A standard set of person-centred outcomes for diabetes mellitus: results of an international and unified approach.

AIMS: To select a core list of standard outcomes for diabetes to be routinely applied internationally, including patient-reported outcomes. METHODS: We conducted a structured systematic review of outcome measures, focusing on adults with either type 1 or type 2 diabetes. This process was followed by a consensus-driven modified Delphi panel, including a multidisciplinary group of academics, health professionals and people with diabetes. External feedback to validate the set of outcome measures was sought from people with diabetes and health professionals. RESULTS: The panel identified an essential set of clinical outcomes related to diabetes control, acute events, chronic complications, health service utilisation, and survival that can be measured using routine administrative data and/or clinical records. Three instruments were recommended for annual measurement of patient-reported outcome measures: the WHO Well-Being Index for psychological well-being; the depression module of the Patient Health Questionnaire for depression; and the Problem Areas in Diabetes scale for diabetes distress. A range of factors related to demographic, diagnostic profile, lifestyle, social support and treatment of diabetes were also identified for case-mix adjustment. CONCLUSIONS: We recommend the standard set identified in this study for use in routine practice to monitor, benchmark and improve diabetes care. The inclusion of patient-reported outcomes enables people living with diabetes to report directly on their condition in a structured way.

Live birth sex ratios and father's geographic origins in Jerusalem, 1964-1976.

OBJECTIVE: To examine whether ancestry influenced sex ratios of offspring in a birth cohort before parental antenatal sex selection influenced offspring sex. METHODS: We measured the sex ratio as the percent of males according to countries of birth of paternal and maternal grandfathers in 91,459 live births from 1964 to 1976 in the Jerusalem Perinatal Study. Confidence limits (CI) were computed based on an expected sex ratio of 1.05, which is 51.4% male. RESULTS: Of all live births recorded, 51.4% were male. Relative to Jewish ancestry (51.4% males), significantly more males (1,761) were born to Muslim ancestry (54.5, 95% CI = 52.1-56.8, P = 0.01). Among the former, sex ratios were not significantly associated with paternal or maternal age, education, or offspring's birth order. Consistent with a preference for male offspring, the sex ratio decreased despite increasing numbers of births over the 13-year period. Sex ratios were not affected by maternal or paternal origins in North Africa or Europe. However, the offspring whose paternal grandfathers were born in Western Asia included fewer males than expected (50.7, 50.1-51.3, P = 0.02), whether the father was born abroad (50.7) or in Israel (50.8). This was observed for descendents of paternal grandfathers born in Lebanon (47.6), Turkey (49.9), Yemen & Aden (50.2), Iraq (50.5), Afghanistan (50.5), Syria (50.6), and Cyprus (50.7); but not for those from India (51.5) or Iran (51.9). The West Asian group showed the strongest decline in sex ratios with increasing paternal family size. CONCLUSIONS: A decreased sex ratio associated with ancestry in Western Asia is consistent with reduced ability to bear sons by a subset of Jewish men in the Jerusalem cohort. Lower sex ratios may be because of pregnancy stress, which may be higher in this subgroup. Alternatively, a degrading Y chromosome haplogroup or other genetic or epigenetic differences on male germ lines could affect birth ratios, such as differential exposure to an environmental agent, dietary differences, or stress. Differential stopping behaviors that favor additional pregnancies following the birth of a daughter might exacerbate these lower sex ratios.

Postpartum depression and infant development up to 24 months: A nationwide population-based study.

AIMS: Postpartum depression (PPD) is the most common complication women experience after delivery. We aimed to examine the association of maternal PPD with delays in child development, in a population-based study, in the first two years of life. METHODS: A nation-wide population-based historical cohort study in the setting of the Mother and Child Health Clinics in Israel, where infants are routinely evaluated for growth and development. Data were retrieved on 96,623 infants born in 2014-2015 whose mothers had PPD screening. Logistic regressions were used to estimate the associations of PPD with the achievements of developmental milestones, controlling for potential confounders. RESULTS: PPD was identified in 4,268 mothers (4.7%). PPD was associated with delays in language skills, including the production of voices in dialogue (OR=1.88, 95% CI: 1.41-2.52) and speaking 2-3 words (OR=1.24, 95% CI: 1.13-1.37). PPD was associated with about 1.5 times increased odds of delays in personal-social skills, including reacting to voices (OR=1.43, 95% CI: 1.22-1.67) and pointing to selected objects (OR=1.47 95% CI: 1.10-1.97). Associations were also seen with delays in fine motor and adaptive skills, such as pinching (OR=1.50, 95% CI: 1.20-1.86), and gross motor skills, such as ground crawling (OR=1.36, 95% CI: 1.15-1.60). CONCLUSIONS: In this population-based large cohort study, PPD as estimated in a national screening program, was associated with delays in early child development, which were shown in all assessed domains. Future studies should confirm our results and intervention programs should be developed to effectively minimize these gaps.

Biennial hyperepidemic shigellosis in an observant Jewish community.

We aimed to study patterns of shigellosis in a large observant Jewish community in Israel and to describe local interventions during outbreaks. Surveillance data from the Ministry of Health were used to calculate incidence rates in 1998-2006, both in the city of Bene Beraq and the Tel Aviv district. Information on isolates was collected from the bacteriological laboratory of a community hospital. Public notices and educational conferences conveyed a message to increase personal hygiene and keep ill children at home. During a 9-year period, a clear biennial pattern of outbreaks was noticed. Annual incidence rates ranged between 18 and 353/100,000 population. Shigellosis outbreaks tended to occur in the winter and were attributed to clonally related Shigella sonnei strains. Outbreaks in Bene Beraq preceded those in the other cities of Tel Aviv district, suggesting propagation of disease. In this population with highly endemic as well as superimposed outbreaks of shigellosis, short-term interventions had no lasting effect on prevention; future studies should focus on community-based programmes to avoid anticipated outbreaks.

Cancer risk after exposure to treatments for ovulation induction.

Uncertainty continues as to whether treatments for ovulation induction are associated with increased risk of cancer. The authors conducted a long-term population-based historical cohort study of parous women. A total of 15,030 women in the Jerusalem Perinatal Study who gave birth in 1974-1976 participated in a postpartum survey. Cancer incidence through 2004 was analyzed using Cox's proportional hazards models, controlling for age and other covariates. Women who used drugs to induce ovulation (n = 567) had increased risks of cancer at any site (multivariate hazard ratio (HR) = 1.36, 95% confidence interval (CI): 1.06, 1.74). An increased risk of uterine cancer was found among women treated with ovulation-inducing agents (HR = 3.39, 95% CI: 1.28, 8.97), specifically clomiphene (HR = 4.56, 95% CI: 1.56, 13.34). No association was noted between use of ovulation-inducing agents and ovarian cancer (age-adjusted HR = 0.61, 95% CI: 0.08, 4.42). Ovulation induction was associated with a borderline-significant increased risk of breast cancer (multivariate HR = 1.42, 95% CI: 0.99, 2.05). Increased risks were also observed for malignant melanoma and non-Hodgkin lymphoma. These associations appeared stronger among women who waited more than 1 year to conceive. Additional follow-up studies assessing these associations by drug type, dosage, and duration are needed.

Emergency room visit: a red-flag indicator for poor diabetes care.

AIM: To determine the association between emergency room (ER) admission and quality of diabetes care in the community. METHODS: In a nested case-control study of patients with Type 2 diabetes mellitus (DM) within a large health maintenance organization (HMO) in Israel, 919 patients who were admitted to one of West Jerusalem's ERs between 1 May and 30 June 2004 were compared with 1952 control subjects not admitted. Data on study covariates were retrieved from the HMO's computerized database and a subset of the study population was interviewed. Logistic regressions were conducted to estimate the odds ratios of being admitted according to different measures of quality of care, controlling for socio-demographic variables, co-morbidities and type of DM treatment. RESULTS: The main indices of quality of primary care that were inversely associated with visiting an ER during the study period included performance of a cholesterol test in the year prior to the index date [adjusted odds ratio (OR) 0.23, 95% confidence interval (CI) 0.19-0.29, P < 0.001], performance of glycated haemoglobin test (OR 0.26, 95% CI 0.24-0.29, P < 0.001), visiting an ophthalmologist (OR 0.47, 95% CI 0.32-0.68, P = 0.001), and recommendations to stop smoking (OR 0.10, 95% CI 0.05-0.21, P < 0.001). CONCLUSIONS: Admission to the ER can be used as an indicator for poor quality of diabetes care. There is an association between ER admission and poor quality of diabetes care.

Consanguinity and birth defects in the jerusalem perinatal study cohort.

BACKGROUND: While parental consanguinity is known to increase the risk of birth defects in offspring, it is hard to quantify this risk in populations where consanguinity is prevalent. METHODS: To support ongoing studies of cancer and of psychiatric disease, we studied relationships of consanguinity to 1,053 major birth defects in 29,815 offspring, born in 1964-1976. To adjust for confounding variables (geographic origin, social class and hospital), we constructed logistic regression models, using GEE to take into account correlations between sibs. Odds ratios (ORs) and 95% confidence limits were estimated in comparison to a reference group of offspring with grandfathers born in different countries. RESULTS: With 10.1% of offspring having consanguineous parents, the adjusted OR for major birth defect was 1.41 (1.12-1.74). Offspring of marriages between uncles-nieces, first cousins and more distant relatives showed adjusted ORs of 2.36 (0.98-5.68), 1.59 (1.22-2.07) and 1.20 (0.89-1.59) respectively. For descendents of grandfathers born in the same country, but not known to be related, the OR was 1.05 (0.91-1.21); these showed increased risk associated with ancestries in Western Asia (1.27, 1.04-1.55, p < 0.02) or Europe (1.13, 0.79-1.80). CONCLUSIONS: A strong association of consanguinity with poverty and low education points to the need to avoid exposure to environmental hazards in these families.

Twin pregnancy and the risk of schizophrenia.

BACKGROUND: Twins are exposed to intrauterine environments that differ significantly from those of singletons. These diverse environments might alter the risk for schizophrenia in twins and make it difficult to generalize from findings in twins when studying the risk of schizophrenia in the general population. Previous studies report contradictory findings on the risk for schizophrenia in twins. METHODS: We studied the incidence of schizophrenia spectrum disorders, ascertained from Israel's National Psychiatric Registry, in a cohort of 2124 twins and 87,955 singletons. These offspring were followed from their birth in 1964-76 in the Jerusalem Perinatal study. Cox proportional hazards methods were used to compare outcomes over 28-41 years, adjusting for ages of parents. RESULTS: Twins showed a relative risk [RR] of .84 relative to singletons, with a 95% confidence interval [CI] of (.51-1.4). RRs and CIs for males and females were .68 [.34-1.4] and 1.1 [.55-2.2] respectively. Twins in male-male, female-female or opposite-sex sets showed no significant variation in RRs; furthermore, first- or second-born twins did not differ significantly from each other. Siblings of twins had the same risk of schizophrenia as siblings of singletons. CONCLUSION: Twins have the same risk for schizophrenia as the general population.

Associations of socioeconomic position in childhood and young adulthood with cardiometabolic risk factors: the Jerusalem Perinatal Family Follow-Up Study.

BACKGROUND: Several stages in the life course have been identified as important to the development of cardiovascular disease. This study aimed to assess the associations of childhood and adulthood socioeconomic position (SEP) and social mobility with cardiometabolic risk factors (CMRs) later in life. METHODS: We conducted follow-up examinations of 1132 offspring, aged 32, within a population-based cohort of all births in Jerusalem from 1974 to 1976. SEP was indicated by parents' occupation and education, and adulthood SEP was based on offspring's occupation and education recorded at age 32. Linear regression models were used to investigate the associations of SEP and social mobility with CMRs. RESULTS: Childhood-occupational SEP was negatively associated with body mass index (BMI; ß=-0.29, p=0.031), fat percentage (fat%; ß=-0.58, p=0.005), insulin (ß=-0.01, p=0.031), triglycerides (ß=-0.02, p=0.024) and low-density lipoprotein cholesterol (LDL-C; ß=-1.91, p=0.015), independent of adulthood SEP. Adulthood-occupational SEP was negatively associated with waist-to-hip ratio (WHR; ß=-0.01, p=0.002), and positively with high-density lipoprotein cholesterol (HDL-C; ß=0.87, p=0.030). Results remained similar after adjustment for smoking and inactivity. Childhood-educational SEP was associated with decreased WHR and LDL-C level (p=0.0002), and adulthood-educational SEP was inversely associated with BMI (p=0.001), waist circumference (p=0.008), WHR (p=0.001) and fat% (p=0.0002) and positively associated with HDL-C (p=0.030). Additionally, social mobility (mainly upward) was shown to have adverse cardiometabolic outcomes. CONCLUSIONS: Both childhood and adulthood SEP contribute independently to CMR. The match-mismatch hypothesis may explain the elevated CMRs among participants experiencing social mobility. Identification of life-course SEP-related aspects that translate into social inequality in cardiovascular risk may facilitate efforts for improving health and for reducing disparities in cardiovascular disease.

Clinicians' attitudes toward general screening of the Ashkenazi-Jewish population for prevalent founder BRCA1/2 and LRRK2 mutations.

AIMS: Advances in genomics may eventually lead to genetic susceptibility screening of the general population, regardless of a personal or familial history of the disease in question. Yet, little is known about clinicians' attitudes toward such programs. We explored attitudes of family practitioners, medical geneticists and genetic counselors toward genetic screening of the general Ashkenazi-Jewish population for the common founder mutations in BRCA1/2 and LRRK2 genes (which increase the risk of hereditary breast/ovarian cancers and Parkinson's disease, respectively). METHODS: Participants (n = 204) completed a specially designed questionnaire, distributed by e-mail, regular mail or in-person. RESULTS: Slightly more than half (52%) were in favor of BRCA screening, while the vast majority (86%) opposed to LRRK2 screening. About two-thirds (68%) of the respondents supported pre-test genetic counseling. Attitudes were largely independent of professional background and sociodemographic characteristics, though a correlation was found with personal interest in genetic self-testing for the above genes. Adverse psychological impact and discrimination in insurance and employment were the major concerns cited by respondents with regard to screening programs. CONCLUSION: Our findings suggest that the availability of measures for prevention and/or treatment is a major factor in the attitudes of healthcare providers toward population screening for late-onset conditions.

Varicocoele among 1 300 000 Israeli adolescent males: time trends and association with body mass index.

Scarce data are available on epidemiology of varicocoele, the most common surgically correctable cause of male infertility. The objectives of this study were to evaluate the association between body mass index (BMI) and varicocoele and to assess trends in prevalence over time. We conducted a nationwide population-based long-term (1967-2010) study among 1 323 061 Israeli adolescent males using data from mandatory medical examination. BMI was grouped into underweight, normal weight, overweight and obese categories by percentiles adjusted for age in months and by further classification to five categories within normal weight. Univariable and multivariable logistic regression models were constructed, adjusting for possible confounders. Varicocoele prevalence (N = 47 398) increased during the study period from 1.6% for the 1950-1954 birth cohort to 4.6% for the 1990-1993 birth cohort, with the steepest rise in the normal weight group. Varicocoele unadjusted rates were highest (4.1%) among underweight and lowest (1.6%) among obese. In a multivariable model, adjusted for birth cohort, height, age and socio-demographic factors, we found a decreased risk for varicocoele in the overweight group [odds ratio (OR) = 0.51, 95% confidence interval (CI): 0.49, 0.54] and the obese group (OR = 0.34, 95% CI: 0.32, 0.37), compared with the normal weight group. Within the normal weight group, a monotonic inverse association between BMI percentile and varicocoele was observed, most notable among 75-84.9 percentile compared to 25-49.9 percentile (OR = 0.65, 95% CI: 0.63, 0.68). In conclusion, varicocoele is common among adolescents in Israel, and its prevalence had increased in recent decades, providing clues to direct further andrological research on the role of modern lifestyle and environment in the aetiology of varicocoele. BMI, across percentiles, was found to be monotonically inversely associated with varicocoele, thus directing research and clinical efforts.

Prospective association of serum androgens and sex hormone-binding globulin with subclinical cardiovascular disease in young adult women: the "Coronary Artery Risk Development in Young Adults" women's study.

CONTEXT: The role of endogenous androgens and SHBG in the development of cardiovascular disease in young adult women is unclear. OBJECTIVE: Our objective was to study the prospective association of serum androgens and SHBG with subclinical coronary and carotid disease among young to middle-aged women. DESIGN AND SETTING: This was an ancillary study to the Coronary Artery Risk Development in Young Adults (CARDIA) study, a population-based multicenter cohort study with 20 yr of follow-up. PARTICIPANTS: Participants included 1629 women with measurements of serum testosterone and SHBG from yr 2, 10, or 16 and subclinical disease assessment at yr 20 (ages 37-52 yr). MAIN OUTCOME MEASURES: Coronary artery calcified plaques (CAC) and carotid artery intima-media thickness (IMT) were assessed at yr 20. The IMT measure incorporated the common carotid arteries, bifurcations, and internal carotid arteries. RESULTS: SHBG (mean of yr 2, 10, and 16) was inversely associated with the presence of CAC (multivariable adjusted odds ratio for women with SHBG levels above the median = 0.59; 95% confidence interval = 0.40-0.87; P = 0.008). SHBG was also inversely associated with the highest quartile of carotid-IMT (odds ratio for women with SHBG levels in the highest quartile = 0.56; 95% confidence interval = 0.37-0.84; P for linear trend across quartiles = 0.005). No associations were observed for total or free testosterone with either CAC or IMT. CONCLUSION: SHBG levels were inversely associated with subclinical cardiovascular disease in young to middle-aged women. The extent to which low SHBG is a risk marker or has its own independent effects on atherosclerosis is yet to be determined.

Paternal age and twinning in the Jerusalem Perinatal Study.

OBJECTIVE: To investigate whether incidence of twin deliveries is related to father's age, independently of mother's age, and whether it differs for same-sex or opposite-sex twin sets. STUDY DESIGN: In a program of research on effects of paternal age, this study used data from a prospective cohort of 92,408 offspring born in Jerusalem from 1964 to 1976. Of the 91,253 deliveries in the Jerusalem Perinatal Study, 1115 were twin deliveries. The data were analyzed with General Estimate Equations to inform unconditional logistic regression. RESULTS: After controlling for maternal age, odds ratios (ORs) and 95% confidence intervals (95% CI) associated with father's ages 25-34 and 35+ were 1.3 (1.1, 1.7) and 1.5 (1.2, 2.1) respectively, compared with fathers <25 years old. The effect of maternal age was partly explained by paternal age. The ORs for opposite-sex twin sets and male-male twin sets increased slightly with paternal age, while the OR for same-sex and female-female twin decreased. CONCLUSION: Studies of twins are used to estimate effects of genes and environment in a variety of diseases. Our findings highlight the need to consider paternal as well as maternal age when analyzing data on twins to explore etiology of diseases.

Gestational diabetes and the risk of breast cancer among women in the Jerusalem Perinatal Study.

Gestational diabetes is becoming increasingly common; it is important to determine how it relates to future risk of disease. We investigated the relation of gestational diabetes to breast cancer in 37,926 women who had one or more live births in 1964-1976 for whom information had been collected on complications of pregnancy. In this cohort there were 1,626 cases of breast cancer reported to the Israel Cancer Registry before January 1, 2005 and 410 cases of gestational diabetes recorded from birth records. There were 29 cases of breast cancer among women diagnosed with gestational diabetes. Using Cox proportional hazards models to control for age and birth order at the first observed birth and other characteristics, we found that the incidence of breast cancer was increased among women diagnosed with gestational diabetes (relative rate = 1.5, 95% confidence interval 1.0-2.1). This effect was seen only among women 50 years and older (relative rate 1.7, 95% confidence interval 1.1-2.5) but not among women <50 (relative rate = 1.0, 95% confidence interval 0.5-2.1). The findings suggest that gestational diabetes may be an important early marker of breast cancer risk among post-menopausal women, but these results need to be confirmed in future studies.

A large-scale gastroenteritis outbreak associated with Norovirus in nursing homes.

An increase in gastroenteritis outbreaks due to Norovirus has been reported worldwide. We investigated a large-scale outbreak affecting 246 residents and 33 staff members in six nursing homes in the Tel-Aviv district, Israel, during 3 weeks in 2002. Person-to-person spread was noticed in all nursing homes. The spread of disease could not be attributed to social interactions. Among the elderly residents, the hospitalization rate was 10.2% and the case-fatality rate was 2.0%. Bacteriological cultures were negative. Overall, 7 out of 15 stool specimens were positive for Norovirus by RT-PCR. All were sequenced and found to be 90% identical. The characteristics of this outbreak and the RT-PCR results suggest that illness was caused by Norovirus. Due to the high case-fatality rate of Norovirus gastroenteritis, there should be a high index of suspicion when encountering a gastroenteritis outbreak among the elderly. This will enable prompt action to stop the spread of illness.