Immediate Unilateral Subpectoral Implant-Based Breast Reconstruction does not Impair Pulmonary Functions: A Preliminary Prospective Study.

BACKGROUND: Implant-based breast reconstruction is one of the most common procedures among women with breast cancer undergoing mastectomy. Prosthetic devices may be positioned either beneath or above the pectoralis major muscle, which is considered an accessory muscle of ventilation. This preliminary prospective study aimed to investigate whether subpectoral unilateral implant-based breast reconstruction has any effect on patients' pulmonary functions. METHODS: A prospective study of fourteen women who underwent immediate unilateral implant-based subpectoral breast reconstruction by a single surgeon over 10 months was conducted. Spirometry and maximal voluntary ventilation tests were conducted 1 day prior to surgery, and 1- and 3 months following breast reconstruction. ANOVA or Friedman test were used to compare pulmonary function tests before and after surgery. RESULTS: Fourteen patients completed the study protocol. No statistically significant differences were found when comparing spirometry parameters in the three time points. CONCLUSIONS: Pectoralis muscle release does not impair pulmonary function among patients undergoing immediate unilateral implant-based breast reconstruction following mastectomy. LEVEL OF EVIDENCE III: This journal requires that authors assign a level of evidence to each article. For a full description of these Evidence-Based Medicine ratings, please refer to the Table of Contents or the online Instructions to Authors www.springer.com/00266 .

Treatment Persistence of Apremilast Among Patients with Psoriatic Arthritis.

Introduction: Persistence in drug therapy reflects treatment effectiveness and tolerability. We aim to estimate the persistence of apremilast prescribed to patients with psoriatic arthritis (PsA) and to identify characteristics associated with treatment discontinuation in a real-world setting. Methods: Patients with PsA treated with apremilast from January 2016 were identified from a large health database and followed until medication stop date (using 3-months grace period), death or the end of observation period (June 2021). Demographic data, Charlson comorbidity index and concomitant and previous use of conventional and biologic DMARDs were extracted. The reasons for drug discontinuation were manually retrieved from patient charts. Time to discontinuation was estimated using survival analysis using Kaplan-Meier functions. Results: Overall, 568 PsA patients treated with apremilast were identified. The mean age was 55.3±14.0 years, of whom 332 (58.5%) were females, 38.4% were obese (BMI>30), 75.2% had a Charlson comorbidity index>1, 24.1% were on concomitant treatment with methotrexate and 72.4% were biologic naïve. The median persistent period was 6.1,95% CI (5.2-6.9) months in which only 16.9% remained persistent on apremilast. No difference was found with regard to age, sex, socioeconomic status, ethnicity and obesity between patients who were persistent compared to patients who discontinued apremilast. Concomitant treatment with methotrexate and prior history of biologic therapy did not affect drug persistency (log rank P=0.957 and 0.082, respectively). Causes for treatment discontinuation were due to lack of skin efficacy in 19.4%, lack of joint efficacy in 33.3%, combined skin and joint inefficacy at 2.3% and due to side effects in 24.1%. Conclusion: In this large observational retrospective cohort of patients treated with apremilast, a relatively low drug persistence was observed with 6-month and 1-year survival rates of 50.3% and 31.3%, respectively. Treatment discontinuation was mainly due to joint inefficacy, advocating for more studies for proper patient selection to assure treatment effectiveness and persistency.

Risk of breakthrough COVID-19 after vaccination among people with multiple sclerosis on disease-modifying therapies.

BACKGROUND: Disease-modifying therapies (DMTs) for people with multiple sclerosis (pwMS) may decrease vaccine effectiveness. We aimed to explore the association between various DMTs and the risk for breakthrough COVID-19. METHODS: Population-based data from Clalit Health Services, Israel's largest healthcare organization, were used. PwMS treated with DMTs without prior COVID-19 were followed from the commencement of the mass vaccination campaign in December 2020. The end of follow-up was at the time of COVID-19 infection, the receipt of a third vaccine dose or until the end of August 2021. Time-dependent multivariate Cox proportional hazard models were used to estimate hazard ratios for COVID-19 according to vaccination, DMT, age, gender, disability and comorbidities. RESULTS: 2511 PwMS treated with DMTs were included (Age: 46.2 ± 14.6, 70% Female, EDSS: 3.0 ± 2.1). Of whom, 2123 (84.5%) received 2 vaccine doses. On multivariate models that included all pwMS, vaccination was protective (HR = 0.41, P < 0.001). On multivariate models that included only fully vaccinated pwMS cladribine, ocrelizumab, S1P receptor modulators and natalizumab were associated with breakthrough COVID-19 (HR = 6.1, 4.7, 3.7 and 3.3; P = 0.004, 0.008, 0.02 and 0.05, respectively). On multivariate models that included unvaccinated and fully vaccinated pwMS on each DMT separately, a protective trend was noted for vaccination on all DMTs (0.09 < HR < 0.65), except for cladribine (HR = 1.1). This protective trend was not statistically significant on ocrelizumab, S1P receptor modulators and natalizumab. COVID-19 among pwMS was generally mild. Only 2 vaccinated pwMS had a severe infection with eventual recovery. CONCLUSIONS: Vaccination effectively protects pwMS from COVID-19. An increased risk of breakthrough infection was noted on high-efficacy DMTs, however COVID-19 after vaccination was usually mild.

Predictors and Long-Term Prognostic Significance of Acute Renal Function Change in Patients Who Underwent Surgical Aortic Valve Replacement.

There are few reports on short-term changes in renal function after surgical aortic valve replacement, and data are scarce regarding its impact on long-term outcomes. This is a retrospective study of patients who underwent isolated aortic valve replacement between 2009 and 2020 in four medical centers. Patients with end-stage renal disease were excluded. Renal function was assessed based on short-term changes. Multivariable regression models were used to identify predictors of improvement/deterioration. Cox proportional hazard models were used to assess survival trends. The study included 2402 patients, with a mean age of 69.3 years and a mean eGFR of 82.3 mL/min/1.73 m2. Short-term improvement rates were highest in stage 4 (24.4%) and stage 3 (16.8%) patients. Deterioration rates were highest in stage 1 (38.1%) and stage 2 (34.8%) patients. Deterioration in the chronic kidney disease stage was associated with a higher ten-year mortality (p < 0.001, HR 1.46); an improved stage trended toward improved survival (p = 0.14, HR 0.722). Patients with stage 3 and 4 kidney disease tended to remain stable or improve in the short term after aortic valve replacement while patients at stages 1 and 2 were at increased risk of deteriorating.

Safety of troclosene sodium solution in decontamination of wounds: A prospective clinical and laboratory study.

Debate persists regarding the safety of hypochlorite-containing solutions in the decontamination of infected wounds. In 2006, the Israeli Ministry of Health withdrew licensing approval for troclosene sodium as a wound irrigation solution. The aim of this prospective clinical and laboratory study was to investigate the safety of troclosene sodium solution for decontamination of infected wounds. Troclosene sodium solution was used to treat 30 patients with 35 infected skin wounds of various etiologies and body areas, over a treatment period of 8 days. Data were gathered according to a prospectively designed protocol including general findings, wound-specific observations on Day 1 and Day 8 and laboratory parameters on Day 1 and Day 8. Wound swabs and tissue biopsy for culture were taken on Day 1 and Day 8. Statistical analysis was executed. Tests were 2-sided and p values of <0.05 were considered statistically significant. Eighteen males and 12 females, with 35 infected skin wounds were enrolled. There were no adverse clinical events. No significant changes were observed in general clinical observations. Statistically significant improvements were observed in: pain (p < 0.0001); edema (p < 0.0001); area of wound covered by granulation tissue (p < 0.0001); exudate (p < 0.0001); and erythema (p = 0.002). Prior to treatment, bacteria were demonstrated on microscopy or on culture in 90% of wound samples. On Day 8, this frequency reduced to 40%. There were no abnormal laboratory tests. Serum sodium concentration increased significantly between Day 1 and Day 8, whilst serum concentration of urea and concentrations of thrombocytes, leucocytes and neutrophils showed statistically significant reductions, but all values remained within normal laboratory ranges throughout the study period. Troclosene sodium solution is clinically safe in the management of infected wounds. These findings were presented to the Israel Ministry of Health and as a result, troclosene sodium was re-approved and licensed for decontamination of infected wounds in Israel.

Risk factors associated with accidental fetal skin lacerations during cesarean delivery.

OBJECTIVE: To identify risk factors associated with accidental fetal skin lacerations (AFL) during cesarean section (CS). METHODS: This retrospective cohort study was obtained from the registry of two large medical centers between 2014 and 2019. The study group comprised all newborns identified with AFL. The rates of various potential risk factors were compared between the study group and a group of CS at which no AFL had occurred (the control group). RESULTS: Of the 14 666 CS deliveries, 48 cases of AFL (0.33%) were documented, 52% of these following urgent CS. Compared with the control group (n = 14 618), the only risk factors associated with AFL were premature rupture of membranes (PROM) (odds ratio [OR] 5.38, 95% convidence interval [CI] 2.97-9.74) and meconium-stained amniotic fluid (OR 6.50, 95% CI 2.55-16.54). In subgroup analysis by CS urgency, no significance for these factors was noted in elective CS group; but higher rates of both PROM and meconium-stained amniotic fluid were noted in the AFL during urgent CS (OR 14.23, 95% CI 6.30-32.16 and OR 15.36, (95% CI 5.65-41.75, respectively). CONCLUSIONS: During urgent CS, the surgeon should bear in mind that the presence of PROM or meconium-stained amniotic fluid should prompt extra care and application of preventive measures to decrease the rates of AFL.

Serum cholesterol increase in statin users associated with antibiotic use: Case-crossover study.

PURPOSE: 3-hydroxy-3-methyl-glutaryl-coenzyme A (HMG-CoA) reductase inhibitors ("statins") reduce risk of atherosclerotic disease. However, statins need secondary bile acids, produced by the gut microbiota, for absorption. Our hypothesis was that a change in the gut microbiota induced by antibiotics might cause a decrease in statin absorption, and decreased statin effectiveness. Our objective was to study the association between antibiotic treatment and increased cholesterol level in statin users. METHODS: Case-crossover study, in which an individual serves as his own control, by comparing outcome risk among the same individual at different times, adjusting for time-dependent comorbidity index. The study is based on adherent statin users' cohort and two cohorts of patients not treated with statins, in Clalit Health Services. Exposure were antibiotic prescriptions dispensed in the 3 months prior to LDL-C measurements. RESULTS: There were 25,496 statin users and 72,638 time-points. A significant association was found between LDL-C increase and exposure to macrolides and clindamycin, OR = 1.237 (1.138-1.345), p = 6.5*10-7, number needed to harm (NNH) = 19. There was no association between LDL-C increase and negative control objects such as anti-viral treatments; nor between LDL-C and exposure to antibiotics in non-statin users. As a secondary outcome, we have found an association between LDL-C increase and a following atherosclerotic ischemic event. CONCLUSION: An increase in LDL-C in highly adherent statin users is associated with precedent macrolides or clindamycin treatment.

Effect of Femtosecond Laser Cataract Surgery on Peripapillary Retinal Nerve Fiber Layer Thickness.

PRCIS: Femtosecond laser-assisted cataract surgery (FLACS) may cause thinning of the peripapillary retinal nerve fiber layer (pRNFL) in healthy eyes. PURPOSE: This prospective cohort study aimed to compare changes of pRNFL after FLACS using a liquid patient interface and conventional phacoemulsification cataract surgery (CPCS). PATIENTS AND METHODS: Included were 261 eyes (261 patients) with age-related cataracts and no ocular diseases scheduled either for FLACS (222 eyes) or CPCS (39 eyes). FLACS was performed using a Ziemer LDV Z8 laser. Average and quadrant pRNFL thickness was measured using optical coherence tomography before surgery and at 1, 3, and 6 months postoperatively. Postoperative changes in pRNFL thickness were compared within and between groups. RESULTS: Mean quadrant and average pRNFL thicknesses significantly increased after both surgeries (P<0.001). However, pRNFL thinning occurred after FLACS and CPCS (17% vs. 5.1%, respectively, P>0.05). FLACS eyes showed a significant and stable decrease of average pRNFL thickness (P=0.057) and a gradual decrease in pRNFL thickness of all quadrants (P≤0.018). CPCS eyes showed an initial increase of pRNFL thickness, followed by a decrease only in the nasal quadrant and average pRNFL. Preoperative pRNFL thickness was associated with thinning of the temporal quadrant (P=0.04). CONCLUSIONS: Both FLACS and CPCS demonstrated pRNFL thinning in some healthy eyes. Although the higher rate of pRNFL thinning after FLACS compared with CPCS lacked statistical significance, a consistent decrease in pRNFL thickness occurred in all quadrants and average pRNFL of FLACS eyes, suggesting that FLACS may lead to pRNFL thinning. Eyes with thinner preoperative pRNFL may be prone to temporal quadrant thinning after FLACS.

Association of CYP2C19 Polymorphism With Proton Pump Inhibitors Effectiveness and With Fractures in Real-Life: Retrospective Cohort Study.

Symptom refractoriness of patients treated with proton pump inhibitors (PPIs) might be explained by polymorphism in CYP2C19. This is a retrospective cohort study in which we used the computerized database of Clalit Health Services to compose a cohort from cancer case-control studies' participants that had been genotyped, and that have been dispensed PPI (January 1, 2002 to November 10, 2020). We retrieved demographic and clinical variables on date of PPI initiation (cohort entry), and studies' questionnaires-reported consumption of foods/beverages known to increase peptic-related symptoms. Primary outcome was an abdominal pain diagnosis; secondary outcome was a composite of abdominal pain, visit to a gastroenterology clinic, change to another PPI, PPI dose increase, or metoclopramide prescription, reflecting symptoms persistence/recurrence; in a 2-year follow-up. We also evaluated the association between genetic groups and hip/wrist/spine fractures, in a long-term follow-up. Of 3,326 PPI initiators, there were 66 (2.0%), 739 (22.2%), 1394 (41.9%), 947 (28.5%), and 180 (5.4%) CYP2C19 poor, intermediate, normal, rapid, and ultra-rapid metabolizers, respectively. Being a poor metabolizer was associated with lower risk for the primary outcome, hazard ratio (HR) = 0.50 (95% confidence interval (CI) 0.27-0.91), HR = 0.52 (95% CI 0.28-0.94); and for the secondary outcome, HR = 0.57 (95% CI 0.38-0.86), HR = 0.58 (95% CI 0.39-0.87), in univariate and multivariable cox regression analyses, respectively. In long-term follow-up with 20,142 person-years of follow-up: 7.6% (5 cases) within the poor metabolizers group, and 11.6%, 12.9%, 12.8%, and 11.1% in the normal, intermediate, rapid, and ultra-rapid metabolizers groups, respectively, had a new fracture (nonsignificant). We conclude that CYP2C19 poor metabolizer status is associated with higher effectiveness of PPIs, and is not associated with higher risk for fractures.

The association between psoriatic arthritis and venous thromboembolism: a population-based cohort study.

BACKGROUND: Although the risk of cardiovascular disease has been discussed extensively in both psoriasis (PsO) and psoriatic arthritis (PsA), very few studies have addressed the occurrence of venous thromboembolic (VTE) events among PsO patients, and even fewer in PsA. Thus, our goal was to assess the association between PsA and VTE events using a large population-based database. METHODS: This retrospective cohort study includes all 5,275 patients with newly diagnosed PsA from the largest health care provider in Israel between January 2003 and December 2018. Identified PsA patients were matched by age, sex, ethnicity, and index date with 21,011 controls without PsA from the same database. Both groups were followed through June 30, 2019 for the occurrence of VTE event. Cox proportional hazard regression models were used to assess the association between PsA and VTE. RESULTS: PsA cohort consisted of 53.2% females with mean age of 51.7±15.4 Sixty-two patients (1.2%) were diagnosed with VTE in the PsA group and 176 patients (0.8%) in the control group (p=0.023, HR=1.40, 95% CI 1.05-1.87). However, there was no increased risk of VTE among PsA patients on multivariable analysis (p=0.16, HR=1.27, 95% CI 0.91-1.80). Within the PsA group, patients with VTE were more often of older age and with history of VTE. CONCLUSIONS: This study suggests that the increased risk of VTE in PsA patients appears to be related to the underlying comorbidities and not independently associated with PsA. Age and previous history of VTE were the only risk factors associated with increased risk of VTE in patients with PsA. Addressing VTE risk is recommended especially in the era of Janus kinase inhibitors.

The Association of Psoriatic Arthritis With All-cause Mortality and Leading Causes of Death in Psoriatic Arthritis.

OBJECTIVE: To examine the association between psoriatic arthritis (PsA) and all-cause mortality from a large population-based database. METHODS: Patients with PsA from the Clalit Health Services database were identified between 2003-2018 and matched to 4 controls by age, sex, ethnicity, and index date. Patient demographics, comorbidities, and treatments were extracted. Mortality data were obtained from the Israeli Notification of Death certificate. The proportionate mortality rate (PMR) of the leading causes of death was calculated and compared to that of the general population. Cox proportional hazard regression models were used to estimate the crude and the multivariate adjusted HR for the association between PsA and all-cause mortality and for factors associated with mortality within the PsA group. RESULTS: There were 5275 patients with PsA and 21,011 controls included and followed for 7.2 ± 4.4 years. The mean age was 51.7 ± 15.4 years, and 53% were females. Among patients with PsA, 38.2% were on biologics. Four hundred seventy-one (8.9%) patients died in the PsA group compared to 1668 (7.9%) in the control group. The crude HR for the association of PsA and all-cause mortality was 1.16 (95% CI 1.04-1.29) and 1.02 (95% CI 0.90-1.15) on multivariate analysis. Malignancy was the leading cause of death (26%), followed by ischemic heart disease (15.8%); this is in keeping with the leading causes of death in the general population. Older age, male sex, lower socioeconomic status, increased BMI, increased Charlson comorbidity index scores, and history of psoriasis or hospitalization in 1 year prior to entry were positive predictors for mortality. CONCLUSION: No clinically relevant increase in mortality rate was observed in patients with PsA, and specific PMRs were similar to those of the general population.

Bridging Care Transition After Hospitalization for Atrial Fibrillation and Coronary Interventions.

ABSTRACT: Treatment fragmentation between hospitals and the community can result in catastrophic outcomes; uninterrupted treatment with anticoagulant and platelet aggregation inhibitors is particularly important. We assessed the proportion and characteristics of patients who did not visit their primary community-based physician within 1 week of discharge from our department of cardiovascular medicine and the proportion that failed to procure essential drugs at the community pharmacy. We prospectively studied 423 patients who were discharged from our department. They were provided detailed explanations, tablets for 7 days, prescriptions, and a printed drug plan. We traced the time from discharge until a visit with a primary community-based physician, and the time until the procurement of medications, using our computerized community-hospital-integrated system. Complete data were available for 313 patients, of whom 220 were treated with anticoagulants or platelet aggregation inhibitors. For 175 patients, these drugs were initiated during index hospitalizations. Only 1 patient did not receive platelet aggregation inhibitors despite recommendations. Seventy-nine patients (25%) first visited their primary care physicians more than 1 week after discharge. Predictors for delayed visits were living alone (hazard ratio 1.91) and having an in-house caregiver (hazard ratio 2.01). In conclusion, all but 1 patient continued drug therapy after discharge from the hospital. The simple predischarge steps included patient education and provision of a 1-week supply of tablets and prescriptions. Treatment continuation was independent of visits to the community-based primary physician. Patients living alone or with an in-house caregiver more often delayed visits to primary physicians yet continued relevant drug therapy.

Implementation of the Treat-to-Target Concept in Evaluation of Psoriatic Arthritis Patients.

BACKGROUND: The treat-to-target approach was recently adopted for psoriatic arthritis (PsA) management. OBJECTIVE: To assess the implementation of the "treat-to-target" (T2T) concept in daily management of PsA by use of composite scores of disease activity versus clinical judgement alone. METHODS: A total of 117 PsA patients from a longitudinal PsA cohort were enrolled consecutively in the study during each patient's first clinic visit during 2016-2017. Clinic notes from the treating rheumatologist were reviewed by an independent rheumatologist, noting clinical impression of disease activity, treatment changes based on clinical judgement, and rationale. Treatment changes were then compared to the use of formal disease activity parameters in Minimal Disease Activity (MDA) and Disease Activity Index for Psoriatic Arthritis (DAPSA) composite measures. All associations were assessed using the chi-square test or the Mann-Whitney test, as appropriate. RESULTS: The 117 PsA patient cohort consisted of 65.5% women, mean age 58.4 ± 13.6 years. Clinical judgement of treating rheumatologist concorded with MDA and DAPSA in 76 (65.5%) and 74 (64.9%) patients, respectively. Agreement between clinical judgement and composite measure criteria did not correlate with patient age, sex, alcohol/tobacco use, or treatment regimens chosen. Disagreement between physician assessment and MDA occurred in 40 (34.5%) cases: in 30 cases, the MDA status was overestimated due to disregard of patient reported outcomes (PRO), while underestimation of MDA status occurred in 25% of cases with treatment changes made in patients with a single active joint or enthesis. Underestimation of disease activity using DAPSA occurred in 22 cases and could be attributed to disregarding tender joint count, patient pain visual analogue scale and C-reactive protein level. CONCLUSION: In our cohort, agreement between clinical impression and formal composite measure utilization for implementation of T2T strategy occurred in 65% of patients. Discordance resulted from physicians' overlooking PRO and emphasizing objective findings when using clinical judgement alone.

Research Productivity among Plastic Surgeons in the State of Israel: h-index and M-quotient Assessment.

The h-index has been proven in the US and Canada to be a solid tool to assess the quality and impact of individual scientific work in the field of plastic surgery. M-quotient is an additional metric that mitigates the h-index's inherent bias toward more seasoned researchers. The objective of this study was evaluating the relationship between h-index and M-quotient and research productivity among plastic surgeons in the state of Israel. METHODS: A list of all Israeli board-certified plastic surgeons registered in the Israeli Society of Plastic and Aesthetic Surgery was obtained from the organization's website. Relevant demographic and academic factors of each surgeon were retrieved. The Scopus database was queried to determine each surgeon's h-index and M-quotient, among other bibliometric parameters. RESULTS: Our study included 173 plastic surgeons, 90% of whom were men. In total, 49.7% were working in academically affiliated hospitals; 14.4% of the surgeons had an academic rank. The mean h-index was 6.13; mean M-quotient was 0.27. Statistical analysis demonstrated a positive correlation between total number of publications (P < 0.0001), total number of citations (P < 0.0001), the surgeon's seniority (P < 0.0001), academic rank (P = 0.007), appointed as past/present plastic surgery department director (P < 0.0001), and working in an academic affiliated hospital (P < 0.025). The same parameters were found to have a positive correlation with M-quotient. CONCLUSIONS: The h-index is an effective measure to compare plastic surgeons' research productivity in Israel. M-quotient is an ancillary tool for the assessment of research productivity among plastic surgeons, with the advent of neutralizing the surgeon's seniority.

Global longitudinal strain and long-term outcome in patients presenting to the emergency department with suspected acute coronary syndrome.

AIMS: We have previously shown that 2-dimentional strain is not a useful tool for ruling out acute coronary syndrome (ACS) in the emergency department (ED). The aim of the present study was to determine whether in patients with suspected ACS, global longitudinal strain (GLS), measured in the ED using 2-dimensional strain imaging, can predict long-term outcome. METHODS: Long-term (median 7.7 years [IQR 6.7-8.2]) major adverse cardiac events (MACE; cardiac death, ACS, revascularization, hospitalization for heart failure, or atrial fibrillation) and all-cause mortality data were available in 525/605 patients (87%) enrolled in the Two-Dimensional Strain for Diagnosing Chest Pain in the Emergency Room (2DSPER) study. The study prospectively enrolled patients presenting to the ED with chest pain and suspected ACS but without a diagnostic ECG or elevated troponin. GLS was computed using echocardiograms performed within 24 hours of chest pain. MACE of patients with worse GLS (>median GLS) were compared to patients with better GLS (≤ median GLS). RESULTS: Median GLS was -18.7%. MACE occurred in 47/261 (18%) of patients with worse GLS as compared with 45/264 (17%) with better GLS, adjusted HR 0.87 (95% CI 0.57-1.33, P = .57). There was no significant difference in all-cause mortality or individual endpoints between groups. GLS did not predict MACE even in patients with optimal 2-dimensional image quality (n = 164, adjusted HR=1.51, 95% CI 0.76-3.0). CONCLUSIONS: Global longitudinal strain did not predict long-term outcome in patients presenting to the ED with chest pain and suspected ACS, supporting our findings in the 2DSPER study.

Beliefs about medication as predictors of medication adherence in a prospective cohort study among persons with multiple sclerosis.

BACKGROUND: Though adherence to disease-modifying therapies (DMTs) among persons with multiple sclerosis (PwMS) varies and is often below 80%, only few prospective studies on adherence examined predictors beyond demographic and clinical characteristics. OBJECTIVES: Identify antecedents to adherence and persistence to DMT in a prospective design among PwMS. METHODS: PwMS (n = 186) were prospectively assessed at three time points: baseline, 6 (Time 1) and 12 months later (Time 2). Clinical, demographic information and patient-reported medication beliefs, illness perceptions, medication habits, perceived health and affect were surveyed in-person. Adherence and persistence were assessed by a combination of self-reports and retrospective review of medication claims. FINDINGS: PwMS were 69.9% (Time 1) and 71% (Time 2) adherent to their DMTs and 64.5.9% were persistent. Beliefs about Medications were consistently predictive at both time points (baseline to Time 1 and Time 1 to Time 2) of medication adherence and persistence whereas other perceptions were predictive in some analyses; clinical and demographic characteristics were mostly not predictive of adherence nor persistence. The prospective association of beliefs about medication with adherence held also in multivariate analyses (OR = 0.88, 95% CI 0.78-0.99, p = 0.029). CONCLUSIONS: Adherence and persistence are predicted by medication beliefs of PwMS. As medication beliefs are modifiable, they should be assessed periodically and targeted as a focus of tailored interventions aimed to improve adherence and consequently health outcomes in PwMS. REGISTRATION: Clinical trials registry # NCT02488343 , date: 06/08/2015.

Ischemic stroke and myocardial ischemia in clopidogrel users and the association with CYP2C19 loss-of-function homozygocity: a real-world study.

Reduced clopidogrel effectiveness in preventing recurrent myocardial ischemia following percutaneous coronary intervention has been demonstrated in CYP2C19 loss-of-function carriers. Less is known about the effect of CYP2C19 genotype on the effectiveness of clopidogrel for stroke prevention, particularly in Caucasians. This is a retrospective cohort study, in which we used the Clalit clinical database to follow genotyped clopidogrel initiators, for up to 3 years. Endpoint was a new primary discharge diagnosis of ischemic stroke; secondary endpoints were new primary discharge diagnoses of coronary angioplasty, myocardial infarction (MI), or a composite endpoint of: stroke, MI, or coronary angioplasty. After 3 years of follow up over 628 clopidogrel initiators, 2 out of 12 (16.7%) poor metabolizers, 9 out of 144 intermediate metabolizers (6.3%), and 29 out of 472 (6.1%) normal/rapid/ultrarapid metabolizers have been newly diagnosed with ischemic stroke. Poor metabolizer status was associated with higher risk for ischemic stroke, marginally significant in univariate analysis and in multivariable models; and higher risk for the composite outcome of stroke, myocardial infarction and coronary angioplasty, HR = 3.32 (1.35-8.17) p = 0.009, 2.86 (1.16-7.06) p = 0.02 (univariate and multivariate analyses, respectively). Poor metabolizer status was associated with higher risk for stroke HR = 5.80 (1.33-25.24) p = 0.019, HR = 4.13 (0.94-18.13) p = 0.06 (univariate and multivariate analyses, respectively) in patients who "survived" the first year, and were in the cohort 1-3 years. Caucasian treated with clopidogrel who are homozygote for the CYP2C19 loss-of function allele might be at increased risk for ischemic stroke, and for the composite outcome of ischemic stroke, myocardial infarction and coronary angioplasty.

Treatment persistence of biologics among patients with psoriatic arthritis.

BACKGROUND: Persistence of biologic therapy in psoriatic arthritis (PsA) patients is an important factor in individualized patient treatment planning and healthcare policy and guideline development. OBJECTIVE: To estimate the persistence of biologic agents prescribed to PsA patients in a real-life setting as well as factors associated with improved biologic drug survival in these patients. METHODS: Patients with PsA from a large healthcare provider database with at least two consecutive dispensed prescriptions of a biologic agent indicated for PsA from January 1, 2002, until December 31, 2018, were identified and followed until medication stop date or the end of observation period. Patients were considered non-persistent whenever a permissible lag time of 6 months from the time of prescription issuance until medication filling date was exceeded. Treatment changes were based on physician decisions and patient preferences. Demographic data including age, sex, body mass index (BMI), ethnicity, smoking history, and socioeconomic status as well as Charlson comorbidity index were retrieved. Data regarding use of steroids and conventional disease-modifying anti-rheumatic drugs (cDMARDs) were also extracted. Descriptive statistics, including means (standard deviations) for continuous variables and frequencies (%) for categorical variables, were used. Persistence estimates were derived using non-parametric survival analysis using Kaplan-Meier functions, with treatment discontinuations as failure events. Cox regression hazard ratio models were conducted to investigate factors associated with drug persistence. RESULTS: A total of 2301 PsA patients with 2958 treatment periods were identified and included in the analyses. Mean age of the study population was 50.9 ± 14 years, 54% were females, 70.4% were with BMI > 25, 40% were current smokers, and 76% were with a Charlson comorbidity index > 1. The most commonly prescribed drug was etanercept (33%), followed by adalimumab (29%), golimumab (12%), secukinumab (10%), ustekinumab (8%), and infliximab (8%). While approximately 40% of patients persisted on therapy following 20 months of treatment, only about 20% of patients remained on any particular biologic agent after 5 years. Analyzing the data for all treatment periods while taking into account all lines of therapy revealed that secukinumab had a higher persistency than adalimumab, infliximab, and ustekinumab, with a log rank of 0.022, 0.047, and 0.001, respectively. Female sex and smoking were associated with lower drug persistence (HR = 1.25, 95% CI = 1.13-1.38 and HR = 1.109, 95% CI = 1.01-1.21, respectively). On analyzing the data using only the first indicated biologic line, no superiority of any single anti-tumor necrosis factor-alpha (anti-TNFα) agent was observed, while secukinumab was found to be superior as second line therapy to adalimumab, etanercept, infliximab, and ustekinumab but not to golimumab with a log rank P value of 0.001, 0.004, 0.025, and 0.002, respectively. CONCLUSIONS: In this large observational cohort studied in the era of biologic therapy, a relatively low drug persistence was observed, with female sex and smoking having a negative impact on persistency. None of the anti-TNFα agents was found to be more persistent than others as first line therapy, while secukinumab was found to be superior to other biologics when indicated as second line of therapy.

High Dimensional Analyses of Circulating Immune Cells in Psoriatic Arthritis Detects Elevated Phosphorylated STAT3.

Psoriatic arthritis (PsA) is a chronic inflammatory arthritis, affecting up to 40% of patients with psoriasis. Constitutive expression by CD4+ T cells of an active form of STAT3, a signal transducer and transcription factor, has been shown to induce many of the major features of PsA in an animal model. We used high dimensional mass cytometry (CyTOF) to probe ex-vivo levels of phosphorylated STAT3 (pSTAT3) in circulating immune cell subpopulations from PsA patients during active and inactive states. We evaluated the frequency of 16 immune cell populations and the levels of the activated forms of STAT3 (pSTAT3) and, for comparison, STAT1 (pSTAT1) and Src (pSrc) in whole blood fixed shortly after collection. In addition to PsA patients, we studied active rheumatoid arthritis (RA) patients. Increased levels of pSTAT3 were found in all the CD4+ T cell subsets analyzed, specifically, Th1, Th2, Th17, T follicular helper (Tfh) and T regulatory (Treg) as well as in CD14+CD16- (classical) monocytes from active PsA patients compared to inactive patients. After correcting for body mass index (BMI), smoking and conventional disease modifying antirheumatic drugs (c-DMARDs), levels of pSTAT3 levels remained increased in Th1 and Tfh CD4+ T cells, and in CD14+CD16- monocytes from active patients compared to inactive patients. No differences between the patient groups were observed for pSTAT1 or pSrc. No differences were found between the active PsA and active RA groups after correction for multiple testing. During active PsA, circulating Th1 and Tfh CD4+ T cells, and CD14+CD16- monocytes expressing high levels of pSTAT3 may play a role in PsA pathophysiology, perhaps by migration to inflamed sites.