COVID-19 community care in Israel-a nationwide cohort study from a large health maintenance organization.

BACKGROUND: Among the many medical challenges presented by the COVID-19 pandemic, management of the majority of patients in community outpatient settings is crucial. The aim of this study was to describe the characteristics and outcomes among confirmed COVID-19 cases who were managed at three settings: two outpatient settings and one inpatient. METHODS: A retrospective database cohort study was conducted in a large Israeli Health Maintenance Organization. All COVID-19 cases diagnosed between 28 February 2020 and 20 July 2020 were included. Cases in the community settings were managed through a nationwide remote monitoring center, using preliminary telehealth triage and 24/7 virtual care. Outcome parameters included hospital admission, disease severity, need for respiratory support and mortality. RESULTS: About 5448 cases, aged range 0-97 years, were enrolled; 88.7% were initially managed as outpatient either at home or in designated hotels, 3.1 and 2.1% of them, respectively, later required hospitalization. The main reason for hospitalization was dyspnea; 12 were diagnosed with severe disease; 56 patients (1.3%) died, five (0.1%) of whom were initially allocated to the outpatient settings. CONCLUSIONS: Care for appropriately selected COVID-19 patients in the community provides a safe and effective option. This can contribute to reducing the hospitalization burden, with no evidence of increased morbidity or mortality.

The role of readily available clinical, laboratory and radiologic findings in distinguishing a/H1N1/2009 influenza from other causes of acute febrile respiratory illness under pandemic conditions.

BACKGROUND: During an influenza pandemic, clinicians need easily available clinical and laboratory criteria to distinguish influenza from similar respiratory illnesses. We compared A/H1N1/2009-polymerase chain reaction (PCR)-positive and matched PCR-negative hospitalized patients with suspected H1N1 influenza to identify factors that could assist physicians at patient admission. OBJECTIVES: To identify factors significantly associated with A/ H1N1/2009 infection. METHODS: A group of 145 patients with PCR-confirmed A/H1N1 2009 influenza admitted between 27 May 2009 and 3 December 2009 was matched with 145 PCR-negative patients by age, epidemiological week and pregnancy status. Epidemiological and clinical parameters and radiological findings on initial chest X-ray were compared between the two groups. RESULTS: Asthma (PCR+ 26%, PCR- 12%, P = 0.006) and military service (PCR+ 13%, PCR- 4%, P = 0.15) were associated with PCR-positive status in non-pregnant patients. At presentation, fever, cough, myalgia and fulfilling the pandemic influenza case definition were significantly more frequent in nonpregnant PCR+ patients (62/90/43/59% in PCR+ versus 38/69/30/35% in PCR-). In pregnant patients, fever and fulfilling the case definition were significantly associated with PCR-positive status. Mean leukocyte and absolute lymphocyte counts were significantly lower in both pregnant and nonpregnant PCR-positive patients. Significantly more PCR-negative non-pregnant patients (43% vs. 22% PCR+, P = 0.004) had abnormal chest X-ray (CXR) findings on presentation. In PCR-positive patients, patchy consolidation and interstitial infiltrates were the most common abnormalities. CONCLUSIONS: Under the conditions generated by the A/ H1 1/2009 pandemic, radiological findings did not distinguish reliably between influenza and other febrile respiratory illnesses. Asthma, military service, the pandemic case definition (particularly fever, cough and myalgia)

Clinical efficacy and adverse effects of golimumab in the treatment of rheumatoid arthritis.

Golimumab is a fully human monoclonal antibody targeting tumor necrosis factor-alpha (TNFalpha), an important cytokine in the pathogenesis of rheumatoid arthritis (RA) and other arthritides. Golimumab was approved for the treatment of rheumatoid arthritis with methotrexate (MTX) and with or without MTX for psoriatic arthritis and ankylosing spondylitis. Administration is by monthly subcutaneous injection. In this review we present some of the major clinical trials evaluating the efficacy of golimumab with or without concomitant MTX in RA patients, including patients resistant to previous biologic treatments. In addition, we collected data on safety and adverse effects encountered in clinical trials. Current data show golimumab to be an effective and safe choice for the treatment of various inflammatory arthritides.

Neurocysticercosis in travelers: a nation-wide study in Israel.

BACKGROUND: Cysticercosis, a human infestation by Taenia solium is endemic in many resource-limited countries. In developed countries it is mostly encountered among immigrant populations. Only few cases are reported in travelers. This report summarizes a nation-wide study of neurocysticercosis (NCC) diagnosed among Israeli travelers to endemic countries, with an estimation of disease incidence among the traveler population. METHODS: We performed a retrospective, nation-wide survey of travel-related NCC in Israel between the years 1994 and 2009. RESULTS: Nine cases of NCC were diagnosed in Israeli travelers during the study years. Most patients had traveled to South and/or Southeast Asia. The most common symptom at diagnosis was a seizure. The average interval between return from the suspected travel and symptom onset was 3.2 ± 1.8 years. Two patients suffered from multiple lesions, whereas the rest had a single lesion. Antihelminthic treatment was given to most patients with resolution of symptoms. Median duration of antiepileptic treatment was 16 ± 41 months after albendazole was given. Antiepileptic treatment was discontinued without any complications. The estimated attack rate of clinical disease was 1 : 275,000 per travel episode to an endemic region. CONCLUSIONS: NCC in travelers is a rare phenomenon commonly presenting as seizure disorder manifesting months to years post-travel. Antihelminthic therapy followed by 12 to 24 months of antiepileptic therapy resulted in complete resolution of symptoms in our patients.

National multicenter study of predictors and outcomes of bacteremia upon hospital admission caused by Enterobacteriaceae producing extended-spectrum beta-lactamases.

Extended-spectrum ß-lactamase (ESBL)-producing Enterobacteriaceae are pathogens that may lead to a spectrum of clinical syndromes. We aimed to identify predictors and outcomes of ESBL bacteremia upon hospital admission (UHA) in a nationwide prospective study. Thus, a multicenter prospective study was conducted in 10 Israeli hospitals. Adult patients with bacteremia due to Enterobacteriaceae diagnosed within 72 h of hospitalization were included. Patients with ESBL producers (cases) were compared to those with non-ESBL producers (controls), and a 1:1 ratio was attempted in each center. A case-control study to identify predictors and a cohort study to identify outcomes were conducted. Bivariate and multivariate logistic regressions were used for analyses. Overall, 447 patients with bacteremia due to Enterobacteriaceae were recruited: 205 cases and 242 controls. Independent predictors of ESBL were increased age, multiple comorbid conditions, poor functional status, recent contact with health care settings, invasive procedures, and prior receipt of antimicrobial therapy. In addition, patients presenting with septic shock and/or multiorgan failure were more likely to have ESBL infections. Patients with ESBL producers suffered more frequently from a delay in appropriate antimicrobial therapy (odds ratio [OR], 4.7; P, <0.001) and had a higher mortality rate (OR, 3.5; P, <0.001). After controlling for confounding variables, both ESBL production (OR, 2.3; P, 9.1) and a delay in adequate therapy (OR, 0.05; P, 0.001) were significant predictors for mortality and other adverse outcomes. We conclude that among patients with bacteremia due to Enterobacteriaceae UHA, those with ESBL producers tend to be older and chronically ill and to have a delay in effective therapy and severe adverse outcomes. Efforts should be directed to improving the detection of patients with ESBL bacteremia UHA and to providing immediate appropriate therapy.

Cutaneous toxoplasmosis after bone marrow transplantation with molecular confirmation.

Toxoplasmosis is a rare and often fatal complication of hematopoietic stem cell transplantation (HSCT). The diagnosis of toxoplasmosis is usually made at autopsy because of the variety of systemic manifestations and the difficulty of diagnosis by serologic methods in the severely immunocompromised patient. Cutaneous toxoplasmosis in this setting is extremely rare and is difficult to diagnose with certainty because of the morphologic similarity of Toxoplasma gondii to other organisms, such as Leishmania and Histoplasma species. We report a patient who developed systemic toxoplasmosis, manifested as encephalitis and cutaneous lesions, after HSCT. Findings of a skin biopsy led to a tentative histologic diagnosis of toxoplasmosis, confirmed by polymerase chain reaction (PCR) examination of the skin biopsy and cerebrospinal fluid. This is, to our knowledge, the first report of cutaneous toxoplasmosis diagnosed by skin biopsy confirmed by PCR and sequencing. This disease may be more common than is generally appreciated in severely immunocompromised patients. PCR is a valuable adjunct to diagnosis.

Role of high expression levels of CXCR4 in tumor growth, vascularization, and metastasis.

Hormone refractory metastatic prostate cancer remains an incurable disease. We found that high expression levels of the chemokine receptor CXCR4 correlated with the presence of metastatic disease in prostate cancer patients. Positive staining for CXCL12, the ligand for CXCR4, was mainly present in the tumor-associated blood vessels and basal cell hyperplasia. Subcutaneous xenografts of PC3 and 22Rv1 prostate tumors that overexpressed CXCR4 in NOD/SCID mice were two- to threefold larger in volume and weight vs. controls. Moreover, blood vessel density, functionality, invasiveness of tumors into the surrounding tissues, and metastasis to the lymph node and lung were significantly increased in these tumors. Neutralizing the interactions of CXCL12/CXCR4 in vivo with CXCR4 specific antibodies inhibited the CXCR4-dependent tumor growth and vascularization. In vitro, CXCL12 induced the proliferation and VEGF secretion but not migration of PC3 and 22Rv1 cells overexpressing CXCR4. Similar effects of CXCR4 overexpression on tumor growth in vivo were also noted in two breast cancer lines, suggesting that the observed effect of CXCR4 is not unique to prostate tumor cells. Thus high levels of the chemokine receptor CXCR4 induce a more aggressive phenotype in prostate cancer cells and identify CXCR4 as a potential therapeutic target in advanced cases of metastatic prostate cancer.