Israel Medical Association Journal

Background: The effect of repeated intravenous amantadine (IVAM) in advanced Parkinsonism has not been studied in depth.

Objectives: To report the experience of our medical center with repeated IVAM infusions in patients with advanced Parkinsonism.

Methods: Thirty patients with advanced Parkinsonism of various etiologies were enrolled in an open-label retrospective study. All patients were treated with IVAM infusions in a neurological daycare center. Treatment was initiated with a loading dose of 200/400 mg per day for 5 days followed by a once-daily maintenance dose of 200/400 mg every 1 to 3 weeks. Patients and their caregivers participated in a structured interview and independently completed a clinical global impression of changes scale questionnaire on various motor and non-motor symptoms.

Results: Patient mean age was 73.3 ± 9.7 years, average disease duration was 6.2 ± 5.7 years, and mean Hoehn and Yahr score was 3.2 ± 0.84. Mean duration of the IVAM treatment was 15.1 ± 11.6 months. An improvement in general function was reported by 91% of the patients and 89% of the caregivers. Most of the patients reported improvement in tremor and rigidity, as well as in gait stability, freezing of gait, and reduced falls. The treatment was safe with few side effects.

Conclusions: Our data suggest that repeated IVAM infusions could be an effective treatment against various motor symptoms and for improvement of mobility in patients with advanced Parkinsonism. Further randomized clinical trials with a larger sample size using objective measures are warranted to validate our results.

Giacomo Ceruti was a renowned painter in northern Italy during the middle third of the 18th century, although he is not well-known today. He produced pictures in several different genres but his reputation after his death was based primarily on his portrayal of beggars and poor working people; hence, his posthumous nickname, il Pitocchetto, the little beggar. Of medico-artistic interest is the realism with which he depicted the hands of his impoverished subjects, a quality that enables them to be examined for signs of pathology or trauma.

The present article displays some representative examples of hand deformities in Ceruti’s paintings, thus extending into the 18th century the authors' previous research on medical aspects of art works from the 15th to the 17th century.

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: Statins and selective serotonin reuptake inhibitors (SSRIs) have beneficial effects on health outcomes in the general population. Their effect on survival in debilitated nursing home residents is unknown.

Objectives: To assess the relationships between statins, SSRIs, and survival of nursing home residents.

Methods: Baseline patient characteristics, including chronic medications, were recorded. The association of 5-year survival with different variables was analyzed. A sub-group analysis of survival was performed according to baseline treatment with statins and/or SSRIs.

Results: The study comprised 993 residents from 6 nursing homes. Of them, 285 were males (29%), 750 (75%) were fully dependent, and 243 (25%) were mobile demented. Mean age was 85 ± 7.6 years (range 65–108). After 5 years follow-up, the mortality rate was 81%. Analysis by sub-groups showed longer survival among older adults treated with only statins (hazard ratio [HR] for death 0.68, 95% confidence intervals [95%CI] 0.49–0.94) or only SSRIs (HR 0.6, 95%CI 0.45–0.81), with the longest survival among those taking both statins and SSRIs (HR 0.41, 95%CI 0.25–0.67) and shortest among residents not taking statins or SSRIs (P < 0.001). The survival benefit remained significant after adjusting for age and after conducting a multivariate analysis adjusted for sex, functional status, body mass index, mini-mental state examination, feeding status, arrhythmia, diabetes mellitus, chronic kidney disease, and hemato-oncological diagnosis.

Conclusion: Treatment with statins and/or SSRIs at baseline was associated with longer survival in debilitated nursing home residents and should not be deprived from these patients, if medically indicated. 

Background: The frequency of increased high-sensitivity C-reactive protein (hs-CRP) and the time course of evolution of their levels in patients with acute idiopathic pericarditis (AIP) are not well established.

Objective: To assess the time course of evolution of hs-CRP levels and the possible clinical significance of maximal hs-CRP levels in patients with AIP

Methods: We retrospectively reviewed the medical files of 241 patients admitted to the hospital with a diagnosis of AIP between March 2006 and March 2017. Data on demographics, time of symptom onset, laboratory and imaging findings, and outcome were collected.

Results: Data on serum hs-CRP levels were available for 225 patients (age 18–89 years, 181 men). Fever, pleural effusion, and age were independently associated with hs-CRP levels. Major cardiac complications (MCC) (death, cardiac tamponade, cardiogenic shock, large pericardial effusion, ventricular tachycardia, pericardiocentesis, or pericardiectomy) were more common in patients with hs-CRP levels above the median compared to those below (21.2% vs. 4.5%, respectively, P < 0.001). Hs-CRP levels were independently associated with MCC (odds ratio [OR] 1.071, 95% confidence interval [95%CI] 1.016–1.130, P = 0.011). Hs-CRP levels were elevated in 76.0%, 92.3% and 96.0% of the patients tested <6 hours, 7-12 hours, and >12 hours of symptom onset, respectively (P = 0.003). The frequency of elevated hs-CRP among patients tested > 24 hours was 98.1%.

Conclusions: Hs-CRP levels rise rapidly among patients with AIP. Maximal hs-CRP levels are associated with MCC. A normal hs-CRP level is rare among patients tested > 24 hours of symptom onset.

Background: Surgery is a core activity in hospitals. Operating rooms have some of the most important and vital functions in medical centers. The operating rooms and their staff are a valuable infrastructure resource and their availability and preparedness affect human life and quality of care.

Objectives: To prepare operational suggestions for improving operating room utilization by mapping current working processes in the operating rooms of a large private medical center.

Methods: Data on 23,585 surgeries performed at our medical center between August 2016 and March 2017 were analyzed by various parameters including utilization, capacity, working hours, and surgery delays.

Results: Average operating room utilization was 79%, while 21% was considered lost operating room time. The two major factors that influenced the lost operating room time were the time intervals between planned usage blocks and the partial utilization of operating room time. We calculated that each percent of utilized operating room time translates into 440 surgeries annually, resulting in a potential annual increase in income.

Conclusions: Increasing operating room utilization would result in an improvement of operating room availability and an increased number of procedures. Our analysis shows that operating room utilization in the private healthcare system is efficient compared to the public healthcare system in Israel. Therefore the private healthcare system should be treated as a contributing factor to help lower surgery waiting times and release bottlenecks, rather than being perceived as contributing to inequality.

Background: Male breast cancer (MBC) is a rare disease representing less than 1% of breast cancers. In the absence of a screening program, such as for females, the diagnostic workup is critical for early detection of MBC.

Objectives: To summarize our institutional experience in the workup of male patients referred for breast imaging, emphasizing the clinical, imaging, and histopathological characteristics of the MBC cohort.

Methods: All male patients who underwent breast imaging between 2011 and 2016 in our institution were retrospectively reviewed. Clinical, radiological, and histopathological data were collected and statistically evaluated. All images were reviewed using the American College of Radiology Breast Imaging Reporting and Data System.

Results: 178 male patients (average age 61 years, median age 64), underwent breast imaging in our institution. The most common indication for referral was palpable mass (49%) followed by gynecomastia (16%). Imaging included mostly mammography or ultrasound. Biopsies were performed on 56 patients, 38 (68%) were benign and 18 (32%) were malignant. In all, 13 patients had primary breast cancer and 5 had metastatic disease to the breast. Palpable mass at presentation was strongly associated with malignancy (P = 0.007).

Conclusion: Mammography and ultrasound remain the leading modalities in breast imaging among males for diagnostic workup of palpable mass, with gynecomastia being the predominant diagnosis. However, presentation with palpable mass was also associated with malignancy. Despite a notable MBC rate in our cohort, the likelihood of cancer is low in young patients and in cases of gynecomastia.

Background: Recently, Israel established the first national-level adult cardiac surgery database, which was linked to the Society of Thoracic Surgeons (STS).

Objectives: To validate and compare the STS predicted risk of mortality (PROM) to logistic EuroSCORE I (LESI) and EuroSCORE II (ESII) in Israeli patients undergoing cardiac surgery.

Methods: We retrospectively studied 1279 consecutive patients who underwent cardiac surgeries with a calculable PROM. Data were prospectively entered into our database and used to calculate PROM, LESI, and ESII. Scores were normalized and correlated using linear regression and Pearson's test. To examine model calibration, we plotted the total observed versus expected mortality for each score and across five risk-score subgroups. Model discrimination was assessed by measuring the area under the receiver operating curves.

Results: The observed 30-day operative mortality was 1.95%. The median (IQ1; IQ3) PROM, LESI, and the ESII scores were 1.45% (0.69; 3.22), 4.54% (2.28; 9.27), and 1.88% (1.18; 3.54), respectively, with observed over expected ratios of 0.63 (95% confidence interval [95%CI] 0.42–0.93), 0.59 (95%CI 0.40–0.87), and 0.24 (95%CI 0.17–0.36), respectively, (STS vs. ESII P = 0.36, STS vs. LESI P = 0.0001). There was good correlation among all scores. All models overestimated mortality. Model discrimination was high and similar for all three scores. Model calibration of the STS, PROM, and ESII were more accurate than the LESI, particularly in higher risk subgroups.

Conclusions: All scores overestimated mortality. In Israeli patients, the STS, PROM, and ESII risk-scores were more reliable metrics than LESI, particularly in higher risk patients.

Background: Recurrent miscarriages are associated with a high prevalence of thrombophilia. Use of a calibrated automated thrombogram (CAT) can serve as a universal test for thrombophilia.

Objectives: To examine whether thrombin generation measured by CAT is elevated during the first trimester in women with unexplained recurrent miscarriages.

Methods: This study comprised 25 pregnant women with recurrent pregnancy loss referred for thrombophilia screening and treated with low-molecular-weight heparin (LMWH). Thrombin generation parameters were measured in women who had miscarriages or live births and who were diagnosed as positive or negative for thrombophilia.

Results: Of the pregnancies, 76% resulted in live birth and 24% ended in miscarriages. Among the women, 76% were positive for thrombophilia. Thrombin generation parameters between pregnancies that ended in miscarriage compared to live births were not significantly different, and CAT parameters failed to predict pregnancy outcome. Although the CAT parameters demonstrated a trend toward a hypercoagulable state in women with thrombophilia, there was no statistical significance (P > 0.05).

Conclusions: Women with unexplained pregnancy loss demonstrated similar thrombin generation in the first trimester, regardless of the pregnancy outcome. CAT parameters failed to predict pregnancy outcome in women with recurrent unexplained pregnancy loss. Our results should be interpreted with caution due to the small number of participants.

Background: Data suggest that subclinical hypothyroidism (SCH) is associated with progression of chronic renal disease; however, no study to date has assessed the possible relation between SCH and acute deterioration of renal function.

Objectives: To investigate the possible relation between SCH and acute kidney injury (AKI) in a large cohort of patients with ST-elevation myocardial infarction (STEMI) treated with primary coronary intervention (PCI).

Methods: We evaluated thyroid stimulating hormone (TSH) and free T4 levels of 1591 STEMI patients with no known history of hypothyroidism or thyroid replacement treatment who were admitted to the coronary care unit (October 2007–August 2017). The presence of SCH was defined as TSH levels ≥ 5 mU/ml in the presence of normal free T4 levels. Patients were assessed for development of AKI ( 0.3 mg/dl increase in serum creatinine, according to the KDIGO criteria).

Results: The presence of SCH was demonstrated in 68/1593 (4.2%) STEMI patients. Patients presenting with SCH had more AKI complications during the course of STEMI (20.6% vs. 9.6 %; P = 0.003) and had significantly higher serum creatinine change throughout hospitalization (0.19 mg/dl vs. 0.08 mg/dl, P = 0.04). No significant difference was present in groups regarding baseline renal function and the amount of contrast volume delivered during coronary angiography. In multivariate logistic regression model, SCH was independently associated with AKI (odds ratio = 2.19, 95% confidence interval 1.05–4.54, P =0.04).

Conclusions: Among STEMI patients treated with PCI, the presence of SCH is common and may serve as a significant marker for AKI.

Background: Cryptosporidium is a major threat to water supplies worldwide. Various biases and obstacles in case identification are recognized. In Israel, Cryptosporidiosis was included among notifiable diseases in 2001 in order to determine the burden of parasite-inflicted morbidity and to justify budgeting a central drinking water filtration plant.

Objective: To summarize the epidemiologic features of 14 years of Cryptosporidium surveillance and to assess the effects of advanced water purification treatment on the burden of disease.

Methods: From 2001 to 2014, a passive surveillance system was used. Cases were identified based on microscopic detection in stool samples. Confirmed cases were reported electronically to the Israeli Ministry of Health. Overall rates as well as age, gender, ethnicity and specific annual incidence were calculated per 100,000 population in five age groups: 0–4, 5–14, 15–44, 45–64, > 65 years.

Results: A total of 522 Cryptosporidium cases were reported in all six public health districts. More cases were detected among Jews and among males, and mainly in young children, with a seasonal peak during summer. The Haifa sub-district reported 69% of the cases. Most were linked to an outbreak from the summer of 2008, which was attributed to recreational swimming pool activity. Cases decreased after installation of a central filtration plant in 2007.

Conclusions: As drinking water in Israel is treated to maximal international standards, the rationale for further inclusion of Cryptosporidium among mandatory notifiable diseases should be reconsidered. Future surveillance efforts should focus on timely detection of outbreaks using molecular high-throughput testing.

Background: Adenovirus is responsible for 2–7% of childhood viral respiratory infections, 5–11% of viral pneumonia and bronchiolitis. Most are self-limited but may cause severe respiratory infection.

Objectives: To describe adenovirus respiratory infection in immunocompetent children in a pediatric intensive care unit (PICU).

Methods: Children with adenovirus respiratory infection in our PICU from 2007 to 2016 were included. Data were retrospectively retrieved, including background, clinical manifestation, and treatment. Adenovirus was diagnosed by polymerase chain reaction, immune fluorescence, or both.

Results: Of 9397 samples, 956 were positive for adenovirus in children hospitalized during the study period. In total, 49 patients (aged 2 months–11.5 years) were admitted to our PICU, five were immunocompromised and excluded from the study, 19/44 (43%) were referred from other hospitals. Twenty-eight (64%) had underlying conditions, 66% had fever and cough, 11% had conjunctivitis, and 34% received antibiotics before admission. White blood cell counts ranged from 790 to 34,300 (mean 14,600) and 36% had counts above 15,000. Chest X-ray was consistent with viral infection in 77% of patients and normal in three (13.6%). Viral co-infection was found in 9 patients, 7 had presumed bacterial super-infection, and 27 (61.4%) needed mechanical ventilation. Two patients received cidofovir, 33 (75%) steroids, and 37 (84 %) antibiotics. Four patients died.

Conclusions: Adenovirus respiratory infection may cause severe disease necessitating PICU admission and mechanical ventilation, mostly in patients with underlying conditions. Many patients received steroids and antibiotics, which may be unnecessary. Mortality was 9%, mainly among young infants and those with underlying conditions.

Background: With the recent introduction of high-sensitivity troponin (hsTn), the incremental benefit of stress myocardial perfusion imaging (MPI) in the evaluation of patients who present to the emergency department (ED) with acute coronary syndrome (ACS) is unclear.

Objectives: To assess the added value of stress MPI in low-risk ACS patients with normal range hsTnI.

Methods: We analyzed all patients who were hospitalized at our medical center from February 2016 to November 2017, who presented with low-risk ACS and underwent stress MPI, and in whom hsTnI was in the normal range after the introduction of hsTnI.

Results: During the study period, 161 patients were admitted with a diagnosis of unstable angina (i.e., ACS with normal range hsTnI) and underwent stress MPI during index admission. The study population included 52/161 patients (31.7%) with low-risk ACS who had no indication for initial invasive strategy. No patients had positive MPI. One patient underwent coronary angiography due to suggestive history; however, he did not have a significant coronary artery disease and had no indication for percutaneous coronary intervention.

Conclusions: In patients with low-risk ACS and normal range hsTnI without additional high-risk features, stress MPI has little additional value for the correct diagnosis and management. Prospective studies are warranted to confirm whether resting hsTnI could serve as a powerful triage tool in chest pain patients in the ED before diagnostic testing and thus, improve patient management.