Epidemiological trends in psoriatic arthritis: a comprehensive population-based study.

BACKGROUND: Psoriatic arthritis (PsA) is a chronic, potentially debilitating inflammatory arthritis often associated with psoriasis. Understanding the epidemiology of PsA across diverse populations can provide valuable insights into its global burden and the role of genetic and environmental factors. This study aimed to estimate PsA's temporal trends, prevalence, and incidence, while assessing variations in age, gender, and ethnicity in Israel from 2016 to 2022. METHODS: Data were sourced from the Clalit Health Services (CHS) database, covering over half of the Israeli population. Algorithm-based definitions for PsA and psoriasis cases were used. Demographic factors, including age, gender, socioeconomic status (SES), ethnicity, urban/rural residence, BMI, and smoking status, were analyzed. Standardized prevalence and incidence rates were calculated. Logistic regression analyses examined associations of sociodemographic variables with PsA. RESULTS: In 2022, the prevalence of PsA was 0.221%, with an incidence rate of 13.54 per 100,000 population. This prevalence has tripled since 2006, reflecting a rising trend in PsA over time. Females exhibited a higher prevalence (1.15; 95%CI 1.09-1.21), and PsA was more common in Jewish individuals (1.58; 95%CI 1.45-1.71) those with higher SES (1.4; 95% CI 1.31, 1.5), and those with obesity (2.17; 95%CI 2.04-2.31). CONCLUSIONS: This comprehensive population-based study pointed to an increase prevalence of PsA, emphasizing the rising healthcare demands and economic burden faced by this patient population. Further research is essential to delve into the factors driving these trends.

Factors associated with keratoconus in Israel-A cross-sectional population-based study.

PURPOSE: To identify potential factors associated with keratoconus. METHODS: This cross-sectional study included data from Israel's largest healthcare provider for the years 2005-2020. Keratoconus patients and age-matched controls were identified. Demographic factors and comorbid conditions, including smoking, diabetes mellitus, asthma, myalgia, mental retardation, Down syndrome, atopic dermatitis and allergy/allergic rhinitis, were compared between the two cohorts. The independent risk factors associated with keratoconus were determined using a multivariable conditional logistic regression model. RESULTS: Overall, 145 508 subjects were reviewed of which 13 228 were keratoconus patients. A ten-fold group (n = 132 280) of age-matched control subjects served as controls for comparisons. In multivariable analysis, several factors were found to be significantly associated with keratoconus. Male gender (OR = 1.27, p < 0.001), Arab ethnicity (OR = 1.50, p < 0.001), diabetes (OR = 1.19, p < 0.001), asthma (OR = 1.50, p < 0.001), myalgia (OR = 1.09, p = 0.02), mental retardation (OR = 2.63, p < 0.001), atopic dermatitis (OR = 1.35, p < 0.001) and allergic rhinitis (OR = 1.21, p < 0.001) were significantly associated with keratoconus. Smoking was significantly protective of keratoconus (OR = 0.66, p < 0.001). CONCLUSIONS: This population-based study reports male gender, Arab ethnicity, diabetes, asthma, myalgia, mental retardation/Down syndrome, atopic dermatitis and allergic rhinitis as factors associated with keratoconus while smoking demonstrates a protective effect. The results of this study could guide enhanced screening strategies and early interventions, particularly for high-risk groups.

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 .

Identifying Factors Associated With Disparities in Access to Integrative Oncology Program.

CONTEXT AND OBJECTIVES: Cancer centers are increasingly providing complementary medicine as part of an emerging discipline termed 'integrative oncology' (IO). The present study explored factors associated with disparities in referral and adherence to a freely-provided IO program. METHODS: The databases of three oncology centers in northern Israel were searched retrospectively for chemotherapy-treated oncology patients eligible for referral by their oncology healthcare professionals to an integrative physician (IP) consultation. Demographic and cancer-related variables associated with the referral, and attendance by patients at the consultation were identified, as was adherence to the 6-week IO treatment program (high adherence, attending ≥4 IO treatment sessions; low adherence, 0-3 sessions). RESULTS: Of 4988 eligible patients, 1694 (34%) were referred to the IP consultation, with 1331 (78.6%) attending the consultation of which 766 (57.6%) were adherent to IO treatments. Multivariate analysis revealed lower referral rates among patients speaking primarily Arabic and Russian vs. Hebrew (OR = 3.0, 95% CI = 2.0-4.6, P < 0.0001); males vs. females (OR = 1.94, CI = 1.3-2.9, P = 0.001); those not reporting emotional distress (OR = 1.5, CI = 1.02-2.16, P = 0.037); and older age (OR = 1.04, CI = 1.03-1.06, P < 0.0001). Arabic and Russian-speaking patients were less likely to adhere to IO treatments (OR = 0.52, 95% CI = 0.32-0.83, P = 0.006). CONCLUSION: Patients' ethno-national origin and immigration status (primary language, Arabic and Russian), male gender and older age were associated with lower rates of referral to and attendance of the IP consultation, with reduced adherence to weekly IO treatments. These findings require further study to identify barriers toward diversity, equity and inclusion in IO care, increasing awareness among healthcare professionals regarding the benefits of these services for improving patient wellbeing.

Risk factors for recurrent acute mastoiditis in pediatric patients: a registry-based cohort study.

OBJECTIVE: To describe characteristics of pediatric patients with recurrent acute mastoiditis, and to identify risk factors for this condition. STUDY DESIGN: A retrospective cohort study. SETTING: Data based on electronic medical records of the largest Health Maintenance Organization in Israel. METHODS: Children hospitalized due to acute mastoiditis during the years 2008-2018 were identified, and their diagnosis was verified. Patients with recurrent acute mastoiditis were identified and grouped, and their characteristics were outlined and compared to those of the original group to identify risk factors for recurrence. RESULTS: During the 11-year period, a total of 1115 cases of children hospitalized due to acute mastoiditis were identified with a weighted incidence rate of 7.8/100,000. Of this group, 57 patients were diagnosed with recurrence following a full clinical recovery. The incidence proportion of recurrent acute mastoiditis was 5.1% (57/1115), male-to-female ratio was 27:30, 73.4% were younger than 24 months, the median period from the first episode was 3.4 months (IQR 2.0;10.0), and 82.5% of the patients (n = 47) had a single recurrence, whereas 18.5% (n = 10) had two recurrences or more. Mastoidectomy and swelling over the mastoid area during the first episode were identified as the main risk factors for recurrent mastoiditis HR = 4.7 [(2.7-8.2), p < 0.001] and HR = 2.55 [(1.4-4.8), p = 0.003], respectively. Mastoidectomy was the only independent significant risk factor for recurrence in a multivariate analysis. CONCLUSIONS: Mastoidectomy and swelling over the mastoid area during the first episode of acute mastoiditis were found strongly related independent risk factor for future recurrent episodes of acute mastoiditis.

The Risk of Herpes Zoster Events in Patients with Spondyloarthritis and the Effect of BNT162b2 mRNA COVID-19 Vaccine.

The data on the risk of herpes zoster (HZ) in spondyloarthropathy (SpA) patients are sparse, especially regarding its association with the novel mRNA COVID-19 vaccines and immunosuppressants. We aimed to evaluate whether SpA diagnosis and/or immunosuppressant use affect HZ risk and the influence of mRNA COVID-19 vaccination. We assessed the association between SpA (psoriatic arthritis (PsA) and ankylosing spondylitis (AS)) diagnoses and HZ in a large population database with patients matched by age and sex to controls. We also assessed the association between the COVID-19 vaccine and new-onset HZ using two nested case-control studies, identifying all new HZ cases diagnosed from 1 January-31 December 2021 within the SpA and general population cohorts, matched randomly by sex, age and HZ index date to controls without HZ. Exposure to mRNA COVID-19 vaccination was ascertained in the 6 weeks prior to the index date both in cases and controls. In our results, the incidence rate of HZ was higher in PsA patients vs. the general population, at 1.03 vs. 0.64 per 100 person-years, respectively (adjusted HR = 1.55; 95%CI, 1.19-2.02). Within the SpA group, Jak-I treatment was associated with a higher risk of developing new-onset HZ (adjusted OR = 3.79; 1.15-12.5). Multivariable conditional logistic regression models we used showed no association between COVID-19 vaccination and new-onset HZ among the SpA patients (OR = 1.46; 0.68-3.14).

Bronchiectasis with Chronic Rhinosinusitis Is Associated with Eosinophilic Airway Inflammation and Is Distinct from Asthma.

Rationale: Bronchiectasis is an airway inflammatory disease that is frequently associated with chronic rhinosinusitis (CRS). An eosinophilic endotype of bronchiectasis has recently been described, but detailed testing to differentiate eosinophilic bronchiectasis from asthma has not been performed. Objectives: This prospective observational study aimed to test the hypotheses that bronchiectasis with CRS is enriched for the eosinophilic phenotype in comparison with bronchiectasis alone and that the eosinophilic bronchiectasis phenotype exists as a separate entity from bronchiectasis associated with asthma. Methods: People with idiopathic or postinfectious bronchiectasis were assessed for concomitant CRS. We excluded people with asthma or primary ciliary dyskinesia and smokers. We assessed sputum and blood cell counts, nasal NO and fractional excreted NO, methacholine reactivity, skin allergy testing and total and specific immunoglobulin (Ig) E, cytokines in the sputum and serum, and the microbiome in the sputum and nasopharynx. Results: A total of 22 people with CRS (BE + CRS) and 17 without CRS (BE - CRS) were included. Sex, age, Reiff score, and bronchiectasis severity were similar. Median sputum eosinophil percentages were 0% (IQR, 0-1.5%) in BE - CRS and 3% (1-12%) in BE + CRS (P = 0.012). Blood eosinophil counts were predictive of sputum eosinophilia (counts ⩾3%; area under the receiver operating characteristic curve, 0.68; 95% confidence interval, 0.50-0.85). Inclusion of CRS improved the prediction of sputum eosinophilia by blood eosinophil counts (area under the receiver operating characteristic curve, 0.79; 95% confidence interval, 0.65-0.94). Methacholine tests were negative in 85.7% of patients in the BE - CRS group and 85.2% of patients in the BE + CRS group (P > 0.99). Specific IgE and skin testing were similar between the groups, but total IgE levels were increased in people with increased sputum eosinophils. Microbiome analysis demonstrated distinct microbiota in nasopharyngeal and airway samples in the BE + CRS and BE - CRS groups, without significant differences between groups. However, interactome analysis revealed altered interactomes in individuals with high sputum eosinophil counts and CRS. Conclusions: Bronchiectasis with CRS is associated with an eosinophilic airway inflammation that is distinct from asthma.

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.

A randomized-controlled trial assessing the effect of intraoperative acupuncture on anesthesia-related parameters during gynecological oncology surgery.

CONTEXT AND OBJECTIVES: The present study examined the impact of intraoperative acupuncture on anesthesia-related parameters in patients undergoing gynecological oncology surgery. METHODS: Participants underwent preoperative integrative oncology (IO) touch/relaxation treatments, followed by intraoperative acupuncture (Group A); preoperative IO treatments without acupuncture (Group B); or standard care only (Group C). Mean arterial pressure (MAP), heart rate (HR), MAP variability (mean of MAP standard deviation), bispectral index (BIS), and calculated blood pressure Average Real Variability (ARV) were measured intraoperatively. RESULTS: A total of 91 patients participated: Group A, 41; Group B, 24; Group C, 26. Among patients undergoing open laparotomy, Group A showed lower and more stable MAP and HR compared to Group B, (MAP, p = 0.026; HR, p = 0.029) and Group C (MAP, p = 0.025). Mean BIS, from incision to suture closing, was lower in Group A (vs. controls, p = 0.024). In patients undergoing laparoscopic surgery, MAP was elevated within Group A (p = 0.026) throughout surgery, with MAP variability significantly higher in Group A (P = 0.023) and Group B (P = 0.013) 10 min post-incision (vs. pre-incision). All groups showed similar intraoperative and post-anesthesia use of analgesic medication. CONCLUSION: Intraoperative acupuncture was shown to reduce and stabilize MAP and HR, and reduce BIS in gynecology oncology patients undergoing laparotomy, with no impact on perioperative analgesic medication use. In the laparoscopic setting, intraoperative acupuncture was associated with elevated MAP. Further research is needed to explore the hemodynamic and BIS-associated benefits and risks of intraoperative acupuncture, and the impact on the use of analgesic drugs in response to these changes.

Acupuncture during gynecological oncology surgery: A randomized controlled trial assessing the impact of integrative therapies on perioperative pain and anxiety.

BACKGROUND: In this study, the impact of a multimodal integrative oncology pre- and intraoperative intervention on pain and anxiety among patients undergoing gynecological oncology surgery was explored. METHODS: Study participants were randomized to three groups: Group A received preoperative touch/relaxation techniques, followed by intraoperative acupuncture; Group B received preoperative touch/relaxation only; and a control group (Group C) received standard care. Pain and anxiety were scored before and after surgery using the Measure Yourself Concerns and Wellbeing (MYCAW) and Quality of Recovery (QOR-15) questionnaires, using Part B of the QOR to assess pain, anxiety, and other quality-of-life parameters. RESULTS: A total of 99 patients participated in the study: 45 in Group A, 25 in Group B, and 29 in Group C. The three groups had similar baseline demographic and surgery-related characteristics. Postoperative QOR-Part B scores were significantly higher in the treatment groups (A and B) when compared with controls (p = .005), including for severe pain (p = .011) and anxiety (p = .007). Between-group improvement for severe pain was observed in Group A compared with controls (p = .011). Within-group improvement for QOR depression subscales was observed in only the intervention groups (p <0.0001). Compared with Group B, Group A had better improvement of MYCAW-reported concerns (p = .025). CONCLUSIONS: A preoperative touch/relaxation intervention may significantly reduce postoperative anxiety, possibly depression, in patients undergoing gynecological oncology surgery. The addition of intraoperative acupuncture significantly reduced severe pain when compared with controls. Further research is needed to confirm these findings and better understand the impact of intraoperative acupuncture on postoperative pain. PLAIN LANGUAGE SUMMARY: Integrative oncology programs are increasingly becoming part of supportive/palliative care, with many working within the Society for Integrative Oncology. This study examined the impact of a multimodal integrative oncology program on pain and anxiety among 99 patients undergoing gynecological oncology surgery. Participants were randomized to three groups: preoperative touch/relaxation treatments, followed by intraoperative acupuncture; preoperative touch/relaxation without acupuncture; and a control group receiving standard care only. The preoperative touch/relaxation intervention significantly reduced perioperative anxiety, with the addition of intraoperative acupuncture significantly reducing severe pain as well, when compared with controls. Further research is needed to confirm these findings.

Treatment effects of Elexacaftor/Tezacaftor/Ivacaftor in people with CF carrying non-F508del mutations.

BACKGROUND: In vitro studies have demonstrated rescue of CFTR function with Elexacaftor/Tezacaftor/Ivacaftor (ETI) in several mutations other than F508del. However, clinical efficacy was not tested in vivo in people with CF (pwCF) carrying mutations other than F508del. We report effects of treatment with ETI in pwCF with non-F508del mutations. METHODS: We retrospectively analyzed pwCF with non-F508del mutations who received treatment with ETI. We evaluated sweat chloride, nutritional status, spirometry, antibiotic treatment, and pulmonary exacerbations (PEx), at baseline and 3-6 months after commencing treatment with ETI. RESULTS: We included 16 pwCF, including eight without previous use of CFTR modulators. Median time on treatment was 5.3 (range, 1.8-7.7) months. Compared to baseline, in the "naïve" group sweat chloride concentration was reduced from 113.0 (98-129) to 64.0 (32-97) mEq/L (n=7; median (IQR), p=0.018), and rate of pulmonary exacerbations declined from a median of 1.5 (IQR 1, 2.75) in the previous year to 0 (0,0) (p= 0.019) with a significant decline in annualized days with antibiotics (oral + parenteral) per year: 36 (17.5; 42) in the year before to 0 (0,0) (median (IQR), p= 0.027). Mean FEV1% changed from 66.3±25 to 72.4±29 % (mean ± SD, p=0.058). In the group of patients previously treated with Ivacaftor or Tezacaftor/Ivacaftor, we didn't observe significant improvements in any of the parameters. CONCLUSIONS: We demonstrate the clinical efficacy of ETI in pwCF carrying CFTR processing non-F508del mutations which are predicted to respond by in vitro studies. Our results support routine clinical use of ETI in this patient group.

Epidemiology of pediatric acute mastoiditis in Israel: A National Registry 10-year perspective.

Background and Objectives: Previous small studies have proposed a higher incidence of acute mastoiditis in Israeli pediatric patients than in other Western countries. The aim of this study was to describe the incidence of acute mastoiditis and its epidemiological features over a decade, in order to identify variables that could possibly affect the incidence. Methods: All admitted patients aged <18 years diagnosed with acute mastoiditis between 2008 and 2018 at Clalit Healthcare Services were identified and a database was generated. Results: A total of 1189 and 1115 patients met the inclusion criteria, respectively. Acute mastoiditis diagnosis was confirmed in 95.2% of the patients. The incidence was 7.78 cases per 100,000 children-years but was significantly higher in children under 2 years of age (average of 38.31 per 100,000 children-years). No specific pattern was observed in the annualized incidence rate during the study period. Acute mastoiditis was significantly more common in children of Jewish descent than non-Jewish (10.4 vs. 3.03 per 100,000 children-years, P < 0.001) and of high socioeconomic status and is more common in the winter. The prevalence of household parental smoking (52%) was more than double that previously reported in the Israeli population. Conclusions: A higher incidence of acute mastoiditis was observed in the Israeli population than in other reports. The age-dependent rate was identified along with unique epidemiological features such as seasonality, higher incidence in patients of Jewish descent, or high socioeconomic status. Related parental smoking habits lend further support against the exposure of young children to household smoking.Level of evidence: Individual retrospective cohort study.

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.

Biological or mechanical mitral valve replacement in patients 50-70 years of age-a propensity-adjusted analysis.

OBJECTIVES: The choice of a bioprosthetic valve (BV) over a mechanical valve (MV) in middle-aged adults in the mitral position is still under debate. Each valve type has benefits and drawbacks. We examined the mid-term survival of patients aged 50-70 years after BV versus MV mitral valve replacement (MVR). METHODS: We conducted a multicentre, retrospective analysis of patients aged 50-70 years undergoing MVR from 2005 to December 2018 in 4 medical centres in Israel. To control for between-group differences, we used propensity-adjusted analysis. The primary end point was all-cause mortality. Secondary end points included reoperation, cerebrovascular accident and bleeding. RESULTS: During the study period, 2125 MVR procedures were performed. Of these, 796 were eligible for inclusion [539 (67.8%) MV replacement and 257 (32.2%) BV]. The mean age was 61.0 ± 5.4. There were 287 deaths during 4890 person-years of follow-up. The adjusted hazard ratio was (1.13 [0.85-1.49], P = 0.672). There was also no difference in the secondary end points. Subgroup analysis of patients aged 50-64 years showed a higher risk of mortality with BV (hazard ratio = 1.50 [1.07-2.1], P = 0.018). Reoperation was a strong predictor of mortality during the study period (72.2%). CONCLUSIONS: In patients aged 50-70 years, we found an interaction between age and MV or BV outcomes-those younger than 65 years gained a mortality advantage with MV, while outcomes were similar in the 65-70 age group. this supports the current guidelines recommending using MV in patients <65 years of age.

Culprit Medications and Risk Factors Associated with Stevens-Johnson Syndrome and Toxic Epidermal Necrolysis: Population-Based Nested Case-Control Study.

OBJECTIVE: Our objective was to describe the incidence of Stevens-Johnson syndrome/toxic epidermal necrolysis (SJS/TEN) in a large unselected cohort, to validate the culprit drugs involved and the frequency of SJS/TEN for each drug, and to analyze the clinical risk factors for SJS/TEN. METHODS: Using the computerized database of Clalit Health Services, we identified all adult patients with a new SJS/TEN diagnosis between 1 January, 2008 and 30 June, 2019 and validated each case. Cumulative incidence of SJS/TEN for each culprit drug was calculated by dividing the number of valid cases by the total number of new users of the drug in the study period. Using risk-set sampling, 20 controls were matched to each case by sex and age on the index date for a nested case-control analysis. Multivariable conditional logistic regression was used to estimate the odds ratio and 95% confidence interval for the association of incident SJS/TEN with chronic diseases. RESULTS: We identified 87 adult cases of true/probable SJS/TEN between 1 January, 2008 and 30 June, 2019. Culprit drugs [with ALDEN scores ascertained as at least probable (≥ 4)] associated with the highest absolute risks were phenytoin, lamotrigine, and allopurinol with 3.56, 2.82, and 1.10 SJS/TEN cases/10,000 new users, respectively. Additional drugs with mean ALDEN scores ≥ 4 were sunitinib, sulfasalazine, carbamazepine, etoricoxib, etodolac, and cefuroxime, cumulative incidence: 13.57, 0.72, 0.32, 0.05, 0.02, and 0.02/10,000 new users, respectively. Previous diagnosis of systemic lupus erythematosus, psoriasis, previous drug allergies, epilepsy, malignancy, history of cerebrovascular accident, and history of diabetes mellitus were associated with an increased risk for SJS/TEN, odds ratios (95% confidence interval):17.41 (1.31-230.72), 10.28 (3.61-29.31), 5.21 (2.95-9.19), 4.92 (1.88-12.85), 3.17 (1.77-5.66), 2.61 (1.26-5.41), and 1.98 (1.12-3.53), respectively. CONCLUSIONS: Attention should be drawn to drugs assessed by high ALDEN scores that were associated with high absolute risks for SJS/TEN. Psoriasis, former drug allergies, in addition to systemic lupus erythematosus, malignancy, history of cerebrovascular accident, and diabetes mellitus were associated with increased SJS/TEN risk in our analysis.

Correlation between cumulative mammographic density and age-specific incidence of breast cancer: A biethnic study in Israel.

Women with the most extensive breast density, have a 4- to 6-fold higher cancer risk than women with the lowest density. This cross-sectional study evaluated associations of cumulative mammographic density in two distinct ethnic groups with the respective age-specific breast cancer incidences in the population. The study compared four cohorts of 200 women each aged 35 to 49 and 50 to 74, representing Jewish and Arab ethnicity. Breast density measures were calculated from screening mammograms, using a thresholding software (Cumulus). Breast cancer specific incidence values were obtained from the National Cancer Registry. The percent mammographic density was lower for women aged 50 to 74 than 35 to 49 years, both for Jews: 11.7 vs 23.1 and for Arabs: 11.6 vs 18.3. In contrast, the cumulative density increased with age, from 37.30 to 181.24 in Jews, compared to 21.26 to 108.03 in Arabs. Similar trends in breast cancer incidence rates per 100 000 in the Israeli population were apparent, with an increase from 92.95 to 381.91 in Jews, compared to 48.6 to 244.44 in Arabs. Comparing cumulative density of the cohort with respective age-specific breast cancer incidence in the population yielded a highly significant correlation: Jews; r = .97, P < .0001 and Arabs: r = .86, P = .007. A strong association was found between the log of cumulative density and the log of cancer incidence, as well. Our study identified correlations between cumulative mammographic density and breast cancer incidence in two distinct populations. The findings should prompt research to enhance our understanding of the pathogenesis of breast cancer, and lead to novel insights into measures of prevention.

Exploring the effectiveness of a patient-tailored integrative oncology program on emotional distress during chemotherapy for localized cancer.

STUDY OBJECTIVE: There is a need to explore how patient-tailored integrative oncology (IO) programs reduce emotional distress. This study set out to bridge the IO research gap between non-specific, quality of life-related and specific emotional-related concerns in chemotherapy-treated patients. METHODS: This pragmatic, prospective and preference-controlled study examined patients attending an integrative-physician consultation and weekly IO treatments during adjuvant/neo-adjuvant chemotherapy for localized cancer. Patients choosing to attend ≥4 IO sessions (highly adherent to integrative care, AIC) were compared to low AIC patients using the ESAS (Edmonton Symptom Assessment Scale) anxiety, depression and sleep; and the EORTC QLQ-C30 (European Organization for Research and Treatment of Cancer Quality of Life Questionnaire) emotional functioning scale, at baseline, 6 and 12 weeks. Emotional distress was assessed by ESAS anxiety and depression, considered as the primary study outcomes. RESULTS: Of 439 participants, 260 (59%) were high-AIC and 179 low-AIC, both with similar baseline demographic and cancer-related characteristics. At 6 weeks, high-AIC patients reported greater improvement on ESAS sleep (p = 0.044); within-group improvement on ESAS anxiety and; and EORTC emotional functioning. Compared with low-AIC, high-AIC patients showed greater improvement on ESAS depression (p = 0.022) and sleep (p = 0.015) in those with high baseline ESAS anxiety scores (≥7); and ESAS anxiety (p = 0.049) for patients moderately anxious (4-6) at baseline. CONCLUSIONS: High-AIC was associated with significantly reduced anxiety, depression and sleep severity at 6 weeks, especially those with high-to-moderate baseline anxiety levels. These findings reduce the research gap, suggesting specific emotional-related effects of IO.

Exploring factors associated with acquisition and chronicity of infection in bronchiectasis: A population-based study.

INTRODUCTION: Chronic infection is associated with adverse outcomes among people with bronchiectasis. However, it is not known which factors are associated with a bacterial infection, and with persistence of an infection after the first episode. We aimed to determine factors associated with a new infection and with chronicity of Pseudomonas aeruginosa (PA) and H. influenzae (HI), the most common organisms in bronchiectasis infection. METHODS: Using an Israeli population database, we identified individuals diagnosed with bronchiectasis. Cox proportional hazard models were used to assess risk factors for first isolation and Logistic regression for chronicity of infection after a first isolation of PA and HI. RESULTS: We included 1305 people with a median of 5 respiratory samples per individual. PA was initially isolated in 297 people, of whom 97 (33%) developed chronic PA infection. HI was newly identified in 169 people, of whom 39 (23%) developed chronic infection (p = 0.029). Factors associated with increased risk of a new infection with PA were COPD (HR 1.87 [1.52-2.28], previous isolation of HI (HR 1.38 [1.07-1.78]), and alcohol abuse (HR 2.22 [1.13-4.3]). Younger age was associated with increased risk of HI infection, while COPD was associated with a lower risk of HI infection. Prescription of an anti- PA antibiotic was associated with chronic PA after a new infection (OR = 1.8 [1.09-2.9], p = 0.02). A landmark analysis showed that survival was worse in people with chronic PA infection vs. single or intermittent infection (Log rank: p = 0.034) CONCLUSIONS: Younger age and presence of PCD are associated with a new isolation of HI. A new infection with PA is associated with previous HI infection, PCD, COPD, and alcohol abuse. Unexpectedly, treatment with appropriate anti-PA antimicrobials was not associated with a reduced risk of chronicity.

Correlation between an integrative oncology treatment program and survival in patients with advanced gynecological cancer.

OBJECTIVE: Integrative oncology (IO) is increasingly becoming part of palliative cancer care. This study examined the correlation between an IO treatment program and rates of survival among patients with advanced gynecological cancer. METHODS: Patients were referred by their oncology healthcare professionals to an integrative physician (IP) for consultation and IO treatments. Those undergoing at least 4 treatments during the 6 weeks following the consultation were considered adherence to the integrative care program (AIC), versus non-adherent (non-AIC). Survival was monitored for a period of 3 years, comparing the AIC vs. non-AIC groups, as well as controls who did not attend the IP consultation. RESULTS: A total of 189 patients were included: 71 in the AIC group, 44 non-AIC, and 74 controls. Overall 3-year survival was greater in the AIC group (vs. non-AIC, p = 0.012; vs. controls, p = 0.003), with no difference found between non-AIC and controls (p = 0.954). Multimodal IO programs (≥ 3 modalities) were correlated in the AIC group with greater overall 3-year survival (p = 0.027). Greater rates of survival were also found in the AIC group at 12 (p = 0.004) and 18 months (p = 0.001). When compared with the AIC group, a multivariate analysis found higher crude and adjusted hazard ratios for 3-year mortality in the non-AIC group (HR 95% CI 2.18 (1.2-3.9), p = 0.010) and controls (2.23 (1.35-3.7), p = 0.002). CONCLUSION: Adherence to an IO treatment program was associated with higher survival rates among patients with advanced gynecological cancer. Larger prospective trials are needed to explore whether the IO setting enhances patients' resilience, coping, and adherence to oncology treatment.