Methylphenidate and the Response to Growth Hormone Treatment in Short Children Born Small for Gestational Age

Background: Growth hormone (GH) treatment has become a frequently applied growth promoting therapy in short children born small for gestational age (SGA). Children born SGA have a higher risk of developing attention deficit hyperactivity disorder (ADHD). Treatment of ADHD with methylphenidate (MP) has greatly increased in recent years, therefore more children are being treated with GH and MP simultaneously. Some studies have found an association between MP treatment and growth deceleration, but data are contradictory. Objective: To explore the effects of MP treatment on growth in GH-treated short SGA children Methods: Anthropometric measurements were performed in 78 GH-treated short SGA children (mean age 10.6 yr), 39 of whom were also treated with MP (SGA-GH/MP). The SGA-GH/MP group was compared to 39 SGA-GH treated subjects. They were matched for sex, age and height at start of GH, height SDS at start of MP treatment and target height SDS. Serum insulin-like growth factor-I (IGF-I) and IGF binding protein-3 (IGFBP-3) levels were yearly determined. Growth, serum IGF-I and IGFBP-3 levels during the first three years of treatment were analyzed using repeated measures regression analysis. Results: The SGA-GH/MP group had a lower height gain during the first 3 years than the SGA-GH subjects, only significant between 6 and 12 months of MP treatment. After 3 years of MP treatment, the height gain was 0.2 SDS (±0.1 SD) lower in the SGA-GH/MP group (P = 0.17). Adult height was not significantly different between the SGA-GH/MP and SGA-GH group (-1.9 SDS and -1.9 SDS respectively, P = 0.46). Moreover, during the first 3 years of MP treatment IGF-I and IGFBP-3 measurements were similar in both groups. Conclusion: MP has some negative effect on growth during the first years in short SGA children treated with GH, but adult height is not affected

Two-level system with a thermally fluctuating transfer matrix element: Application to the problem of DNA charge transfer

Charge transfer along the base-pair stack in DNA is modeled in terms of thermally-assisted tunneling between adjacent base pairs. Central to our approach is the notion that tunneling between fluctuating pairs is rate-limited by the requirement of their optimal alignment. We focus on this aspect of the process by modeling two adjacent base pairs in terms of a classical damped oscillator subject to thermal fluctuations as described by a Fokker-Planck equation. We find that the process is characterized by two time scales, a result that is in accord with experimental findings.Comment: original file is revtex4, 10 pages, three eps figure

Drug Utilisation Patterns of Alternatives to Ranitidine-Containing Medicines in Patients Treated with Ranitidine:A Network Analysis of Data from Six European National Databases

Introduction: Ranitidine, a histamine H2-receptor antagonist (H2RA), is indicated in the management of gastric acid-related disorders. In 2020, the European Medicines Agency (EMA) recommended suspension of all ranitidine-containing medicines in the European Union (EU) due to the presence of N-nitrosodimethylamine (NDMA) impurities, which were considered to be carcinogenic. The aim of this study was to investigate the impact of regulatory intervention on use patterns of ranitidine-containing medicines and their therapeutic alternatives. Objectives: The aim was to study drug utilisation patterns of ranitidine and report discernible trends in treatment discontinuation and switching to alternative medications. Methods: This retrospective, population-based cohort study was conducted using primary care records from six European countries between 2017 and 2023. To explore drug utilisation patterns, we calculated (1) incident use of ranitidine, other H2RAs, and other alternative drugs for the treatment of gastric ulcer and/or gastric bleeding; (2) ranitidine discontinuation; and (3) switching from ranitidine to alternative drugs (H2RAs, proton-pump inhibitors [PPIs], and other medicinal products for acid-related disorders). Results: During the study period, 385,273 new ranitidine users were observed, with most users being female and aged 18–74 years. Ranitidine was the most commonly prescribed H2RA in the pre-referral period (September 2017–August 2019), with incidence rates between 0.8 and 9.0/1000 person years (PY). A steep decline to 0.3–3.8/1000 PY was observed in the referral period (September 2019–March 2020), eventually dropping to 0.0–0.4/1000 PY in the post-referral period (April 2020–March 2022). Switching from ranitidine to alternative drugs increased in the post-referral period, with the majority of patients switching to PPIs. Discontinuation of ranitidine use ranged from 270 to 380/1000 users in 2017 and decreased over time. Conclusions:Ranitidine was commonly used prior to referral, but it was subsequently discontinued and replaced primarily with PPIs.</p

Green manure in coffee systems in the region of Zona da Mata, Minas Gerais: characteristics and kinetics of carbon and nitrogen mineralization.

The use of green manure may contribute to reduce soil erosion and increase the soil organic matter content and N availability in coffee plantations in the Zona da Mata, State of Minas Gerais, in Southeastern Brazil. The potential of four legumes (A. pintoi, C. mucunoides, S. aterrimum and S. guianensis)to produce above-ground biomass, accumulate nutrients and mineralize N was studied in two coffee plantations of subsistence farmers under different climate conditions. The biomass production of C. mucunoides was influenced by the shade of the coffee plantation.C. mucunoides tended to mineralize more N than the other legumes due to the low polyphenol content and polyphenol/N ratio. In the first year, the crop establishment of A. pintoi in the area took longer than of the other legumes, resulting in lower biomass production and N2 fixation. In the long term, cellulose was the main factor controlling N mineralization. The biochemical characteristics, nutrient accumulation and biomass production of the legumes were greatly influenced by the altitude and position of the area relative to the sun

Detecting Endometrial Cancer by Blood Spectroscopy: A Diagnostic Cross-Sectional Study

Endometrial cancer is the sixth most common cancer in women, with a rising incidence worldwide. Current approaches for the diagnosis and screening of endometrial cancer are invasive, expensive or of moderate diagnostic accuracy, limiting their clinical utility. There is a need for cost-effective and minimally invasive approaches to facilitate the early detection and timely management of endometrial cancer. We analysed blood plasma samples in a cross-sectional diagnostic accuracy study of women with endometrial cancer (n = 342), its precursor lesion atypical hyperplasia (n = 68) and healthy controls (n = 242, total n = 652) using attenuated total reflection-Fourier transform infrared (ATR-FTIR) spectroscopy and machine learning algorithms. We show that blood-based infrared spectroscopy has the potential to detect endometrial cancer with 87% sensitivity and 78% specificity. Its accuracy is highest for Type I endometrial cancer, the most common subtype, and for atypical hyperplasia, with sensitivities of 91% and 100%, and specificities of 81% and 88%, respectively. Our large-cohort study shows that a simple blood test could enable the early detection of endometrial cancer of all stages in symptomatic women and provide the basis of a screening tool in high-risk groups. Such a test has the potential not only to differentially diagnose endometrial cancer but also to detect its precursor lesion atypical hyperplasia—the early recognition of which may allow fertility sparing management and cancer prevention

Comorbidity in incident osteoarthritis cases and matched controls using electronic health record data

Background: Comorbidities are common in patients with osteoarthritis (OA). This study aimed to determine the association of a wide range of previously diagnosed comorbidities in adults with newly diagnosed OA compared with matched controls without OA. Methods: A case–control study was conducted. The data were derived from an electronic health record database that contains the medical records of patients from general practices throughout the Netherlands. Incident OA cases were defined as patients with one or more diagnostic codes recorded in their medical records that correspond to knee, hip, or other/peripheral OA. Additionally, the first OA code had to be recorded between January 1, 2006, and December 31, 2019. The date of cases’ first OA diagnosis was defined as the index date. Cases were matched (by age, sex, and general practice) to up to 4 controls without a recorded OA diagnosis. Odds ratios were derived for each 58 comorbidities separately by dividing the comorbidity prevalence of cases by that of their matched controls at the index date. Results: 80,099 incident OA patients were identified of whom 79,937 (99.8%) were successfully matched with 318,206 controls. OA cases had higher odds for 42 of the 58 studied comorbidities compared with matched controls. Musculoskeletal diseases and obesity showed large associations with incident OA. Conclusions: Most of the comorbidities under study had higher odds in patients with incident OA at the index date. While previously known associations were confirmed in this study, some associations were not described earlier

Occurrence of comorbidity following osteoarthritis diagnosis: a cohort study in the Netherlands

Objective To determine the risk of comorbidity following diagnosis of knee or hip osteoarthritis (OA). Design A cohort study was conducted using the Integrated Primary Care Information database, containing electronic health records of 2.5 million patients from the Netherlands. Adults at risk for OA were included. Diagnosis of knee or hip OA (=exposure) and 58 long-term comorbidities (=outcome) were defined by diagnostic codes following the International Classification of Primary Care (ICPC) coding system. Time between the start of follow-up and incident diagnosis of OA was defined as unexposed, and between diagnosis of OA and the end of follow-up as exposed. Age and sex adjusted hazard ratios (HRs) comparing comorbidity rates in exposed and unexposed patient time were estimated with 99.9% confidence intervals (CI). Results The study population consisted of 1,890,712 patients. For 30 of the 58 studied comorbidities, exposure to knee OA showed a HR larger than 1. Largest positive associations (HR with (99.9% CIs)) were found for obesity 2.55 (2.29-2.84) and fibromyalgia 2.06 (1.53-2.77). For two conditions a HR<1 was found, other comorbidities showed no association with exposure to knee OA. For 26 comorbidities, exposure to hip OA showed a HR larger than 1. The largest were found for polymyalgia rheumatica 1.81 (1.41-2.32) and fibromyalgia 1.70 (1.10-2.63). All other comorbidities showed no associations with hip OA. Conclusion This study showed that many comorbidities were diagnosed more often in patients with knee or hip OA. This suggests that the management of OA should consider the risk of other long-term-conditions