Factors associated with disease control failure in acromegaly patients treated with pegvisomant: an ACROSTUDY analysis.

Purpose: The aim of this study was to examine the probability of achieving acromegaly disease control according to several patient-, disease- and treatment-related factors longitudinally. Methods: We analyzed data from ACROSTUDY, an open-label, noninterventional, post-marketing safety surveillance study conducted in 15 countries. A total of 1546 patients with acromegaly and treated with pegvisomant, with available information on baseline IGF-1 level, were included. Factors influencing IGF-1 control were assessed up to 10 years of follow-up by mixed-effects logistic regression models, taking into account changing values of covariates at baseline and at yearly visits. Twenty-eight anthropometric, clinical and treatment-related covariates were examined through univariate and multivariate analyses. We tested whether the probability of non-control was different than 0.50 (50%) by computing effect sizes (ES) and the corresponding 95% CI. Results: Univariate analysis showed that age <40 years, normal or overweight, baseline IGF-1 <300 µg/L or ranged between 300 and 500 µg/L, and all pegvisomant dose <20 mg/day were associated with a lower probability of acromegaly uncontrol. Consistently, in multivariate analyses, the probability of uncontrolled acromegaly was influenced by baseline IGF-1 value: patients with IGF-1 <300 µg/L had the lowest risk of un-controlled acromegaly (ES = 0.29, 95% CI: 0.23-0.36). The probability of acromegaly uncontrol was also lower for values 300-500 µg/L (ES = 0.37, 95% CI: 0.32-0.43), while it was higher for baseline IGF-1 values ≥700 µg/L (ES = 0.58, 95% CI: 0.53-0.64). Conclusion: Baseline IGF-l levels were a good predictor factor for long-term acromegaly control. On the contrary, our data did not support a role of age, sex, BMI and pegvisomant dose as predictors of long-term control of acromegaly. Significance statement: Among factors that could influence and predict the efficacy of pegvisomant therapy in controlling acromegaly, a central role of baseline IGF-1 values on the probability of achieving a biochemical control of acromegaly during the treatment with pegvisomant was identified, in a real-life setting.

Real-world long-term effects on blood pressure and other cardiovascular risk factors for patients in digital therapeutics.

PURPOSE: Hypertension is a leading causeof premature death worldwide and a major public health problem. This study investigated the long-term effects (>1 year) of digital hypertension monitoring by home blood pressure (HBP) measurements in combination with individualized remote treatment via a Swedish Digital Therapeutics platform in a large patient population. METHODS: The primary endpoint, HBP, and exploratory endpoints, BMI, alcohol consumption, stress level, physical activity, and smoking, were assessed every 3 months for 540 and 360 days, respectively, in 7752 Swedish primary hypertension patients. Patients received individualized medical treatments and lifestyle advice via asynchronous text-based communication in an app. Changes from baseline in endpoints were calculated for the whole population and for subgroups defined by baseline SBP ≥135 (high SBP), 125-135 (suboptimal SBP), 115-125 (optimal SBP), and <115 mmHg (low SBP). RESULTS: After 360 days of treatment, the whole population showed a significant increase of 57% (from 37 to 58%) in the proportion of patients with controlled SBP (i.e. SBP of 115-135 mmHg). The largest reduction in SBP of 13.8 mmHg was observed for the high SBP subgroup, whereas for the low SBP subgroup, SBP increased by 13.4 mmHg. BP improved most in the first three months, and for both the high and low BP subgroups, the improvement continued during the 540-day study period. Significant beneficial changes were also observed for some exploratory endpoints including BMI and smoking. CONCLUSIONS: In conclusion, the digital therapeutics platform was associated with significant improvement in BP control and associated risk factors, which were maintained over a longer period.

Safety and Efficacy of Pediatric Growth Hormone Therapy: Results From the Full KIGS Cohort.

CONTEXT: The Kabi/Pfizer International Growth Database (KIGS) is a large, international database (1987-2012) of children treated with recombinant human growth hormone (rhGH) in real-world settings. OBJECTIVE: This work aimed to evaluate the safety and efficacy of rhGH from the full KIGS cohort. METHODS: Data were collected by investigators from children with growth disorders treated with rhGH (Genotropin [somatropin]; Pfizer). Safety was evaluated in all treated patients, and efficacy in those treated for 1 year or more. A subgroup included patients treated for 5 years or more (≥ 2 years prepubertal) who had reached near-adult height (NAH). Main outcomes included adverse events (AEs), serious AEs (SAEs), and height growth. RESULTS: The full KIGS cohort (N = 83 803 [58% male]) was treated for idiopathic GH deficiency (IGHD; 46.9%), organic GHD (10.0%), small for gestational age (SGA; 9.5%), Turner syndrome (TS; 9.2%), idiopathic short stature (ISS; 8.2%), and others (16.2%). Median rhGH treatment duration was 2.7 years and observation 3.1 years. SAEs occurred in 3.7% of patients and death in 0.4%. The most common SAEs were recurrence of craniopharyngioma (n = 151), neoplasm (n = 99), and cancer (n = 91); and scoliosis (n = 91). Median first-year delta height-SD score (SDS) (Prader) in prepubertal patients was 0.66 (IGHD), 0.55 (ISS), 0.58 (TS), and 0.71 (SGA). Median gains in NAH-SDS were 1.79 (IGHD), 1.37 (ISS), and 1.34 (SGA) for boys, and 2.07 (IGHD), 1.62 (ISS), 1.07 (TS), and 1.57 (SGA) for girls. CONCLUSION: Data from KIGS, the largest and longest running international database of rhGH-treated children, show that rhGH is safe and increases short-term height gain and adult height across GHD and non-GHD conditions.

A plain language summary of the likelihood of symptom relief for patients taking fesoterodine for overactive bladder.

WHAT IS THIS SUMMARY ABOUT?: This is a summary of a study originally published in Neurourology and Urodynamics. Overactive bladder is a medical condition that causes an urgent need to urinate, which can cause accidental urination. Fesoterodine is a medication used to treat overactive bladder. Because we don't know how likely it is that an individual patient will achieve a level of improvement in their overactive bladder symptoms, researchers analyzed results of 6 studies of patients with overactive bladder who were treated with fesoterodine. WHAT WERE THE RESULTS?: Although complete resolution of all symptoms was rare with fesoterodine treatment, a resolution of accidental urination was more common, which is the most important treatment goal for many patients. After taking fesoterodine, episodes of accidental urination were more likely to be reduced or completely absent than episodes of an urgent need to urinate. WHAT DO THE RESULTS OF THE STUDY MEAN?: These results can help patients with overactive bladder understand their own chances of treatment success with fesoterodine and can help doctors support their patients on what to expect regarding their specific symptoms and concerns. ▪Toviaz (fesoterodine) is approved to treat the condition that is discussed in this summary. Approval varies from country to country; please check with your local health provider for more details. ▪This summary reports the combined results of 6 studies. The results of individual studies may vary from the combined study results presented here. Individuals should make treatment decisions based on all available evidence. ClinicalTrials.gov NCT number: NCT01302054, NCT01302067, NCT00444925, NCT00611026, NCT00220363, and NCT00138723.

Pituitary function and the response to GH therapy in patients with Langerhans cell histiocytosis: analysis of the KIMS database.

Objective: To analyze the effectiveness and safety of growth hormone (GH) replacement treatment in adult patients with Langerhans cell histiocytosis (LCH) and GH deficiency (GHD) enrolled in KIMS (Pfizer International Metabolic Database). Patients and methods: Patients with LCH and GHD were studied at baseline and some of them after 1 year of GH treatment. The effectiveness of GH is presented as change after 1 year of treatment (mean, 95% CI). The LCH population was compared to two other groups of patients enrolled in KIMS, granulomatous and lymphocytic hypophysitis. Results: At baseline, 81 adults with LCH (27 with childhood onset, 56% females), mean age at GHD onset of 29 (15) years were studied. Diabetes insipidus was diagnosed in 86% of patients. Analysis of 1 year of GH treatment was possible in 37 patients. One-year cross-sectional values for the GH dose were 0.39 (s.d.± 0.21) mg and -0.5 (-1.2 to 0.2) for insulin-like growth factor-1 s.d. Total cholesterol decreased 0.9 (-1.5 to -0.3 (mmol/L); P < 0.05); AGHDA-QoL-score (n = 20) was improved by 2.8 points (-5.6 to 0.0; P < 0.05), while mean BMI increased 0.6 ± 3 kg/m2 (95% CI: -0.2 to 1.4). All these effects did not differ from the two other groups after adjusting for age, gender, and baseline values. In 20 of 77 patients included in the safety analysis, 36 serious adverse events were reported during 435 patient-years (82.8/1000); no new safety signals were reported. Conclusion: After 1 year of GH treatment in patients with LCH, metabolic variables and quality of life improved, with no new safety signals.

Long-term Safety of Growth Hormone in Adults With Growth Hormone Deficiency: Overview of 15 809 GH-Treated Patients.

CONTEXT: Data on long-term safety of growth hormone (GH) replacement in adults with GH deficiency (GHD) are needed. OBJECTIVE: We aimed to evaluate the safety of GH in the full KIMS (Pfizer International Metabolic Database) cohort. METHODS: The worldwide, observational KIMS study included adults and adolescents with confirmed GHD. Patients were treated with GH (Genotropin [somatropin]; Pfizer, NY) and followed through routine clinical practice. Adverse events (AEs) and clinical characteristics (eg, lipid profile, glucose) were collected. RESULTS: A cohort of 15 809 GH-treated patients were analyzed (mean follow-up of 5.3 years). AEs were reported in 51.2% of patients (treatment-related in 18.8%). Crude AE rate was higher in patients who were older, had GHD due to pituitary/hypothalamic tumors, or adult-onset GHD. AE rate analysis adjusted for age, gender, etiology, and follow-up time showed no correlation with GH dose. A total of 606 deaths (3.8%) were reported (146 by neoplasms, 71 by cardiac/vascular disorders, 48 by cerebrovascular disorders). Overall, de novo cancer incidence was comparable to that in the general population (standard incidence ratio 0.92; 95% CI, 0.83-1.01). De novo cancer risk was significantly lower in patients with idiopathic/congenital GHD (0.64; 0.43-0.91), but similar in those with pituitary/hypothalamic tumors or other etiologies versus the general population. Neither adult-onset nor childhood-onset GHD was associated with increased de novo cancer risks. Neutral effects were observed in lipids/fasting blood glucose levels. CONCLUSION: These final KIMS cohort data support the safety of long-term GH replacement in adults with GHD as prescribed in routine clinical practice.

A novel index to assess low energy fracture risks in patients prescribed antiepileptic drugs.

OBJECTIVE: To develop an index assessing the risks of low energy fractures (LEF) in patients prescribed antiepileptic drugs (AED) by exploring five previously suggested risk factors; age, gender, AED-type, epilepsy diagnosis and BMI. METHODS: In a population-based retrospective open cohort study we used real world data from the Electronic Health Register (EHR) in Region Kalmar County, Sweden. 23 209 patients prescribed AEDs at any time from January 2008 to November 2018 and 23 281 matching controls were followed from first registration in the EHR until the first documented LEF, disenrollment (or death) or until the end of the study period, whichever came first. Risks of LEF measured as hazard rate ratios in relation to the suggested risk factors and in comparison to matched controls were analyzed using Cox regression. The index was developed using a linear combination of the statistically significant variables multiplied by the corresponding regression coefficients. RESULTS: Data from 23 209 patients prescribed AEDs and 2084 documented LEFs during a follow-up time of more than 10 years resulted in the Kalmar Epilepsy Fracture Risk Index (KEFRI). KEFRI = Age-category x (1.18) + Gender x (-0.51) + AED-type x (0.29) + Epilepsy diagnosis-category x (0.31) + BMI-category x (-0.35). All five previously suggested risk factors were confirmed. Women aged 75 years and older treated with an inducing AED against epilepsy and BMIs of 25 kg/m2 or below had 48 times higher LEF rates compared to men aged 50 years or younger, treated with a non-inducing AED for a condition other than epilepsy and BMIs above 25 kg/m2. CONCLUSION: The KEFRI is the first weighted multifactorial assessment tool estimating risks of LEF in patients prescribed AEDs and could serve as a feasible guide within clinical practice.

What are the chances of improvement or cure from overactive bladder? A pooled responder analysis of efficacy and treatment emergent adverse events following treatment with fesoterodine.

AIM: This study describes patients with different degrees and combinations of symptom resolution in response to fesoterodine exposure to aid physicians in counselling patients with overactive bladder (OAB) on the likelihood of treatment success. METHODS: Data came from 12-week fixed-dose studies of fesoterodine. The proportions of patients experiencing symptom resolution and change in patient-reported outcome measures (PROM) at 4, 8, and 12 weeks were calculated. Treatment-emergent adverse events (TEAE) were reported according to response in urinary urgency episodes (UUE). The relationship between PROM and response was examined. RESULTS: Out of 6689 patients, 81.6% female, urgency urinary incontinence (UUI) episodes/24 h were more responsive to fesoterodine than UUE; with roughly 50% of patients reporting a 50% reduction and fewer than 10% reporting absence of UUE at 12 weeks compared to approximately 40%-50% reporting absence of UUI. TEAE was numerically lower in patients with greater response. There was a statistically significant relationship between improvement in urinary urgency and associated change in OAB-q symptom bother scores, r = 0.54, p < 0.001. At Week 4, 64.0%-76.7% of patients who had achieved a significant change in Patient Perception of Bladder Condition (PPBC) had a 50% reduction in UUI. At Week 12 this proportion was between 80% and 87.9%, with those being exposed to fesoterodine treatment reporting response in PPBC at numerically higher rates. CONCLUSION: These data provide clinicians with information from which they may usefully communicate the likelihood of symptom resolution in response to pharmacotherapy for OAB and answer a key clinical question posed by many care providers. Roughly ⅓ of fesoterodine treated patients reported a 50% reduction urgency and ¾ reported 50% resolution of incontinence at 12 weeks. Total resolution of all symptoms was seldom achieved.

Modestly degraded microarchitecture and high serum levels of osteopontin in Swedish females with anorexia nervosa.

PURPOSE: Adult women with long-time anorexia nervosa (AN) are believed to have osteopenia (T-score ≤ 1.0) in 93 % and osteoporosis (T-score ≤ 2.5) in 38 %. Bone microarchitecture assessed by Trabecular Bone Score (TBS) predicts osteoporotic fractures. Our aim was to evaluate the microarchitecture in adult females with AN by determining TBS and to identify factors potentially associated with TBS, such as bone turnover markers. METHODS: 20 female patients with AN (DSM IV), aged 27.8 ± 4.4 years, BMI 16.6 ± 0.6 kg/m2 and duration of illness of 8.5 ± 5 years had previously been evaluated with dual-energy X-ray absorptiometry (DXA). TBS measurements were now obtained, using iNsight software, from spinal DXA images. Serum levels of bone turnover markers were determined in patients and healthy normal-weight controls. RESULTS: Compared to controls serum values of osteopontin were higher (p = 0.009). BMD in patients with AN was reduced by at least 1.0 SD at one or more skeletal sites in 65 % of patients and by at least 2.5 SD in 20 %. Only one of the patients (5%) had suffered a fracture. TBS (mean 1.35 ± 0.06; median 1.36 (1.23-1.44) was in the lower normal range (≥ 1.35). 40 % of patients showed partially (> 1.20 and < 1.35) but none showed a fully degraded micro-architecture. CONCLUSIONS: In Swedish AN patients we found a low reduction of BMD and fracture history. The bone microarchitecture, evaluated for the first time for this group by TBS, was only modestly compromised, and to a lesser extent than expected for this group of patients with AN. LEVEL OF EVIDENCE: Level V; cross-sectional descriptive study.

Response to GH Treatment After Radiation Therapy Depends on Location of Irradiation.

OBJECTIVES: Cancer survivors with GH deficiency (GHD) receive GH therapy (GHT) after 1+ year observation to ensure stable tumor status/resolution. HYPOTHESIS: Radiation therapy (RT) to brain, spine, or extremities alters growth response to GHT. AIM: Identify differences in growth response to GHT according to type/location of RT. METHODS: The Pfizer International Growth Database was searched for cancer survivors on GHT for ≥5 years. Patient data, grouped by tumor type, were analyzed for therapy (surgery, chemotherapy, RT of the focal central nervous system, cranial, craniospinal, or total body irradiation [TBI] as part of bone marrow transplantation), sex, peak stimulated GH, age at GHT start, and duration from RT to GHT start. Kruskal-Wallis test and quantile regression modeling were performed. RESULTS: Of 1149 GHD survivors on GHT for ≥5 years (male 733; median age 8.4 years; GH peak 2.8 ng/mL), 431 had craniopharyngioma (251, cranial RT), 224 medulloblastoma (craniospinal RT), 134 leukemia (72 TBI), and 360 other tumors. Median age differed by tumor group (P < 0.001). Five-year delta height SD score (SDS) (5-year ∆HtSDS; median [10th-90th percentile]) was greatest for craniopharyngioma, 1.6 (0.3-3.0); for medulloblastoma, 5-year ∆HtSDS 0.9 (0.0-1.9); for leukemia 5-year ∆HtSDS, after TBI (0.3, 0-0.7) versus without RT (0.5, 0-0.9), direct comparison P < 0.001. Adverse events included 40 treatment-related, but none unexpected. CONCLUSIONS: TBI for leukemia had significant impact on growth response to GHT. Medulloblastoma survivors had intermediate GHT response, whereas craniopharyngioma cranial RT did not alter GHT response. Both craniospinal and epiphyseal irradiation negatively affect growth response to GH therapy compared with only cranial RT or no RT.

Near-Adult Height After Growth Hormone Treatment in Children Born Prematurely-Data From KIGS.

CONTEXT: Children born prematurely have been treated with growth hormone (GH), and a significant improvement in height during the first years of treatment has been described. OBJECTIVE: To evaluate the influence of prematurity on near-adult height (NAH) after GH treatment. DESIGN: KIGS (Pfizer International Growth Database) was queried for children born preterm treated with GH. SETTING: KIGS database. PATIENTS: A total of 586 children short in stature born preterm with various GH status and with available gestational age (GA), birth weight, and NAH, all treated with GH. INTERVENTION: GH treatment. MAIN OUTCOME MEASURE: NAH. RESULTS: Values were expressed as median. From the 586 children included, 482 born appropriate for GA (AGA; median age 8.26 years) and 104 born small for gestational age (SGA) (median age 8.54 years); 66.6% of preterm AGA had GH peak < 7 µg/L during a provocation test, whereas only 8.6% of preterm SGA. Change in height standard deviation scores (SDS) from GH start to NAH after 8.04 years of GH treatment was 1.82 in preterm AGA. Respective values were 7.08 years and 1.08 SDS for preterm SGA (P < 0.001); 57% of the variability of the growth response to NAH could be explained, and the distance to parental height was the strongest predictor. No significant changes in height SDS were observed from puberty start to NAH. No correlation was found with GA. GH treatment was well tolerated. CONCLUSION: GH treatment resulted in significant improvement in height in children born preterm, particularly during prepubertal years and for those with GH deficiency. The degree of prematurity did not influence the growth response.

Adult height prediction by bone age determination in children with isolated growth hormone deficiency.

BACKGROUND: The precision of adult height prediction by bone age determination in children with idiopathic growth hormone deficiency (IGHD) is unknown. METHODS: The near adult height (NAH) of patients with IGHD in the KIGS database was compared retrospectively to adult height prediction calculated by the Bayley-Pinneau (BP) prediction based on bone age by Greulich-Pyle (GP) in 315 children and based on the Tanner-Whitehouse 2 (TW2) method in 121 children. Multiple linear regression analyses adjusted for age at GH start, age at puberty, mean dose and years of of GH treatment, and maximum GH peak in stimulation test were calculated. RESULTS: The mean underestimation of adult height based on the BP method was at baseline 4.1 ± 0.7 cm in girls and 6.1 ± 0.6 cm in boys, at 1 year of GH treatment 2.5 ± 0.5 cm in girls and 0.9 ± 0.4 cm in boys, while at last bone age determination adult height was overestimated in mean by 0.4 ± 0.6 cm in girls and 3.8 ± 0.5 cm in boys. The mean underestimation of adult height based on the TW2 method was at baseline 5.3 ± 2.0 cm in girls and 7.9 ± 0.8 cm in boys, at 1 year of GH treatment adult height was overestimated in girls 0.1 ± 0.6 cm in girls and underestimated 4.1 ± 0.4 cm in boys, while at last bone age determination adult height was overestimated in mean by 3.1 ± 1.5 cm in girls and 3.6 ± 0.8 cm in boys. CONCLUSIONS: Height prediction by BP and TW2 at onset of GH treatment underestimates adult height in prepubertal IGHD children, while in mean 6 years after onset of GH treatment these prediction methods overestimated adult height.

A pilot study of hypertension management using a telemedicine treatment approach.

We recruited 78 men and 94 women to investigate if the proportion of subjects with well-controlled home blood pressure levels could be increased when treatment was guided by smartphone-based telemonitoring. All patients were prescribed one to three antihypertensive drugs. The Accumbo smartphone telemonitoring application was downloaded to the Iphones of the participants and home blood pressure information was gathered from semi-automatic oscillometric blood pressure-recorders by Bluetooth. The study physician adjusted the medications based on home blood pressure for 3 months. home blood pressure was controlled (<135/<85 mmHg) in 55 participants at baseline and in 56 subjects after 3 months (Chi-square P = 0.91). The 117 patients with initially uncontrolled home blood pressure had a drop in home blood pressure (from 138.0 ± 9.0/91.3 ± 6.5 mmHg to 133.4 ± 8.0/88.6 ± 6.1 mmHg, P < 0.001) and prescribed antihypertensive drugs increased from 1.71 ± 0.94/day to 2.00 ± 0.92/day, P < 0.0001. Thus, while the proportion of participants with controlled home blood pressure remained unchanged, the home blood pressure levels were lowered in participants who had uncontrolled home blood pressure at study start.

Near Adult Height in Girls with Turner Syndrome Treated with Growth Hormone Following Either Induced or Spontaneous Puberty.

OBJECTIVE: To understand whether spontaneous vs induced puberty and the type and route of estrogen influence the height of girls with Turner syndrome on growth hormone (GH). STUDY DESIGN: Search of an international database of children treated with GH revealed 772 girls with Turner syndrome followed from GH initiation to near adult height. Data from girls with sustained spontaneous puberty (n = 145) were compared with those requiring estrogens for induction or maintenance of puberty (n = 627). RESULTS: At GH start, mean age (7.5 vs 7.9 years), weight (-1.7 vs -1.7 SDS), and body mass index (0.2 SDS vs 0.1 SDS) were similar for girls with spontaneous puberty and with induced puberty. Although those girls with spontaneous puberty were shorter than those with induced puberty, when midparental height was taken into consideration, starting heights in both groups averaged -2.8 SDS. Both groups received approximately 0.3 mg/kg/week of GH. Girls with spontaneous puberty initiated puberty and reached near adult height earlier than girls with induced puberty (12.6 ± 1.8 years vs 13.4 ± 1.4 years and 16.0 ± 1.3 years vs 16.9 ± 1.4 years, respectively). Although girls with spontaneous puberty grew more in the first year of GH therapy and between the onset of puberty and near adult height (11.0 cm vs 9.3 cm), height SDS at near adult height and the length of time in puberty before reaching near adult height were comparable. A 45,X karyotype was detected in 22.1% of girls with spontaneous puberty and in 58.4% of girls with induced puberty. Patients receiving transdermal estrogens did not grow better than those on oral estrogens. Adverse event reporting was comparable between groups. CONCLUSIONS: Girls with Turner syndrome with spontaneous puberty tended to grow better in response to GH than girls with induced puberty, but not enough to produce a difference in height SDS at near adult height.

Adherence to risk management guidelines for drugs which cause vitamin D deficiency - big data from the Swedish health system.

PURPOSE: Several medications are known to cause vitamin D deficiency. The aim of this study is to describe vitamin D testing and supplementation in patients using these "risk medications", thereby assessing adherence to medical guidelines. PATIENTS AND METHODS: A database with electronic health records for the population in a Swedish County (≈240,000 inhabitants) was screened for patients prescribed the pre-defined "risk medications" during a 2-year period (2014-2015). In total, 12,194 patients were prescribed "risk medications" pertaining to one of the three included pharmaceutical groups. Vitamin D testing and concomitant vitamin D supplementation, including differences between the included pharmaceutical groups, was explored by matching personal identification numbers. RESULTS: Corticosteroids were prescribed to 10,003 of the patients, antiepileptic drugs to 1,101, and drugs mainly reducing vitamin D uptake to 864. Two hundred twenty-six patients were prescribed >1 "risk medication". Seven hundred eighty-seven patients (6.5%) had been tested during the 2-year period. There were no differences regarding testing frequency between groups. Concomitant supplements were prescribed to 3,911 patients (32.1%). It was more common to be prescribed supplements when treated with corticosteroids. Vitamin D supplementation was more common among tested patients in all three groups. Women were tested and supplemented to a higher extent. The mean vitamin D level was 69 nmol/L. Vitamin D deficiency was found in 24.1% of tested patients, while 41.3% had optimal levels. It was less common to be deficient and more common to have optimal levels among patients prescribed corticosteroids. CONCLUSION: Adherence to medical guidelines comprising testing and supplementation of patients prescribed drugs causing vitamin D deficiency needs improvement in Sweden.

Treatment with Growth Hormone in Noonan Syndrome Observed during 25 Years of KIGS: Near Adult Height and Outcome Prediction.

BACKGROUND/AIMS: There is little information how rhGH treatment affects height in NS. This study aims to analyze data from the NS patients assembled in KIGS over 25 years. PATIENTS/METHODS: Of 613 (389 m/224 f) NS patients documented, 476 (302 m/174 f) were treated for 1 year, 237 (160 m/77 f) of which served to develop a 1st year height velocity (HV) prediction algorithm. One-hundred and forty (74 m/66 f) had reached near adult height (NAH). Factors affecting NAH on rhGH were determined. RESULTS: At the start of rhGH, the NAH groups were (median, m, f) 11.0 and 10.3 years, with a height SDS of -3.2 and -3.8 SDS (Prader), respectively. The total gain after 6.3 and 5.6 years on rhGH (0.27 and 0.30 mg/kg/week) was 1.2 and 1.3 SDS. Age at the start of rhGH (negative), height at the start of rhGH, rhGH dose, number of rhGH injections/wk and birth weight (all positive) explained 36% of the variability of 1st year HV. Height at the start of rhGH, 1st year growth on rhGH, birth weight, and gender explained 74% of the variability of NAH. Causes for rhGH treatment discontinuation and adverse events were also analyzed. CONCLUSION: rhGH treatment increases NAH in NS. Prediction algorithms may optimize treatment in the future.

Do patient characteristics predict which patients with overactive bladder benefit from a higher fesoterodine dose?

INTRODUCTION AND HYPOTHESIS: We sought to determine whether baseline characteristics predict which overactive bladder (OAB) patients benefit from fesoterodine 8 mg versus 4 mg. METHODS: In double-blind, placebo-controlled, flexible-dose trials, baseline characteristics of OAB patients with ≥ 1 urgency urinary incontinence (UUI) episodes/24 h who escalated from fesoterodine 4 mg to 8 mg were evaluated. Possible dose-escalation predictors (age; sex; previous antimuscarinic use; UUI, micturitions, and urgency episodes/24 h; race; body mass index; time to dose escalation; OAB duration) were compared in escalators versus non-escalators. Patients from fixed-dose trials with dose-escalator characteristics were identified (matched dose-escalator sample) to assess changes from baseline with fesoterodine 4 mg, 8 mg, and placebo. RESULTS: In flexible-dose trials, significant predictors of fesoterodine dose escalation were younger age (≤ 65.8 years), greater number of baseline micturitions (≥ 13.1) and urgency episodes/24 h (≥ 10.9), greater OAB duration (≥ 9.1 years), and more frequent previous antimuscarinic use (58.3%), but not baseline UUI episodes/24 h. In the matched dose-escalator sample (fesoterodine 4 mg: n = 215; 8 mg: n = 198; placebo: n = 217), change from baseline in UUI episodes significantly improved with fesoterodine 8 mg versus 4 mg (P = 0.043) and with both doses versus placebo (P < 0.001). Dry mouth and constipation rates were higher with fesoterodine 8 mg. CONCLUSIONS: Dose-escalator patients had a significantly greater UUI response with fesoterodine 8 mg versus 4 mg. Given the potential for adverse events, fesoterodine 4 mg is recommended to start; however, patients with UUI and identified predictors may benefit from initial treatment with fesoterodine 8 mg or rapid dose escalation.

Evaluation of screening for coeliac disease in children with juvenile idiopathic arthritis.

AIM: To study the prevalence of coeliac disease (CD) in children with Juvenile idiopathic arthritis (JIA), by screening a population-based cohort of children with JIA using autoantibodies against tissue transglutaminase (anti-TG2). METHODS: All children diagnosed with JIA in three Swedish counties, with disease onset between 2007 and 2014, were included prospectively. Serum levels of IgA anti-TG2 antibodies, IgG anti-TG2 antibodies, and total IgA were analysed. Children with positive levels of IgA anti-TG2 antibodies and children with IgA deficiency in combination with positive levels of IgG anti-TG2 antibodies were referred to the paediatric gastroenterology unit for gastroscopy and small intestine biopsy. RESULTS: A total of 216 children were included, and analysis of IgA and IgG anti-TG2 antibodies was performed in 213 children. Three children were diagnosed with CD prior to the diagnosis of JIA, and three additional children were found through screening, resulting in a CD point prevalence of 2.8% (95% CI 0.6-5.0%). CONCLUSION: We found a point prevalence of CD close to previous described prevalence in the general population of Swedish children. Therefore, general screening for CD in children with JIA is not supported by our data. However, this study shows that asymptomatic CD in children with JIA may be found by screening.

Myocardial Contraction Fraction by M-Mode Echocardiography Is Superior to Ejection Fraction in Predicting Mortality in Transthyretin Amyloidosis.

BACKGROUND: Transthyretin amyloidosis (ATTR) is often associated with cardiac involvement manifesting as conduction disease as well as restrictive cardiomyopathy causing heart failure and death. Myocardial contraction fraction (MCF), the ratio of left ventricular stroke volume (SV) to myocardial volume (MV), is a volumetric measure of myocardial shortening that is superior to ejection fraction (EF) in predicting mortality in patients with primary amyloid light chain cardiac amyloidosis. We hypothesized that MCF would be an independent predictor of survival in TTR-CA. METHODS AND RESULTS: MCF was derived from 2-dimensional echocardiography-guided M-mode data for 530 subjects in the Transthyretin Amyloidosis Outcomes Survey (THAOS) database: age 61 ± 16years, 74% male, 158 wild-type (ATTRwt) and 372 mutant (ATTRm), follow-up 1.5 ± 1.7years. Using multivariate Cox proportional hazard regression models, MCF <25% was highly associated with survival (hazard ratio [HR] 8.5, 95% confidence interval [CI] 4.8-14.9,-P < .0001), which was stronger than the association of EF dichotomized at 50% (HR 2.8, 95% CI 1.8-4.4; P < .0001). MCF <25% remained significantly predictive of survival in a multivariate model that included systolic blood pressure, estimated glomerular filtration rate <65 mL·min-1·m-2, New York Heart Association (NYHA) functional class, and health status based on the EuroQol-5D-3L questionnaire (area under the receiver operating characteristic curve [AUC] = 0.83, 95% CI 0.78-0.89). CONCLUSIONS: MCF was superior to EF in predicting mortality in patients with ATTR. A predictive model combining MCF with systolic blood pressure, renal function, NYHA functional class, and health status was strongly associated with survival in patients with ATTR. CLINICALTRIALS. GOV IDENTIFIER: NCT00628745.