Which domains of the theoretical domains framework should be targeted in interventions to increase adherence to antihypertensives? A systematic review.

Nonadherence to antihypertensives is prevalent and is associated with poorer health outcomes. This study aimed to identify psychological factors associated with adherence in patients taking antihypertensives as these are potentially modifiable, and can, therefore, inform the development of effective interventions to increase adherence. PubMed, EMBASE and PsychINFO were searched to identify studies that tested for significant associations between psychological domains and adherence to antihypertensives. The domains reported were categorized according to the Theoretical Domains Framework. The quality of included studies was evaluated using the National Institute for Clinical Excellence critical appraisal of questionnaire checklist. Thirty-one studies were included. Concerns about medicines (a subdomain of 'beliefs about consequences') and 'beliefs about capabilities' consistently showed association with adherence in over five studies. Healthcare professionals should actively ask patients if they have any concerns about their antihypertensives and their belief in their ability to control their blood pressure through taking antihypertensives.

Cost-Effectiveness of Combination of Baricitinib and Remdesivir in Hospitalized Patients with COVID-19 in the United States: A Modelling Study.

INTRODUCTION: Baricitinib-remdesivir (BARI-REM) combination is superior to remdesivir (REM) in reducing recovery time and accelerating clinical improvement among hospitalized patients with coronavirus disease 2019 (COVID-19), specifically those receiving high-flow oxygen/noninvasive ventilation. Here we assessed the cost-effectiveness of BARI-REM versus REM in hospitalized patients with COVID-19 in the USA. METHODS: A three-state model was developed addressing costs and patient utility associated with COVID-19 hospitalization, immediate post hospital care, and subsequent lifetime medical care. Analysis was performed from the perspective of a payer and a hospital. Both perspectives evaluated two subgroups: all patients and patients who required oxygen. The primary measures of benefit in the model were patient quality-adjusted life years (QALYs) accrued during and after hospitalization, cost per life years gained, cost per death avoided, and cost per use of mechanical ventilation avoided. RESULTS: In the base-case payer perspective with a lifetime horizon, treatment with BARI-REM versus REM resulted in an incremental total cost of $7962, a gain of 0.446 life years and gain of 0.3565 QALYs over REM. The incremental cost-effectiveness ratios of using BARI-REM were estimated as $22,334 per QALY and $17,858 per life year. The base-case and sensitivity analyses showed that the total incremental cost per QALY falls within the reduced willingness-to-pay threshold of $50,000/QALY applied under health emergencies. In all hospitalized patients, treatment with BARI-REM versus REM reduced total hospital expenditures per patient by $1778 and total reimbursement payments by $1526, resulting in a $252 reduction in net costs per patient; it also resulted in a net gain of 0.0018 QALYs and increased survival of COVID-19 hospitalizations by 2.7%. CONCLUSION: Our study showed that BARI-REM is cost-effective compared to using REM for hospitalized patients with COVID-19. The base-case results of this cost-effectiveness model were most sensitive to average annual medical costs for recovered patients.

Vapour, gas, dust and fume occupational exposures in male patients with rheumatoid arthritis resident in Cornwall (UK) and their association with rheumatoid factor and anti-cyclic protein antibodies: a retrospective clinical study.

OBJECTIVES: To quantify exposure to vapour, gas, dust and fumes (VGDF) and smoking in male rheumatoid arthritis (RA) and investigate impact on rheumatoid factor (RF) and anti-citrullinated protein antibody (ACPA) levels. DESIGN: A retrospective observational study. SETTING: The Royal Cornwall Hospital Trust, UK. A single university hospital setting. PARTICIPANTS: 726 men followed up between February 2015 and August 2016, fulfilling RA diagnostic criteria. MAIN OUTCOME MEASURES: Prevalence of VGDF exposure and smoking prior to RA diagnosis. Determination of association between VGDF, smoking and autoantibody levels. RESULTS: 546/726 (75%) had been exposed to VGDF for >1 year. 561/726 (77%) had been smokers. Only 58/726 (8%) had no exposure to VGDF and had never smoked. A significant difference in RF levels was observed between unexposed and VGDF exposed never smokers (median RF 24 vs 36, p=0.03), more marked when comparing unexposed with ≥2 VGDF exposures (median RF 24 vs 57, p=0.02). A significant difference in RF levels was also observed between unexposed and VGDF exposed smokers (median RF 71 vs RF 95, p=0.04), more marked when comparing unexposed with ≥2 VGDF exposures (median RF 71 vs RF 113, p=0.01). A significant difference in RF titre was observed between never smokers >2 VGDF exposures and smokers with >2 VGDF exposures (RF 57 vs RF 113, p=0.02). No association of ACPA seropositivity rates or titres with VGDF exposure was observed. Smokers with >2 VGDF exposures had a significantly lower age of RA diagnosis than smokers with no VGDF exposure (53 years vs 57 years, p=0.03). All results remained similar when corrected for social class. CONCLUSIONS: VGDF exposure increases RF levels. Combination exposure to smoking and VDGF results in higher RF levels, particularly with multiple exposures. These compelling findings demonstrate the importance of combined inhaled exposures in RF generation.

Mycetoma in Timor-Leste and first report of nocardiosis.

Mycetoma is a neglected tropical disease with an unknown global burden. Although considered endemic to South-east Asia, it has not previously been reported from Timor-Lest. We describe two cases in Timor-Leste, highlighting the challenges surrounding microbiological diagnosis and management shared by many low to middle-income countries. As characteristically described, both patients lived rurally and presented late with marked soft tissue involvement and multiple draining sinuses following a prolonged period of high morbidity. Nocardia brasiliensis, a beadedbranched, modified acid-fast, gram-positive bacilli, was isolated and confirmed by molecular testing in the first case. The causative organism in the second case could not be confirmed due to limited microbiological capabilities. Due to limited local laboratory capabilities, Nocardia spp. infection cannot be routinely confirmed in Timor- Leste. However, the microbiology laboratory is essential for the successful diagnosis and management of Mycetoma. In both cases, medical therapy alone resulted in cure and favorable outcomes, although supply of antibiotic remains an ongoing resource issue.

Is Male Rheumatoid Arthritis an Occupational Disease? A Review.

BACKGROUND: Rheumatoid arthritis (RA) is a systemic, inflammatory disease with an estimated global prevalence of 0.3-1.0%. An unexplained association exists between low formal education and the development of RA independent of smoking. It is established that RA is initiated in the lungs and that various occupations associated with dust, fume and metal inhalation can increase the risk of RA development. OBJECTIVE: The objective of this review is to evaluate published clinical reports related to occupations associated with RA development. We highlight the concept of a "double-hit" phenomenon involving adsorption of toxic metals from cigarette smoke by dust residing in the lung as a result of various work exposures. We discuss the relevant pathophysiological consequences of these inhalational exposures in relation to RA associated autoantibody production. METHOD: A thorough literature search was performed using available databases including Pubmed, Embase, and Cochrane database to cover all relative reports, using combinations of keywords: rheumatoid arthritis, rheumatoid factor, anti-citrullinated peptide antibody silica, dust, fumes, metals, cadmium, cigarette smoking, asbestos, mining, bronchial associated lymphoid tissue, heat shock protein 70, and adsorption. CONCLUSION: We postulate that the inhalation of dust, metals and fumes is a significant trigger factor for RA development in male patients and that male RA should be considered an occupational disease. To the best of our knowledge, this is the first review of occupations as a risk factor for RA in relation to the potential underlying pathophysiology.

Anti-citrullinated protein antibody positive rheumatoid arthritis is primarily determined by rheumatoid factor titre and the shared epitope rather than smoking per se.

OBJECTIVE: To analyse the relationship between rheumatoid factor (RF) titre, smoking and HLA-DRB1 alleles coding a "shared epitope" (SE) in relation to anti-citrullinated protein antibody (ACPA) positivity in rheumatoid arthritis (RA). METHODS: RA patients (n = 658) attending rheumatology clinics in Cornwall, UK (cohort 1) were stratified according to RF and ACPA titre, and smoking pack years at diagnosis. A further 409 RA patients from North Staffordshire, UK (cohort 2) were studied to confirm the relationship between RF levels, smoking and ACPA positivity in relation to SE status. RESULTS: In cohort 1 there was a trend (p<0.01) of increasing ACPA positivity rates with increasing levels of RF without statistically significant differences between patients who had never smoked and smokers (never smoked: 15/71 (21%) RF -ve, vs. 43/64 (67%) RF weak +ve, vs 88/100 (88%) RF strong +ve, ever smoked: 18/70 (26%) RF -ve vs. 66/83 (80%) RF weak +ve vs. 196/210 (93%) RF strong +ve). No significant gender difference was observed. No significant difference between smoking and ACPA positivity was seen in RF negative patients. Smoking >20 pack years conferred an increased risk of anti-CCP positive RA (158/200 (79%)), compared to having never smoked (146/235 (62%), p = <0.01), but this increased risk correlated with smokers' RF positivity as the principal determinant on subsequent regression analysis of cohort 2. In cohort 2, ACPA positivity rates significantly increased with RF positivity and carriage of 1 or 2 SE alleles (p<0.01). Little or no relationship was observed in patients lacking SE. CONCLUSIONS: ACPA positivity in RA strongly associates with increasing RF titre independent of smoking. This relationship is dependent on carriage of SE alleles. There is no relationship between ACPA and smoking in RF negative patients.

Prevalence of hepatitis B infection in women delivering at a community health centre in Dili, Timor-Leste and discussion of programmatic challenges.

BACKGROUND: Limited data regarding prevalence of hepatitis B virus infection in Timor-Leste exist. METHODS: An observational study of hepatitis B surface antigen (HBsAg) results of women delivering at Bairo Pite Clinic in Dili, Timor-Leste was carried out. RESULTS: Of the 781 women included in the study, 80.5% (626/777) of women who had accessed antenatal care had been tested for HBsAg, of whom 2.2% (14/626) were positive. Of the remaining women, 83.2% (129/155) received a test at the time of delivery, of whom 5.4% (7/129) were positive. Overall prevalence of HBsAg positivity was 2.8% (21/755). CONCLUSIONS: Further studies are urgently needed to establish the prevalence of HBV infection in Timor-Leste, particularly in pregnant women. Findings from this study suggest that routine HBV immunisation of newborns should be instituted promptly.

Reptile-associated salmonellosis in children aged under 5 years in South West England.

OBJECTIVE: To determine the proportion of Salmonella cases in children aged <5 years that were reptile-associated salmonellosis (RAS) and to compare the severity of illness. DESIGN: To analyse all cases of salmonellosis reported to public health authorities in children aged under 5 years in the South West of the UK from January 2010 to December 2013 for reptile exposure, age, serotype, hospitalisation and invasive disease. RESULTS: 48 of 175 (27%) Salmonella cases had exposure to reptiles. The median age of RAS cases was significantly lower than non-RAS cases (0.5 vs 1.0 year). RAS cases were 2.5 times more likely to be hospitalised (23/48) compared with non-RAS cases (25/127; p=0.0002). This trend continued in cases aged under 12 months, with significantly more RAS cases hospitalised (19/38) than non-RAS cases (8/42; p=0.003). Significantly more RAS cases had invasive disease (8/48: 5 bacteraemia, 2 meningitis, 1 colitis) than non-RAS cases (4/127: 3 bacteraemia, 1 meningitis). CONCLUSIONS: Reptile exposure was found in over a quarter of all reported Salmonella cases in children under 5 years of age. RAS is associated with young age, hospitalisation and invasive disease.

Mass spectrometry based approach to study the kinetics of O6-alkylguanine DNA alkyltransferase-mediated repair of O6-pyridyloxobutyl-2'-deoxyguanosine adducts in DNA.

O(6)-POB-dG (O(6)-[4-oxo-4-(3-pyridyl)but-1-yl]deoxyguanosine) are promutagenic nucleobase adducts that arise from DNA alkylation by metabolically activated tobacco-specific nitrosamines such as 4-(methylnitrosamino)-1-(3-pyridyl)-1-butanone (NNK) and N-nitrosonicotine (NNN). If not repaired, O(6)-POB-dG adducts cause mispairing during DNA replication, leading to G → A and G → T mutations. A specialized DNA repair protein, O(6)-alkylguanine-DNA-alkyltransferase (AGT), transfers the POB group from O(6)-POB-dG in DNA to a cysteine residue within the protein (Cys145), thus restoring normal guanine and preventing mutagenesis. The rates of AGT-mediated repair of O(6)-POB-dG may be affected by local DNA sequence context, potentially leading to adduct accumulation and increased mutagenesis at specific sites within the genome. In the present work, isotope dilution high performance liquid chromatography-electrospray ionization-tandem mass spectrometry (HPLC-ESI(+)-MS/MS)-based methodology was developed to investigate the influence of DNA sequence on the kinetics of AGT-mediated repair of O(6)-POB-dG adducts. In our approach, synthetic DNA duplexes containing O(6)-POB-dG at a specified site are incubated with recombinant human AGT protein for defined periods of time. Following spiking with D(4)-O(6)-POB-dG internal standard and mild acid hydrolysis to release O(6)-POB-guanine (O(6)-POB-G) and D(4)-O(6)-POB-guanine (D(4)-O(6)-POB-G), samples are purified by solid phase extraction (SPE), and O(6)-POB-G adducts remaining in DNA are quantified by capillary HPLC-ESI(+)-MS/MS. The new method was validated by analyzing mixtures containing known amounts of O(6)-POB-G-containig DNA and the corresponding unmodified DNA duplexes and by examining the kinetics of alkyl transfer in the presence of increasing amounts of AGT protein. The disappearance of O(6)-POB-dG from DNA was accompanied by pyridyloxobutylation of AGT Cys-145 as determined by HPLC-ESI(+)-MS/MS of tryptic peptides. The applicability of the new approach was shown by determining the second order kinetics of AGT-mediated repair of O(6)-POB-dG adducts placed within a DNA duplex representing modified rat H-ras sequence (5'-AATAGTATCT[O(6)-POB-G]GAGCC-3') opposite either C or T. Faster rates of alkyl transfer were observed when O(6)-POB-dG was paired with T rather than with C (k = 1.74 × 10(6) M(-1) s(-1) vs 1.17 × 10(6) M(-1) s(-1)).

Increase of urban lake salinity by road deicing salt.

Over 317,000 tonnes of road salt (NaCl) are applied annually for road deicing in the Twin Cities Metropolitan Area (TCMA) of Minnesota. Although road salt is applied to increase driving safety, this practice influences environmental water quality. Thirteen lakes in the TCMA were studied over 46 months to determine if and how they respond to the seasonal applications of road salt. Sodium and chloride concentrations in these lakes were 10 and 25 times higher, respectively, than in other non-urban lakes in the region. Seasonal salinity/chloride cycles in the lakes were correlated with road salt applications: High concentrations in the winter and spring, especially near the bottom of the lakes, were followed by lower concentrations in the summer and fall due to flushing of the lakes by rainfall runoff. The seasonal salt storage/flushing rates for individual lakes were derived from volume-weighted average chloride concentration time series. The rate ranged from 9 to 55% of a lake's minimum salt content. In some of the lakes studied salt concentrations were high enough to stop spring turnover preventing oxygen from reaching the benthic sediments. Concentrations above the sediments were also high enough to induce convective mixing of the saline water into the sediment pore water. A regional analysis of historical water quality records of 38 lakes in the TCMA showed increases in lake salinity from 1984 to 2005 that were highly correlated with the amount of rock salt purchased by the State of Minnesota. Chloride concentrations in individual lakes were positively correlated with the percent of impervious surfaces in the watershed and inversely with lake volume. Taken together, the results show a continuing degradation of the water quality of urban lakes due to application of NaCl in their watersheds.

Why do boomers plan to work longer?

OBJECTIVE: . Recent changes in retirement trends and patterns have raised questions about the likely retirement behavior of baby boomers, the large cohort born between 1946 and 1964. This study examined recent changes in retirement expectations and the factors that drove them. METHODS: Using data from the Health and Retirement Study, the analysis compared self-reported probabilities of working full time past ages 62 and 65 among workers aged 51 to 56 in 1992 and 2004. The study modeled retirement expectations for both generations and used the estimated regression coefficients to identify the forces that accounted for generational differences. RESULTS: . Between 1992 and 2004, the mean self-reported probability of working full time past age 65 among workers aged 51 to 56 increased from 27% to 33%. Lower rates of retiree health insurance offers from employers, higher levels of educational attainment, and lower rates of defined benefit pension coverage accounted for most of the growth. DISCUSSION: Given the continued erosion in employer-sponsored retiree health benefits and defined benefit pension plans, boomers will likely remain at work longer than members of the previous generation. Lengthier careers will likely promote economic growth, increase government revenue, and improve individual financial security at older ages.

Nasofacial phycomycosis: persistence pays.

Nasofacial phycomycosis caused by Conidiobolus is a rare fungal infection most often encountered in the developing world in conditions of poverty. A clinical presentation of the natural history of this condition observed over a period of 6 years by a visiting volunteer surgical team demonstrates the role of multimodality surgical and antifungal drug treatment in producing a successful outcome. The particular sensitivity of this infection to the new generation antifungal Voriconazole is noted.

Comparison of transthoracic echocardiography versus cardiovascular magnetic resonance imaging for the assessment of ventricular function in adults after atrial switch procedures for complete transposition of the great arteries.

Adult patients with a history of transposition of the great arteries and atrial switch operation were studied with transthoracic echocardiography and cardiovascular magnetic resonance imaging. Measurements of ventricular dimensions and function by these 2 techniques in 18 consecutive patients were well correlated.