Mutant adenosine deaminase 2 in a polyarteritis nodosa vasculopathy.

BACKGROUND: Polyarteritis nodosa is a systemic necrotizing vasculitis with a pathogenesis that is poorly understood. We identified six families with multiple cases of systemic and cutaneous polyarteritis nodosa, consistent with autosomal recessive inheritance. In most cases, onset of the disease occurred during childhood. METHODS: We carried out exome sequencing in persons from multiply affected families of Georgian Jewish or German ancestry. We performed targeted sequencing in additional family members and in unrelated affected persons, 3 of Georgian Jewish ancestry and 14 of Turkish ancestry. Mutations were assessed by testing their effect on enzymatic activity in serum specimens from patients, analysis of protein structure, expression in mammalian cells, and biophysical analysis of purified protein. RESULTS: In all the families, vasculitis was caused by recessive mutations in CECR1, the gene encoding adenosine deaminase 2 (ADA2). All the Georgian Jewish patients were homozygous for a mutation encoding a Gly47Arg substitution, the German patients were compound heterozygous for Arg169Gln and Pro251Leu mutations, and one Turkish patient was compound heterozygous for Gly47Val and Trp264Ser mutations. In the endogamous Georgian Jewish population, the Gly47Arg carrier frequency was 0.102, which is consistent with the high prevalence of disease. The other mutations either were found in only one family member or patient or were extremely rare. ADA2 activity was significantly reduced in serum specimens from patients. Expression in human embryonic kidney 293T cells revealed low amounts of mutant secreted protein. CONCLUSIONS: Recessive loss-of-function mutations of ADA2, a growth factor that is the major extracellular adenosine deaminase, can cause polyarteritis nodosa vasculopathy with highly varied clinical expression. (Funded by the Shaare Zedek Medical Center and others.).

A longitudinal PRINTO study on growth and puberty in juvenile systemic lupus erythematosus.

OBJECTIVE: To obtain longitudinal data on growth/puberty in a large-scale, multi-national prospective cohort of juvenile systemic lupus erythematosus (SLE). METHODS: Data from 331/557 (59.4%) patients ≤18 years old with juvenile SLE in active phase, with anthropometric data available at four follow-up visits, were studied. RESULTS: There was a significant reduction in parent-adjusted height z score with time in females and males (p<0.0001), with a significant gender difference (p<0.0001) and with male height being most affected. Median body mass index z score peaked at 6 months and was still significantly above baseline after 26 months (p<0.01), with no gender difference. Standardised height reduction was inversely related to age at onset. Females with onset age <12 years had a median parent-adjusted height z score of -0.87 with no catch-up growth. At the end of the study, growth failure was seen in 14.7% of the females and 24.5% of the males. Height deflection (less than -0.25/year) was found in 20.7% of the females and 45.5% of the males. Delayed pubertal onset was seen in 15.3% and 24% of the females and males, respectively, and delayed/absent menarche was seen in 21.9%, while 36.1% of the females and 44% of the males had some degree of delayed pubertal development. Growth failure baseline determinants were previous growth failure (OR: 56.6), age at first visit ≤13.4 years (OR: 4.2) and cumulative steroid dose >426 mg/kg (OR: 3.6). CONCLUSIONS: The children at risk of having a negative effect on height and pubertal development are prepubertal and peripubertal children treated with >400 mg/kg cumulative dose of corticosteroids.

Multiple hymenoptera stings in children: clinical and laboratory manifestations.

Multiple hymenoptera stings are a cause of rhabdomyolysis, elevated liver enzymes, clotting abnormalities, kidney injury, and even death. However, the progression of the clinical and laboratory findings has been described mainly in sporadic case reports. We report the clinical and laboratory manifestations of multiple hymenoptera stings in six children who were hospitalized and referred for a nephrology evaluation and follow-up over a 12-year period. One patient succumbed 13 h after the stinging accident. In the five surviving patients, we found somewhat similar pattern of clinical and laboratory course: rhabdomyolysis with elevated liver enzymes are the earliest manifestations, followed by kidney injury and anemia. An asymptomatic phase of several days between the stinging accident and severe kidney injury can occur. There was a strong seasonal association, with all six events occurring in August or September. In children with multiple hymenoptera stings, a somewhat predictable clinical and laboratory course is expected and an initial laboratory evaluation is needed, and even in asymptomatic children, a repeated laboratory evaluation is highly recommended.

Unrealistic concerns about fever in children: the influence of cultural-ethnic and sociodemographic factors.

BACKGROUND: Parental fear and misconceptions about fever are widespread in western society. Ethnicity and sociodemographic factors have been suggested as contributing factors. OBJECTIVES: To test the hypothesis that undue parental concern about fever is less in traditional than in western cultural-ethnic groups. METHODS: Bedouin (traditional society) and Jewish (western society) parents of children aged 0-5 years with fever were interviewed in a pediatric emergency unit. Interviews were conducted in the parents' most fluent language (Arabic or Hebrew). A quantitative variable (a 9 item "fever phobia" scale) was constructed. RESULTS: The parents of 101 Jewish and 100 Bedouin children were interviewed. More Bedouin parents were unemployed, had less formal education and had more and younger children than the Jewish parents. Parents in both groups expressed erroneous beliefs and practices about fever; quantitative but not qualitative differences in fever phobia variables were documented. Compared with their Jewish counterparts, more Bedouin parents believed that fever may cause brain damage and death, administered antipyretic medications for temperature < or = 38 degrees C and at excessive doses, and consulted a physician within 24 hours even when the child had no signs of illness other than fever (all Pvalues <0.001). The mean fever phobia score was higher in the Bedouin than in the Jewish group (P< 0.001). By multivariate analysis, only the cultural-ethnic origin correlated with fever phobia. CONCLUSIONS: A higher degree of fever phobia was found among parents belonging to the traditional Bedouin group as compared to western society parents.

Flow cytometry and morphology analysis of bone marrow in a child with brucellosis and hematologic manifestations.

Constitutional symptoms and pancytopenia are occasionally the initial presentation of pediatric brucellosis. Therefore, in endemic areas, in children with pancytopenia, both brucellosis and malignancy should be included in the deferential diagnosis. We report here a child with pancytopenia and hepatosplenomegaly as manifestations of brucellosis in whom bone marrow morphology and flow cytometry data revealed hemophagocytosis, left shift in myeloid cells and activation changes in antigenic properties of T and B lymphocytes and monocytes. The patient had an uneventful and complete recovery after appropriate antibiotic therapy. Our report demonstrates that bone marrow and flow cytometry findings in children with brucellosis may include significant reactive changes in hematopoiesis.

Referral criteria from community clinics to pediatric emergency departments.

Referral of patients to a pediatric emergency department (PED) should be medically justified and the need for referral well communicated. The objectives of this paper were (1) to create a list of criteria for referral from the community to the PED, (2) to describe how community physicians categorize their need for referral, and (3) to determine agreement between the physician's referral letter and the selected criteria. We present a descriptive study of referrals to the PED of Soroka University Medical Center, Beer-Sheva, Israel, during February to April 2003. A list of 22 criteria for referral was created, using the Delphi method for reaching consensus. One or more criteria could be selected from this list for each referral, by the referring community physicians and, independently, based on the physicians' referral letters, by two consultants, and compared. There were 140 referrals included in the study. A total of 262 criteria for referral were selected by the referring community physicians. The criteria most frequently selected were: "Need for same-day consultation/laboratory/imaging result not available in the community" (32.1%), "Suspected life- or organ-threatening infection" (16.4%), and "Need for hospitalization" (15.7%). Rates of agreement regarding criteria for referral between the referring physicians and the two consultants, and a senior community pediatrician and a senior PED pediatrician, were 57.9 and 48.6%, respectively. We conclude that the standard referral letter does not convey in full the level of need for referral to the PED. A list of criteria for referral could augment efficient utilization of emergency department services and improve communication between community physicians and the PED.

Nitrous Oxide sedation for intra-articular injection in juvenile idiopathic arthritis.

BACKGROUND: Intra-articular corticosteroid injection in juvenile idiopathic arthritis (JIA) is often associated with anxiety and pain. Recent reports advocate the use of nitrous oxide (NO), a volatile gas with analgesic, anxiolytic and sedative properties. OBJECTIVE: To prospectively evaluate the effectiveness and safety of NO analgesia for intra-articular corticosteroid injection in JIA, and to assess patients and staff satisfaction with the treatment. METHODS: NO was administered to JIA patients scheduled for joint injection. The patient, parent, physician and nurse completed visual-analog scores (VAS) (0-10) for pain, and a 5-point satisfaction scale. Change in heart rate (HR) during the procedure was recorded in order to examine physiologic response to pain and stress. Patient's behavior and adverse reactions were recorded. RESULTS: 54 procedures (72 joints) were performed, 41 females, 13 males; 39 Jewish, 13 Arab; mean age was 12.2 +/- 4.7 year. The median VAS pain score for patients, parents, physicians and nurses was 3. The HR increased >/= 15% in 10 patients. They had higher VAS scores as evaluated by the staff. The median satisfaction level of the parents and staff was 3.0 and 5.0 respectively. Adverse reactions were mild. CONCLUSION: NO provides effective and safe sedation for JIA children undergoing intra-articular injections.

Influenza vaccination of patients with systemic lupus erythematosus: safety and immunogenecity issues.

The influenza vaccine is highly efficacious in the general population; however there have been concerns about the safety, and immunogenecity of the vaccine in patients with SLE. Several studies have suggested that the immune response of patients with SLE to influenza vaccine is significantly lower than the general population, mainly in patients with age > or =50 years and those treated with prednisone. The vaccine is safe for patients with SLE and it does not affect the clinical manifestations of SLE including renal features, disease activity, or the requirement for steroids or cytotoxic drugs. However, the vaccine may trigger the generation of autoantibodies which is usually short term and is not associated with clinical significance.

Increased proportion of CD3+CD4-CD8- double-negative T cells in peripheral blood of children with Behcet's disease.

INTRODUCTION: Behcet's disease (BD) is a multi-system inflammatory disorder of poorly understood pathogenesis, which is characterized by oral aphtosis, genital ulcers and uveitis. OBJECTIVE: To assess the role of CD3+CD4-CD8- double negative (DN) T cells in pathogenesis of Behcet's disease. PATIENTS: Ten BD patients (age 12.2+/-2.2 years, 7 in remission, 3 in exacerbation state) treated at the Pediatric Rheumatology unit of Soroka University Medical Center and 3 age-matched controls participated in the study. METHODS: Peripheral blood lymphocytes of study subjects were isolated and stained with fluorescein-labeled anti-CD45, CD3, CD4, CD8 antibodies and analyzed by FACS assay. RESULTS: Proportion of CD4-CD8- DN T cells was significantly increased in BD patients (n=10) as compared to healthy controls (6.2+/-3.4% vs. 3.2+/-1.1% of total CD3+ cells, p<0.05), this cell group was additionally enhanced in BD exacerbation, compared to patients in remission (10+/-4.1% vs. 4.7+/-1.2%, p<0.05, respectively). DN T cells were significantly increased in BD patients in remission, compared to healthy controls (4.7+1.2% vs. 3.2+1.1% of total CD3+ cells, p<0.05, respectively). CONCLUSIONS: Behcet's disease is characterized by increased proportion of CD3+CD4-CD8- double negative T cells in peripheral blood. Further studies, that include additional immunophenotyping and analysis of gene expression, aimed at characterization of these cells are currently underway.

Community-acquired bloodstream infections in children > one month old in southern Israel (1992-2001): epidemiological, clinical and microbiological aspects.

We studied the epidemiology, microbiology, clinical picture and outcome of community-acquired bloodstream infections (CABI) in children in southern Israel during 1992-2001. Information was collected prospectively by daily surveillance. CABI was diagnosed when a positive blood culture was reported in a patient discharged from the emergency room or during <48 h since admission if hospitalized. There were 1439 CABI episodes in 1396 children aged 1 month to 14 y. CABI incidence was 100/100,000 children with no increase during the study period. Risk of CABI was 3.8 times higher in a Bedouin than in a Jewish child. 1561 bacteria (793, 50%, gram-positive and 768, 49% gram-negative organisms, respectively) and 13 fungi were recovered. Most frequent gram-positive organisms were Streptococcus pneumoniae (509 isolates, 32% of all isolates, 64% of all gram-positive), Staphylococcus aureus (137, 9%, 17%) and Streptococcus pyogenes (46, 3%, 6%). Enterobacteriaceae spp. were the most frequent gram-negative pathogens (279, 18%, 36%), followed by Brucella (205, 13%, 27%). S. pneumoniae was the most common pathogen in children <12 months and 1-5 y age; Brucella was the most frequent pathogen in children >5 y of age. Coverage of 7-valent pneumococcal conjugated vaccine for CABI was 38.5%. 38 (2.7%) patients died; 16 cases were caused by S. pneumoniae.

Determinants of antipyretic misuse in children up to 5 years of age: a cross-sectional study.

BACKGROUND: Fever in children is a common and usually benign symptom. It is known that antipyretic treatment is ineffective in the prevention of simple febrile seizures. Caregivers' administration of antipyretic medications to children has been reported, but data concerning the formulations used, actual doses administered, and effects of ethnicity and socioeconomic status on administration practices are incomplete. OBJECTIVE: The aim of this study was to identify the factors affecting antipyretic administration (higher-than-recommended doses in particular) by caregivers to their febrile children in 2 differing cultural-ethnic backgrounds. METHODS: This cross-sectional survey study, conducted from January to March 2002, was part of a larger, ongoing survey study of the differences in care givers' knowledge, beliefs, and attitudes concerning children's fever in the 2 major cultural-ethnic groups in the Negev District in Israel: Jews and Bedouin Moslems. It was conducted at the Pediatric Emergency Department (PED), Soroka Medical Center, Beer-Sheva, Israel. A structured questionnaire was administered to Jewish and Bedouin Moslem parents or usual caregivers of young (age, 0-60 months) children attending the PED due to fever. Each child's weight was obtained from the PED medical record. After completion of the interview, the reported antipyretic dose per kilogram of body weight was calculated. Less-than-recommended dose was defined as <9 mg/kg for acetaminophen and <4.5 mg/kg for ibuprofen. Higher-than-recommended dose was defined as >16.5 mg/kg for acetaminophen and >11 mg/kg for ibuprofen. RESULTS: The caregivers of a total of 201 children (mean [SD] age, 20 [17] months; mean [SD] weight, 10.4 [4.0] kg) were included in the study. The study included 101 Jewish and 100 Bedouin Moslem caregivers. The proportion of people surveyed who were parents was 98%; grandmothers, 2%. Differences existed between the 2 cultural-ethnic groups in the source of knowledge regarding antipyretic use in children (a significantly larger proportion of Jewish caregivers received their knowledge concerning antipyretic use from package inserts compared with Bedouin caregivers [25.7% vs 6.0%; P < 0.001], and a significantly lower proportion of Jewish caregivers used "other" sources [15.8% vs 39.0%; P < 0.001]). Most (65.2%) caregivers indicated that they administered antipyretics for no or minimal elevations in body temperature (<-38 degrees C); 52.7% administered individual acetaminophen doses within 10% of the recommended dose, 34.8 % administered a higher-than-recommended dose, and 21.4% repeated the dose at intervals of

Blood culture contamination in pediatric patients: young children and young doctors.

OBJECTIVE: The objective of this study was to assess the role played by the patient's age and physician's experience in determining the contamination rate of pediatric blood cultures. METHODS: The proportion of true-positive (isolation of a pathogen) and false-positive (isolation of a contaminant) results among blood cultures obtained by in-training physicians and experienced pediatricians from young children (aged 1-35 months) and older children (>or=36 months of age) and the value of a positive blood culture to predict a true-positive result were retrospectively determined. RESULTS: The odds of a positive blood culture to predict isolation of a true-pathogen was 0.366 only when the sample was obtained by an inexperienced physician and 0.523 when it was drawn by an experienced physician (P < 0.001), 0.419 when it was obtained from a young child and 0.429 when it was drawn from an older child (P = 0.781). The predictive value of a positive result for isolating a pathogen was significant higher when an experienced physician drew the blood culture regardless of the patient's age. CONCLUSIONS: Patient's young age and lack of experience of the physician who draws the specimen increase the risk of blood culture contamination. These results strengthen the need to improve the technical skills of young physicians.

Increased prevalence of antithyroid antibodies and subclinical hypothyroidism in children with juvenile idiopathic arthritis.

OBJECTIVE: To estimate the occurrence of antithyroid antibodies (ATA) and hypothyroidism in children with juvenile idiopathic arthritis (JIA) compared to matched healthy controls. METHODS: The occurrence of ATA, including antithyroglobulin (anti-TG) and antithyroid peroxidase (anti-TPO) antibodies, was evaluated by quantitative immunometric ELISA in children with JIA and in a healthy matched control group. Thyroid function was assessed in both groups. RESULTS: The study group included 66 patients with JIA (50 girls, 16 boys) of mean age 11.7 +/- 4.4 years (range 2-23). The control group included 89 children (71 girls, 18 boys) of mean age 10.8 +/- 4.2 years (range 2-18). Mean age at onset of joint disease was 7.3 +/- 3.6 years (range 1-15). Anti-TG antibodies were found in 7 of 62 patients (11.3%) in the JIA group and 2 of 89 controls (2.2%) (p = 0.03); anti-TPO antibodies were found in 5 of 65 patients (7.9%) and one of 89 controls (1.1%) (p = 0.08). All patients with ATA had oligoarticular type JIA (p = 0.01). Mean thyroid stimulating hormone (TSH) levels were higher in the study group than in controls (2.6 +/- 2.3 vs 1.9 +/- 1.0 mIU/l; p = 0.01); levels were above normal range (0.4-4 mIU/l) in 8 study patients (12%) and 3 controls (3.4%) (p = 0.055). Overall, ATA were found in 9 of the 150 study participants, 4 (44%) of whom had TSH levels above 4 mIU/l (p = 0.001). CONCLUSION: Children with JIA have a higher than normal incidence of ATA and subclinical hypothyroidism and should be routinely screened for these variables.

Adherence to therapeutic guidelines for acute otitis media in children younger than 2 years.

OBJECTIVES: to analyze adherence to therapeutic guidelines for AOM. METHODS: Descriptive retrospective study of community primary care providers in southern Israel. Study population (n = 590) included all children aged 0-48 months diagnosed with AOM in PED during the year 2000 who had a referral letter from a community physician and an AOM diagnosis confirmed by tympanocentesis. AOM antibiotic treatment was considered appropriate when in accord with CDC and local therapeutic guidelines. RESULTS: Referral letter data allowing characterization of AOM by category were available in 471 (79.8%) children, 320 (68%) with simple AOM and 151(32%) with complicated AOM. AOM diagnosis made by the primary care physician was in accord with PED diagnosis in 365/590 (62%) patients. Three hundred and fifty-five (60.2%) patients did not receive antibiotics in the community. Of 365 (62%) children diagnosed with AOM in the community, 235 (64.4%) were treated with antibiotics prior to arrival to PED. Amoxicillin was prescribed to 109 (46.4%), cefuroxime axetil to 48 (20.4%), amoxicillin/clavulanate to 31 (13.2%) and i.m. ceftriaxone to 20 (8.5%) of the patients. Eighty-three (25.9%) patients with simple AOM were treated with antibiotics in the community and only 46 (55.4%) received amoxicillin according to the therapeutic guidelines. Eighty-one (53.6%) patients with complicated AOM were treated with antibiotics in the community and only 41 (50.6%) of them received antibiotics according to AOM therapeutic guidelines. More antibiotics were prescribed in the community to patients with complicated AOM than to patients with simple AOM (81/151, 53.6% versus 83/320, 25.9%, respectively, p < 0.001). Adherence to therapeutic guidelines was similar between the simple and the complicated AOM groups (46/83, 55.4% versus 41/81, 50.6%, respectively, p = 0.5). CONCLUSION: We found partial adherence to AOM therapeutic guidelines among primary care providers in the community in Southern Israel.

Accuracy of acute otitis media diagnosis in community and hospital settings.

AIM: To evaluate the accuracy rates of acute otitis media (AOM) diagnosis in the community by analyzing the initial AOM diagnosis (according to information from the referral letters to the Pediatric Emergency Department [PED]) among children with AOM diagnosis confirmed by tympanocentesis at PED. METHODS: A descriptive, retrospective study conducted during the year 2000, including 590 children aged 0-48 mo diagnosed with AOM at PED. AOM was confirmed by tympanocentesis. We defined: (1) simple AOM as < 3 or < 4 episodes during the last 6 or 12 mo, respectively; (2) complicated AOM as > or = 3 or > or = 4 episodes during the last 6 or 12 mo, respectively, and/or not improving with antibiotics. RESULTS: 571 (96.8%) were < 24 mo of age; 355 (60%) were Arab Bedouins and 235 (40%) Jews. Seventy-three pediatricians, 57 general practitioners and 27 family practitioners provided referral letters. Information on disease severity was available in 471/590 (79.8%) patients, of whom 320 (68%) had simple and 151 (32%) complicated AOM. Three hundred and sixty-five (62%) of 590 patients were accurately diagnosed by referring physicians, more frequently in patients with complicated than simple AOM (p < 0.001). Diagnostic accuracy was similar among physician specialties (p = 0.33) and ethnic groups (p = 0.11). Multivariable logistic regression analysis showed that complicated AOM, adjusted for age, sex, ethnic origin, and physician specialty, was the only predictive factor for accurate AOM diagnosis (odds ratio 4.0, p < 0.001). CONCLUSIONS: Inaccurate diagnosis of AOM in community settings is common, occurring more frequently in simple than in complicated AOM, and is unrelated to physician specialty and children's ethnicity.

Genetic factors in neuromuscular pain.

Recent evidence suggests that fibromyalgia, a chronic widespread pain condition and related syndromes (chronic fatigue syndrome, irritable bowel syndrome, etc.) may share heritable pathophysiologic features. We review the recent literature on genetic and familial factors found to participate in the pathogenesis of these syndromes, specifically fibromyalgia, including evidence suggesting that serotonin- and dopamine-related genes may play a role in the pathogenesis of these illnesses. The importance of environmental factors triggering these conditions in predisposed individuals is also discussed.

[Evaluation of hospital admissions: admission guidelines implementation in a pediatric emergency department].

OBJECTIVES: To develop and implement locally tailored pediatric admission guidelines for use in a pediatric emergency department and evaluate the appropriateness of admissions based on these guidelines. METHODOLOGY: Our Study was based on the development of admission guidelines by senior physicians, using the Delphi Consensus Process, for use in the Pediatric Emergency Department (PED) at Soroka University Medical Center (Soroka). We evaluated the appropriateness of admissions to the pediatric departments of Soroka on 33 randomly selected days in 1999 and 2000 prior to guideline implementation and 30 randomly selected days in 2001, after guideline implementation. A total of 1037 files were evaluated. FINDINGS: A rate of 12.4% inappropriate admissions to the pediatric departments was found based on locally tailored admission guidelines. There was no change in the rate of inappropriate admissions after implementation of admission guidelines in PED. Inappropriate admissions were associated with age above 3 years, hospital stay of two days or less and the season. The main reasons for evaluating an admission as inappropriate were that the admission did not comply with the guidelines and that the case could be managed in an ambulatory setting. There were distinctive differences in the characteristics of the Bedouin and Jewish populations admitted to the pediatric departments, although no difference was found in the rate of inappropriate admissions between these populations. CONCLUSIONS: Patient management in Soroka PED is tailored to the conditions of this medical center and to the characteristics of the population it serves. The admission guidelines developed reflect these special conditions. Lack of change in the rate of inappropriate admissions following implementation of the guidelines indicates that the guidelines reflect the physicians' approach to patient management that existed in Soroka PED prior to guideline implementation. Hospital admission guidelines have a role in the health management system; however, these guidelines must be tailored to reflect local characteristics and needs.

Adolescent injury risk behavior.

Health-risk behaviors that contribute to the leading causes of morbidity and mortality among adolescents and young adults are often established during adolescence and extended into adulthood. Unintentional motor vehicle injury is the leading cause of mortality in childhood and adolescence in developed countries. This review presents some of the risk factors found in research on unintentional injury and death in adolescence, including risk factors for siblings and adolescents with intellectual disability. These findings should be connected with the findings of a recent study that showed that about one third of all unintentional childhood injury deaths in the United States were preventable. For injury prevention to take place and being effective a multidisciplinary approach is needed to identify host, agent and environmental factors using epidemiology research and biomechanics. In the population of adolescents with intellectual disability there has been little research on injury epidemiology or injury prevention and the service provider will need to focus and educate staff on this issue in order to prevent injury that can result in further disability.

Clinical holistic medicine: holistic adolescent medicine.

The holistic medical approach seems to be efficient and can also be used in adolescent medicine. Supporting the teenager to grow and develop is extremely important in order to prevent many of the problems they can carry into adulthood. The simple consciousness-based, holistic medicine--giving love, winning trust, giving holding, and getting permission to help the patient feel, understand, and let go of negative beliefs--is easy for the physician interested in this kind of practice and it requires little previous training for the physician to be able to care for his/her patient. A deeper insight into the principles of holistic treatment and a thorough understanding of our fellow human beings are making it work even better. Holistic medicine is not a miracle cure, but rather a means by which the empathic physician can support the patient in improving his/her future life in respect to quality of life, health, and functional capacity--through coaching the patient to work on him/herself in a hard and disciplined manner. When the patient is young, this work is so much easier. During our lifetime, we have several emotional traumas arranged in the subconscious mind with the smallest at the top, and it is normal for the person to work on a large number of traumatic events that have been processed to varying degrees. Some traumas have been acknowledged, some are still being explored by the person, and yet others are still preconscious, which can be seen for example in the form of muscle tension. Sometimes the young dysfunctional patient carries severe traumas of a violent or sexual nature, but the physician skilled in the holistic medical toolbox can help the patient on his/her way to an excellent quality of life, full self-expression, a love and sex life, and a realization of his/her talents--all that a young patient is typically dreaming about. Biomedicine is not necessary or even recommended when the physical or mental symptoms are caused by disturbances in the personal development that can be corrected with love and understanding. If possible, biomedicine must be avoided, even if this means suffering for the young person, who needs to confront the tough realities of life in order to grow into an able and sound adult.