Opportunities and challenges in delivering remote primary care during the Coronavirus outbreak.

BACKGROUND: Social distancing and lockdowns were implemented during the first period of the COVID-19 pandemic. Primary care physicians needed to adapt quickly to deliver remote care/telemedicine. METHODS: A cross-sectional, 47-item online Google Survey was distributed through the Israel Association of Family Physicians (IAFP) mailing list between March 31-May 5, 2020. The questionnaire included demographics, physician characteristics, and information on usage and perceived telemedicine quality. Sampling weights by sex and age groups were applied. RESULTS: One hundred fifty-nine primary care physicians (10.6% of registered IAFP members; 63.5% women; mean age 53.4 ± 10.4 years and median professional experience 21.3 years) replied to the survey. The majority (59.7%) of the participants performed a mixture of in-person along with phone counseling. About 40% had no former telemedicine experience. The majority indicated that telephone and video formats were inferior to in-person consultation (68%, 57.1% online and phone, respectively). The overall counseling quality grade (on a 1-10 scale,)median (IQR)) was 6.2 (3) for telephone and 7(2) for video. While 66.9% reported experiencing no challenges, 10% had technical problems, 10% interpersonal problems, 5.6% scheduling difficulties, and 7.5% other difficulties. Majority of 56.6% physicians indicated they prescribed more antibiotics,16.4% sent more blood tests, 24.5% referred more to experts, and 49.7% referred more to imaging in comparison to usual counseling. Higher phone quality score was significantly associated with physicians who indicated not prescribing more antibiotics during the pandemic (OR = 0.30, 95%CI 0.134-0.688, p = 0.004). Higher online quality score was associated with physicians who indicated not sending more blood tests during the pandemic (OR = 0.06 95%CI 0.008-0.378, P = 0.003). CONCLUSIONS: Our findings suggest telehealth holds considerable promise for counseling in the primary care setting. However, interpersonal challenges raised by physicians should be understood in-depth to develop tailored training and further examine it in randomized trials while integrating patient-reported outcomes. Finally, further research on utility, cost, and cost-efficiency during remote counseling with follow-ups, medical prescribing, and additional referrals is needed.

Altered T cell receptor beta repertoire patterns in pediatric ulcerative colitis.

The antigenic specificity of T cells occurs via generation and rearrangement of different gene segments producing a functional T cell receptor (TCR). High-throughput sequencing (HTS) allows in-depth assessment of TCR repertoire patterns. There are limited data concerning whether TCR repertoires are altered in inflammatory bowel disease. We hypothesized that pediatric ulcerative colitis (UC) patients possess unique TCR repertoires, resulting from clonotypical expansions in the gut. Paired blood and rectal samples were collected from nine newly diagnosed treatment-naive pediatric UC patients and four healthy controls. DNA was isolated to determine the TCR-ß repertoire by HTS. Significant clonal expansion was demonstrated in UC patients, with inverse correlation between clinical disease severity and repertoire diversity in the gut. Using different repertoire variables in rectal biopsies, a clear segregation was observed between patients with severe UC, those with mild-moderate disease and healthy controls. Moreover, the overlap between autologous blood-rectal samples in UC patients was significantly higher compared with overlap among controls. Finally, we identified several clonotypes that were shared in either all or the majority of UC patients in the colon. Clonal expansion of TCR-ß-expressing T cells among UC patients correlates with disease severity and highlights their involvement in mediating intestinal inflammation.

Thirty years of family medicine publications in Israel (1975-2004): what, where, and how much?

BACKGROUND: Departments of family medicine in Israel were established in the 1970s. Until now, little or no effort has been made to characterize the productivity of Israeli board-certified family medicine physicians in publishing peer-reviewed scientific articles. METHODS: Publications were identified by 2 methods. First, a PubMed search by names of current and past faculty from all the departments of family medicine in Israel (1975-2004). Secondly, all of the departments in Israel forwarded a list of all publications by their faculty (including those that do not appear in Medline). The abstracts of all publications were extracted and were separately and blindly evaluated by 2 reviewers. Publications were classified according to Medline citation, language, journal impact factor, and publication type. RESULTS: A total of 1165 publications were identified and analyzed. More than half of the articles were published in the last 10 years. Seventy-two percent were cited in Medline. Publications in English encompassed 64.7% of the publications, Hebrew 34.6%, and 0.7% other. Approximately 6% of the articles were published in journals with impact factor > or =3, with research articles accounting for 46.9%. The publication output of family medicine in Israel averaged 85.4 publications per 1000 family medicine physicians per year. Almost 70% of the articles were published in non-family medicine journals. Academically affiliated, board-certified family medicine physicians published at higher rates, averaging 334.3 per 1000 academic family medicine physicians per year (data available for 2000-2004 only). CONCLUSIONS: Publishing and research are important to the development of family medicine as an academic profession, in which Israeli family physicians show significant productivity.

Attitudes of couples identified through screening as carriers of Gaucher disease type 1.

Gaucher disease (GD) type 1 is the most frequent autosomal recessive disorder among Ashkenazi Jews, but because the phenotype is tremendously variable, including it in the 'Ashkenazi Panel' of carrier screening is controversial. As part of a nationwide study conducted in Israel to evaluate the outcomes of carrier screening for GD, we studied the experience of 65/82 (79%) of the couples identified as being at risk for an affected child. We found that pre-test information was regarded as insufficient and improved in post-result counseling. About 70% of the subjects interpreted the genetic counseling as directive, mostly toward prenatal diagnosis (PND) but against pregnancy termination of affected fetuses. We evaluated the various motivations that had led couples to utilize PND. Subjects' attitudes toward pregnancy termination correlated with their specific genotypes, with their perception of the severity of GD and with attending additional medical consultation. Of the 30 interviewed participants who were faced with having an affected fetus, 80% came to terms with their decision to utilize PND, but about half of the few who terminated the pregnancy regret their decision. Despite questionable benefits of screening, most of the participants did not regret having been tested and supported the continuation of this program. We offer explanations for these findings and suggest extensive genetic and medical counseling for any future carrier screening for low penetrance, treatable disease.

Insoles for prevention and treatment of back pain.

BACKGROUND: There is lack of theoretical and clinical knowledge of the use of insoles for prevention or treatment of back pain. The high incidence of back pain and the popularity of shoe insoles call for a systematic review of this practice. OBJECTIVES: To determine the effectiveness of shoe insoles in the prevention and treatment of non-specific back pain compared to placebo, no intervention, or other interventions. SEARCH STRATEGY: We searched the following databases: The Cochrane Back Group Trials Register and The Cochrane Central Register of Controlled Trials (CENTRAL) to March 2005, and MEDLINE, EMBASE, and CINAHL to February 2007; reviewed reference lists in review articles, guidelines and in the included trials; conducted citation tracking; contacted individuals with expertise in this domain. SELECTION CRITERIA: We included randomized controlled trials that examined the use of customized or non-customized insoles, for the prevention or treatment of back pain, compared to placebo, no intervention or other interventions. Study outcomes had to include at least one of the following: self-reported incidence or physician diagnosis of back pain; pain intensity; duration of back pain; absenteeism; functional status. Studies of insoles designed to treat limb length inequality were excluded. DATA COLLECTION AND ANALYSIS: One review author conducted the searches and blinded the retrieved references for authors, institution and journal. Two review authors independently selected the relevant articles. Two different review authors independently assessed the methodological quality and clinical relevance and extracted the data from each trial using a standardized form. MAIN RESULTS: Six randomized controlled trials met inclusion criteria: Three examined prevention of back pain (2061 participants) and three examined mixed populations (256 participants) without being clear whether they were aimed at primary or secondary prevention or treatment. No treatment trials were found. There is strong evidence that the use of insoles does not prevent back pain. There is limited evidence that insoles alleviate back pain or adversely shift the pain to the lower extremities. LIMITATIONS: This review largely reflects limitations of the literature, including low quality studies with heterogeneous interventions and outcome measures, poor blinding and poor reporting. AUTHORS' CONCLUSIONS: There is strong evidence that insoles are not effective for the prevention of back pain. The current evidence on insoles as treatment for low-back pain does not allow any conclusions.High quality trials are required for stronger conclusions.

[Israeli guidelines for prevention of low back pain].

INTRODUCTION: Due to the lack of international consensus regarding the efficiency of various methods for prevention of low back pain (LBP), this article describes the Israeli guidelines for prevention of L.B.P., based on the recommendations of the European Commission, COST Action B13. OBJECTIVE: Consolidation of Israeli guidelines for prevention of L.B.P. METHOD: In September 2004, the Israeli low back pain work group gathered in Haifa, to discuss and reach a consensus relating to the LBP prevention guidelines. The forum was sponsored by the Israeli Medical Association. LITERATURE SEARCH: The recommendations of the European committee, COST B13, served as the main source of information. The European group based its conclusions on systematic reviews mainly from the Cochrane, Embase, and Medline databases, and other smaller databases for more specific topics. The search covered the years 1966-2003. Information was also gathered through personal contacts with experts in the field. Additional searches were conducted for recent RCT's, published following the most recent systematic reviews. The final recommendations were sent to be reviewed by international experts in LBP. Summary of recommendations for the general population: Physical exercise is recommended for prevention of sick leave due to LBP and for the occurrence or duration of further episodes (Level A). There is insufficient consistent evidence to recommend for or against any specific type or intensity of exercise (Level C). Information and education on back problems, if based on bio-psychosocial principles, should be considered (Level C), but information and education focused principally on a biomedical or biomechanical model cannot be recommended (Level C). Back schools based on traditional biomedical/biomechanical information, advice and instruction are not recommended for prevention in LBP (Level A). High intensity programs, which comprise both an educational/skills program and exercises, can be recommended for patients with recurrent and persistent back pain (Level B). Lumbar supports or back belts are not recommended (Level A). There is no robust evidence for or against recommending any specific chair or mattress for prevention in LBP (Level C), though persisting symptoms may be reduced with a medium-firm rather than a hard mattress (Level C). There is no evidence to support recommending manipulative treatment for prevention in LBP (Level D). Shoe insoles are not recommended for the prevention of back problems (Level A). There is insufficient evidence to recommend for or against correction of leg length (Level D). Despite the intuitive appeal of the idea, there is no evidence, at this time, that attempts to prevent LBP in schoolchildren will have any impact on LBP in adults (Level D).

Does pneumococcal vaccine reduce influenza morbidity in humans?

A retrospective study was conducted to verify the possibility that people immunized with pneumococcal vaccine (PV) show lower morbidity not only for pneumonia but also for influenza. A total of 450 individuals were enrolled between 1999 and 2003 and allocated to one of the following groups: (A) not vaccinated; (B) immunized with PV during 1999; (C) immunized with anti-influenza vaccine (Flu-V) each year; and (D) immunized with PV once in 1999 and Flu-V every consecutive year. People from group B showed significantly lower percentage of influenza-related diseases during the year 2000 in comparison with those from group A (p<0.01), whereas in the course of 2001 the morbidity of patients from group B was lower compared with the other groups (p<0.01). The results point to a way to decrease the morbidity of influenza-related diseases by immunization with PV only, at least for 2-3 years, avoiding Flu-V administration and permitting considerable saving for health care providers. Therefore, it is concluded that PV can reduce the morbidity of influenza at a greater rate than the Flu-V.

How to prevent low back pain.

This chapter summarizes the European Guidelines for Prevention in Low Back Pain, which consider the evidence in respect of the general population, workers and children. There is limited scope for preventing the incidence (first-time onset) of back pain and, overall, there is limited robust evidence for numerous aspects of prevention in back pain. Nevertheless, there is evidence suggesting that prevention of various consequences of back pain is feasible. However, for those interventions where there is acceptable evidence, the effect sizes are rather modest. The most promising approaches seem to involve physical activity/exercise and appropriate (biopsychosocial) education, at least for adults. Owing to its multidimensional nature, no single intervention is likely to be effective at preventing the overall problem of back pain, although there is likely to be benefit from getting all the players onside. However, innovative studies are required to better understand the mechanisms and delivery of prevention in low back pain.

High prevalence of low serum vitamin B12 in a multi-ethnic Israeli population.

This study ascertained serum vitamin B12 levels among patients with Gaucher disease and among healthy Israelis. Serum B12 and metabolites' levels were studied in consecutive adult patients with Gaucher disease not treated with enzyme plus Ashkenazi Jewish neighbour-controls, together with healthy blood-donor volunteers of various ethnicities. Each group showed a high incidence of low serum B12 concentrations, with a 22.3% incidence among Ashkenazi Jews and 40% among patients with Gaucher disease. These findings raise questions on the individual and community levels of serum B12. We recommend evaluation of B12 levels among geographically contingent peoples.

A single nucleotide polymorphism in the RAD51 gene modifies cancer risk in BRCA2 but not BRCA1 carriers.

BRCA1 and BRCA2 carriers are at increased risk for both breast and ovarian cancer, but estimates of lifetime risk vary widely, suggesting their penetrance is modified by other genetic and/or environmental factors. The BRCA1 and BRCA2 proteins function in DNA repair in conjunction with RAD51. A preliminary report suggested that a single nucleotide polymorphism in the 5' untranslated region of RAD51 (135C/G) increases breast cancer risk in BRCA1 and BRCA2 carriers. To investigate this effect we studied 257 female Ashkenazi Jewish carriers of one of the common BRCA1 (185delAG, 5382insC) or BRCA2 (6174delT) mutations. Of this group, 164 were affected with breast and/or ovarian cancer and 93 were unaffected. RAD51 genotyping was performed on all subjects. Among BRCA1 carriers, RAD51-135C frequency was similar in healthy and affected women [6.1% (3 of 49) and 9.9% (12 of 121), respectively], and RAD-135C did not influence age of cancer diagnosis [Hazard ratio (HR) = 1.18 for disease in RAD51-135C heterozygotes, not significant]. However, in BRCA2 carriers, RAD51-135C heterozygote frequency in affected women was 17.4% (8 of 46) compared with 4.9% (2 of 41) in unaffected women (P = 0.07). Survival analysis in BRCA2 carriers showed RAD51-135C increased risk of breast and/or ovarian cancer with an HR of 4.0 [95% confidence interval 1.6-9.8, P = 0.003]. This effect was largely due to increased breast cancer risk with an HR of 3.46 (95% confidence interval 1.3-9.2, P = 0.01) for breast cancer in BRCA2 carriers who were RAD51-135C heterozygotes. RAD51 status did not affect ovarian cancer risk. These results show RAD51-135C is a clinically significant modifier of BRCA2 penetrance, specifically in raising breast cancer risk at younger ages.

Health behavior in a kibbutz population: correlations among different modalities of healthcare utilization.

BACKGROUND: Alternative medicine use is increasing worldwide and the associated expenditures are significant. In Israel 19% of patients who consulted their family physician had also sought treatment by an alternative medicine practitioner. OBJECTIVES: To explore the correlation between different modalities of healthcare utilization, health behavior, and health belief among adult members of a kibbutz (rural communal settlement). This unique study population enabled the use of a simplified quantitative model due to the minimal individual differences in cost and access. METHODS: Healthcare utilization data were obtained for 220 kibbutz members aged 15-70 years from patient medical files and self-administered questionnaires over a 45 month period. Patient visits to the family practitioner and other specialist physicians were tallied, and individuals reported alternative medicine consultations during the previous year. Multiple regression analysis was used to control for age, chronic disease, and other background characteristics. RESULTS: The mean number of patient FP visits was 3.6 per patient per year. Women and chronic disease sufferers visited the doctor more frequently. A patient's number of FP visits and other specialist physician visits were closely correlated, with each specialist physician consult resulting in an additional 0.64 FP visit for a given individual (P = 0.007). Our analysis indicated that self-reported alternative therapy utilization was positively associated with the number of FP visits; patients reporting alternative therapy use visited their primary care physician once additionally per year (P = 0.03). Low self-rated health status was correlated with increased likelihood of alternative therapy use (borderline significance). CONCLUSION: These results suggest that a patient who seeks treatment from one type of healthcare practitioner will seek out other practitioners as well. This study supports the notion that unconventional therapies are used in conjunction with, rather than instead of, mainstream medical care.

Doctor-patient concordance and patient initiative during episodes of low back pain.

Doctor-patient concordance and patient initiative were examined in a prospective network interview study, with telephone follow-up, of a cohort of 100 patients presenting with low back pain to their family physician. The average overall rate of concordance was 60% (95% CI = 53 to 66), with the highest rates for radiographic imaging studies and sick leave. No correlation was found between concordance and patient parameters. Subjects initiated an average of two (95% CI = 1.7 to 2.3) diagnostic or therapeutic procedures, the most common of which were for medications (40%), followed by bed rest (26%) and back school (22%). One out of every six subjects initiated a referral to a complementary therapist. Positive correlation was found between patient initiatives and pain severity (P = 0.022) and disability (P = 0.02). There was a negative correlation between the subjects' initiatives and their belief that the physician understood the cause of their pain and its influence on their life (P = 0.02). Overall, those patients who described more pain or disability sought more types of diagnostic and therapeutic measures, while those who felt they had been understood sought less.

BRCA1 and BRCA2 mutation carriers as potential candidates for chemoprevention trials.

The identification of cancer susceptibility genes offers new avenues for selecting high-risk individuals as subjects for chemoprevention trials. Because carriers of predisposing mutations are at high risk, they are more likely to enroll and comply with chemoprevention trials, and meaningful results can be achieved with smaller numbers of participants and shorter periods of follow-up. Such studies have immediate benefits for carriers themselves, but they are also likely to result in effective chemopreventive strategies for the general population. In this review, we discuss BRCA1 and BRCA2 carriers as potential candidates for breast and ovarian cancer chemoprevention trials. The existence of a large population with a high frequency of easily identifiable BRCA1/2 mutations can provide ample opportunity for such studies. However, the possibility that tumor characteristics and hormonal profile of BRCA1/BRCA2 related cancers are not completely equivalent to cancers in the general population should be borne in mind.

Is there a correlation between degree of splenomegaly, symptoms and hypersplenism? A study of 218 patients with Gaucher disease.

Despite the prevalence of splenomegaly as a sign in many disorders, there have been no studies that correlate the degree of organomegaly with the symptoms generally ascribed to splenic enlargement. The degree of splenomegaly was compared with five overt symptoms of mechanical displacement, i.e. chronic abdominal pain, abdominal discomfort, early satiety, pain while lying on the side, or attacks of acute (colicky) left upper quadrant pains. We have also employed splenomegaly as seen in Gaucher disease as a paradigm to determine whether there is a correlation between the degree of splenomegaly and the parameters of hypersplenism. Although there was a statistically significant correlation between degree of splenomegaly and blood counts, this proved to be clinically negligible. Surprisingly, there was also no correlation between degree of splenomegaly and any of symptoms investigated.

Asymptomatic Gaucher disease implications for large-scale screening.

Gaucher disease, the most prevalent genetic disorder among Ashkenazi Jews, is characterized by significant phenotypic heterogeneity. Because seven mutations account for more than 96% of the disease alleles in this population, large-scale screening is feasible, and genotyping is commercially available. To date, only 400 Gaucher patients have been diagnosed in Israel, although 2,500 patients are predicted by gene frequency; hence, there is the probability that those uncovered by population screening will prove to be very mild or asymptomatic since these patients have generally escaped medical attention until now. We studied objective and subjective aspects in 68 asymptomatic/very mild patients, followed for a mean of 2.6 years, to assess the implications of identifying many more such patients if large-scale screening were to be implemented. We found there were no medically significant changes in disease severity during follow-up. The patients' subjective reports of their general health status were similar to those of normal subjects, and there were no significant changes in quality of life during follow-up. Our findings suggest that asymptomatic/mild Gaucher patients do not require frequent monitoring; there is no justification for "prophylactic" enzyme therapy in this group, and, hence, no rationale for large-scale screening in the Ashkenazi population. Furthermore, one needs to be concerned with the adverse effects of labeling large numbers of asymptomatic individuals as affected because of the potential for stigmatization and discrimination.

Echocardiographic assessment of pulmonary hypertension in Gaucher's disease.

BACKGROUND: Enzyme therapy has been shown to decrease the signs and symptoms of Gaucher's disease. A few patients, however, develop pulmonary hypertension on such treatment. We investigated the frequency of pulmonary hypertension in Gaucher's disease. METHODS: We studied 134 adults with type 1 Gaucher's disease, including 73 patients on enzyme replacement, with echocardiography. We measured tricuspid incompetence (TI) with continuous-wave doppler. Pulmonary hypertension was indicated by a TI gradient of more than 30 mm Hg. FINDINGS: Nine (7%) patients had pulmonary hypertension: all were treated and six had undergone splenectomy. Chest radiographs confirmed the presence of pulmonary hypertension in these patients as well as in most patients with TI gradients of 25-29 mm Hg. INTERPRETATION: The confounding effects of disease severity and splenectomy in many treated patients precluded definitive conclusion of cause and effect. Nonetheless, we found an unexpectedly high rate of pulmonary hypertension and recommended routine echocardiographic monitoring of all treated and untreated patients with type 1 Gaucher's disease. We also suggest consideration of treatment withdrawal if the TI gradient progresses to more than 30 mm Hg.

Gilbert syndrome and glucose-6-phosphate dehydrogenase deficiency: a dose-dependent genetic interaction crucial to neonatal hyperbilirubinemia.

Severe jaundice leading to kernicterus or death in the newborn is the most devastating consequence of glucose-6-phosphate dehydrogenase (EC 1.1.1.49; G-6-PD) deficiency. We asked whether the TA repeat promoter polymorphism in the gene for uridinediphosphoglucuronate glucuronosyltransferase 1 (EC 2.4.1.17; UDPGT1), associated with benign jaundice in adults (Gilbert syndrome), increases the incidence of neonatal hyperbilirubinemia in G-6-PD deficiency. DNA from term neonates was analyzed for UDPGT1 polymorphism (normal homozygotes, heterozygotes, variant homozygotes), and for G-6-PD Mediterranean deficiency. The variant UDPGT1 promoter allele frequency was similar in G-6-PD-deficient and normal neonates. Thirty (22.9%) G-6-PD deficient neonates developed serum total bilirubin >/= 257 micromol/liter, vs. 22 (9.2%) normals (P = 0.0005). Of those with the normal homozygous UDPGT1 genotype, the incidence of hyperbilirubinemia was similar in G-6-PD-deficients and controls (9.7% and 9.9%). In contrast, in the G-6-PD-deficient neonates, those with the heterozygous or homozygous variant UDPGT1 genotype had a higher incidence of hyperbilirubinemia than corresponding controls (heterozygotes: 31.6% vs. 6.7%, P < 0.0001; variant homozygotes: 50% vs. 14.7%, P = 0.02). Among G-6-PD-deficient infants the incidence of hyperbilirubinemia was greater in those with the heterozygous (31.6%, P = 0.006) or variant homozygous (50%, P = 0.003) UDPGT1 genotype than in normal homozygotes. In contrast, among those normal for G-6-PD, the UDPGT1 polymorphism had no significant effect (heterozygotes: 6.7%; variant homozygotes: 14.7%). Thus, neither G-6-PD deficiency nor the variant UDPGT1 promoter, alone, increased the incidence of hyperbilirubinemia, but both in combination did. This gene interaction may serve as a paradigm of the interaction of benign genetic polymorphisms in the causation of disease.

Hostility, aggression and the risk of nonfatal myocardial infarction in postmenopausal women.

Hostility can predict coronary heart disease (CHD) and total mortality in men. However, in women this association has not been as thoroughly explored. This study examines whether hostile and aggressive attitudes are associated with myocardial infarction (MI) in postmenopausal women. Cases included 277 women who presented with an incident MI. Controls included a random sample of 988 female health maintenance organization enrollees. Women were asked the Hostile-Affect and the Aggressive-Responding factors of the Cook-Medley Hostility Scale. The Hostile-Affect score was linearly associated with increased risk for MI (odds ratio [OR] per point = 1.22; 95% confidence interval [CI95%] = 1.07-1.38), whereas the Aggressive-Responding score had a modest protective effect (OR = 0.92 per point; CI95% = 0.84-1.02); p = 0.009. Adjustment for sociodemographic and MI risk factors altered these results only slightly. These hostility measures are easily administered, and could help to identify women who are at high risk for CHD and who may benefit from preventive measures.