Promoting community stakeholder engagement in research on treatment for pregnant women with opioid use disorder.

Aim: Community stakeholder engagement in research (CSER) can improve research relevance and efficiency as well as prevent harmful practices, particularly for vulnerable populations. Despite potential benefits, researchers lack familiarity with CSER methods. Methods: We describe CSER strategies used across the research continuum, including proposal development, study planning and the first years of a comparative effectiveness study of care for pregnant women with opioid use disorder. Results: We highlight successful strategies, grounded in principles of engagement, to establish and maintain stakeholder relationships, foster bidirectional communication and trust and support active participation of women with opioid use disorder in the research process. Conclusion: CSER methods support research with a disenfranchised population. Future work will evaluate the impact of CSER strategies on study outcomes and dissemination.

Community stakeholder engagement in research on treatment for pregnant women with opioid use disorder builds and maintains stakeholder relationships, fosters communication and trust and supports active patient participation.

Improving care for individuals with serious infections who inject drugs.

Background: Hospitalizations for serious infections requiring long-term intravenous (IV) antimicrobials related to injection drug use have risen sharply over the last decade. At our rural tertiary care center, opportunities for treatment of underlying substance use disorders were often missed during these hospital admissions. Once medically stable, home IV antimicrobial therapy has not traditionally been offered to this patient population due to theoretical concerns about misuse of long-term IV catheters, leading to discharges with suboptimal treatment regimens, lengthy hospital stays, or care that is incongruent with patient goals and preferences. Methods: A multidisciplinary group of clinicians and patients set out to redesign and improve care for this patient population through a health care innovation process, with a focus on increasing the proportion of patients who may be discharged on home IV therapy. Baseline assessment of current experience was established through retrospective chart review and extensive stakeholder analysis. The innovation process was based in design thinking and facilitated by a health care delivery improvement incubator. Results: The components of the resulting intervention included early identification of hospitalized people who inject drugs with serious infections, a proactive psychiatry consultation service for addiction management for all patients, a multidisciplinary care conference to support decision making around treatment options for infection and substance use, and care coordination/navigation in the outpatient setting with a substance use peer recovery coach and infectious disease nurse for patients discharged on home IV antimicrobials. Patients discharged on home IV therapy followed routine outpatient parenteral antimicrobial therapy (OPAT) protocols and treatment protocols for addiction with their chosen provider. Conclusion: An intervention developed through a design-thinking-based health care redesign process improved patient-centered care for people with serious infections who inject drugs.

Atypia of Undetermined Significance in Thyroid Fine Needle Aspirates: a 4-Year Audit of Thy3a Reporting.

OBJECTIVE: Thyroid nodules are common within the general population. Cytological analysis of fine needle aspirates (FNAs) of these lesions allows for identification of those that require further surgery. A numerical classification system is in place to streamline reporting. The 3a category is used for lesions that are neither benign nor malignant but show atypia of undetermined significance. We reviewed our use and clinical outcomes of Thy3a over a 4-year period. METHODS: All thyroid FNAs performed at this institute from January 2012 to December 2015 were identified from our laboratory information system using SNOMED codes. Cytology was correlated with histology. RESULTS: Of the 1,259 FNAs reported at this institute, Thy3a constituted only 1.2% (n = 16) of all cases, with a malignancy rate of 7%. Five Thy3a cases had a repeat FNA that was reported as Thy2 (benign), 1 as Thy1c (cyst), 1 as Thy3f (follicular lesion), and 1 as Thy5 (malignant). Six cases without repeat FNA were follicular adenomas at resection. Two cases were lost to follow-up. Within all thyroid cytology categories in this 4-year period, we had a false-positive rate of 1.9% and a false-negative rate of 0.3%. CONCLUSIONS: The Thy3a subclassification has varied diagnostic criteria and lacks reproducibility. Despite the rare use of the Thy3a category at our centre, our diagnostic accuracy remained high. At this time, further Thy3a cohort studies are required to assess the real benefits of this category.

Comparison of radium-228 determination in water among Australian laboratories.

The National Health and Medical Research Council and Natural Resource Management Ministerial Council of Australia developed the current Australian Drinking Water Guidelines which recommend an annual radiation dose value of 1 mSv year-1. One of the potential major contributors to the radiation dose from drinking water is radium-228, a naturally occurring radionuclide arising from the thorium decay series. Various methods of analysing for radium-228 in water have been established and adapted by analytical radiochemistry laboratories. Seven laboratories in Australia participated in analysing radium-228 spiked water samples with activity concentrations ranging from 6 mBq L-1 to 20 Bq L-1. The aim of the exercise was to compare and evaluate radium-228 results reported by the participating laboratories, the methods used and the detection limits. This paper presents the outcome of the exercise.

Steroidal contraceptives and bone fractures in women: evidence from observational studies.

BACKGROUND: Age-related decline in bone mass increases the risk of skeletal fractures, especially those of the hip, spine, and wrist. Steroidal contraceptives have been associated with changes in bone mineral density in women. Whether such changes affect the risk of fractures later in life is unclear. Hormonal contraceptives are among the most effective and most widely-used contraceptives. Concern about fractures may limit the use of these effective contraceptives. Observational studies can collect data on premenopausal contraceptive use as well as fracture incidence later in life. OBJECTIVES: We systematically reviewed the evidence from observational studies of hormonal contraceptive use for contraception and the risk of fracture in women. SEARCH METHODS: In May 2012, we searched for observational studies. The databases included MEDLINE, POPLINE, Cochrane Central Register of Controlled Trials (CENTRAL), LILACS, EMBASE, CINAHL, and Web of Science. We also searched for recent clinical trials through ClinicalTrials.gov and the ICTRP. For other studies, we examined reference lists of relevant articles and wrote to investigators for additional reports. SELECTION CRITERIA: We included cohort and case-control studies of hormonal contraceptive use. Interventions included comparisons of a hormonal contraceptive with a nonhormonal contraceptive, no contraceptive, or another hormonal contraceptive. The primary outcome was the risk of fracture. DATA COLLECTION AND ANALYSIS: Two authors independently extracted the data. One author entered the data into RevMan, and a second author verified accuracy. We examined the quality of evidence using the Newcastle-Ottawa Quality Assessment Scale (NOS), developed for case-control and cohort studies. Sensitivity analysis included studies of moderate or high quality based on our assessment with the NOS.Given the need to control for confounding factors in observational studies, we used adjusted estimates from the models as reported by the authors. Where we did not have adjusted analyses, we calculated the odds ratio (OR) with 95% confidence interval (CI). Due to varied study designs, we did not conduct meta-analysis. MAIN RESULTS: We included 14 studies (7 case-control and 7 cohort studies). These examined oral contraceptives (OCs) (N=12), depot medroxyprogesterone acetate (DMPA) (N=4), and the hormonal intrauterine device (IUD) (N=1). This section focuses on evidence from the six studies with moderate or high quality evidence that we included in the sensitivity analysis.All six studies examined oral contraceptive use. We noted few associations with fracture risk. One cohort study found OC ever-users had increased risk for all fractures (reported RR 1.20; 95% CI 1.08 to 1.34). However, a case-control study with later data from a subset reported no association except for those with 10 years or more since use (reported OR 1.55; 95% CI 1.03 to 2.33). Another case-control study reported increased risk only for those who had 10 or more prescriptions (reported OR 1.09; 95% CI 1.03 to 1.16). A cohort study of postmenopausal women found no increased fracture risk for OC use after excluding women with prior fracture. Two other studies found little evidence of association between OC use and fracture risk. A cohort study noted increased risk for subgroups, such as those with longer use or specific intervals since use. A case-control study reported increased risk for any fracture only among young women with less than average use.Two case-control studies in the sensitivity analysis also examined progestin-only contraceptives. One reported increased fracture risk for DMPA ever-use (reported OR 1.44 (95% CI 1.01 to 2.06), more than four years of use (reported OR 2.16; 95% CI 1.32 to 3.53), and women over 50 years old. The other noted increased risk for any past use, including one or two prescriptions (reported OR 1.17; 95% CI 1.07 to 1.29), and for current use of 3 to 9 or 10 or more prescriptions. In addition, one study reported reduced fracture risk for ever-use of the hormonal IUD (reported OR 0.75; 95% CI 0.64 to 0.87) and longer use of that IUD. AUTHORS' CONCLUSIONS: Observational studies do not indicate an overall association between OC use and fracture risk. Some reported increased risk for specific user subgroups. DMPA users may have an increased fracture risk. One study indicated hormonal IUD use may be associated with decreased risk. Observational studies need adjusted analysis because the comparison groups usually differ. Researchers should be clear about the variables examined in multivariate analysis.

Pegylated interferon-α induced hypoferremia is associated with the immediate response to treatment in hepatitis C.

UNLABELLED: Pegylated interferon-α (PEG-IFN-α) forms an integral part of the current treatment for hepatitis C virus (HCV) infection. PEG-IFN-α suppresses HCV production by augmenting the innate antiviral immune response. Recent studies have reported the induction of hepcidin, the iron regulatory hormone, by IFN-α in vitro. As hepcidin plays an important role in innate immunity, we hypothesized that this finding may be of clinical relevance to HCV and investigated the changes in iron homeostasis during the first 24 hours of treatment. Blood samples were obtained from HCV patients immediately prior to and 6, 12, and 24 hours following the first dose of PEG-IFN-α/ribavirin (RBV). Samples were analyzed for hepcidin, cytokine, iron levels, and HCV viral load, and hepcidin messenger RNA (mRNA) expression was quantified in peripheral blood mononuclear cells. Hepcidin induction by IFN-α was further analyzed in cell culture. In HCV patients a single dose of PEG-IFN-α/RBV resulted in a significant increase in serum hepcidin, peaking at 12 hours, coinciding with a 50% reduction in serum iron and transferrin saturation over the 24-hour period. Patients with a ≥ 2 log decline in HCV viral load over the first 24 hours had significantly lower SI and TS levels at 12 and 24 hours. Moreover, 24-hour SI levels were an independent predictor of the immediate HCV viral decline, an indicator of ultimate treatment outcome. In cell culture, a direct induction of hepcidin by IFN-α was seen, controlled by the STAT3 transcription factor. CONCLUSION: Hepcidin induction occurs following the initiation of PEG-IFN-α treatment for HCV, and is mediated by way of STAT3 signaling. The subsequent hypoferremia was greatest in those with the most significant decline in viral load, identifying systemic iron withdrawal as a marker of immediate interferon-α efficacy in HCV patients.

Ask and act: Delaware physicians demonstrate the effectiveness of the American Academy of Family Physicians' initiative to promote tobacco cessation counseling.

The Ask and Act program of the American Academy of Family Physicians promotes family physician tobacco cessation counseling. Smoking and cessation counseling rates were obtained by cross-sectional analysis of electronic medical record data before and after initiation of the Ask and Act program in Delaware. Before the intervention, 24% of the patient population sampled were smokers and 70% of smokers had been counseled to quit smoking. After the intervention, 17% of the patient population sampled were smokers and 98% of smokers had been counseled. Our observations suggest that the Ask and Act program increases counseling, thereby increasing smoking cessation.

Olefination and group transfer reactions of an electron deficient tantalum methylidene complex.

The reactivity of an electronically unsaturated tantalum methylidene complex [TolC(NSiMe(3))(2)](2)Ta(CH(2))CH(3) supported by [TolC(NSiMe(3))(2)] amidinate ligands is described. Electrophilic addition and olefination reactions of the Ta=CH(2) functionality are reported. Alkylidene participates in group-transfer reactions not observed in sterically similar, but electronically saturated, analogues. Reactions with substrates containing unsaturated C-X (X = C, N, O) bonds yield [Ta]=X compounds and vinylated organic products; carbon-sulfur cleavage reactions to produce tantalum thioformaldehyde and tantalum sulfido complexes.