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Diabetes mellitus poses major public health and economic challenges which necessitate national‐level intervention. The ultimate goal of the Israel National Diabetes Program is to ensure that all people with diabetes, or at high risk of developing diabetes, will live well and have access to high‐quality services that meet their individual needs. The integrated National Diabetes Program in Israel was established in 2014. Prevailing needs were identified and working groups assigned to delineate deficiencies and propose mode of action. Program leaders summarized and prioritized the needs, and identified main targets of action for the preliminary years. The program was achieved by a combined approach: top‐bottom, having the Director General of the Ministry of Health (MoH) personally involved, and bottom‐up, by routine meetings with representatives of the health organizations, clinical experts, patient representatives and other stakeholders. Main achievements during the first five years of the program included setting up a novel funding mechanism for diabetes prevention, substantiating the field of diabetes education in Israel, designing the infrastructure of diabetic foot care in Israel, updating the national health‐budget allocation formula with incentives to improve provision of services, and promoting a mandatory system for judgemental labelling of food products. The program is in progress with ongoing monitoring, evaluation and improvement with particular emphasis on translational learning. Although there is much to be done, diabetes care in Israel has taken an enormous step forward in the past five years. [ABSTRACT FROM AUTHOR]

Background: We evaluated the impact of flash continuous glucose monitoring (FCGM) on glycemic control and healthcare burden in a large real‐world cohort of patients with type 1 diabetes (T1D) initiating FCGM technology. Methods: In this retrospective cohort study, we included adults (age ≥18 years) with T1D from a large Health Maintenance Organization in Israel, who initiated FCGM during 2018. Primary outcomes included change in HbA1c ≥3 months following FCGM commencement and change in rate of internal‐medicine hospitalization. Additional outcomes included changes in glucose test strip purchases, diabetes related outpatient health care visits and hospitalization for diabetic ketoacidosis (DKA) and/or severe hypoglycemia. Results: The study included 3490 patients, followed for a median of 14 (inter‐quartile range 11‐15) months after FCGM commencement. Among 2682 patients with an HbA1c measured both at baseline and ≥3 months after FCGM initiation, average HbA1c declined from 8.1% ± 1.46% to 7.9% ± 1.31% (P <.001) at first measurement and was maintained during follow up. Specifically, in those with HbA1c ≥8%, a mean decline of 0.5% (P <.001) was observed. A clinically significant HbA1c reduction of ≥0.5% was experienced by 25.5% of the patients. The rate of internal medicine hospitalization, visits to primary care, or visits to endocrine/diabetes specialists in the period following FCGM commencement vs the 6 months prior was significantly reduced (P <.001). Hospitalization for DKA and/or hypoglycemia declined as well (P =.004). Conclusions: FCGM was associated with significant and durable improvement in glycemic control as well as reduced consumption of healthcare services. [ABSTRACT FROM AUTHOR]

In 2008, melioidosis was diagnosed in an agricultural worker from Thailand in the southern Jordan Valley in Israel. He had newly diagnosed diabetes mellitus, fever, multiple abscesses, and osteomyelitis. Burkholderia pseudomallei was isolated from urine and blood. Four of 10 laboratory staff members exposed to the organism received chemoprophylaxis, 3 of whom had adverse events. [ABSTRACT FROM AUTHOR]

Introduction: Diabetic foot ulcers and amputations are the most dreaded diabetes complications. The annual incidence of diabetic foot ulcers in Israel is estimated at 1.8% of all patients with diabetes. The number of patients with diabetes undergoing major amputation in the recent decade has been relatively stable in Israel, and in 2018, 887 patients with diabetes had undergone a major amputation. The proportion of patients undergoing a vascular intervention in the year prior to a major amputation has remained steady over the recent decade, and ranges between 20-40% depending on the patient's age. Aiming to reduce amputation rate, efforts should be made at three levels: 1) Primary care - increasing awareness of patients and health care teams to diabetic foot complications, the means to avoid them, and the delivery of preliminary care. Efforts to further increase awareness should be undertaken. Identification of the foot at-risk and incorporation of professional teams in the care of these patients, as well as provision of appropriate preventive offloading footwear should be sought. 2) Secondary clinics - these multidisciplinary clinics tend to all complications which cannot be adequately addressed in primary care. The professional standard of these clinics should be determined, and the access to these clinics improved. Adequate equipment in these clinics is mandatory as well. 3) Tertiary hospitals - care for the patients who require hospitalization. A national standard for inpatient diabetic foot care should be implemented and multi-disciplinary departments incorporating internists, orthopedists and vascular surgeons should be established aiming to address the medical and surgical complexity of these patients. Qualified nursing staff as well as additional health care professionals including physiotherapists, dieticians, clinical pharmacists, social workers, occupational therapists and others should also be included. Documentation of diabetic foot ulcers is lacking, both in the community and in hospitals. Use of uniform diagnostic codes should be implemented to enable close monitoring of disease trends.

Aims: Identification, a priori, of those at high risk of progression from pre-diabetes to diabetes may enable targeted delivery of interventional programmes while avoiding the burden of prevention and treatment in those at low risk. We studied whether the use of a machine-learning model can improve the prediction of incident diabetes utilizing patient data from electronic medical records., Methods: A machine-learning model predicting the progression from pre-diabetes to diabetes was developed using a gradient boosted trees model. The model was trained on data from The Health Improvement Network (THIN) database cohort, internally validated on THIN data not used for training, and externally validated on the Canadian AppleTree and the Israeli Maccabi Health Services (MHS) data sets. The model's predictive ability was compared with that of a logistic-regression model within each data set., Results: A cohort of 852 454 individuals with pre-diabetes (glucose ≥ 100 mg/dL and/or HbA1c ≥ 5.7) was used for model training including 4.9 million time points using 900 features. The full model was eventually implemented using 69 variables, generated from 11 basic signals. The machine-learning model demonstrated superiority over the logistic-regression model, which was maintained at all sensitivity levels - comparing AUC [95% CI] between the models; in the THIN data set (0.865 [0.860,0.869] vs 0.778 [0.773,0.784] P < .05), the AppleTree data set (0.907 [0.896, 0.919] vs 0.880 [0.867, 0.894] P < .05) and the MHS data set (0.925 [0.923, 0.927] vs 0.876 [0.872, 0.879] P < .05)., Conclusions: Machine-learning models preserve their performance across populations in diabetes prediction, and can be integrated into large clinical systems, leading to judicious selection of persons for interventional programmes., (© 2020 John Wiley & Sons, Ltd.)

Aims: To assess the validity of the diagnostic codes relating to diabetic foot ulcer (DFU) in the electronic medical records of a large integrated care provider and to assess the prevalence of DFU among its members., Materials and Methods: Data were obtained from the diabetes registry of Maccabi Healthcare Services (MHS), a 2.1-million-member sick-fund in Israel, which included 125 665 patients in 2015. We randomly selected and reviewed ~400 patient files from each of the following categories during study period: (1) had a diagnostic code of DFU; (2) had a diagnostic code, or clinical condition suggestive of DFU including: leg-ulcer, amputation, DFU in quartiles proximate to 2015 or abnormality reported by nurse; (3) patients at high risk for DFU (age > 35 and one of the following: peripheral artery disease, neuropathy, DFU during 2011-2014, eGFR<30 mL/min/m 2 or foot deformity). The patients' charts were reviewed by study physicians, and DFU was validated or refuted., Results: Relying upon diagnostic codes entered by physicians, the positive predictive value (PPV) was 73.1% (95% CI 67.6-78.2), and the sensitivity was 48.2% (95% CI 45.8-50.7%). The PPV of the diagnostic codes listed by podiatrists were significantly lower, while that of codes listed by nurses was higher but with lower sensitivity. The estimated annual prevalence of DFU in the diabetes registry of MHS was 1.2% (95%CI 1.0-1.5%)., Conclusions: Diagnostic codes alone cannot be used reliably to create a DFU registry. Nevertheless, the data collected provide an estimate of the prevalence of DFU among patients included in the MHS diabetes registry., (© 2018 John Wiley & Sons, Ltd.)

Aim: To assess the possible risk of acute kidney injury (AKI) with the use of sodium-glucose co-transporter-2 inhibitors (SGLT2-i) as well as changes in estimated glomerular filtration rate (eGFR), hospitalizations and mortality in a real-world setting., Materials and Methods: Included in this historical cohort study were patients with type 2 diabetes in a large health organization in Israel who initiated therapy with SGLT2-i or dipeptidyl peptidase-4 inhibitors (DPP-4i) during 1 April 2015 to 30 June 2017. We collected data on serum creatinine measurements taken between 180 days prior to and 24 weeks after therapy initiation. Study endpoints included ≥30% reduction in eGFR, hospitalization with AKI, any hospitalization and all-cause mortality., Results: Overall 6418 and 5604 patients initiated SGLT2-i and DPP-4i, respectively. Baseline mean (SD) eGFR was higher among the SGLT2-i group compared with the DPP-4i group (88.3 [17.4] and 82.8 [23.7], respectively) but were similar when stratifying by chronic kidney disease (CKD) stages. The adjusted odds ratio (OR) (95% confidence interval [CI]) for ≥30% reduction in eGFR with SGLT2-i versus DPP4-i was 0.70 (0.49-1.00) and ORs ranged from 1.97 (0.62-6.26) to 0.45 (0.21-0.99) in patients with baseline eGFR 30 to 45 and ≥90 mL/min/1.73 m 2 , respectively. Risks of AKI (OR = 0.47, 95% CI 0.27-0.80), hospitalization (OR = 0.66, 95% CI 0.56-0.78) or all-cause mortality (OR = 0.43, 95% CI 0.20-0.95) were lower in patients initiating SGLT2-i versus DPP-4i., Conclusions: This real-world data analysis supports reassuring findings from previous randomized clinical trials showing no increased AKI risk among SGLT2-i users. Nevertheless, because of the more prominent decrease in eGFR in patients with moderate CKD, cautious use of SGLT2-i in patients with reduced eGFR is advised., (© 2018 John Wiley & Sons Ltd.)

Background: Reduced sensitivity to thyroid hormone (RSTH) syndrome describes a group of rare heterogeneous genetic disorders. Precise diagnosis is essential to avoid unnecessary treatment., Objectives: To identify and characterize previously undiagnosed patients with RSTH in Israel., Methods: Patients with suspected RSTH throughout Israel were referred for study. After clinical evaluation, genomic DNA was obtained and all coding exons of the thyroid hormone receptor beta (THRB) gene were sequenced. If mutations were found, all available blood relatives were evaluated. The common polymorphism rs2596623, a putative intronic regulatory variant, was also genotyped. Genotype/phenotype correlations were sought, and the effect of mutation status on pregnancy outcome was determined., Results: Eight mutations (one novel; two de-novo, six dominant) were identified in eight probands and 13 family members. Clinical and genetic features were similar to those reported in other populations. Previous suggestions that rs2596623 predicts clinical features were not confirmed. There was no evidence of increased risk of miscarriage or fetal viability. Mothers carrying a THRB mutation tended to have increased gestational hypertension and low weight gain during pregnancy. Their affected offspring had increased risk of small-for-gestational age and poor postnatal weight gain., Conclusions: Clinical heterogeneity due to THRB mutations cannot be explained by the variant rs2596623. Mothers and newborns with THRB mutations seem to be at increased risk of certain complications, such as gestational hypertension and poor intrauterine and postnatal growth. However, these issues are usually mild, suggesting that routine intervention to regulate thyroid hormone levels may not be warranted in these patients.

Objective: To investigate whether human immunodeficiency virus (HIV) infection or its treatment is a risk factor for thyroid dysfunction and whether thyroid function changes over time in 2 distinct subpopulations with HIV or acquired immunodeficiency syndrome (AIDS) in Israel: Ethiopian immigrants and Israeli patients., Methods: Serum thyroid-stimulating hormone (TSH) and free thyroxine levels were determined in HIV carriers undergoing follow-up at the Hadassah-Hebrew University Medical Center HIV clinic in Jerusalem, Israel, and these thyroid measurements were correlated with clinical and laboratory variables pertaining to their disease, including disease duration, drug therapy, viral load, CD4 count, low-density lipoprotein cholesterol, and creatine kinase. Serum samples stored at -20°C from the time of referral were tested as well., Results: We recruited 121 consecutive patients with HIV or AIDS for this study: 60 Ethiopians and 61 Israeli patients. Of the 121 patients, 4 (3%) had abnormal thyroid function-subclinical hypothyroidism in 2, overt hypothyroidism in 1, and overt hyperthyroidism in 1. Previously stored serum samples were available for 60 of the 121 patients and revealed 2 additional patients with subclinical hypothyroidism, whose TSH has normalized in the subsequent test. Throughout the follow-up period of 3.2 ± 1.9 years, the mean TSH level remained unchanged in the Israeli cohort but significantly declined in the Ethiopian cohort., Conclusion: Thyroid function abnormalities were uncommon in these Israeli patients with HIV or AIDS. This finding does not support the need for routine thyroid function tests in this patient population. The decline in TSH level in the Ethiopian population over time probably represents a shift from an iodine-deficient to an iodine-sufficient country.

Background: Primary pulmonary hypertension is a rare disorder, characterized by progressive pulmonary hypertension and right heart failure. It may be familial or sporadic. Mutations in bone morphogenetic protein receptor II (BMPR2), a member of the transforming growth factor-beta receptor superfamily of receptors, underlie many cases of the disorder., Objectives: To perform molecular analysis of a patient with familial PPH and provide her and her family with suitable genetic counseling., Methods: DNA was extracted from 10 ml whole blood, and the BMPR2 gene was screened for mutations. Individual exons were amplified by polymerase chain reaction and sequenced. Mutation confirmation and molecular characterization of additional family members was performed using restriction enzyme analysis followed by appropriate genetic counseling., Results: We identified a novel T to C missense mutation expected to result in substitution of arginine for a conserved cysteine in the ligand-binding domain of BMPR2. Screening of family members demonstrated the presence of the mutation in the father and a younger asymptomatic sister of the index patient., Conclusions: Molecular diagnosis in PPH allows for identification of at-risk family members and raises the option of earlier diagnosis and possibly instituting earlier treatment in affected individuals. However, molecular screening of asymptomatic family members raises difficult ethical questions that can only be resolved by conducting large multicenter prospective studies in BMPR2 carriers.