ABSTRACT. Objective. To determine whether there was a correlation between the incidence of infantile hypertrophic pyloric stenosis (IHPS) and the incidence of sudden infant death syndrome (SIDS) during the period 1970 to 1997 and to discuss different causative factors that could be influencing the changing trend in incidence.Methods. We compared the incidence of IHPS in the Stockholm Health Care Region with the incidence of SIDS in Sweden each year between 1970 and 1997. First, the relation was assessed by calculation of a correlation coefficient; second, the relative linear decrease was estimated for the time period 1990 to 1997.Results. The incidence of IHPS increased steadily during the 1970s, from 0.5 per 1000 live births in 1970 to 2.7 in 1979. During the 1980s, the average incidence was 2.8. During the 1990s, there was a significant decrease in the number of IHPS cases in Stockholm. The incidence rate of IHPS parallels the incidence of SIDS during the study period (r ‫؍‬ 0.58). The incidence of SIDS dropped after the risk-reduction campaign in the beginning of the 1990s, which recommended that infants sleep on their back. We could not identify any other changes of behavioral risk factors in early exposures that could explain the temporal trends.Conclusions. The statistical findings suggest that IHPS and SIDS have causative factors in common. We suggest that prone sleeping is one of those factors. Pediatrics 2001;108(4). URL: http://www.pediatrics.org/ cgi/content/full/108/4/e70; infantile hypertrophic pyloric stenosis, sudden infant death syndrome, epidemiology.ABBREVIATIONS. IHPS, infantile hypertrophic pyloric stenosis; SIDS, sudden infant death syndrome; CI, confidence interval. I nfantile hypertrophic pyloric stenosis (IHPS) is a hypertrophy of the pyloric circular muscle sphincter of unknown cause. IHPS is categorized as a congenital malformation, but most often the muscular hypertrophy is absent at birth. 1 The hypertrophy develops gradually until it obstructs the gastric outlet, resulting in postprandial nonbilious projectile vomiting. The onset of clinical symptoms usually occurs at 2 to 4 weeks of age. IHPS is effectively treated with surgical pyloromyotomy, which permanently relieves the obstruction.The prevalence of a family history of IHPS is 13% to 14%, and the sex ratio (male:female) is 4 to 4.5:1. [1][2][3][4][5][6][7] The increased risk among relatives and the sex distribution strongly suggest that genetic factors are important. The inheritance pattern cannot be explained by Mendelian genetics; instead, IHPS has served as a prototype for the multifactorial threshold model of inheritance. 8 IHPS has been reported to be associated with a number of different exposures. Apart from male sex and white ethnicity, the results from different studies have been contradictory. 6 Feeding habits, maternal stress, high birth weight, and primogeniture are some exposures that have been implicated. 9 -13 A recent report suggested oral erythromycin intake as a possible risk factor for IHPS. 14 Erythromycin in...

Objective: To assess the risk of type 2 diabetes (T2D) in women with polycystic ovary syndrome (PCOS) in relation to body mass index (BMI) and the hyperandrogenic (HA) PCOS phenotype. Design: Population-based cohort study. Setting: Data from six Swedish national registers, with participants being followed for a maximum of 19 years. Patient(s): All women with an International Statistical Classification of Diseases and Related Health Problems, version 10, diagnosis of PCOS, androgen excess, or anovulatory infertility born between 1950 and 1999 (n ¼ 52,535) were identified in the Patient Register. The HA PCOS phenotype was defined by two filled prescriptions for anti-androgenic drugs. For each woman with PCOS, five control women (n ¼ 254,624) were randomly chosen from the Total Population Register, matched for age and geographic area. Intervention(s): No interventions were performed. Main Outcome Measure(s): International Statistical Classification of Diseases and Related Health Problems, version 10, diagnosis of T2D or prescription of antidiabetic treatment other than metformin.Result(s): The cumulative incidence rates of T2D were 1.3%, 4.4%, and 14.2% in controls (non-PCOS women) and women with normoandrogenic (NA) and HA PCOS, respectively. After adjustment for BMI, women with PCOS had a twofold higher rate of T2D than non-PCOS women (adjusted hazard ratio, 2.52 [95% confidence interval, 2.15-2.96]). Women with HA PCOS had a higher rate of T2D than those with NA PCOS (adjusted hazard ratio, 3.86 [95% confidence interval, 3.16-4.72]). Conclusion(s):Polycystic ovary syndrome is an independent risk factor for T2D, even after adjustment for BMI. Women with the HA PCOS phenotype face an even higher risk of T2D than those with the NA PCOS phenotype.

STUDY QUESTION Does the long-term fecundity of women with polycystic ovary syndrome (PCOS) differ from those without PCOS? SUMMARY ANSWER Cumulative probability of childbirth is similar between women with and without PCOS. WHAT IS KNOWN ALREADY PCOS is the main cause of anovulatory infertility in women after menarche. Previous studies indirectly suggest that fecundity in women with PCOS over the longer term may not be lower than in women without PCOS. STUDY DESIGN, SIZE, DURATION This is a population-based study using four linked Swedish national registries. A total of 45 395 women with PCOS and 217 049 non-PCOS women were included. Follow-up began at the age of 18 years and continued for a maximum of 26 years, from 1989 to the end of 2015. Childbirth was the main outcome, as identified from the Medical Birth Register. PARTICIPANTS/MATERIALS, SETTING, METHODS All women born between 1971 and 1997 who were identified with a PCOS diagnosis in the Swedish Patient Registry between 1 January 2001 and 31 December 2016 were included in the study population. Five controls per women with PCOS were randomly drawn from the Total Population Registry. The control women were born in the same year and living in the same municipality as the patient. The fecundity ratio (FR) was calculated by clustered Cox regression using a robust variance, adjusted for maternal birth period, country of birth and level of education. MAIN RESULTS AND THE ROLE OF CHANCE The cumulative probability of childbirth was 80.2% (95% CI, 79.5–80.9%) in women with PCOS and 78.2% (95% CI, 77.9–78.5%) in those without PCOS. Adjusted FR was 0.81 (95% CI, 0.80–0.82) for first childbirth and 0.58 (95% CI, 0.57–0.60) for first childbirth following a spontaneous pregnancy. The FR for second childbirth was 0.79 (95% CI, 0.77–0.80). Women with PCOS had more than one child less frequently than the comparison group. Within the PCOS group, early age at diagnosis, later birth year, Nordic country of origin and low educational level positively influenced the FR. LIMITATIONS, REASONS FOR CAUTION Results are not adjusted for BMI, and time from intention to conceive to first childbirth could not be captured. Data on pregnancies, miscarriages or abortions and fertility treatment are unknown for women who did not give birth during the study period. Women with PCOS who did not seek medical assistance might have been incorrectly classified as not having the disease. Such misclassification would lead to an underestimation of the true association between PCOS and outcomes. WIDER IMPLICATIONS OF THE FINDINGS While cumulative probability of childbirth is similar between groups, women with PCOS need longer time to achieve their first childbirth. Women with PCOS have a lower FR and give birth to fewer children per woman than women without PCOS. Early diagnosis of and information about PCOS may improve affected women’s reproductive potential. STUDY FUNDING/COMPETING INTEREST(S) This study was funded by the Swedish Society of Medicine. Inger Sundström Poromaa has, over the past 3 years, received compensation as a consultant and lecturer for Bayer Schering Pharma, MSD, Gedeon Richter, Peptonics and Lundbeck A/S. The other authors declare no competing interests.

Background The Clinical Frailty Scale (CFS) is frequently used to measure frailty in critically ill adults. There is wide variation in the approach to analysing the relationship between the CFS score and mortality after admission to the ICU. This study aimed to evaluate the influence of modelling approach on the association between the CFS score and short-term mortality and quantify the prognostic value of frailty in this context. Methods We analysed data from two multicentre prospective cohort studies which enrolled intensive care unit patients ≥ 80 years old in 26 countries. The primary outcome was mortality within 30-days from admission to the ICU. Logistic regression models for both ICU and 30-day mortality included the CFS score as either a categorical, continuous or dichotomous variable and were adjusted for patient’s age, sex, reason for admission to the ICU, and admission Sequential Organ Failure Assessment score. Results The median age in the sample of 7487 consecutive patients was 84 years (IQR 81–87). The highest fraction of new prognostic information from frailty in the context of 30-day mortality was observed when the CFS score was treated as either a categorical variable using all original levels of frailty or a nonlinear continuous variable and was equal to 9% using these modelling approaches (p < 0.001). The relationship between the CFS score and mortality was nonlinear (p < 0.01). Conclusion Knowledge about a patient’s frailty status adds a substantial amount of new prognostic information at the moment of admission to the ICU. Arbitrary simplification of the CFS score into fewer groups than originally intended leads to a loss of information and should be avoided. Trial registration NCT03134807 (VIP1), NCT03370692 (VIP2)

STUDY QUESTION Is anti-androgen treatment during adolescence associated with an improved probability of spontaneous conception leading to childbirth in women with polycystic ovary syndrome (PCOS)? SUMMARY ANSWER Early initiation of anti-androgen treatment is associated with an increased probability of childbirth after spontaneous conception among women with PCOS. WHAT IS KNOWN ALREADY PCOS is the most common endocrinopathy affecting women of reproductive age. Hyperandrogenism and menstrual irregularities associated with PCOS typically emerge in early adolescence. Previous work indicates that diagnosis at an earlier age (&lt;25 years) is associated with higher fecundity compared to a later diagnosis. STUDY DESIGN, SIZE, DURATION This population-based study utilized five linked Swedish national registries. A total of 15 106 women with PCOS and 73 786 control women were included. Women were followed from when they turned 18 years of age until the end of 2015, leading to a maximum follow-up of 10 years. First childbirth after spontaneous conception was the main outcome, as identified from the Medical Birth Registry. PARTICIPANTS/MATERIALS, SETTING, METHODS Participants included all women born between 1987 and 1996 with a diagnosis of PCOS in the Swedish Patient Registry and randomly selected non-PCOS controls (ratio 1:5). Information on anti-androgenic treatment was retrieved from the Swedish Prescribed Drug Registry with the use of Anatomic Therapeutic Chemical (ATC) codes. Women with PCOS who were not treated with any anti-androgenic medication were regarded as normo-androgenic, while those treated were regarded as hyperandrogenic. Women were further classified as being mildly hyperandrogenic if they received anti-androgenic combined oral contraceptive (aaCOC) monotherapy, or severely hyperandrogenic if they received other anti-androgens with or without aaCOCs. Early and late users comprised women with PCOS who started anti-androgenic treatment initiated either during adolescence (≤ 18 years of age) or after adolescence (&gt;18 years), respectively. The probability of first childbirth after spontaneous conception was analyzed with the use of Kaplan–Meier hazard curve. The fecundity rate (FR) and 95% confidence interval for the time to first childbirth that were conceived spontaneously were calculated using Cox proportional hazards regression models, with adjustment for obesity, birth year, country of birth and education level. MAIN RESULTS AND THE ROLE OF CHANCE The probability of childbirth after spontaneous conception in the PCOS group compared to non-PCOS controls was 11% lower among normo-androgenic (adjusted FR 0.68 (95% CI 0.64–0.72)), and 40% lower among hyperandrogenic women with PCOS (adjusted FR 0.53 (95% CI 0.50–0.57)). FR was lowest among severely hyperandrogenic women with PCOS compared to normo-androgenic women with PCOS (adjusted FR 0.60 (95% CI 0.52–0.69)), followed by mildly hyperandrogenic women with PCOS (adjusted FR 0.84 (95% CI 0.77–0.93)). Compared to early anti-androgenic treatment users, late users exhibited a lower probability of childbirth after spontaneous conception (adjusted FR 0.79 (95% CI 0.68–0.92)). LIMITATIONS, REASONS FOR CAUTION We lacked direct information on the intention to conceive and the androgenic biochemical status of the PCOS participants, applying instead the use of anti-androgenic medications as a proxy of hyperandrogenism. The duration of anti-androgenic treatment utilized is not known, only the age at prescription. Results are not adjusted for BMI, but for obesity diagnosis. The period of follow-up (10 years) was restricted by the need to include only those women for whom data were available on the dispensing of medications during adolescence (born between 1987 and 1996). Women with PCOS who did not seek medical assistance might have been incorrectly classified as not having the disease. Such misclassification would lead to an underestimation of the true association between PCOS and outcomes. WIDER IMPLICATIONS OF THE FINDINGS Early initiation of anti-androgen treatment is associated with better spontaneous fertility rate. These findings support the need for future interventional randomized prospective studies investigating critical windows of anti-androgen treatment. STUDY FUNDING/COMPETING INTEREST(S) This study was funded by the Health Research Council of New Zealand (18-671), the Swedish Society of Medicine and the Uppsala University Hospital. Evangelia Elenis has, over the past year, received lecture fee from Gedeon Richter outside the submitted work. Inger Sundström Poromaa has, over the past 3 years, received compensation as a consultant and lecturer for Bayer Schering Pharma, MSD, Gedeon Richter, Peptonics and Lundbeck A/S. The other authors declare no competing interests. TRIAL REGISTRATION NUMBER N/A