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We had previously reported short-term efficacy, immunogenicity, and safety of the BNT162b2 vaccine among cancer patients with solid tumors. We aimed to evaluate these outcomes at six months postvaccination. The study cohort comprised patients who were on treatment during vaccination and throughout six months postvaccination. Serologic tests were performed after second vaccination and six months afterward. An age-matched cohort of health care workers served as controls. Documentation of COVID-19 infection, blood tests, and imaging studies during the study period was reviewed. Participants included 154 patients and 135 controls. Six months postvaccination, 122 (79%) patients were seropositive compared with 114 (84%) controls (P = 0.32). Serology titer dramatically decreased in a similar manner in both cohorts. No COVID-19 cases were documented in controls, and one case occurred in patient cohort. All previously reported adverse effects resolved. Taken together, the pattern of immunogenicity, efficacy, and safety of BNT162b2 in patients with cancer with solid tumors at six months postvaccination resembles that of the general population. Significance: Evidence regarding efficacy and safety of COVID-19 vaccines in patients with cancer indicate a favorable short-term profile. Immunomodulation due to anticancer treatments may affect immunity and immunogenicity of patients with cancer to the BNT162b2 vaccine over time. Our study sheds light on these long-term outcomes and portrays a trend that resembles the general population. This article is highlighted in the In This Issue feature, p. 2355

Background: Respiratory viral infections may be associated with high morbidity and mortality among immunosuppressed children. Our aim was to characterize clinical course and epidemiology of respiratory infections suspected as viral among children treated in a single hematology-oncology department in a tertiary hospital. Methods: Prospective, observational study during 1.10.2014–1.10.2015. All children with respiratory infection event in the Pediatric Hematology-oncology department at the Ruth Rappaport Children Hospital, Haifa, who were tested for respiratory viruses, were included. Collected data included signs and symptoms, pathogens, background disease, epidemiological characteristics, complications and duration of illness. Viruses were detected by molecular methods. Results: 159 events were observed among 102 children (55 males). Age range: 3 months-19 years. Single event was observed in 62%. In 79 events (50%) a respiratory virus was detected. Children who underwent allogeneic bone marrow transplantation had more events compared with those with other diseases (58% vs. 32%, p = 0.018). Viral detection was positively associated with symptoms of cough and rhinitis (p

Objective: In response to the coronavirus disease 2019 (COVID-19) pandemic, the Israeli government strategy initially focused on containment. The Ministry of Health mandated isolation of COVID-19 patients in hospitals and instructed healthcare institutions to make necessary arrangements. As the second Israeli hospital to establish a COVID-19 department, this article describes our experience in its rapid establishment, while maintaining normal medical center activities. Setting: Establishing the COVID-19 department involved planning, set-up, and implementations phases, each one based on knowledge available regarding the pandemic and established medical standards for isolation and protection of patients and staff. Wherever possible, new innovative technologies were utilized to provide maximum protection for both patients and staff, together with special online training that was developed for medical teams. Results: A COVID-19 department was successfully established on the hospital campus, remote from other ongoing patient activities. A novel methodology of disease-adapted medicine was implemented successfully among the department's medical staff, who underwent training tailored to expected clinical scenarios. The COVID-19 department is receiving patients, with no contamination of medical personnel to date. A recent survey of COVID-19 patients revealed a very high patient satisfaction rate. Conclusion: Based on the experience described herein and lessons learned, the hospital is preparing for a potential large-scale COVID-19 wave, aimed at full readiness through utilization of a fortified underground emergency hospital to treat up to 900 COVID-19 patients, and establishment of versatile in-hospital infrastructure for quick conversion from standard conditions to COVID-19 appropriate conditions.

Objective: This paper describes how a large academic medical center solved the challenges of war preparedness and subsequently adapted them for the COVID-19 pandemic.Setting: A 1,000-bed academic medical center in Northern Israel has faced two extreme challenges since 2006: operating under missile attack during the 2006 Second Lebanon War, and rapid establishment of a scalable infrastructure for COVID-19 patients. The first challenge led to construction of a dual-use facility: a parking lot during peacetime, and a fully functioning fortified underground emergency hospital (FUEH) in times of emergency. Several drills have confirmed readiness for various scenarios including conventional and unconventional warfare, and treating isolated patients during the Ebola and SARS threats.Results: The hospital achieved preparedness for patient care during the COVID-19 pandemic, including all facilities and personnel, including infrastructure, laboratories, and innovations, to maintain standard patient care and separate COVID-19 treatment facilities. The hospital’s second challenge represented by the COVID-19 pandemic led to adaptation of the FUEH as a key strategic facility in Northern Israel for treating hundreds of COVID-19 patients. Each solution was supported by innovations targeted for specific purposes and needs.Conclusions: The function and unique mechanisms used to leverage use of a dual facility was proven viable for several emergency conditions, including the COVID-19 pandemic. Infrastructure and technological flexibility is essential when planning for handling different emergencies situations.

Introduction The coronavirus disease 2019 (COVID-19) pandemic has led to worldwide vaccination development efforts. In December 2020 the Pfizer BNT162b2 vaccine was approved in the United States. This study describes the first BNT162b2 vaccine dose effect on a large cohort. Methods This retrospective study examined first vaccine dose effect on serology and investigated the associations between seroconversion and age or sex. Results Serological blood tests were performed on 1898 participants following first vaccine dose; 81% were tested on day 21, before receiving the second dose (mean age 47.5 ± 12.45; median 47.7, range 18–90). Positive serology was found in 92.7% of day 21 tests. Overall positivity was 86.8%, with rates increasing from 2.5% within 1–14 days to 89.8% (14–20 days), 92.7% (21 days), and 95.9% (>21 days). Mean antibody levels 21 days after first dose were 64.3 ± 33.01 AU/ml, (range 15–373 AU/ml, median 61 AU/ml). Seropositivity was greater in females than males (88.3%. vs 83.3% respectively, p 60 years was associated with decreased likelihood of seropositivity (p

Mucormycosis has emerged as an increasingly important cause of morbidity and mortality in immunocompromised patients, but contemporary data in children are lacking. We conducted a nationwide multicentre study to investigate the characteristics of mucormycosis in children with haematological malignancies. The cohort included 39 children with mucormycosis: 25 of 1136 children (incidence 2·2%) with acute leukaemias prospectively enrolled in a centralized clinical registry in 2004-2017, and an additional 14 children with haematological malignancies identified by retrospective search of the databases of seven paediatric haematology centres. Ninety-two percent of mucormycosis cases occurred in patients with acute leukaemias. Mucormycosis was significantly associated with high-risk acute lymphoblastic leukaemia (OR 3·75; 95% CI 1·51-9·37; P = 0·004) and with increasing age (OR 3·58; 95% CI 1·24-9·77; P = 0·01). Fifteen patients (38%) died of mucormycosis. Rhinocerebral pattern was independently associated with improved 12-week survival (OR 9·43; 95% CI 1·47-60·66; P = 0·02) and relapsed underlying malignancy was associated with increased 12-week mortality (OR 6·42; 95% CI, 1·01-40·94; P = 0·05). In patients receiving frontline therapy for their malignancy (n = 24), one-year cumulative mucormycosis-related mortality was 21 ± 8% and five-year overall survival was 70 ± 8%. This largest paediatric population-based study of mucormycosis demonstrates that children receiving frontline therapy for their haematological malignancy are often salvageable.

Background The Flavobacteriaceae family includes rare pathogens in children; Chryseobacterium indologenes and Elizabethkingia meningosepticum are the most common pathogenic species, with a wide range of clinical presentations and high mortality rate. Although rare, diagnosis is important due to inherent resistance to multiple antibiotics, especially those typically prescribed for empiric treatment of aerobic Gram-negative bacterial infections. Methods A multicenter retrospective study conducted in 5 Israeli hospitals, describing Flavobacteriaceae bacteremia confirmed by positive blood culture from 1998 to 2018. Results Thirteen cases were included; 9 isolates were C. indologenes. Bacteremia was nosocomial or healthcare-associated in all cases. Bacteremia was associated with young age (median, 1 year, range 24 days-17 years), with only 2 (15.4%) cases in neonates, Central line-associated bloodstream infection as a source (5/13, 38%) and malignancy (7/13, 54.8%). Thirty-day all-cause mortality was 23% (3/13). Ninety-one percent of isolates were susceptible to trimethoprim-sulfamethoxazole, 82% to piperacillin-tazobactam and 92% to ciprofloxacin. Conclusions C. indologenes and E. meningosepticum are rare, nosocomial- or healthcare-associated pediatric bacteremia pathogens. Bacteremia was associated with young age, but in contrast to the literature, the majority of our cases were older than the neonatal age period. In addition, they were associated with central line-associated bloodstream infection and malignancy. The most adequate antibiotics according to resistance patterns were ciprofloxacin, trimethoprim-sulfamethoxazole and piperacillin-tazobactam.

Key Points Question What is the serologic status and incidence of adverse effects in patients with cancer who are receiving therapy after administration of the SARS-CoV-2 BNT162b2 vaccine? Findings This cohort study evaluated serologic status and safety of the BNT162b2 vaccine in 232 patients receiving active treatment for cancer and 261 health care workers who served as controls. After the first dose of the vaccine, 29% of the patients were seropositive compared with 84% of the controls; after the second dose, the seropositive rate of the patients reached 86%, and reported adverse events resembled those of healthy individuals. Meaning The SARS-CoV-2 BNT162b2 vaccine appears to be safe with satisfactory levels of seropositivity in patients undergoing treatment for cancer, although protection may occur later compared with the healthy population., Importance The efficacy and safety profile of SARS-CoV-2 vaccines have been acquired from phase 3 studies; however, patients with cancer were not represented in these trials. Owing to the recommendation to prioritize high-risk populations for vaccination, further data are warranted. Objective To evaluate the use and safety of the BNT162b2 vaccine in patients undergoing treatment for cancer. Design, Setting, and Participants In January 2021, mass SARS-CoV-2 vaccination of high-risk populations, including patients with cancer, was initiated in Israel. This cohort study prospectively enrolled and followed up patients with cancer and healthy participants between January 15 and March 14, 2021. The study was conducted at the Division of Oncology of Rambam Health Care Campus, the major tertiary (referral) medical center of northern Israel. Participants included 232 patients with cancer who were receiving active treatment after the first and second doses of the BNT162b2 vaccine and 261 healthy, age-matched health care workers who served as controls. Exposures Serum samples were collected after each vaccine dose and in cases of seronegativity. Questionnaires regarding sociodemographic characteristics and adverse reactions were administered at serum collection. A regulatory agencies–approved assay was used to assess IgG at all time points. Patients’ electronic medical records were reviewed for documentation of COVID-19 infection and results of blood cell counts, liver enzyme levels, and imaging studies. Main Outcomes and Measures Seroconversion rate after the first and second doses of the BNT162b2 vaccine and documented COVID-19 infection. Results Of the 232 patients undergoing treatment for cancer, 132 were men (57%); mean (SD) age was 66 (12.09) years. After the first dose of BNT162b2 vaccine, 29% (n = 25) patients were seropositive compared with 84% (n = 220) of the controls (P, This cohort study examines the serologic status of patients receiving active treatment for cancer after administration of the SARS-CoV-2 BNT162b2 vaccine.

Background Most pediatric coronavirus disease 2019 (COVID-19) is mild. We assessed nationally severe COVID-19, including pediatric inflammatory multisystem syndrome (PIMS), in hospitalized children. Methods An ongoing, prospective, national surveillance was conducted from March 2020 through March 2021, at 20 hospitals treating children, We assessed pediatric COVID-19 in 20/26 Israeli hospitals. Overall, 568 cases (82% mild disease, 8% moderate/severe disease, and 10% PIMS), representing

Background: Mucormycosis is a life-threatening infection with a tendency for angioinvasion that may lead to progressive dissemination. Disseminated mucormycosis, defined as the involvement of two or more non-contiguous sites, is rare in children, and data concerning its management and outcome are scarce. The aim of this study was to assess the contemporary management strategies and outcomes of disseminated mucormycosis in the pediatric population. Methods: We conducted a retrospective search in six large tertiary medical centers for all cases of disseminated mucormycosis that occurred between 2009–2020 in patients aged 1–20 years. Results: Twelve cases were identified. Underlying conditions included hematological malignancies (n = 10), solid tumor (post-autologous hematopoietic stem cell transplantations, n = 1), and solid organ (liver) transplantation (n = 1). In all cases, amphotericin B formulations were administered as first-line therapy, in eight cases, they were also administered in combination with an echinocandin or triazole. Seven patients underwent surgical debridement procedures. The six-week mortality was 58%. Among the patients diagnosed between 2009–2015, one of the six survived, and of those diagnosed between 2016–2020, four of the six were salvaged. Conclusions: Disseminated mucormycosis is a life-threatening and often fatal disease, and improved diagnostic and therapeutic strategies are needed. Nevertheless, in this population-based study, five patients (42%) were salvaged through combined liposomal amphotericin/triazole treatment and extensive surgical interventions.

Pediatric inflammatory multisystem syndromes associated with Severe Acute Respiratory Syndrome Coronavirus 2 are emerging in recent reports. We describe a patient with critical illness consistent with atypical Kawasaki disease with cardiac dysfunction and abdominal involvement presenting weeks after Severe Acute Respiratory Syndrome Coronavirus 2 infection. Our patient showed unique central nervous system involvement with small vessel vasculitis and profound hypocomplementemia, both not previously reported in case descriptions and may hint at possible disease mechanisms.

Objectives We evaluated antibody response to the BNT162B2 vaccine among healthcare workers (HCWs) to identify factors associated with decreased immunogenicity. Methods This prospective cohort study included consenting HCWs who completed a questionnaire regarding background illnesses, medications, and post vaccination allergic reactions or rash. All HCWs were tested for anti-spike antibodies (LIAISON SARS-CoV-2 S1/S2 IgG assay) one and three months after second vaccine dose. A multivariate mixed linear model was adjusted to participant's data and fit to predict antibody levels after second BNT162B2 vaccine dose, based on antibody levels at 1 month and the slope between 3 and 1 month. Multivariate analyses identified factors associated with lower antibody levels. Results A total of 1,506 HCWs were tested for SARS-CoV-2 antibodies. Older age was associated with lower mean antibody levels (-1.22 AU/ml, p Conclusions Most HCWs had measurable antibodies at 3 months. Risk factors for lower antibody levels were older age, male sex, underlying condition, and immunosuppressive treatment. These factors may be considered when planning booster doses during vaccine shortage.

Kingella kingae has been recognized as a common etiology of pediatric osteoarticular infections, especially among children younger than 5 years of age. In recent years, there have been reported cases of unusual manifestations. We report a rare case of a chest mass mimicking a tumor in an 11-month-old baby.

Background Respiratory syncytial virus (RSV) is the most common cause of lower respiratory tract infections (LRTI) during the first year of life. Antibiotic treatment is recommended in cases suspected of bacterial coinfection. The aim of this prospective study was to estimate the incidence of bacterial coinfections and the amount of antibiotic overuse in children infected with RSV using expert panel diagnosis. Methods Children 1 month of age and over with LRTI or fever without source were prospectively recruited in hospitals in the Netherlands and Israel. Children with confirmed RSV infection by Polymerase Chain Reaction (PCR) on nasal swabs were evaluated by an expert panel as reference standard diagnosis. Three experienced pediatricians distinguished bacterial coinfection from simple viral infection using all available clinical information, including all microbiologic evaluations and a 28-day follow-up evaluation. Results A total of 188 children (24% of all 784 recruited patients) were positive for RSV. From these, 92 (49%) were treated with antibiotics. All 27 children (29%) with bacterial coinfection were treated with antibiotics. Fifty-seven patients (62%) were treated with antibiotics without a diagnosis of bacterial coinfection. In 8 of the 92 (9%), the expert panel could not distinguish simple viral infection from bacterial coinfection. Conclusion This is the first prospective international multicenter RSV study using an expert panel as reference standard to identify children with and without bacterial coinfection. All cases of bacterial coinfections are treated, whereas as many as one-third of all children with RSV LRTI are treated unnecessarily with antibiotics.

Delayed antibiotic treatment for acute otitis media (AOM) is recommended for children6 months with nonsevere illness, no risk factors for complications or history of recurrent AOM. This study evaluates relationship between delayed antibiotic treatment for antecedent AOM and severity of subsequent acute mastoiditis admission.A prospective observational study of children aged 0-14 years admitted with acute mastoiditis to 8 hospitals between 2007 and 2012 calculates rates of severe acute mastoiditis admission [defined by ≥1 of the following: complication (mastoid subperiosteal abscess, brain abscess and sagittal vein thrombosis), need for surgical procedure and duration of admission6 days].Severe acute mastoiditis admissions in children with antecedent AOM treated with immediate antibiotics were compared with those with delayed antibiotic treatment.Antecedent AOM was diagnosed in 216 of 512 acute mastoiditis admissions (42.1%), of whom 159 (73%) immediately received antibiotics, and 57 (27%) had delayed antibiotic treatment. Higher rate of recurrent AOM was noted in the immediate compared with delayed antibiotic treatment group (29% vs. 8.7%, P = 0.0021). Complication rates were 19.5% versus 10.5% (P = 0.12), rates of surgical procedures required, 30% versus 10% (P = 0.0033); admission rates6 days, 37% versus 29% (P = 0.28) for immediate antibiotic therapy and delayed antibiotic treatment. On logistic regression analysis, immediately treated AOM patients had increased need for surgery for acute mastoiditis with adjustment for history of recurrent AOM (relative risk: 3.2, 95% confidence interval: 1.4-7.0).Delayed antibiotic treatment for antecedent AOM is not associated with an increase in severity parameters in subsequent acute mastoiditis admission.

OBJECTIVES: To examine the long-term motor and neurocognitive outcome of children with acute encephalitis and to look at possible prognostic factors. METHODS: Children who were treated for acute encephalitis in 2000–2010 were reevaluated. All children and their parents were interviewed by using structured questionnaires, and the children underwent full neurologic examinations, along with comprehensive neurocognitive, attention, and behavioral assessments. RESULTS: Of the 47 children enrolled, 1 died and 29 had neurologic sequelae, including motor impairment, mental retardation, epilepsy, and attention and learning disorders. Children with encephalitis had a significantly higher prevalence of attention-deficit/hyperactivity disorder (50%) and learning disabilities (20%) compared with the reported rate (5%–10%) in the general population of Israel (P < .05) and lower IQ scores. Lower intelligence scores and significantly impaired attention and learning were found even in children who were considered fully recovered at the time of discharge. Risk factors for long-term severe neurologic sequelae were focal signs in the neurologic examination and abnormal neuroimaging on admission, confirmed infectious cause, and long hospital stay. CONCLUSIONS: Encephalitis in children may be associated with significant long-term neurologic sequelae. Significant cognitive impairment, attention-deficit/hyperactivity disorder, and learning disabilities are common, and even children who were considered fully recovered at discharge may be significantly affected. Neuropsychological testing should be recommended for survivors of childhood encephalitis.

Complications of acute mastoiditis can occur in about 10-20% of cases. Clival syndrome is a rare complication of mastoiditis, involving the 6th and 12th cranial nerves. We describe a case of a child with mastoiditis and presumed Lemierre syndrome complicated by clival syndrome.

BACKGROUND Prompt evaluation and appropriate treatment with wide-spectrum antibiotics is considered mandatory for febrile oncology patients especially during neutropenia. Central venous catheters are widely used in pediatric oncology patients and are often the source of infections. Patients are usually admitted for follow-up and administration of antibiotics. Aims were to assess the efficacy of the polymerase chain reaction (PCR) method in identifying bacteria in blood samples as compared with standard blood cultures. METHODS This was a prospective study, which included all patients with central venous catheters admitted to the pediatric hematology-oncology department over the 14-month period. Demographic, clinical, and laboratory variables were compared in bacteremic and nonbacteremic patients. Standard microbiological cultures were compared using the PCR technique. RESULTS From September 2004 to November 2005, 148 blood cultures (70 patients) were evaluated. Positive blood cultures were detected on 21 (18.3%) occasions. PCR had sensitivity of 46%, specificity of 98%, positive predictive value 86%, and negative predictive value 89%. The PCR identified fastidious bacteria in 2 occasions when standard cultures were negative. CONCLUSIONS Inspite of low sensitivity, PCR may help with early identification of bacteremia. Improving this technology is warranted.

Background Pseudotumor cerebri or idiopathic intracranial hypertension is characterized by normal spinal fluid composition and increased intracranial pressure in the absence of a space-occupying lesion. Methods This study describes a subgroup of 10 patients with the same typical presenting symptoms (headache, vomiting, and papilledema) but without nuchal rigidity, meningeal signs, or change in mental status. Patients had normal neuroimaging studies and intracranial hypertension but also pleocytosis in the cerebrospinal fluid, suggesting central nervous system infection. From the results it can be hypothesized that those children represent a unique subgroup of viral-induced intracranial hypertension when comparing their risk factors, clinical course, treatment, and outcome with 58 patients who had idiopathic intracranial hypertension. Results All patients with viral-induced intracranial hypertension presented with papilledema but none had reduced visual acuity or abnormal visual fields, compared with 20.7% of patients who had idiopathic intracranial hypertension. They also responded better to treatment with acetazolamide, needed a shorter duration of treatment (7.7 ± 2.6 months vs 12.2 ± 6.3 months, P = 0.03), and had no recurrences. Conclusions The results suggest that children who fulfill the typical presenting signs and symptoms and all diagnostic criteria for pseudotumor cerebri other than the normal cerebrospinal fluid component may represent a unique subgroup of viral-induced intracranial hypertension and should be managed accordingly. The overall prognosis is excellent.

Human parechoviruses (HPeV) have been recognized as the causative agents of central nervous system (CNS) infection of infants and young children in different parts of the world. The role of HPeV in CNS infection of Israeli infants and children is unknown.To assess the detection rate of HPeV in enterovirus RT-PCR-negative cerebrospinal fluid (CSF) samples obtained during the years 2007-2009 from children 0-5 years old with suspected CNS infection or from very young infants with unexplained fever in four medical centers in Israel.A total of 367 CSF samples were retrospectively tested for the presence of HPeV RNA using nested RT-PCR assay. Positive samples were further typed on the basis of molecular sequencing. Retrospective analysis of the medical charts was performed.HPeV3 RNA was detected in CSF obtained between May and September 2008 in 13 patients, all of whom were3 months old (3.5% of all CSFs; 11.3% of all infants3 months in 2008). The HPeV-positive CSF samples were without pleocytosis. All HPeV3-positive patients recovered without obvious short term sequelae.HPeV infection could play an important role in summertime febrile/CNS illness in young infants during specific years with high HPeV activity. PCR detection of parechoviral RNA in CSF should be included in the diagnostic evaluation of fever or CNS infection of neonates and very young infants. The rapid identification of HPeV in CSF could curtail unnecessary empirical antibiotic treatment and shorten hospital stay in selected patients.

Summary Background Carbapenem-resistant Enterobacteriaceae, especially Klebsiella spp., have become a major health problem recently worldwide. Since 2006 the incidence of carbapenem-resistant Klebsiella pneumoniae (CRKP) infections has increased substantially in Israel. Bloodstream infections (BSIs) caused by these strains have been associated with high rates of treatment failure and mortality. Aim This study was designed to identify risk factors for carbapenem resistance among patients with healthcare-related (HCR) K. pneumoniae bacteraemia and predictors of mortality associated with HCR-CRKP bacteraemia compared with carbapenem-susceptible K. pneumoniae (CSKP). Methods In this retrospective case–control study, all cases of K. pneumoniae bacteraemia during 2006–2008 were identified. Resistance patterns, underlying morbidities, risk factors for drug resistance and mortality rates were compared for patients with CRKP and CSKP bacteraemia. Findings Two hundred and fourteen patients with CSKP bacteraemia were compared with 103 patients with CRKP bacteraemia. Severe, chronic comorbidities and prior antibiotic use were more frequent among patients with CRKP bacteraemia. On multivariate analysis prior use of macrolides and antibiotic exposure for ≥14 days remained the only independent factors associated with CRKP bacteraemia. Mortality rates of CRKP patients were significantly higher than those of CSKP patients. On multivariate analyses: bedridden status, chronic liver disease, Charlson comorbidity index ≥5, mechanical ventilation, and haemodialysis remained independently associated with mortality among patients with K. pneumoniae bacteraemia. Carbapenem resistance was not a risk factor for mortality. Conclusions Previous antibiotic exposure is a risk factor for CRKP-BSI. Mortality among patients with K. pneumoniae bacteraemia is associated with serious comorbidities, but not with carbapenem resistance.

BACKGROUND Immunocompromised patients are at increased risk for severe respiratory syncytial virus (RSV) infection. Palivizumab is approved for prevention of RSV in specific populations but not for treatment. Few studies demonstrated the safety and successful treatment with intravenous (IV) palivizumab. We describe our experience with IV palivizumab treatment for RSV in a pediatric hematology-oncology department during an outbreak. METHODS During a short period of renovations, oncology patients were placed in a general pediatric ward. After a case of severe fatal RSV pneumonia in a 2-year-old male patient with acute myeloid leukemia, all patients were actively screened twice weekly regardless of symptoms. Respiratory samples were tested for RSV using rapid immunochromatography detection, immunofluorescence, or reverse transcriptase polymerase chain reaction. A single dose of palivizumab (15 mg/kg) was given to children below 3 years of age who tested positive for RSV. RESULTS Over a 6-week period, 12 patients tested positive for RSV. Seven patients were treated with palivizumab. Five patients had respiratory symptoms, and 2 were asymptomatic. No adverse events were attributed to IV palivizumab treatment. Early-treated patients had no complications attributed to RSV. CONCLUSIONS Containment of RSV outbreak in high-risk children is difficult. Screening with reverse transcriptase polymerase chain reaction and the early use of IV palivizumab is safe and may prevent complications of RSV infection among these patients.

BACKGROUND: Reliably distinguishing bacterial from viral infections is often challenging, leading to antibiotic misuse. A novel assay that integrates measurements of blood-borne host-proteins (tumor necrosis factor-related apoptosis-inducing ligand, interferon γ-induced protein-10, and C-reactive protein [CRP]) was developed to assist in differentiation between bacterial and viral disease. METHODS: We performed double-blind, multicenter assay evaluation using serum remnants collected at 5 pediatric emergency departments and 2 wards from children ≥3 months to ≤18 years without (n = 68) and with (n = 529) suspicion of acute infection. Infectious cohort inclusion criteria were fever ≥38°C and symptom duration ≤7 days. The reference standard diagnosis was based on predetermined criteria plus adjudication by experts blinded to assay results. Assay performers were blinded to the reference standard. Assay cutoffs were predefined. RESULTS: Of 529 potentially eligible patients with suspected acute infection, 100 did not fulfill infectious inclusion criteria and 68 had insufficient serum. The resulting cohort included 361 patients, with 239 viral, 68 bacterial, and 54 indeterminate reference standard diagnoses. The assay distinguished between bacterial and viral patients with 93.8% sensitivity (95% confidence interval: 87.8%–99.8%) and 89.8% specificity (85.6%–94.0%); 11.7% had an equivocal assay outcome. The assay outperformed CRP (cutoff 40 mg/L; sensitivity 88.2% [80.4%–96.1%], specificity 73.2% [67.6%–78.9%]) and procalcitonin testing (cutoff 0.5 ng/mL; sensitivity 63.1% [51.0%–75.1%], specificity 82.3% [77.1%–87.5%]). CONCLUSIONS: Double-blinded evaluation confirmed high assay performance in febrile children. Assay was significantly more accurate than CRP, procalcitonin, and routine laboratory parameters. Additional studies are warranted to support its potential to improve antimicrobial treatment decisions.

Background: Pharmacokinetics (PK), pharmacodynamics and optimal dosing of vancomycin in obese children is not known. Higher trough levels of vancomycin may improve outcomes. This prospective study evaluated the appropriateness of twice-daily regimen for the adherence to guidelines, among obese and non obese children. Methods: Children receiving vancomycin, (20 mg/kg BID) were included. Patients were divided into 3 groups. Adequacy was defined as trough level ≥ 10mg/L and AUC/MIC > 400. An alternative-dosing regimen was calculated based on individual PK parameters. Results: Seventy-seven pairs (trough, peak) were taken from 51 children. Mean trough level was 3.36±2.58, only 3% fell in therapeutic range, no statistical difference was observed between obese, normal weight or underweight groups. One child had an AUC/MIC > 400. All children recovered. Conclusion: PK properties of all weight groups were similar. More frequent and higher doses are needed to achieve the goals of current guidelines.

Patients with infantile spasms, an intractable epileptic disorder, often are treated with adrenocorticotropic hormone. Legionella pneumophila is a rare cause of pneumonia in children. We describe 2 infants with Legionella pneumonia whose infection occurred within 1 month after starting adrenocorticotropic hormone.

Summary Background A physician is frequently unable to distinguish bacterial from viral infections. ImmunoXpert is a novel assay combining three proteins: tumour necrosis factor-related apoptosis-inducing ligand (TRAIL), interferon gamma induced protein-10 (IP-10), and C-reactive protein (CRP). We aimed to externally validate the diagnostic accuracy of this assay in differentiating between bacterial and viral infections and to compare this test with commonly used biomarkers. Methods In this prospective, double-blind, international, multicentre study, we recruited children aged 2–60 months with lower respiratory tract infection or clinical presentation of fever without source at four hospitals in the Netherlands and two hospitals in Israel. A panel of three experienced paediatricians adjudicated a reference standard diagnosis for all patients (ie, bacterial or viral infection) using all available clinical and laboratory information, including a 28-day follow-up assessment. The panel was masked to the assay results. We identified majority diagnosis when two of three panel members agreed on a diagnosis and unanimous diagnosis when all three panel members agreed on the diagnosis. We calculated the diagnostic performance (ie, sensitivity, specificity, positive predictive value, and negative predictive value) of the index test in differentiating between bacterial (index test positive) and viral (index test negative) infection by comparing the test classification with the reference standard outcome. Findings Between Oct 16, 2013 and March 1, 2015, we recruited 777 children, of whom 577 (mean age 21 months, 56% male) were assessed. The majority of the panel diagnosed 71 cases as bacterial infections and 435 as viral infections. In another 71 patients there was an inconclusive panel diagnosis. The assay distinguished bacterial from viral infections with a sensitivity of 86·7% (95% CI 75·8–93·1), a specificity of 91·1% (87·9–93·6), a positive predictive value of 60·5% (49·9–70·1), and a negative predictive value of 97·8% (95·6–98·9). In the more clear cases with unanimous panel diagnosis (n=354), sensitivity was 87·8% (74·5–94·7), specificity 93·0% (89·6–95·3), positive predictive value 62·1% (49·2–73·4), and negative predictive value 98·3% (96·1–99·3). Interpretation This external validation study shows the diagnostic value of a three-host protein-based assay to differentiate between bacterial and viral infections in children with lower respiratory tract infection or fever without source. This diagnostic based on CRP, TRAIL, and IP-10 has the potential to reduce antibiotic misuse in young children. Funding MeMed Diagnostics.

Campylobacter bacteraemia (CB) is rare and usually occurs in immune-compromised patients. In this study we examined the incidence and epidemiology of CB in one institution over 15.5 years.The medical records of all the consecutive patients with CB admitted to our hospital from 2000 to 2015 were retrospectively reviewed. Clinical characteristics, microbiologic and outcome data were collected.During the study period, 65 patients with CB were identified. The majority of the patients were middle aged and immune-compromised. Campylobacter jejuni was the most commonly identified species (33/47, 70%). The main underlying conditions were haematological malignancies (43%) and chronic liver disease (14%). Fifty-seven percent of the patients were receiving immunosuppressive therapy at the time of bacteraemia. The most common presenting symptoms were fever (85%), diarrhoea (40%), abdominal pain (40%), and nausea and vomiting (40%). Of the isolates tested, 97% were susceptible to macrolides, and only 35% were susceptible to quinolones. Susceptibility to quinolones decreased over the years. Most patients did not receive adequate empiric antibiotic treatment (81.5%) and about 20% never received directed therapy. Mortality and relapse rates were low (5% each). There was no association between adequate empirical or definitive antibiotic therapy and adverse outcomes.The main predisposing factor for Campylobacter bacteraemia in our cohort was immunosuppression. Prognosis was generally favourable regardless of appropriateness of antibiotic therapy.

Aggregatibacter actinomycemcomitans, previously named Actinobacillus actinomycetemcomitans (Aa), is a facultative Gram-negative slow-growing coccobacillus associated with severe oral and nonoral infections. It is a member of the HACEK group. Pulmonary infection caused by Aa is rare. We describe two cases of Aa pneumonia mimicking malignancy and review published pediatric cases.

Nontuberculous mycobacteria may cause central venous catheter-associated bacteremia. Between March 2011 and October 2013, 6 cases of Mycobacterium phocaicum bacteremia were found in the pediatric hematology-oncology department. All patients recovered. No positive blood culture was documented after removal of the central venous catheter. All 4 patients with pulsed field gel electrophoresis had the same pattern, different from the water sample, suggesting a common water source.

Mucormycosis has emerged as an increasingly important infection in patients with hematological malignancies, and is associated with considerable morbidity and mortality. However, contemporary data concerning epidemiology and outcome in children is lacking. Here we report a nationwide multicenter study of mucormycosis among children with hematological malignancies. Between the years 2004-2017, 1136 Israeli children aged ≤18 years with acute leukemias (acute lymphoblastic leukemia (ALL)-941; acute myeloid leukemia (AML)-195) were prospectively enrolled on a centralized clinical registry. Fungal infections, including mucormycosis, were prospectively and retrospectively captured. In addition, all 7 pediatric hematology centers were required to search hospital medical records, microbiology databases, and pathology information systems for cases of mucormycosis. Following central revision, 39 cases of mucormycosis were identified. Patient characteristics: Median age at mucor diagnosis: 13.5 years. Underlying diseases: ALL-27, AML-9, other-3. In 24 patients mucormycosis occurred during frontline therapy of their disease, and in 15 patients at relapse. Known risk factors included stem cell transplantation (SCT)-13 (33%), severe neutropenia-33 (85%) and corticosteroids-26 (67%). Among 20 patients on frontline ALL therapy, mucormycosis was diagnosed during induction in 13 cases, reinduction-6 cases, consolidation-1 case. Twenty-five patients with mucormycosis were enrolled on the national acute leukemia registry (not included: other malignancies, non-Israeli patients, relapsed leukemia with primary diagnosis preceding registry initiation, secondary AML). An analysis of registry cases demonstrated that the incidence of mucormycosis did not significantly increase during the study period. There was no seasonal clustering. Mucormycosis was significantly more common among patients ≥10 years old (4% vs 1%, p=0.004). Among patients on frontline treatment, mucormycosis was significantly more common in high-risk (HR) ALL patients (6%) than in non-HR (1%) or AML (1%) patients (p=0.001). Mucormycosis: Patterns of infection included sinusitis/sino-orbital-16 (41%), rhinocerebral-8 (21%), pulmonary-3 (8%), mandibular -4 (10%), gastrointestinal-1, cutaneous-1, otomastoiditis-1, disseminated-6 (15%). The majority (46%) were caused by Rhizopus spp. EORTC criteria: proven-30, probable-7, possible-2 (pathognomonic radiological findings and molecular diagnosis). Treatment: Nineteen patients were treated with amphotericin B formulations only and 19 received combined antifungal treatment. Nine patients received step-down treatment with posaconazole/ isavuconazole. In addition, 33 patients underwent surgical interventions, 26 underwent 2 procedures or more (range 2-14). Median time from presentation to antifungal treatment-3 days. Outcome: Twenty-one patients died, 15 of mucormycosis, 3 of other toxicities, 3 of leukemia. Factors significantly associated with mortality from mucormycosis were preceding SCT (p=0.01), less than 2 surgical interventions (p=0.0003) and relapsed disease (p=0.006). Eight-year OS of the whole cohort, those on frontline therapy and relapsed patients was 42% (±21%), 70%(±13%), 13%(±66%), respectively. Eight-year cumulative incidence of death from mucormycosis (CIDM) in those subgroups was 40%(±8), 21%(±8), 67% (±13), respectively. To our knowledge, this is the largest population-based study of mucormycosis in children with hematological malignancies. Our study demonstrates that mucormycosis is an age-dependent toxicity, significantly more common in patients ≥10 years of age. A striking finding was the high incidence of mucormycosis among patients on frontline high-risk ALL therapy, a fact which may reflect the increasing intensity of childhood ALL treatment. In a cohort of 24 patients who developed mucormycosis on frontline therapy, including 2 patients with AML and 13 with HR-ALL, 8y-OS was 70% and 8y-CIDM was 21%.The majority of patients in this cohort were salvageable through control of underlying disease, rapid instigation of antifungal treatment, and surgical debridement procedures, albeit in some cases at a price of mutilation and long-term sequelae. Future research should focus on the complex interactions between fungi and host, and on developing novel therapeutic strategies. Figure. Figure. Disclosures No relevant conflicts of interest to declare.

Aims: Brain abscess is rare in children. Predisposing factors are found in almost 85% of cases. Overall, 25% of brain abscesses develop in children, mostly in the 4–7 years age group. Our study aimed to characterize children with brain abscesses treated in our hospital, identify risk factors, pathogens and short-term outcome. Methods: A retrospective cohort of 20 years period, (1989–2009) included 27children (0–18 years). Medical records were analysed for age, gender, presenting symptoms and signs, predisposing factors, laboratory tests, imaging, microbiology results, treatment and outcome. Results: Of all the children, 63% (17/27) were male patients; mean age was 7.9 years and 52% were referred from other hospitals. Predisposing factors were identified in 81%, congenital heart disease and otitis were rare and sinusitis was found in 22% of the children. Main symptoms and signs included headaches, fever, neurological signs convulsions, (41%, 81%, 78% and 41% respectively). In 30% of cases, cultures were sterile. All patients were operated in addition to antibiotic treatment. Outcome was good with low mortality rate (3.7%). Conclusions: Manifestations of brain abscess may be subtle. A high index of suspicion and early imaging are warranted, different predisposing factors may reflect early intervention for congenital heart diseases. Mortality is rare in the modern medicine era.

The possible association of pseudotumor cerebri and varicella infection was previously mentioned in a few case reports. In those cases, the history and clinical features of active varicella were obvious, and signs were directly related to the varicella infection. We describe three immunocompetent children with pseudotumor cerebri as the only manifestation of Varicella zoster virus reactivation, with a review of the literature. We suggest considering Varicella zoster virus in children with pseudotumor cerebri, even in the absence of a history of recent varicella infection.

Aim The precise role of the influenza virus in the morbidity of hospitalised paediatric pneumonia cases is unknown. We identified how many cases hospitalised during the 2009 pandemic had influenza-associated pneumonia and assessed their severity. Methods Children admitted to three Israeli medical centres during the 2009 influenza pandemic with radiologically confirmed pneumonia were prospectively screened for influenza. We compared the clinical, laboratory and radiologic findings for positive and negative cases. Results The pandemic H1N1 virus was detected in 89 (30%) of the 297 patients hospitalised for pneumonia and 55% of the Paediatric Intensive Care Unit admissions for pneumonia. There were no significant differences in the rates of underlying disease between the two groups. Logistic regression analysis revealed that children with pandemic H1N1 virus-associated pneumonia had significantly increased disease severity than those without, with a higher incidence of hypoxemia (41.6% versus 24%) with a relative risk (RR) of 2.2, higher rate of paediatric intensive care unit admission (16.9% versus 5.8%, RR of 2.7) and higher rate of mechanical ventilation (10.1% versus 2.4%, RR:4.4). Conclusion During the 2009 influenza pandemic, 30% of children hospitalised for pneumonia had the influenza infection and these children displayed increased disease severity.

Objectives To describe the clinical characteristics of children hospitalized with 2009 influenza A(H1N1) infection in Israel and the risk factors associated with this infection. Design Prospective collection of data on children hospitalized with 2009 influenza A(H1N1) infection. Setting Seven medical centers around Israel. Patients From July 12, 2009, to December 24, 2009, all patients 18 years or younger hospitalized with acute respiratory or acute unspecified febrile illness were screened for 2009 influenza A(H1N1) virus by reverse transcription–polymerase chain reaction. Intervention Prospective data collection for patients with confirmed infection. Main Outcome Measures Clinical characteristics of patients and hospitalization rates. Results The mean age of 478 patients studied was 6.1 years. Forty-two patients (8.8%) were admitted to the pediatric intensive care unit; 3 patients (0.6%) died. The most frequent clinical presentations were pneumonia, influenza-like illness, wheezing exacerbation, and convulsions. Predisposing underlying illnesses were detected in 48.7% of patients. Patients with metabolic and neurologic disorders were at highest risk for severe complications (relative risk, 6.5 and 2.9, respectively). In addition, patients with cyanotic heart lesions and infants 3 months or younger who were born at 33 weeks' gestation or earlier tended to require higher rates of mechanical ventilation. The hospitalization rate for 2009 influenza A(H1N1) was 0.7 per 1000 children. The mortality rate was 3.6 per 1 000 000 children. Conclusions The severity variables for 2009 influenza A(H1N1) were similar to the figures reported for seasonal influenza. Patients with underlying metabolic and neurologic metabolic disorders and presumably patients with cyanotic heart lesions and infants born prematurely are at highest risk for severe complications following 2009 influenza A(H1N1) infection.

Background and Aims: Mycobacterium mucogenicum (MM) is a rapidly growing nontuberculous mycobacterium that is commonly identified in tap water that can rarely cause bacteremia. We describe an outbreak of MM bacteremia among pediatric hematology-oncology patients. Methods: Charts of children with MM bacteremia were retrospectively reviewed. Demographic data, underlying conditions, central venous catheter (CVC) type, duration of bacteremia, and treatment were retrieved. Epidemiologic investigation was conducted during the outbreak including environmental sampling. Results: During an 8-month period (September 2005-May 2006), 8 patients aged 1.5 to 17 years had MM bacteremia. Seven patients had underlying malignancy and 1 with thalassemia major had bone marrow transplantation. The mean number of positive blood cultures was 4.2 (1-11) per patient. Two patients received antibiotic treatment in addition to removal of CVC. All patients were cured. Almost 60 environmental samples were obtained from surfaces, ice, and municipal water supply. All were negative and no source was documented. Infection control measures included emphasis on guidelines for prevention of CVC-associated infections. No cases occurred before and after this outbreak. Conclusions: MM is a rare agent of CVC-associated bacteremia. Removal of the CVC may be sufficient for management of bacteremia. In the absence of definite source identification, reinforcement of standard infection control measures can be successful in containing outbreaks.

Anaerobic meningitis may occur alone, but is usually encountered as a complication of a brain abscess. In either case it is rare in a normal host. We present a 6-year old boy with anaerobic meningitis after missed penetrating trauma, stressing the need for a thorough investigation after head trauma.

To examine the efficacy and safety of a new topical anesthetic containing a disinfection ingredient (LidoDin cream) in reducing the pain associated with venipuncture by comparing it with the proven eutectic mixture of lidocaine 2.5% and prilocaine 2.5% (EMLA cream).A single-blind, randomized, controlled trial was conducted on a study population consisting of a convenience sample of patients aged 12 to 16 years who presented at our Emergency Department between November 2007 and April 2008. The Visual Analog Scale (VAS) was used for pain assessment. Before the study, the bactericidal effect of the LidoDin cream on skin flora was tested.Twenty patients were enrolled to each arm of the study. Mean patient age was 13.6 years for the LidoDin group and 14.12 years for the EMLA group (P=0.347). Male patients accounted for 55% of the patients in the LidoDin group, compared with 40% in the EMLA group (P=0.527). Skin reaction scores of the LidoDin group for erythema and edema were not statistically different than those of the EMLA group (P=0.73 and P=0.75, respectively). Patient VAS scores and nurse VAS scores of the LidoDin group were not statistically different than those of the EMLA group (P=0.57 and P=0.93, respectively).This pilot study demonstrated that LidoDin and EMLA seem to be equally safe and effective topical anesthetics for venipuncture. Future studies are planned to determine, if LidoDin reduces the rate of local skin infection in patients treated with multiple daily subcutaneous injections of medications.

We report on a 14-year-old boy who was presented to the emergency department with an acute swelling of the face and scalp 3 days after using a new hair dye. The patient had applied a black henna tattoo 1 year earlier. Patch testing revealed an allergy to the potent skin sensitizer paraphenylenediamine, a common ingredient of hair dyes and also found in black henna tattoo. It is important for emergency physicians to be aware of the possibility of a delayed type-IV hypersensitivity reaction from black henna tattoos manifesting as an acute contact dermatitis. These patients may have gross facial swelling but should not be treated for angioedema.

To reduce the overall time spent in the ED, triage nurses are encouraged to treat patients with a topical anesthetic cream, eutectic mixture of local anesthetics (EMLA). We present a case in which a 28-day-old neonate who was treated with EMLA cream in triage developed severe methemoglobinemia 18 hours post admission to the pediatric ward. This case demonstrates that there may be some risks associated with this approach, and that protocols for the use of EMLA at triage should include not only the indications for its use, but also need to ensure that there is a process to have the EMLA removed before patient discharge or transfer.

Febrile neutropenia (FN) is a common complication among children undergoing chemotherapy for hematologic malignancies. A microbial agent is identified in 15–30% of these episodes. Recently, several studies reported a high incidence (25% -60%) of respiratory viral infections (RVI) in children with FN, using RT- PCR analysis. Implementation of routine RVI workup in children with FN was suggested, in order to minimize the overuse of antibiotics. However, data on the incidence of RVI in children with persistent FN (PFN) is meager. In the setting of PFN, invasive fungal infection (IFI) is a major concern. The incidence of IFI among children with hematologic malignancies varies with clinical settings, although most children who present with PFN do not have IFI eventually. Yet, most international guidelines indicate empiric initiation of antifungal therapy after 4-7 days of FN. Alternatively, a “preemptive” approach using currently available diagnostic modalities (CT and serum specific biomarkers) was suggested in adult patients. In children with PFN, however, this workup resulted only in a modest decline in the antifungal treatment rate. Therefore, there is a growing need to enhance diagnostic resolution, in order to stratify pediatric patients according to their risk for IFI, and minimize the overuse of antifungal drugs, imaging, and invasive procedures. To the best of our knowledge, there are no studies comparing the incidence of RVI to that of IFI in the setting of PFN. Based on previous published data, we hypothesized that RV infection is a significant cause of PFN in children with hematologic malignancies, and that IFI is the cause in a minority of cases. We further aimed to investigate whether detection of RVI, as the cause of PFN in these children, would affect their risk of IFI. For that purpose, we analyzed the clinical charts of children (38oc, for >96 hours and ≤500ANC/µl) and documented PCR results of RV. Patients were considered positive for IFI if they had ‘possible’, ‘probable’ or ‘proven’ infection according to the revised EORTC definition (2008). RVI were detected in nasopharyngeal aspirates using RT-PCR and included: RSV, Influenza A/B, H1N1, Parainfluenza 1/2/3, HMPV, Adenovirus and HHV-6. Additional data included age and gender, specific hematologic malignancy, total number of neutropenia ( A total number of 75 PFN episodes were evaluable, representing 54 patients with ALL (HR n=18; SR n=23), AML (n=6), NHL (n=5) or Hodgkin’s (n=2). Of these, there were 31 episodes with RV-positive infections (41.3%). The most prevalent virus was RSV (29%), followed by Parainfluenza (26%) and Adenovirus (19%).There were 16 possible (21%), 2 probable (2.6%), and 2 proven (2.6%) episodes of IFI. Only in 3 episodes we detected co-infection of IFI (2 possible and 1 probable) and RVI. Multivariate analysis revealed that the total days of neutropenia and antibiotic therapy were independent risk-factors for IFI (p Children with PFN and RVI have a significantly lower risk for IFI. This observation may reduce unnecessary imaging and invasive procedures, antifungal treatment, and hospital expanses. Further studies are needed in order to establish whether RV-status can be implemented in the routine workup algorithm of PFN in children with hematologic malignancies. Disclosures No relevant conflicts of interest to declare.

Legionnaire disease is a rare cause of community-acquired pneumonia in children and an exceedingly rare diagnosis in infants and neonates, with only few reported cases. We describe a case of fatal Legionnaire disease diagnosed by culture and polymerase chain reaction method from sputum and lung biopsy specimens, and emphasize the importance of considering this rare entity in cases of severe neonatal pneumonia.

MRSA infections in NICU are associated with significant morbidity and mortality. Early containment of outbreaks is crucial. Trials comparing different methods of screening and decolonization are lacking

Background The three-year pre-medical programme ‘Becoming a Physician’ focuses on different aspects of medical professionalism. Objectives are to increase awareness and sensitivity to disadvantaged populations, and practise sensitive effective communication skills. Methods The curriculum includes: (1) Visits to treatment centres for people with special needs, mental illnesses, substance abuse issues, physically or sexually abused, and prisoners. Students tour the facility, hold discussions with residents, and discuss ethical professional interrelations to the medical world. Students then write ‘reflective diaries’ summarizing their thoughts and emotions. (2) Participation in a communication course that focuses on learning by practising patient-oriented communication. Qualitative data were collected from three sources: reflective diaries, studentsʼ course evaluations, and interviews with the studentsʼ tutors. Results Data indicated that the students were very satisfied with the programme. They indicated an increase in awareness of the special needs of diverse populations, and in the sense of efficacy for conducting interviews tailored to patients' needs. Tutors reported a sense of ‘personal growth’ following their role as mentors. Reflections Interactions of medical students with diverse populations, when accompanied by appropriate feedback mechanisms and strengthening of communication skills, can improve awareness and sensitivity to patients' special needs. This could help students become more sensitive and thoughtful physicians.