An epidemiologic study on hand osteoarthritis in peri-to-postmenopausal women

Osteoarthritis is a slowly developing chronic joint disease mainly characterized by joint pain and nodes with no curative treatment available except for joint replacement. The etiology of osteoarthritis is not exactly known, but the hypothesis that osteoarthritis not only evolves from wear-and-tear but is also inherent to systemic components is widely accepted. Systemic inflammation as in obesity or dyslipidemia was shown to negatively influence osteoarthritis of non-weight bearing joints such as joints in the hands. Hand osteoarthritis develops frequently in postmenopausal women. Menopausal transition in women mainly occurs from age 45 to 54, involves changes in sex hormones, and is associated with vasomotor and genitourinary symptoms mainly treated with systemic and vaginal hormone replacement therapy, respectively. Further associated symptoms such as joint pain or osteoarthritis (symptomatically treated with painkillers) or increased lipid levels (mainly treated with statins to reduce the risk of a cardiovascular event) are less known to the general public but carry a high disease burden. By means of epidemiologic studies using women’s primary care health records in the United Kingdom, this thesis aimed to help find drugs potentially delaying hand osteoarthritis onset by describing and assessing drugs treating symptoms evolving in menopausal transition in association with hand osteoarthritis. Potential negative associations may result in a decreased burden of this incurable disease. In a first descriptive study, we described incidence rates of hand osteoarthritis and of hormone replacement therapy use in women aged 40 to 69 years. We observed that rates of hormone replacement therapy initiation and of new diagnoses of hand osteoarthritis behaved inversely over time and uniformly in 5-year age groups between 40 to 54 years but not in older age groups. Hormone replacement therapy initiation rates shaped in a skewed Gaussian curve with a tail in older age groups while onset of hand osteoarthritis plateaued from age 55. In a second nested case-control study, observing women from age 45 longitudinally, we assessed the association between systemic hormone replacement therapy initiation and hand osteoarthritis overall and in women with recorded menopause only as recorded menopause was a major confounder. Most hand osteoarthritis cases occurred shortly after menopause, therefore, we assessed the timing of hormone replacement therapy initiation relative to menopause in current users as well as of hormone replacement therapy cessation relative to hand osteoarthritis diagnoses in past users, compared to non-users. The association between hormone replacement therapy use and hand osteoarthritis yielded an increased risk of hand osteoarthritis of 32%. However, in women with recorded menopause, the risk of hand osteoarthritis in hormone replacement therapy users disappeared compared to non users. Furthermore, we observed a 28% decreased risk of hand osteoarthritis if hormone replacement therapy was initiated around menopause and used continuously, compared to non-users. This potential beneficial effect diminished the later hormone replacement therapy was initiated. However, we also observed a statistically non-significant 25% increased risk of hand osteoarthritis shortly after therapy cessation. In a third cohort study, in women aged 45 to 64 years, we assessed the association between statin initiation and hand osteoarthritis and between statin initiation and generalized osteoarthritis (i.e. multiple joints affected, hand osteoarthritis is usually part of generalized osteoarthritis), overall, stratified by age, and by pre-existing dyslipidemia. Furthermore, we used psoriasis and tinnitus as negative control outcomes to control for confounding by differential menopause onset (psoriasis) and healthcare seeking behavior (psoriasis, tinnitus). We observed that statin use was neither associated with hand osteoarthritis nor with generalized osteoarthritis irrespective of age or pre existing dyslipidemia. The use of negative control outcomes corroborated this finding. Our results support the existing hypothesis that menopause is a risk factor of hand osteoarthritis. However, it is likely not the only risk factor for hand osteoarthritis because otherwise we would have expected hand osteoarthritis incidence rates to decline similarly to those of hormone replacement therapy use among older age groups. Furthermore, our results suggest that timely initiation of hormone replacement therapy relative to menopause may be crucial for a potential delay of hand osteoarthritis onset to at least after hormone replacement therapy cessation. Finally, our results suggest that the lipid lowering effect of statins does not seem to translate into a reduced risk of hand osteoarthritis in peri to postmenopausal women

School Counseling and Counseling Psychology Collaboration: A Cautionary Tale

Counseling psychology and school counseling programs have been historically aligned since the inception of their respective professions. Given current trends, there appear to be differences in the foci and approach to training and professional engagement in the two disciplines. The current investigation surveyed programs in which counseling psychology and school counseling programs were housed within the same department or college to identify areas of collaboration. The survey and journal reviews revealed a divide in the areas of curriculum, service delivery, and professional organization engagement. There appeared to be better collaboration in research, although limited in scope. Although counseling psychology and school counseling continue to have shared values, current trends in curriculum needs, accreditation and professional foci suggest a limited scope of collaboration. Research may be an area in which the two professions can remain professionally engaged. We offer suggestions for increasing collaborative activities

Minimal disease activity and remission in patients with psoriatic arthritis with elevated body mass index: an observational cohort study in the Swiss Clinical Quality Management cohort

OBJECTIVE To assess the impact of elevated body mass index (BMI) in the achievement of minimal disease activity (MDA) and several definitions of remission in patients with psoriatic arthritis (PsA) in Switzerland. Secondarily, to assess the overlapping across the study outcomes. METHODS This observational cohort study in the Swiss Clinical Quality Management in Rheumatic Diseases (SCQM) registry included patients with PsA starting their first biologic or targeted synthetic disease-modifying antirheumatic drug (b/tsDMARD) from 1997 to 30 June 2018. Exposure was BMI category at b/tsDMARD start: overweight, obese, and normal weight (reference). Logistic regression was used to assess the achievement of MDA and remission at ≤12 months, as well as treatment persistence at 1 year, in overweight patients and patients with obesity compared with the normal weight group. Remission was defined by Disease Activity for Psoriatic Arthritis (DAPSA), clinical DAPSA (cDAPSA) and 28-joint Disease Activity Score (DAS28). Additionally, overlapping across study outcomes was investigated. RESULTS The study included 306 (39.5%) normal weight patients, 285 (36.8%) overweight patients and 183 (23.6%) patients with obesity. Compared with the normal weight group, patients with obesity had lower odds of achieving MDA at ≤12 months (adjusted OR (ORadj) 0.45, 95% CI 0.24 to 0.82). This was consistent with the observed reduced odds of achieving DAPSA-remission (ORadj 0.42, 95% CI 0.21 to 0.85), cDAPSA-remission (ORadj 0.51, 95% CI 0.27 to 0.96) and DAS28-remission (ORadj 0.51, 95% CI 0.32 to 0.81) in patients with obesity versus normal weight patients. Among the 125 patients achieving MDA, the majority (81.8% normal weight, 80.0% overweight, 78.9% obese) achieved cDAPSA-remission. No differences were observed in the odds to achieving treatment persistence between the BMI strata. CONCLUSIONS Obesity halved the likelihood of achieving MDA and remission in patients with PsA with b/tsDMARDs compared with those with normal weight, while it did not impact treatment persistence. High overlapping of patients achieving the outcomes MDA and cDAPSA-remission was observed across every BMI group

Comparative effectiveness of biologics in patients with rheumatoid arthritis stratified by body mass index: a cohort study in a Swiss registry.

OBJECTIVES Obesity is associated with lower treatment response in patients with rheumatoid arthritis (RA). In patients with obesity, abatacept was suggested as a preferable option to tumour necrosis factor-alpha inhibitors. We aimed to assess the comparative effectiveness of etanercept, infliximab and abatacept, compared with adalimumab, in patients with RA with obesity. Secondarily, we also investigated this in patients with overweight and normal weight for completeness. DESIGN Observational cohort study. SETTING Swiss Clinical Quality Management in Rheumatic Diseases (SCQM) registry (1997-2019). PARTICIPANTS Adult patients with RA from the SCQM registry who received etanercept, infliximab, abatacept or adalimumab as their first biological or targeted synthetic disease-modifying antirheumatic drug were classified based on their body mass index (BMI) at the start of that treatment in three cohorts: obese, overweight, normal weight. They were followed for a maximum of 1 year. EXPOSURE The study exposure of interest was the patients' first biological, particularly: etanercept, infliximab and abatacept, compared with adalimumab. PRIMARY AND SECONDARY OUTCOME MEASURES The primary study outcome was remission within 12 months, defined as 28-joint Disease Activity Score (DAS28) <2.6. Missingness was addressed using confounder-adjusted response rate with attrition correction. Logistic regression was used to compare the effectiveness of etanercept, infliximab and abatacept versus adalimumab. Each BMI cohort was addressed and analysed separately. RESULTS The study included 443 obese, 829 overweight and 1243 normal weight patients with RA. There were no statistically significant differences in the odds of DAS28-remission at ≤12 months for etanercept, infliximab and abatacept, compared with adalimumab, in any of the BMI cohorts. CONCLUSIONS No differences in DAS28-remission were found between the study drugs and adalimumab as first biologic in patients with RA, independently of the BMI cohort. We did not find evidence that treatment with abatacept increased the likelihood of remission compared with adalimumab among obese patients with RA

Lower odds of remission among women with rheumatoid arthritis: A cohort study in the Swiss Clinical Quality Management cohort

OBJECTIVE To compare the likelihood of achieving remission between men and women with rheumatoid arthritis (RA) after starting their first biologic or targeted synthetic disease-modifying anti-rheumatic drug (b/tsDMARD). METHODS This cohort study in the Swiss Clinical Quality Management in Rheumatic Diseases (SCQM) registry included RA patients starting their first b/tsDMARD (1997-31/04/2018). The odds of achieving remission at ≤12-months, defined by disease activity score 28-joints (DAS28) <2.6, were compared between men and women. Secondary analyses were adjusted for age and seropositivity, and we investigated potential mediators or factors that could explain the main findings. RESULTS The study included 2839 (76.3%) women and 883 (23.7%) men with RA. Compared to women, men were older at diagnosis and b/tsDMARD start, but had shorter time from diagnosis to b/tsDMARD (3.4 versus 5.0 years, p<0.001), and they had lower DAS28 at b/tsDMARD start. Compared to women, men had 21% increased odds of achieving DAS28-remission, with odds ratio (OR) 1.21, 95% confidence interval (CI) 1.02-1.42. Adjusting for age and seropositivity yielded similar findings (adjusted OR 1.24, 95%CI 1.05-1.46). Analyses of potential mediators suggested that the observed effect may be explained by the shorter disease duration and lower DAS28 at treatment initiation in men versus women. CONCLUSION Men started b/tsDMARD earlier than women, particularly regarding disease duration and disease activity (DAS28), and had higher odds of reaching remission. This highlights the importance of early initiation of second line treatments, and suggests to target an earlier stage of disease in women to match the benefits observed in men

The impact of the COVID-19 pandemic on incidence and short-term survival for common solid tumours in the United Kingdom: a cohort analysis

Purpose: The COVID-19 pandemic profoundly affected healthcare systems and patients. There is a need to comprehend the collateral effects of the pandemic on non-communicable diseases. We examined the impact of the pandemic on short-term survival for common solid tumours, including breast, colorectal, head and neck, liver, lung, oesophageal, pancreatic, prostate, and stomach cancer in the UK. Methods: This was a population-based cohort study of electronic health records from the UK primary care Clinical Practice Research Datalink GOLD database. In sum, 12,259,744 eligible patients aged ≥ 18 years with ≥ 1 year’s history identified from January 2000 to December 2022 were included. We estimated age-standardised incidence and short-term (one- and two-year) survival for several common cancers from 2000 to 2019 (in five-year strata) and compared these to 2020– 2022 using the Kaplan–Meier method. Results: Incidence decreased for most cancers in 2020 and recovered to different extents in 2021– 2022. Short-term survival improved for most cancers between 2000 and 2019, but then declined, albeit minimally, for those diagnosed in 2020– 2022. This was most pronounced for colorectal cancer, with one-year survival falling from 78.8% (95% CI 78%– 79.6%) in 2015– 2019 to 77% (95% CI 75.6– 78.3%) for those diagnosed in 2020– 2022. Conclusion: Short-term survival for many cancers was impacted, albeit minimally, by the pandemic in the UK, with reductions in survivorship from colorectal cancer equivalent to returning to the mortality seen in the first decade of the 2000s. While data on longer-term survival are needed to fully comprehend the impact of COVID-19 on cancer care, our findings illustrate the need for an urgent and substantial commitment from the UK National Health Service to address the existing backlog in cancer screening and diagnostic procedures to improve cancer care and mortality

Calculating daily dose in the Observational Medical Outcomes Partnership Common Data Model

Purpose: We aimed to develop a standardized method to calculate daily dose (i.e., the amount of drug a patient was exposed to per day) of any drug on a global scale using only drug information of typical observational data in the Observational Medical Outcomes Partnership Common Data Model (OMOP CDM) and a single reference table from Observational Health Data Sciences And Informatics (OHDSI). Materials and Methods: The OMOP DRUG_STRENGTH reference table contains information on the strength or concentration of drugs, whereas the OMOP DRUG_EXPOSURE table contains information on patients' drug prescriptions or dispensations/claims. Based on DRUG_EXPOSURE data from the primary care databases Clinical Practice Research Datalink GOLD (United Kingdom) and Integrated Primary Care Information (IPCI, The Netherlands) and healthcare claims from PharMetrics® Plus for Academics (USA), we developed four formulas to calculate daily dose given different DRUG_STRENGTH reference table information. We tested the dose formulas by comparing the calculated median daily dose to the World Health Organization (WHO) Defined Daily Dose (DDD) for six different ingredients in those three databases and additional four international databases representing a variety of healthcare settings: MAITT (Estonia, healthcare claims and discharge summaries), IQVIA Disease Analyzer Germany (outpatient data), IQVIA Longitudinal Patient Database Belgium (outpatient data), and IMASIS Parc Salut (Spain, hospital data). Finally, in each database, we assessed the proportion of drug records for which daily dose calculations were possible using the suggested formulas. Results: Applying the dose formulas, we obtained median daily doses that generally matched the WHO DDD definitions. Our dose formulas were applicable to &gt;85% of drug records in all but one of the assessed databases. Conclusion: We have established and implemented a standardized daily dose calculation in OMOP CDM providing reliable and reproducible results.</p

Calculating daily dose in the Observational Medical Outcomes Partnership Common Data Model

Purpose: We aimed to develop a standardized method to calculate daily dose (i.e., the amount of drug a patient was exposed to per day) of any drug on a global scale using only drug information of typical observational data in the Observational Medical Outcomes Partnership Common Data Model (OMOP CDM) and a single reference table from Observational Health Data Sciences And Informatics (OHDSI). Materials and Methods: The OMOP DRUG_STRENGTH reference table contains information on the strength or concentration of drugs, whereas the OMOP DRUG_EXPOSURE table contains information on patients' drug prescriptions or dispensations/claims. Based on DRUG_EXPOSURE data from the primary care databases Clinical Practice Research Datalink GOLD (United Kingdom) and Integrated Primary Care Information (IPCI, The Netherlands) and healthcare claims from PharMetrics® Plus for Academics (USA), we developed four formulas to calculate daily dose given different DRUG_STRENGTH reference table information. We tested the dose formulas by comparing the calculated median daily dose to the World Health Organization (WHO) Defined Daily Dose (DDD) for six different ingredients in those three databases and additional four international databases representing a variety of healthcare settings: MAITT (Estonia, healthcare claims and discharge summaries), IQVIA Disease Analyzer Germany (outpatient data), IQVIA Longitudinal Patient Database Belgium (outpatient data), and IMASIS Parc Salut (Spain, hospital data). Finally, in each database, we assessed the proportion of drug records for which daily dose calculations were possible using the suggested formulas. Results: Applying the dose formulas, we obtained median daily doses that generally matched the WHO DDD definitions. Our dose formulas were applicable to &gt;85% of drug records in all but one of the assessed databases. Conclusion: We have established and implemented a standardized daily dose calculation in OMOP CDM providing reliable and reproducible results.</p

The Heart Is an Early Target of Anthrax Lethal Toxin in Mice: A Protective Role for Neuronal Nitric Oxide Synthase (nNOS)

Anthrax lethal toxin (LT) induces vascular insufficiency in experimental animals through unknown mechanisms. In this study, we show that neuronal nitric oxide synthase (nNOS) deficiency in mice causes strikingly increased sensitivity to LT, while deficiencies in the two other NOS enzymes (iNOS and eNOS) have no effect on LT-mediated mortality. The increased sensitivity of nNOS−/− mice was independent of macrophage sensitivity to toxin, or cytokine responses, and could be replicated in nNOS-sufficient wild-type (WT) mice through pharmacological inhibition of the enzyme with 7-nitroindazole. Histopathological analyses showed that LT induced architectural changes in heart morphology of nNOS−/− mice, with rapid appearance of novel inter-fiber spaces but no associated apoptosis of cardiomyocytes. LT-treated WT mice had no histopathology observed at the light microscopy level. Electron microscopic analyses of LT-treated mice, however, revealed striking pathological changes in the hearts of both nNOS−/− and WT mice, varying only in severity and timing. Endothelial/capillary necrosis and degeneration, inter-myocyte edema, myofilament and mitochondrial degeneration, and altered sarcoplasmic reticulum cisternae were observed in both LT-treated WT and nNOS−/− mice. Furthermore, multiple biomarkers of cardiac injury (myoglobin, cardiac troponin-I, and heart fatty acid binding protein) were elevated in LT-treated mice very rapidly (by 6 h after LT injection) and reached concentrations rarely reported in mice. Cardiac protective nitrite therapy and allopurinol therapy did not have beneficial effects in LT-treated mice. Surprisingly, the potent nitric oxide scavenger, carboxy-PTIO, showed some protective effect against LT. Echocardiography on LT-treated mice indicated an average reduction in ejection fraction following LT treatment in both nNOS−/− and WT mice, indicative of decreased contractile function in the heart. We report the heart as an early target of LT in mice and discuss a protective role for nNOS against LT-mediated cardiac damage

Comparison of Psoriatic Arthritis and Rheumatoid Arthritis Patients across Body Mass Index Categories in Switzerland.

Abnormal body mass index (BMI) was associated with worse rheumatic markers in psoriatic arthritis (PsA) and rheumatoid arthritis (RA). Aiming to describe PsA and RA patients stratified by BMI, we performed a descriptive study in PsA and RA patients (two distinct cohorts) in the Swiss Clinical Quality Management in Rheumatic Diseases (SCQM) registry. New users of biologic or targeted synthetic disease-modifying anti-rheumatic drugs (b/tsDMARDs) were stratified by BMI at the start of their treatment (underweight, normal weight, overweight, obese). The PsA underweight and normal weight categories were merged. Age at disease onset and further characteristics at the start of the first b/tsDMARD treatment were compared across BMI categories vs. the corresponding normal weight group. The study included 819 PsA (36.5% overweight, 23.8% obese) and 3217 RA patients (4.4% underweight, 31.8% overweight, 17.0% obese). Compared to the corresponding normal weight group, PsA and RA obese patients had significantly (p < 0.05) higher C-reactive protein, worse disease activity, and lower quality of life (QoL). Obese PsA patients had significantly worse skin manifestation and pain, while obese RA patients had significantly higher erythrocyte sedimentation rate and tender joint counts, as well as lower seropositive prevalence. To conclude, obese PsA and RA patients presented worse disease activity and poorer QoL than those with normal weight