positioning of an oligonucleotide within the insertion sequence IS1296, upstream of this deletion, which then was paired with a reverse primer, upstream of the deletion, within the 8.84 kb-deleted region or downstream of the deletion, generating fragments of 1.1 kb (all M. m. m. SC strains), 1.4 kb (African/Australian strains only) and 1.3 kb (European strains only), respectively. Identification and differentiation was specific for DNA from M. m. m. SC with no amplification of DNA from other cluster members or closely related species. The PCR products did not require differentiation by use of a restriction endonuclease, and have potential for use in detection of this organism in clinical samples.

Targeted Immunomodulatory Therapy: An Overview.

Monoclonal antibodies and other biologic response modifiers have allowed for targeted drug therapy in managing various autoimmune diseases. A number of immune pathways have been exploited in the development of targeted immunomodulatory therapies, including cytokine-directed therapies such as tumor necrosis factor-alpha and interleukins, integrins, B-cells, and co-stimulation modulators. With new targeted therapies in the pipeline, more options are becoming available for treatment of autoimmune diseases. [Full article available at http://rimed.org/rimedicaljournal-2016-12.asp].

16S rDNA PCR and denaturing gradient gel electrophoresis; a single generic test for detecting and differentiating Mycoplasma species.

Diagnosis of Mycoplasma infection is normally based on culture and serological tests, which can be time-consuming and laborious. A number of specific PCRs have been developed but to date there has not been a single generic test capable of detecting and differentiating mycoplasmas to a species level. This report describes the development of a new diagnostic test based on PCR of the 16S rRNA gene with Mycoplasma-specific primers and separation of the PCR product according to primary sequence using denaturing gradient gel electrophoresis (DGGE). DGGE enabled the differentiation of 67 Mycoplasma species of human and veterinary origin and represents a significant improvement on current tests as diagnosis of Mycoplasma infection can be made directly from clinical samples in less than 24 h.

Insertion sequence profiling of UK Mycoplasma bovis field isolates.

The presence and distribution of insertion sequences ISMbov2 and ISMbov3 within Mycoplasma bovis were investigated. Analysis was carried out by Southern blotting using specific probes of 221 bp and 185 bp, to detect ISMbov2 and ISMbov3, respectively, amplified from the homologous sequences ISMmy1 and IS1634 within Mycoplasma mycoides subspecies mycoides small colony type. We present data obtained from 49 field isolates of M. bovis, originating from pneumonic lungs, collected within the United Kingdom between 1996 and 2002. Hybridisation profiles show considerable variation between strains. ISMbov2 sequences are present between 2 and 17 copies while there are between 3 and 14 copies of the IS1634 homologue ISMbov3. These data also provide support for previous analysis by random amplified polymorphic DNA (RAPD) and amplified fragment length polymorphism (AFLP).

Rapid detection of Mycoplasma dispar and M. bovirhinis using allele specific polymerase chain reaction protocols.

We describe an allele specific PCR based approach for the rapid detection of two bovine Mycoplasma species associated with respiratory disease. Specific and universal oligonucleotides were used in combination to detect the presence of single nucleotide polymorphisms within the 16S ribosomal DNA sequence. Presence of Mycoplasma 16S rDNA is indicated by the production of a single control fragment, whilst positive samples generate an alternative smaller specific product over the same region. This technique provides a reliable and sensitive method which, although widely used in human genetic screening, has not been documented for diagnosis of bacterial infection.