Trends in HbA1c thresholds for initiation of hypoglycemic agents:Impact of changed recommendations for older and frail patients

Aims: Less strict glycated hemoglobin (HbA1c) thresholds have been recommended in older and/or frail type 2 diabetes (T2D) patients than in younger and less frail patients for initiating hypoglycemic agents since 2011. We aimed to assess trends in HbA1c thresholds at initiation of a first hypoglycemic agent(s) in T2D patients and the influence of age and frailty on these trends. Materials and methods: The groningen initiative to analyze type 2 diabetes treatment (GIANTT) database was used, which includes primary care T2D patients from the north of the Netherlands. Patients initiating a first non-insulin hypoglycemic agent(s) between 2008 and 2014 with an HbA1c measurement within 120 days before initiation were included. The influence of calendar year, age, or frailty and the interaction between calendar year and age or frailty were assessed using multilevel regression analyses adjusted for confounders. Results: We included 4588 patients. The mean HbA1c threshold at treatment initiation was 7.4% up to 2010, decreasing to 7.1% in 2011 and increasing to 7.4% in 2014. This quadratic change over the years was significant (P 0.05). Conclusions: HbA1c thresholds at initiation of a first hypoglycemic agent(s) changed significantly over time, showing a decrease after 2010 and an increase after 2012. The HbA1c threshold at initiation was not influenced by age or frailty, which is in contrast with recommendations for more personalized treatment

Determining Possible Shared Genetic Architecture Between Myopia and Primary Open-Angle Glaucoma

PURPOSE: To determine genetic correlations between common myopia and primary open-angle glaucoma (POAG). // METHODS: We tested the association of myopia polygenic risk scores (PRSs) with POAG and POAG endophenotypes using two studies: the Australian & New Zealand Registry of Advanced Glaucoma (ANZRAG) study comprising 798 POAG cases with 1992 controls, and the Rotterdam Study (RS), a population-based study with 11,097 participants, in which intraocular pressure (IOP) and optic disc parameter measurements were catalogued. PRSs were derived from genome-wide association study meta-analyses conducted by the Consortium for Refractive Error and Myopia (CREAM) and 23andMe. In total, 12 PRSs were constructed and tested. Further, we explored the genetic correlation between myopia, POAG, and POAG endophenotypes by using the linkage disequilibrium score regression (LDSC) method. // RESULTS: We did not find significant evidence for an association between PRS of myopia with POAG (P = 0.81), IOP (P = 0.07), vertical cup-disc ratio (P = 0.42), or cup area (P = 0.25). We observed a nominal association with retinal nerve fiber layer (P = 7.7 × 10-3) and a significant association between PRS for myopia and disc area (P = 1.59 × 10-9). Using the LDSC method, we found a genetic correlation only between myopia and disc area (genetic correlation [RhoG] = -0.12, P = 1.8 × 10-3), supporting the findings of the PRS approach. // CONCLUSIONS: Using two complementary approaches we found no evidence to support a genetic overlap between myopia and POAG; our results suggest that the comorbidity of these diseases is not influenced by common variants. The association between myopia and optic disc size is well known and validates this methodology

Способы перевода аббревиатур и сокращений в области компьютерных технологий (на примере русского и немецкого языков)

Выпускная квалификационная работа 75 с., 2 главы, 42 источника. Предмет исследования: способы перевода аббревиатур и сокращений в области компьютерных технологий с немецкого языка на русский язык. Объектом исследования: аббревиатуры и сокращения, относящиеся к области компьютерных технологий. Цель работы: выявить эффективные способы перевода аббревиатур и сокращений в области компьютерных технологий с немецкого языка на русский. Результаты исследования: были сформулированы особенности перевода аббревиатур и сокращений в области компьютерных технологий Степень внедрения/апробация работы: Было опубликовано две статьи Область применения: лингвистика, языкознание, переводоведение.Graduation thesis: 75 pg., 2 chapters, 42 resources. Subject of research: translation methods of acronyms and reductions in the field of computer technology from German into Russian. Object of research: Acronyms and reductions in the field of computer technology. Purpose of research: : to identify the translation methods of acronyms and reductions in the field of computer technology from German into Russian. Results of research: The features of the translation of acronyms and reductions in the area of computer technology has been revealed. Degree of implementation /work approbation: two articles were published. Field of application: Linguistic, theory of translatio

Manganese and acute paranoid psychosis: a case report

Contains fulltext : 103167.pdf (publisher's version ) (Open Access)Introduction Manganese regulates many enzymes and is essential for normal development and body function. Chronic manganese intoxication has an insidious and progressive course and usually starts with complaints of headache, fatigue, sleep disturbances, irritability and emotional instability. Later, several organ systems may be affected and, due to neurotoxicity, an atypical parkinsonian syndrome may emerge. With regard to neuropsychiatry, an array of symptoms may develop up to 30 years after intoxication, of which gait and speech abnormalities, cognitive and motor slowing, mood changes and hallucinations are the most common. Psychotic phenomena are rarely reported. Case presentation We describe the case of a 49-year-old Caucasian man working as a welder who was referred to our facility for evaluation of acute paranoid psychotic behavior. Our patient's medical history made no mention of any somatic complaints or psychiatric symptoms, and he had been involved in a professional career as a metalworker. On magnetic resonance imaging scanning of his brain, a bilateral hyperdensity of the globus pallidus, suggestive for manganese intoxication, was found. His manganese serum level was 52 to 97 nmol/L (range: 7 to 20 nmol/L). A diagnosis of organic psychotic disorder due to manganese overexposure was made. His psychotic symptoms disappeared within two weeks of treatment with low-dose risperidone. At three months later, serum manganese was decreased to slightly elevated levels and the magnetic resonance imaging T1 signal intensity was reduced. No signs of Parkinsonism were found and a definite diagnosis of manganese-induced apathy syndrome was made. Conclusion Although neuropsychiatric and neurological symptoms caused by (chronic) manganese exposure have been reported frequently in the past, in the present day the disorder is rarely diagnosed. In this report we stress that manganese intoxication can still occur, in our case in a confined-space welder, and may present clinically with a paranoid psychotic state that necessitates a rapid diagnostic procedure in order to avoid the permanent structural brain damage that may occur with chronic exposure.4 p

Rab proteins and Rab-associated proteins: major actors in the mechanism of protein-trafficking disorders

Ras-associated binding (Rab) proteins and Rab-associated proteins are key regulators of vesicle transport, which is essential for the delivery of proteins to specific intracellular locations. More than 60 human Rab proteins have been identified, and their function has been shown to depend on their interaction with different Rab-associated proteins regulating Rab activation, post-translational modification and intracellular localization. The number of known inherited disorders of vesicle trafficking due to Rab cycle defects has increased substantially during the past decade. This review describes the important role played by Rab proteins in a number of rare monogenic diseases as well as common multifactorial human ones. Although the clinical phenotype in these monogenic inherited diseases is highly variable and dependent on the type of tissue in which the defective Rab or its associated protein is expressed, frequent features are hypopigmentation (Griscelli syndrome), eye defects (Choroideremia, Warburg Micro syndrome and Martsolf syndrome), disturbed immune function (Griscelli syndrome and Charcot–Marie–Tooth disease) and neurological dysfunction (X-linked non-specific mental retardation, Charcot–Marie–Tooth disease, Warburg Micro syndrome and Martsolf syndrome). There is also evidence that alterations in Rab function play an important role in the progression of multifactorial human diseases, such as infectious diseases and type 2 diabetes. Rab proteins must not only be bound to GTP, but they need also to be ‘prenylated’—i.e. bound to the cell membranes by isoprenes, which are intermediaries in the synthesis of cholesterol (e.g. geranyl geranyl or farnesyl compounds). This means that isoprenylation can be influenced by drugs such as statins, which inhibit isoprenylation, or biphosphonates, which inhibit that farnesyl pyrophosphate synthase necessary for Rab GTPase activity. Conclusion: Although protein-trafficking disorders are clinically heterogeneous and represented in almost every subspeciality of pediatrics, the identification of common pathogenic mechanisms may provide a better diagnosis and management of patients with still unknown Rab cycle defects and stimulate the development of therapeutic agents

Implants in the severely resorbed mandibles: whether or not to augment? What is the clinician’s preference?

Contains fulltext : 96000.pdf (publisher's version ) (Open Access)INTRODUCTION: The aim of this study is to inventory in the Netherlands which therapy is the clinician's first choice when restoring the edentulous mandible. MATERIAL AND METHODS: A questionnaire was sent to all Dutch Oral and Maxillofacial surgeons. As part of this, the surgeons were invited to treat five virtual edentulous patients, differing only in mandibular residual height. RESULTS: In cases of a sufficient residual height of 15 mm, all surgeons were in favour to insert solely two implants to anchor an overdenture. In case of a residual height of 12 mm, 10% of the surgeons choose for an augmentation procedure. If a patient was presented with a mandibular height of 10 mm, already 40% of the OMF surgeons executed an augmentation procedure. Most (80%) surgeons prefer the (anterior) iliac crest as donor site. The choice of 'whether or not to augment' was not influenced by the surgeon's age; however, the hospital, where he was trained, did. Surgeons trained in Groningen were more in favour of installing short implants in mandibles with reduced vertical height. DISCUSSION: As the option overdenture supported on two interforaminal implants is reimbursed by the Dutch health assurance, this treatment modality is very popular in the Netherlands. From a point of costs and to minimize bypass comorbidity, surgeons should be more reluctant in executing augmentation procedures to restore the resorbed edentulous mandible as it is dated in literature that also in mandibles with a residual height of 10 mm or less, solely placing implants, thus without an augmentation procedure in advance, is a reliable treatment option

Childhood febrile illness and the risk of myopia in UK Biobank participants

Purpose Historical reports suggest febrile illness during childhood is a risk factor for myopia. The establishment of the UK Biobank provided a unique opportunity to investigate this relationship. Patients and methods We studied a sample of UK Biobank participants of White ethnicity aged 40–69 years old who underwent autorefraction (N=91 592) and were classified as myopic (≤−0.75 Dioptres (D)), highly myopic (≤−6.00 D), or non-myopic (>−0.75 D). Self-reported age at diagnosis of past medical conditions was ascertained during an interview with a nurse at a Biobank assessment centre. Logistic regression analysis was used to calculate the odds ratio (OR) for myopia or high myopia associated with a diagnosis before age 17 years of each of nine febrile illnesses, after adjusting for potential confounders (age, sex, highest educational qualification, and birth order). Results Rubella, mumps, and pertussis were associated with myopia: rubella, OR=1.38, 95% CI: 1.03–1.85, P=0.030; mumps, OR=1.32, 95% CI: 1.07–1.64, P=0.010; and pertussis, OR=1.39, 95% CI 1.03–1.87, P=0.029. Measles, rubella, and pertussis were associated with high myopia: measles, OR=1.48, 95% CI: 1.07–2.07, P=0.019; rubella, OR=1.94, 95% CI: 1.12–3.35, P=0.017; and pertussis, OR=2.15, 95% CI: 1.24–3.71, P=0.006. The evidence did not support an interaction between education and febrile illness in explaining the above risks. Conclusion A history of childhood measles, rubella, or pertussis was associated with high myopia, whereas a history of childhood rubella, mumps, or pertussis was associated with any myopia. The reasons for these associations are unclear

Costs and effects of screening and treating low risk women with a singleton pregnancy for asymptomatic bacteriuria, the ASB study

<p>Abstract</p> <p>Background</p> <p>The prevalence of asymptomatic bacteriuria (ASB) in pregnancy is 2-10% and is associated with both maternal and neonatal adverse outcomes as pyelonephritis and preterm delivery. Antibiotic treatment is reported to decrease these adverse outcomes although the existing evidence is of poor quality.</p> <p>Methods/Design</p> <p>We plan a combined screen and treat study in women with a singleton pregnancy. We will screen women between 16 and 22 weeks of gestation for ASB using the urine dipslide technique. The dipslide is considered positive when colony concentration ≥10⁵ colony forming units (CFU)/mL of a single microorganism or two different colonies but one ≥10⁵ CFU/mL is found, or when Group B Streptococcus bacteriuria is found in any colony concentration. Women with a positive dipslide will be randomly allocated to receive nitrofurantoin or placebo 100 mg twice a day for 5 consecutive days (double blind). Primary outcomes of this trial are maternal pyelonephritis and/or preterm delivery before 34 weeks. Secondary outcomes are neonatal and maternal morbidity, neonatal weight, time to delivery, preterm delivery rate before 32 and 37 weeks, days of admission in neonatal intensive care unit, maternal admission days and costs.</p> <p>Discussion</p> <p>This trial will provide evidence for the benefit and cost-effectiveness of dipslide screening for ASB among low risk women at 16–22 weeks of pregnancy and subsequent nitrofurantoin treatment.</p> <p>Trial registration</p> <p>Dutch trial registry: NTR-3068</p

A study of young peoples' attitudes to opportunistic Chlamydia testing in UK general practice

<p>Abstract</p> <p>Objective</p> <p>The objective of this study was to assess young people's perceptions of being offered a chlamydia screening test in United Kingdom (UK) general practice.</p> <p>Methods</p> <p>This is qualitative study that uses focus groups and individual interviews with young adults (age 16 – 18) to assess their views.</p> <p>Results</p> <p>These young adults were a difficult group to gain access to. Two focus groups, one in a school, the other in a general practice (family practice), and 2 individual interviews were undertaken (total sample 18). Respondents were unfamiliar with Chlamydia, but broadly aware of sexually transmitted infections. General practice (family practice) was perceived as an acceptable place to deliver opportunistic screening, but participants felt that tests should not be initiated by GP receptionists. Novel delivery routes such as schools and "Pub"/Bar dispensing machines were discussed. Issues around stigma and confidentiality were also raised.</p> <p>Conclusion</p> <p>Opportunistic Chlamydia screening in UK general practice (family practic seems acceptable to young adults. While this is a difficult group to gain access to for research, attempts need to made to ensure acceptability to users of this programme.</p

Efficacy of interventions to increase the uptake of chlamydia screening in primary care: a systematic review

<p>Abstract</p> <p>Background</p> <p>As most genital chlamydia infections are asymptomatic, screening is the main way to detect and cases for treatment. We undertook a systematic review of studies assessing the efficacy of interventions for increasing the uptake of chlamydia screening in primary care.</p> <p>Methods</p> <p>We reviewed studies which compared chlamydia screening in the presence and the absence of an intervention. The primary endpoints were screening rate or total tests.</p> <p>Results</p> <p>We identified 16 intervention strategies; 11 were randomised controlled trials and five observational studies, 10 targeted females only, five both males and females, and one males only. Of the 15 interventions among females, six were associated with significant increases in screening rates at the 0.05 level including a multifaceted quality improvement program that involved provision of a urine jar to patients at registration (44% in intervention clinics vs. 16% in the control clinic); linking screening to routine Pap smears (6.9% vs. 4.5%), computer alerts for doctors (12.2% vs. 10.6%); education workshops for clinic staff; internet-based continuing medical education (15.5% vs. 12.4%); and free sexual health consultations (16.8% vs. 13.2%). Of the six interventions targeting males, two found significant increases including the multifaceted quality improvement program in which urine jars were provided to patients at registration (45% vs. 15%); and the offering by doctors of a test to all presenting young male clients, prior to consultation (29 vs. 4%).</p> <p>Conclusions</p> <p>Interventions that promoted the universal offer of a chlamydia test in young people had the greatest impact on increasing screening in primary care.</p