Israel Medical Association Journal

Background: Tocilizumab is an interleukin 6 (IL-6) receptor antagonist used treat moderate to severe active rheumatoid arthritis (RA). Both intravenous (IV) and subcutaneous (SC) routes are approved for the treatment of adults with RA.

Objectives: To evaluate SC tocilizumab in a real-life clinical setting.

Methods: Our study was a multi-center, open-label, single-arm study. Participants were adults with a diagnosis of active RA, previously treated with disease-modifying antirheumatic drugs (DMARDs), with or without biologic agents. Participants received a weekly SC injection of tocilizumab 162 mg as monotherapy or in combination with methotrexate or DMARDs for 24 weeks. Efficacy, safety, and immunogenicity were assessed.

Results: Treatment of 100 patients over 24 weeks resulted in improvement in all efficacy parameters assessed: Clinical Disease Activity Index, Disease Activity Score using 28 joint counts and erythrocyte sedimentation rate, American College of Rheumatology response scores, Simplified Disease Activity Index, tender and swollen joint counts, and patient-reported outcomes including fatigue, global assessment of disease activity, pain, and Health Assessment Quality of Life Disease Index. Improvement was achieved as early as the second week of treatment. There were 473 adverse events (AEs)/100 patient-years (PY) and 16.66 serious AEs/100 PY. The most common AEs were neutropenia (12%), leukopenia (11%), and increased hepatic enzymes (11%). Of a total of 42 PY, the rates of serious infections and AEs leading to discontinuation were 4.8, and 11.9 events/100 PY, respectively.

Conclusions: The safety, tolerability, and efficacy profile of tocilizumab SC were comparable to those reported in other studies evaluating the IV and SC routes of administration.

Background: Emergency department (ED) overcrowding is associated with worse patient outcomes.

Objectives: To determine whether physician assistants (PAs), fairly recently integrated into the Israeli healthcare system, improve patient outcomes and ED timings.

Methods: We compared patients seen by physicians with patients seen by PAs and then by physicians between January and December 2018 using propensity matching. Patients were matched for age, gender, triage level, and decision to hospitalize. Primary endpoints included patient mortality, re-admittance. and leaving on own accord rates. Secondary endpoints were ED timing landmarks.

Results: Patients first seen by PAs were less likely to leave on their own accord (MD1 1.5%, PA 1.0%, P = 0.015), had lower rates of readmission within 48 hours (MD1 2.1%, PA 1.5%, P= 0.028), and were quicker to be seen, to have medications prescribed, and to undergo imaging without differences in timings until decisions were made or total length of stay. Patients seen by a physician with the assistance of a PA were attended to quicker (MD2 47.79 minutes, range 27.70–78.82 vs. MD + PA 30.59 minutes, range 15.77–54.85; P < 0.001) without statistically significant differences in primary outcomes. Mortality rates were similar for all comparisons.

Conclusions: Patients first seen by PAs had lower rates of re-admittance or leaving on their own accord and enjoyed shorter waiting times. Pending proper integration into healthcare teams, PAs can further improve outcomes in EDs and patient satisfaction.

Background: Admission to an intensive care unit (ICU) is an objective marker of severe maternal morbidity (SMM).

Objectives: To determine the prevalence of obstetric ICU admissions in one medical center in Israel and to characterize this population.

Methods: In this retrospective study the files of women coded for pregnancy, birth, or the perinatal period and admission to the ICU were pulled for data extraction (2005–2013).

Results: During the study period, 111 women were admitted to the ICU among 120,279 women who delivered babies (0.09%). Their average age was 30 ± 6 years, most were multigravida, a few had undergone fertility treatments, and only 27% had complicated previous pregnancies. Most pregnancies (71.2%) were uneventful prior to admission. ICU admissions were divided equally between direct (usually hemorrhage) and indirect (usually cardiac disease) obstetric causes.

Conclusions: The indications for obstetrics ICU admission correlated with the proximate causes of maternal arrest observed worldwide. While obstetric hemorrhage is often unpredictable, deterioration of heart disease is foreseeable. Attention should be directed specifically toward improving the diagnosis and treatment of maternal heart disease during pregnancy in Israel.

Background: The use of a high flow nasal cannula (HFNC) was examined for different clinical indications in the critically ill.

Objectives: To describe a single center experience with HFNC in post-extubation critical care patients by using clinical indices.

Methods: In this single center study, the authors retrospectively evaluated the outcome of patients who were connected to the HFNC after their extubation in the intensive care unit (ICU). At 48 hours after the extubation, the patients were divided into three groups: the group weaned from HFNC, the ongoing HFNC group, and the already intubated group.

Results: Of the 80 patients who were included, 42 patients were without HFNC support at 48 hours after extubation, 22 and 16 patients were with ongoing HFNC support and already intubated by this time frame, respectively. The mean ROX index (the ratio of SpO₂ divided by fraction of inspired oxygen to respiratory rate) at 6 hours of the weaned group was 12.3 versus 9.3 in the ongoing HFNC group, and 8.5 in the reintubated group (P = 0.02). The groups were significantly different by the ICU length of stay, tracheostomy rate, and mortality.

Conclusions: Among patients treated with HFNC post-extubation of those who had a higher ROX index were less likely to undergo reintubation.

Background: There is a need for standardized and objective methods to measure postural instability (PI) and gait dysfunction in Parkinson's disease (PD) patients. Recent technological advances in wearable devices, including standard smartphones, may provide such measurements.

Objectives: To test the feasibility of smartphones to detect PI during the Timed Up and Go (TUG) test.

Methods: Ambulatory PD patients, divided by item 30 (postural stability) of the motor Unified Parkinson's Disease Rating Scale (UPDRS) to those with a normal (score = 0, PD-NPT) and an abnormal (score ≥ 1, PD-APT) test and a group of healthy controls (HC) performed a 10-meter TUG while motion sensor data was recorded from a smartphone attached to their sternum using the EncephaLog application.

Results: In this observational study, 44 PD patients (21 PD-NPT and 23 PD-APT) and 22 HC similar in age and gender distribution were assessed. PD-APT differed significantly in all gait parameters when compared to PD-NPT and HC. Significant difference between PD-NPT and HC included only turning time (P < 0.006) and step-to-step correlation (P < 0.05).

Conclusions: While high correlations were found between EncephaLog gait parameters and axial UPDRS items, the pull test was least correlated with EncephaLog measures. Motion sensor data from a smartphone can detect differences in gait and balance measures between PD with and without PI and HC.

Background: Current guidelines for choosing between revascularization modalities may not be appropriate for young patients.

Objectives: To compare outcomes and guide treatment options for patients < 40 years of age, who underwent percutaneous coronary intervention (PCI) or coronary artery bypass grafting (CABG) between 2008 and 2018.

Methods: Outcomes were compared for 183 consecutive patients aged < 40 years who underwent PCI or CABG between 2008 and 2018, Outcomes were compared as time to first event and as cumulative events for non-fatal outcomes.

Results: Mean patient age was 36.3 years and 96% were male. Risk factors were similar for both groups. Drug eluting stents were implemented in 71% of PCI patients and total arterial revascularization in 74% of CABG patients. During a median follow-up of 6.5 years, 16 patients (8.6%) died. First cardiovascular events occurred in 35 (38.8%) of the PCI group vs. 29 (31.1%) of the CABG group (log rank P = 0.022), repeat events occurred in 96 vs. 51 (P < 0.01), respectively. After multivariate adjustment, CABG was associated with a significantly reduced risk for first adverse event (hazard ratio [HR] 0.305, P < 0.01) caused by a reduction in repeat revascularization. CABG was also associated with a reduction in overall repeat events (HR 0.293, P < 0.01). There was no difference in overall mortality between CABG and PCI.

Conclusions: Young patients with coronary disease treated by CABG showed a reduction in the risk for non-fatal cardiac events. Mortality was similar with CABG and PCI.

Background: The policies and practices related to medical cannabis are currently in flux. These changes have been associated with many controversies, and there is a lack of consensus within the medical community regarding medical cannabis practices.

Objectives: To validate clinical vignettes that can be used to examine and improve medical cannabis practices.

Methods: Ten physicians participated in a Delphi survey of two consequent rounds in which they quantified the eligibility of medical cannabis therapy for six clinical vignettes describing both chronic pain and cancer patients.

Results: Higher consensus was achieved for the vignettes of cancer patients, which were additionally rated as more eligible for medical cannabis therapy. The highest level of consent (4.3 out of 5) was achieved regarding a vignette of a metastatic cancer patient. While in some cases physicians consolidated their ratings toward the group's average, in other cases they remained stable in their responses.

Conclusions: While controversies related to medical cannabis are expected to remain rampant, the validated vignettes may facilitate assessment of clinical practices, which is essential for a successful implementation of medical cannabis policies. These vignettes may additionally be used in medical training for appropriate patient selection for medical cannabis authorization.

Background: Complete hydatidiform mole and a co-existing normal fetus (CHMCF) is associated with a high complication rate. A possible association with assisted conception might increase the prevalence of CHMCF.

Objectives: To study the potential association between assisted conception and the risks of CHMCF.

Methods: Case series at a single university hospital from 2008 to 2018 are presented and contrasted with data from a comprehensive literature review (1998–2018). Cases were identified from the institutional database that matched the sonographic criteria for CHMCF. A literature review showed comparable cases.

Results: None of the three pregnancies presented in this article resulted in a viable fetus, all were aborted. One of the three patients needed chemotherapy due to gestational trophoblastic neoplasia (GTN). A literature search identified 248 reported cases in which 22 fetuses (9%) reached term, 88/248 (35%) progressed to GTN, and 25/120 (21%) were conceived following assisted conception. From 2008 until 2018 at our medical facility, there were 3144 twin pregnancies of which 1667 (53%) were conceived using assisted conception. In our cohort, there was no statistical trend for assisted conception as an etiological factor for CHMCF.

Conclusions: No association between assisted conception and the risk for CHMCF was established at our hospital, although approximately one-quarter of all reported CHMCF pregnancies are attributed to assisted conception technology. However, these data are not always reported, making it difficult to draw definitive conclusions.

Background: Young women concerned about a breast cancer diagnosis will visit breast care centers and request breast cancer screening, including imaging studies, on their initial visit.

Objectives: To explore the role of breast examination and breast ultrasound in self-referred asymptomatic women under the age of 40 years.

Methods: We identified 3524 women under the age of 40 at our medical clinic from 1 January 2010 until 1 June 2014. Of this group, 164 women with above average breast cancer risk were excluded and 233 were excluded because of breast complaints. Of 3127 women, 220 underwent breast ultrasound following the initial visit to the clinic and formed the study group.

Results: Of 220 women evaluated with ultrasound, 68 had prior positive clinical findings. Of this group 8 women had no sonographic findings, and in the remaining 60, a total of 30 simple cysts, 15 fibroadenomas, and 15 suspicious solid masses were identified. One infiltrating ductal carcinoma and one ductal carcinoma in situ were found in a biopsy. The remaining 152 of the 220 total women who underwent breast ultrasound without showing prior physical findings did not require follow-up.

Conclusions: In the absence of clinical findings during physical breast examination, the addition of breast ultrasonography does not provide additional information to supplement the physical examination in self-referred women under age 40 who do not have any major risk factors for developing breast cancer.