Abstract
Context
Recent guidelines suggest that patients with nonclassic congenital adrenal hyperplasia (NCCAH) stop glucocorticoid therapy after achieving adult height. However, these guidelines do ...not differentiate between NCCAH genotype groups.
Objective
Compare ACTH-stimulated cortisol and 17-hydroxyprogesterone (17OHP) levels, and the rate of partial cortisol insufficiency in subjects with NCCAH carrying one mild and one severe (mild/severe) mutation vs subjects with biallelic mild (mild/mild) mutations.
Methods
Retrospective evaluation of the medical records of 122 patients who presented with postnatal virilization and were diagnosed with NCCAH. Patients underwent standard intravenous 0.25 mg/m2 ACTH stimulation testing. Those with stimulated 17OHP level ≥40 nmol/L were screened for the 9 most frequent CYP21A2 gene mutations followed by multiplex ligation-dependent probe amplification. A stimulated cortisol level below 500 nmol/L was defined as partial cortisol deficiency.
Results
Patients were subdivided into 3 genotype groups: 77 carried the mild/mild genotype, mainly homozygous for p.V281L mutation; 29 were compound heterozygous for mild/severe mutation, mainly p.V281L/p.I2Splice, and 16 were heterozygous for p.V281L, and were excluded from statistical evaluation. Stimulated cortisol levels were significantly lower in the mild/severe than in the mild/mild group (mean ± SD, 480 ± 90 vs 570 ± 125 nmol/L, P < .001). The mild/severe group exhibited a significantly higher rate of partial cortisol insufficiency (21/28, 75% vs 28/71, 39%, P = .004). Peak 17OHP was significantly higher in the mild/severe group (198 ± 92 vs 118 ± 50 nmol/L, P < .001).
Conclusion
The high rate of partial adrenal insufficiency in the mild/severe group underscores the need to carefully consider the value of glucocorticoid therapy cessation and the importance of stress coverage in this group.
Acute mastoiditis (AM) is a severe infection in the young population, with possible life-threatening complications. This study aimed to characterize AM presentation, symptoms and signs, ...complications, and management, over a period of 10 years.
This large-scale population-based cohort studied "Clalit Health Care" records, to include patients <18 years diagnosed with AM, hospitalized between the years 2008-2018. After validation, we investigated clinical symptoms and signs, pneumococcal vaccination status, complications, laboratory and microbiological parameters, imaging, antibiotic treatment and surgical interventions.
AM was diagnosed in 1189 patients, mean age of 2.71 years and 591 (49.71%) were female. Most presented with protrusion of pinna (83.1%), retro auricular redness (73.5%) and fever (71.8%). Patients <2 years of age had more symptoms (3.8 ± 1.4, opposed to 3.6 ± 1.5, P = 0.006) and showed higher white blood cell count and C-reactive protein values. Local and intracranial complications occurred in 233 (20.8%) and 75 (6.5%) patients, respectively. Complications were associated with increased white blood cell count and C-reactive protein and related to bacterial type, specifically Fusobacterium necrophorum (P < 0.0001), for which 50% had an intracranial complication. Between the years 2008-2018, Streptococcus pneumoniae-positive cultures decreased (30.9% to 10.3%, P > 0.0001) as opposed to group-A Streptococcus (10.9% to 30.9%, P = 0.002).
This study shows a difference in AM appearance in the <2 years population and the association between white blood cell count, C-reactive protein and microbiology results with the occurrence of a complication. This may play a role in the management process, such as imaging and intervention needs. Although performed during the pneumococcal vaccine era, the disease microbiology was shown to change significantly throughout the study.
Proprotein convertase subtilisin/kexin type-9 inhibitors (PCSK9i) effectively reduce low-density lipoprotein cholesterol (LDL-C), improving cardiovascular outcomes in clinical trials when added to ...statin therapy.
As real-world evidence is lacking, we aimed to evaluate treatment and adherence patterns using PCSK9i in clinical practice.
We investigated 1600 patients initiating PCSK9i between January 2016 and December 2019 in a large health maintenance organization. Treatment discontinuation was defined as a gap ≥60 days between last days' supply of one prescription and the start of the next. Re-initiation rates as well as proportion of days covered (PDC) over 1-year period and attainment of lipid goals under PCSK9i, were analyzed.
Evolocumab 140 mg was initiated by 50.7%, alirocumab 75 mg by 29.5% and 150 mg by 19.8%. Cumulative discontinuation rates were 28.1% after 6-months and 49.9% after 3-years. Overall, 58% of the patients that discontinued therapy have re-initiated PCSK9i (31% after 3-months from discontinuation). Mean PDC over 1-year of therapy was 56% ± 29, with PDC ≥80% evident in 29%. Of those with established cardiovascular disease (n = 991), 55% achieved LDL-C<70 mg/dL and 38% LDL-C<55 mg/dL. Attainment rates were lower in patients with PDC<80%, baseline LDL-C>190 mg/dL and in those not treated with concurrent statin therapy.
In real-world practice of patients treated by PCSK9i, high proportion of early treatment discontinuation was evident, with non-negligible re-initiation rates but overall low medication coverage over time. This have contributed to sub-optimal attainment of LDL-C treatment goals, particularly observed in patients with severe hypercholesterolemia, inadequate drug adherence, and those using PCSK9i as monotherapy.
•We evaluated real-world treatment and adherence patterns with PCSK9 inhibitors.•High proportion of early treatment discontinuation was evident (28% over 6-months).•Non-negligible re-initiation rates, but overall low medication coverage over time.•PCSK9 inhibitors often used as monotherapy, with decline in concurrent statin therapy.•Treatment/adherence patterns led to sub-optimal attainment of lipid treatment goals.
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GEOZS, IJS, IMTLJ, KILJ, KISLJ, NLZOH, NUK, OILJ, PNG, SAZU, SBCE, SBJE, UILJ, UL, UM, UPCLJ, UPUK, ZAGLJ, ZRSKP
Background
Clostridioides difficile infection (CDI) causes considerable morbidity, mortality, and economic cost. Advanced age, prolonged stay in healthcare facility, and exposure to antibiotics are ...leading risk factors for CDI. Data on CDI clinical outcomes in the very elderly patients are limited.
Methods
A retrospective cohort study of patients hospitalized between 2016 and 2018 with CDI. We evaluated demographic clinical and laboratory parameters. Major clinical outcomes were evaluated including duration of hospital stay, admission to intensive care unit (ICU), in-hospital mortality, 30 days post-discharge mortality, and readmission/mortality composite outcome. We compared patients aged up to 80 years (elderly) to those of 80 years old or more (very elderly).
Results
Of 196 patients included in the study, 112 (57%) were very elderly with a mean age of 86 versus 67 years in the elderly group. The duration of hospital stays, and intensive care unit admission frequency were significantly reduced in the very elderly (13 vs. 22 days
p
= 0.003 and 1.8% vs. 10.7%
p
= 0.01, respectively). No significant difference was found in the frequencies of in-hospital and in 30 days post-discharge mortality.
Conclusions
In our cohort, the duration of hospital stay seemed to be shorter in the very elderly with no increase of in-hospital and post-discharge mortality. Although admitted less frequently to ICU, the in-hospital survival of the very elderly was not adversely affected compared to the elderly, suggesting that very advanced age per se should not be a major factor to consider in determining the prognosis of a patient with CDI.
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EMUNI, FIS, FZAB, GEOZS, GIS, IJS, IMTLJ, KILJ, KISLJ, MFDPS, NLZOH, NUK, OILJ, PNG, SAZU, SBCE, SBJE, SBMB, SBNM, UKNU, UL, UM, UPUK, VKSCE, ZAGLJ
The purpose of this study was to assess the association between reduced apixaban dose and two outcomes: ischemic stroke/systemic embolism (SE) and major bleeding. We performed a retrospective cohort ...study within the database of the largest healthcare provider in Israel. We identified all patients diagnosed with atrial fibrillation, who started apixaban treatment between 2013 and 2017. Apixaban users were classified into three dosing regimen groups based on their renal function, age, and weight: standard dose (5 mg b.i.d.), adjusted reduced dose (2.5 mg b.i.d.), and underdosing (2.5 mg b.i.d.). Patients were followed through 2018 for the occurrence of stroke/SE and major bleeding. Of the 27,765 included patients, 13,141 (47%) adequately received standard apixaban dose, 4,739 patients (17%) received adjusted reduced dose, and 9,885 patients (36%) were classified as underdosed. The CHA2DS2‐VASc score adjusted hazard ratio for ischemic stroke/SE was 1.1 (95% confidence interval (CI), 0.83–1.43) in the adjusted reduced dose group, and 1.04 (95% CI, 0.83–1.35) in the underdosing group, compared with the standard apixaban dose group. The HAS‐BLED score adjusted hazard ratio for any major bleeding was 1.66 (95% CI, 1.32–2.09) in the adjusted reduced dose group, and 1.51 (95% CI, 1.24–1.83) in the underdosing group, compared with apixaban in the standard dose group. Results were similar for major gastrointestinal bleeding and intracranial hemorrhage separately. We conclude that underdosing with apixaban is very common, and may not disproportionately elevate the risk of ischemic stroke. However, albeit halving the dose, patients treated with reduced apixaban dose (adjusted or underdosing) seem to be at higher risk for major bleeding.
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BFBNIB, FZAB, GIS, IJS, KILJ, NLZOH, NUK, OILJ, SBCE, SBMB, UL, UM, UPUK
Clinical models such as the HAS-BLED (standing for Hypertension, Abnormal liver/renal function, Stroke history, Bleeding history or predisposition, Labile INR, Elderly, Drug/alcohol usage) were ...developed to predict risk of major bleeding on vitamin K antagonists/antiplatelet therapy. We aimed to develop a model that will improve the ability to predict major bleeding events in patients with non-valvular atrial fibrillation (AF) treated with new oral anticoagulants (NOACs).
Clalit Health Services is the largest of four integrated healthcare organisations in Israel, which insures 4.7 million patients (53% of the population). We identified in Clalit Health Services all patients with AF, new users of an NOAC (2013-2017), and followed them until first occurrence of a major bleeding event, death, switch to another oral anticoagulant, 30 days after discontinuation of NOAC or end of follow-up (31 December 2019). Importance of the candidate model variables was estimated by inclusion frequencies across forward selection algorithm applied to 50 bootstrap samples. Then, backward selection algorithm using the modified Bayesian Information Criterion for competing risks was applied to select predictors for the final model.
47 623 patients with AF prescribed NOAC were studied. 28 055 patients with AF, initiators of apixaban (mean age 78.7, SD 9.0), were included in the first phase and had 662 major bleeding events. Nine variables were selected for inclusion in a final points-based risk-scoring system: male sex, anaemia, thrombocytopaenia (<99×10
/µL), concurrent antiplatelet therapy, hypertension, prior major bleeding, risk factors for a fall, low cholesterol level and low estimated glomerular filtration rate, with apparent area-under-curve (AUC) of 0.6546. Applicability of the model was then shown for 14 118 and 5450 patients with AF, initiators of dabigatran and rivaroxaban, where the score achieved c indices of 0.62 and 0.61, respectively.
We present a novel and simple risk score for prediction of major bleeding in patients with non-valvular AF treated with NOACs. Validation in additional cohorts is warranted.
Abstract Background Diabetes mellitus is associated with an increased risk of recurrence in patients with ovarian cancer. Retrospective studies suggested that the use of statins, metformin and beta ...blockers is associated with improved prognosis in these patients. Patients with diabetes often suffer from hypertension and are usually treated concomitantly by several classes of drugs. Our aim was to assess the independent contribution of diabetes mellitus and hypertension and of the use of aspirin, statins, metformin and beta blockers on the risk of ovarian cancer recurrence and mortality. Methods Files of ovarian cancer patients treated between 2000 and 2012 were retrospectively reviewed. Data regarding disease characteristics, presence of diabetes mellitus and hypertension, recurrence and death were extracted. The use of drugs was assessed using the Clalit Health Services (CHS) pharmacy records. Results 143 patients treated by debulking surgery and platinum based chemotherapy were included. Median age was 62.5, 22 (15.4%) had diabetes mellitus, 61 (42.7%) had chronic hypertension. Statins were used by 43 (30%) patients, 31 (21.7%) used aspirin, 25 (17.5%) used beta blockers and 12 (8.4%) used metformin. In multivariate analysis diabetes mellitus was associated with a shorter recurrence free survival (RFS) and the use of aspirin and metformin was associated with a prolonged RFS in this cohort. Overall survival (OS) was longer in patients using aspirin and shorter in patients with hypertension. Conclusions Our data suggests that metabolic comorbidities and commonly used drugs are associated with the prognosis of patients with ovarian cancer. Additional trials are needed to confirm these observations and test therapeutic interventions.
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GEOZS, IJS, IMTLJ, KILJ, KISLJ, NUK, OILJ, PNG, SAZU, SBCE, SBJE, UL, UM, UPCLJ, UPUK, ZRSKP
Abstract
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.
Mitral valve replacement (MVR) still accounts for a large part of mitral operations: even though mitral valve repair is the preferred surgical approach for degenerative mitral valve disease, MVR is still commonly performed for rheumatic mitral valve disease, functional mitral valve disease, mitral valve endocarditis and some degenerative mitral valvulopathy.
To assess whether asking questions about a future behavior changes this behavior (i.e., the question-behavior effect) when applied to a population-level intervention to enhance colorectal cancer ...screening.
In 2013, text-message reminders were sent to a national sample of 50 000 Israeli women and men aged 50 to 74 years following a fecal occult blood test invitation. Participants were randomized into 4 intervention groups (2 interrogative reminders, with or without reference to social context; 2 noninterrogative reminders, with or without social context) and a no-intervention control group. The outcome was fecal occult blood test uptake (n = 48 091, following attrition).
Performance of fecal occult blood test was higher in the interrogative-reminder groups than in the other 3 groups (odds ratio = 1.11; 95% confidence interval = 1.05, 1.19); the effect size was small, varying in the different group comparisons from 0.03 to 0.06.
The question-behavior effect appears to be modestly effective in colorectal cancer screening, but the absolute number of potential screenees may translate into a clinically significant health promotion change.
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CEKLJ, DOBA, FSPLJ, IZUM, KILJ, NUK, ODKLJ, OILJ, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK, VSZLJ
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