[Improved patient safety through a clinical decision support system in laboratory medicine]. / Verbesserte Patientensicherheit durch "clinical decision support systems" in der Labormedizin.

BACKGROUND: Laboratory diagnostics are essential for diagnosis, initiation of therapy, and monitoring of patients. Laboratory results that are overlooked or incorrectly interpreted lead to adverse events and endanger patient safety. Clinical decision support systems (CDSSs) may facilitate appropriate interpretation of results and subsequent medical response. OBJECTIVES: The research project on digital laboratory medicine (AMPEL) aims at developing a CDSS based on laboratory diagnostics, which supports practitioners in ensuring the necessary medical consequences. MATERIALS AND METHODS: A literature review of CDSSs describes the current state of research. The research project AMPEL is presented with its objectives, challenges, and first results. Furthermore, the development of a framework and reporting system is illustrated through the clinical example of severe hypokalemia. RESULTS AND CONCLUSION: Through interdisciplinary development and constant optimization, a specific CDSS with high acceptance among clinicians was developed. Initial results in the case of severe hypokalemia show a positive effect on patient care. Thereby, more complex frameworks such as sepsis diagnostics or acute coronary syndrome are implemented. The limited availability of standardized and digital clinical data is challenging. In addition to the application of classic decision trees in CDSS, the use of machine learning offers a promising perspective for future developments.

Maternal mood disorders and lithium exposure in utero were not associated with poor cognitive development during childhood.

AIM: This study evaluated whether maternal mood disorders (MMD), particularly bipolar disorder, and lithium treatment during pregnancy influenced the neonatal health and cognition of children born from 2006 to 2010. METHODS: Our study at Karolinska University Hospital, Stockholm, Sweden, focused on women with and without mood disorders and their children. Information on pharmacotherapy, mental health, delivery and neonatal complications was retrospectively collected from electronic patient records. Children were tested in a blinded manner at four to five years of age with the Wechsler Preschool and Primary Scale of Intelligence, 3rd edition. Maternal health, child health and social situations were evaluated. RESULTS: Of the 39 children, 20 were exposed to lithium and MMD during pregnancy, eight were exposed to MMD but not lithium and 11 were not exposed to MMD or lithium. The children's full scale intelligence quotient (IQ), performance IQ and verbal IQ results did not differ significantly between the groups. The processing speed quotient was significantly lower in children exposed to mood disorders, but there was a high level of missing data for this subtest. CONCLUSION: This small, clinical cohort showed no significant association between mothers' prenatal exposure to lithium or mood disorders and their offspring's IQ.

First Bosnian Study of the Relationship between APOE rs7412 and rs429358 Variants and Pregnancy Loss.

Due to inconsistent results of APOE variants in the survival of pregnancy we investigated the potential relationship of APOE rs7412 and rs429358 with pregnancy loss (PL) in Bosnian women. We enrolled 154 women with PL. The minimum week of miscarriage was 6, while the maximum was 28. As a control group, an equal number of mothers with at least one live-born child was included. All women were recruited from the Institution of Health Protection of Women and Motherhood in Sarajevo, Bosnia and Herzegovina. Genotyping was performed by real- time PCR at the Department of General Pharmacology and Pharmacoeconomics, Pomeranian Medical University. The prevalence of genotypes E2/E3, E2/E4, E3/E3, E3/E4, E4/E4 in the group with and without PL were: 14.3 %, 1.3 %, 70.8 %, 12.3 %, 1.3 %, and 13.6 %, 1.3 %, 70.1 %, 14.3 %, 0.7 %, respectively. The frequency of the E4/E4 genotype in women with 1-2 and 3-4 PL compared to women without PL did not differ significantly between those three groups (P value = 0.0712). The frequencies of alleles ԑ2, ԑ3, ԑ4 in the group with and without PL were: 6.8 %, 85.1 %, 8.1 % and 7.5 %, 84.1 %, 8.4 %, respectively, and did not differ significantly. We conclude that our study does not confirm rs7412 and rs429358 as a potential risk factor for PL in the studied group. To elucidate the relationship between PL and variants of the APOE gene, studies with a larger sample size and placental histomorphology and genetic diagnosis are required.

Phenotypes optimized for early-life reproduction exhibit faster somatic deterioration with age, revealing a latent cost of high condition.

High condition enables individuals to express a phenotype with greater reproductive potential. However, life-history theory predicts that reproduction will trade off with somatic maintenance and viability, and several studies have reported faster age-related decline in performance in high-condition individuals, suggesting that high condition in early life is associated with accelerated somatic deterioration. This trade-off may be especially pronounced in males, which often express condition-dependent secondary sexual traits that can impose viability costs during development and through damage-inflicting adult sexual behaviours. To test this prediction, we reared larvae of the neriid fly Telostylinus angusticollis on diets of varying nutrient content and quantified somatic deterioration in solitary males, males housed in all-male or mixed-sex groups and immobilized males subjected to mechanical stress. We found that males reared on a nutrient-rich larval diet (high-condition males) suffered a higher rate of somatic deterioration with age, particularly when housed in groups. Perhaps as a result of accelerated somatic deterioration, high-condition males did not outlive low-condition males. In addition, high-condition males housed in all-male groups experienced a greater reduction in escape response with age than males housed in mixed-sex groups, suggesting that male-male combat promotes somatic deterioration. However, even when immobilized, high-condition males were still found to be more susceptible to somatic damage than low-condition males. Our findings suggest that a high-condition male phenotype is more prone to somatic damage, both as a result of associated behaviours such as combat, and because of the inherent fragility of the high-condition body.

[Biocompatibility of composites--literature review].

Composites are a large family of materials composed of polymer matrices imbedded with different types of fillers. The specific properties achievable with diverse chemical combinations provide for a wide range of implications in many industrial fields. Materials designed for medical use must not only efficiently serve the purpose of their use, but also be biocompatible to the tissues they contact and the body as a whole. Dental composites and their components have been studied intensely to assess their potential local and systemic side effects, to establish biocompatibility, in order to receive the proper conformation allowing their safe clinical use. The purpose of the following paper is to summarize several aspects of research focused on determining cytotoxicity, genotoxicity, carcinogenicity, hypersensitivity, and microbial effects of composite components, in order to ascertain in fact how biocompatible dental composite materials are. Research shows that several chemical components may be released from different types of composites, and are able to cause toxic, allergic, mutagenic and other biological effects. However, because of the small amounts applied and the unique conditions in the oral cavity, the clinical relevance of these findings is questionable. Nevertheless, caution should be taken when using these materials, to avoid possible negative outcomes. Future studies should focus on targeting most toxic components and finding biocompatible alternatives and development of materials with high polymerization efficiency in order to reduce the amount of leachable components.

Microgravity studies of aqueous wet foams.

Foams and foaming pose important questions and problems for both fundamental research and practical applications. Despite the fact that foams have been extensively studied, many aspects of foam physics and chemistry still remain unclear. Experiments on foams performed under microgravity can be extended far beyond their counterpart where gravity is fully present (i.e. most experiments on Earth). They allow, in particular, observation of the wet foams obtained during the foaming process; on Earth, foams at this stage evolve too quickly due to gravity drainage and cannot be studied. This paper reviews the existing studies of foams under microgravity, which include studies in parabolic flights, in sounding rockets and in the International Space Station.

[A tooth or an implant--literature based decision making].

The common use of dental implants in the daily practice led to a profound change in the available treatment strategies. The option of replacing a diagnosed doubtful tooth with an implant has become widely accepted and often used. The prognosis systems in use today are based on the three major disciplines: endodontics, periodontics and prosthodontics. Combining these three may impair and bias the decision making process and increase the tendency to base it on subjective clinical experience and personal preference. Reading and reviewing the relevant literature gives no clear tool for use. Root canal treatment is considered a highly predictable treatment procedure and a treated tooth is affected mainly by the quality and type of the fabricated restoration and the risk of caries. Periodontal treatment followed by a suitable maintenance regimen will likely allow long term tooth survival. When comparing the success rates of natural teeth rehabilitation versus implant supported restorations, it appears that with implants an additional treatment is demanded along the years. This coincides with the fact that to date there is no consensus regarding the extent of perimplantitis and perimucositis that is to be expected around a restored implant. In addition, a peri implant tissue problem or a failure of a dental implant may prove to be more challenging than a failure of a tooth. It is important to remember that a dental implant is made to substitute a missing tooth and it is a treatment modality with known and clear indications for rehabilitation of an edentulous space. The aim of this paper is to review and discuss the various aspects of whether to maintain a compromised or a doubtful tooth or to prefer a treatment modality using dental implants. In conclusion it is advised here, to incorporate the discussed issues in the decision making process towards the most suitable treatment plan.

Modulation of follistatin and myostatin propeptide by anabolic steroids and gender.

The purpose of this pilot study was to investigate the impact of training, anabolic steroids and endogenous hormones on myostatin-interacting proteins in order to identify manipulations of myostatin signalling. To identify whether analysis of the myostatin interacting proteins follistatin and myostatin propeptide is suitable to detect the abuse of anabolic steroids, their serum concentrations were monitored in untrained males, bodybuilders using anabolic steroids and natural bodybuilders. In addition, we analysed follistatin and myostatin propeptide serum proteins in females during menstrual cycle. Our results showed increased follistatin concentrations in response to anabolic steroids. Furthermore, variations of sex steroid levels during the menstrual cycle had no impact on the expression of follistatin and myostatin propetide. In addition, we identified gender differences in the basal expression of the investigated proteins. In general, follistatin and myostatin propeptide concentrations were relatively stable within the same individual both in males and females. In conclusion, the current findings provide an insight into gender differences in myostatin-interacting proteins and their regulation in response to anabolic steroids and endogenous hormones. Therefore our data provide new aspects for the development of doping prevention strategies.

[Carbohydrate metabolism disorders among obese children and adolescents. Diabetes mellitus type 2]. / Störungen des Kohlenhydratstoffwechsels bei Kindern und Jugendlichen mit Adipositas. Diabetes mellitus Typ 2.

As obesity has become more prevalent, the incidence of type 2 diabetes mellitus in children and adolescents has also increased. Obesity during adolescence leads to an increased risk for disease and premature death during adulthood, independent of obesity during adulthood. Obesity is the major risk factor impacting insulin sensitivity. Subjects with insulin resistance are at risk for progression to diabetes. Type 2 diabetes mellitus in obese children and adolescents is frequently asymptomatic. It is essential to identify children at high risk who need aggressive lifestyle modification focused on weight reduction and increased physical activity. Early detection and therapy of obese children and adolescents with type 2 diabetes may reduce the risk of cardiometabolic consequences and other long-term complications in adulthood.

[Does childhood obesity affect sexual development?]. / Beeinflusst die kindliche Adipositas die Pubertätsentwicklung?

The process of pubertal development is only partly understood and is influenced by many different factors. During the twentieth century there was a general trend toward earlier pubertal development. Fat mass is thought to be a major inducer of puberty. Owing to the rising epidemic of childhood obesity, the relationship between body composition in children and the rate and timing of puberty needs to be investigated. Some studies suggest that central obesity is associated with an earlier onset of pubertal development. Rapid weight gain in early life is linked to advanced puberty in both sexes. A clear correlation exists between increasing body mass index (BMI) and earlier pubertal development in girls. In boys the data are controversial: The majority of studies propose that there is an earlier puberty and voice break in obese boys, but some studies show the opposite. There are several factors and mechanisms that seem to link obesity and puberty, for example, leptin, adipocytokines, and gut peptides. Important players include genetic variation and environmental factors (e.g., endocrine-disrupting chemicals). This article presents the latest studies and evidence on this topic, underlining the inconsistencies in the data and, therefore, the need for further research in this area.

[Retention or adhesion?].

One of the reasons for immediate or late failure of restorations is the detachment of the restoration from the tooth. Retention for the restoration could be achieved from axial walls (macromechanical retention) or from adhesion of the restoration to the remaining tooth structure. Adhesion relies on bonding of resin cement to enamel or dentin on one side and to the restorative material on the other side. Bonding to enamel is predictable. Good bonding to dentin is more of a challenge especially with indirect restorations. In those cases the restoration is delivered usually a few days after the tooth was prepared during this time the exposed dentin might be contaminated or damaged. The question is whether you can rely on adhesion when cementing indirect restorations? In order to achieve the maximal bonding strength to dentin, the hybrid layer on the dentin must be built immediately after tooth preparation. This procedure is called Immediate Dentin Sealing. In vitro and clinical studies have shown better performance of restorations cemented following the IDS procedure. The article discusses the rational and the protocol of this procedure. A clinical case is presented as an example for the possibilities following this philosophy.

Strong correlation between liver and serum levels of hepatitis C virus core antigen and RNA in chronically infected patients.

HCV core antigen (Ag) and HCV RNA levels were evaluated in matched liver biopsy samples and sera from 22 patients with hepatitis C infection by using the quantitative Architect HCV Ag immunoassay and a real-time RT-qPCR assay, respectively. The data showed a strong correlation between liver and serum compartments of HCV Ag levels (r = 0.80) and HCV RNA levels (r = 0.87). In summary, the serum HCV Ag and RNA levels reflect the intrahepatic values.

The influence of laboratory-induced MELD score differences on liver allocation: more reality than myth.

BACKGROUND: Liver allocation in Eurotransplant (ET) is based on the MELD score. Interlaboratory MELD score differences in INR and creatinine determination have been reported. The clinical implication of this observation has not been demonstrated. METHODS: MELD scores were calculated in 66 patients with liver cirrhosis using bilirubin, creatinine, and INR analyzed in six liver transplant centers. Based on allocation results of ET, patients transplanted from December 2006 to June 2007 were divided according to MELD score in four groups. For each group, the influence of the match MELD on the probability of receiving a transplant was studied (Cox proportional hazards model). RESULTS: Laboratory-dependent significant differences in MELD score were demonstrated. Cox proportional hazards model showed a significant association between MELD score and the probability of organ allocation. The unadjusted hazard ratio for receiving a liver transplant was significantly different between group 2 and group 4 (group 2: MELD 19-24; group 4: MELD > 30). CONCLUSION: Laboratory-dependent significant differences in MELD score were observed between the six transplant centers. We demonstrated a significant association between the MELD score and the probability of organ allocation. The observed interlaboratory variation might yield a significant difference in organ allocation in patients with high MELD scores.

Randomized clinical trials underestimate the efficacy of antidepressants in less severe depression.

OBJECTIVE: Demonstrating the superiority of antidepressants over placebo in randomized clinical trials of antidepressants (RCT-ADs) has been difficult. A recent meta-analysis of six RCT-ADs concluded that the efficacy of antidepressants was 'non-existent to negligible' in mild and moderate depression. The aim of this study was to reanalyze the same data in order to investigate whether the meta-analysis could be biased from the shortcomings of the rating scale used, the Hamilton Depression Rating Scale (HDRS). METHOD: We got access to the primary data on item and individual level from five of the six meta-analyzed RCT-ADs (597 individuals). We reanalyzed these data by means of item response theory. RESULTS: Each study showed rapidly decreasing reliability of measurement with diminishing depression; 38% of the combined sample at endpoint was measured with less than half the maximal reliability. CONCLUSION: The HDRS Scale provides unreliable primary data. Low effect sizes can be expected because of the scale's low precision and low sensitivity to change, particularly in mild and moderate depression. The conclusion of the meta-analysis by Fournier et al. is therefore unfounded. The clinical value of antidepressants cannot be evaluated from unreliable data. It is urgent that better measurement techniques for depression severity are developed.

Follicular fluid protein content (FSH, LH, PG4, E2 and AMH) and polar body aneuploidy.

PURPOSE: Our objective was to identify a marker for oocyte aneuploidy in follicular fluid (FF) in women with an increased risk of oocyte aneuploidy after controlled ovarian hyperstimulation. MATERIALS AND METHODS: Three groups of oocytes were constituted for polar body screening by FISH (chromosomes 13, 16, 18, 21 and 22): Group 1, advanced maternal age (n = 156); Group 2, implantation failure (i.e. no pregnancy after the transfer of more than 10 embryos; n = 101) and Group 3, implantation failure and advanced maternal age (n = 56). FSH and other proteins were assayed in the corresponding FF samples. RESULTS: Of the 313 oocytes assessed, 35.78 % were abnormal. We found a significant difference between the follicular FSH levels in normal oocytes and abnormal oocytes (4.85 ± 1.75 IU/L vs. 5.41 ± 2.47 IU/L, respectively; p = 0.021). We found that the greater the number of chromosomal abnormalities per oocyte (between 0 and 3), the higher the follicular FSH level. CONCLUSION: High FF FSH levels were associated with oocyte aneuploidy in women having undergone controlled ovarian hyperstimulation.

[Inhaled marijuana and the lung, a toxic cocktail?] / Cannabis inhalé et poumon, une liaison dangereuse ?

Unlike the well-documented effects of tobacco smoke on the lung, the effects of cannabis smoke remain controversial, the main bias consisting in co-consumption of tobacco. That said, the composition of joint smoke is close to that of cigarettes, containing many compounds that are carcinogenic and/or alter the respiratory epithelium. Confirmed respiratory effects in chronic cannabis smokers include aggravated chronic bronchitis symptoms, a cumulative effect with tobacco on COPD and emphysema occurrence, an increased risk of bullous emphysema, and pneumothorax with heightened risk of recurrence after pleural symphysis. Recent prospective studies have shown a negative impact on lung function, with not only damage to the airways, but also DLCO alteration and an accelerated drop in FEV1. Finally, cannabis smoking is very common among young patients with lung cancer. Its consumption could lead to a different lung cancer profile, potentially more undifferentiated and less accessible to targeted therapy. Questioning about cannabis consumption must be systematic and targeted medical care should be offered.

The dissimilar costs of love and war: age-specific mortality as a function of the operational sex ratio.

Lifespan and ageing are strongly affected by many environmental factors, but the effects of social environment on these life-history traits are not well understood. We examined effects of social interaction on age-specific mortality rate in the sexually dimorphic neriid fly Telostylinus angusticollis. We found that although interaction with other individuals reduced longevity of both sexes, the costs associated with variation in operational sex ratio were sex specific: males' early-life mortality rate increased, and lifespan decreased, with increasing male bias in the sex ratio, whereas surprisingly, the presence of males had no effect on early-life mortality or lifespan of females. Intriguingly, early-life (immediate) mortality costs did not covary with late-life (latent) costs. Rather, both sexes aged most rapidly in a social environment dominated by the opposite sex. Our findings suggest that distinct reproductive activities, such as mating and fighting, impose different age-specific patterns of mortality, and that such costs are strongly sex specific.

Homeopathic Individualized Q-Potencies versus Fluoxetine for Moderate to Severe Depression: Double-Blind, Randomized Non-Inferiority Trial.

Homeopathy is a complementary and integrative medicine used in depression, The aim of this study is to investigate the non-inferiority and tolerability of individualized homeopathic medicines [Quinquagintamillesmial (Q-potencies)] in acute depression, using fluoxetine as active control. Ninety-one outpatients with moderate to severe depression were assigned to receive an individualized homeopathic medicine or fluoxetine 20 mg day(-1) (up to 40 mg day(-1)) in a prospective, randomized, double-blind double-dummy 8-week, single-center trial. Primary efficacy measure was the analysis of the mean change in the Montgomery & Åsberg Depression Rating Scale (MADRS) depression scores, using a non-inferiority test with margin of 1.45. Secondary efficacy outcomes were response and remission rates. Tolerability was assessed with the side effect rating scale of the Scandinavian Society of Psychopharmacology. Mean MADRS scores differences were not significant at the 4th (P = .654) and 8th weeks (P = .965) of treatment. Non-inferiority of homeopathy was indicated because the upper limit of the confidence interval (CI) for mean difference in MADRS change was less than the non-inferiority margin: mean differences (homeopathy-fluoxetine) were -3.04 (95% CI -6.95, 0.86) and -2.4 (95% CI -6.05, 0.77) at 4th and 8th week, respectively. There were no significant differences between the percentages of response or remission rates in both groups. Tolerability: there were no significant differences between the side effects rates, although a higher percentage of patients treated with fluoxetine reported troublesome side effects and there was a trend toward greater treatment interruption for adverse effects in the fluoxetine group. This study illustrates the feasibility of randomized controlled double-blind trials of homeopathy in depression and indicates the non-inferiority of individualized homeopathic Q-potencies as compared to fluoxetine in acute treatment of outpatients with moderate to severe depression.

Transdermal nicotine in non-smokers: A systematic review to design COVID-19 clinical trials.

Recent data show an interaction between COVID-19 and nicotine and indicate the need for an assessment of transdermal nicotine use in non-smokers. Assessments have been conducted into the short-term cognitive effects of nicotine and into diseases such as Parkinson's, Tourette syndrome, ADHD or ulcerative colitis. METHODS: Analyses of nicotine administration protocols and safety were conducted after reviewing Medline and Science Direct databases performing a search using the words [transdermal nicotine] AND [non-smoker] AND selected diseases. RESULTS: Among 298 articles identified, there were 35 reviewed publications reporting on 33 studies of non-smokers receiving transdermal nicotine for >48hours. In the 16 randomized trials, 7 crossover, 1 case/control and 9 open studies patients received an initial nicotine dose of between 2.5mg and 15mg/day. In 22 studies, daily doses increased by 2 to 7 steps in 3 to 96 days until the dose was between 5mg and 105mg/day. The target nicotine dose was 19.06±20.89mg/day. The 987 non-smokers (534 never-smokers, 326 ex-smokers and 127 classified as "non-smokers") received or did not receive nicotine. The most common side-effects were nausea and skin itching. Forty-three (7.1%) non-smokers stopped treatment because of an adverse event of nicotine. No hospitalization related to nicotine side-effects were reported. CONCLUSION: Despite a relatively safe tolerance profile, transdermal nicotine therapy in non-smokers can only be used in clinical trials. There is a lack of formal assessment of the potential risk of developing a tobacco addiction. This review offers baseline data to set a transdermal nicotine protocol for non-smokers with a new purpose.

Take action to prevent diabetes--the IMAGE toolkit for the prevention of type 2 diabetes in Europe.

When we ask people what they value most, health is usually top of the list. While effective care is available for many chronic diseases, the fact remains that for the patient, the tax payer and the whole of society: prevention is better than cure. Diabetes and its complications are a serious threat to the survival and well-being of an increasing number of people. It is predicted that one in ten Europeans aged 20-79 will have developed diabetes by 2030. Once a disease of old age, diabetes is now common among adults of all ages and is beginning to affect adolescents and even children. Diabetes accounts for up to 18 % of total healthcare expenditure in Europe. The good news is that diabetes is preventable. Compelling evidence shows that the onset of diabetes can be prevented or delayed greatly in individuals at high risk (people with impaired glucose regulation). Clinical research has shown a reduction in risk of developing diabetes of over 50 % following relatively modest changes in lifestyle that include adopting a healthy diet, increasing physical activity, and maintaining a healthy body weight. These results have since been reproduced in real-world prevention programmes. Even a delay of a few years in the progression to diabetes is expected to reduce diabetes-related complications, such as heart, kidney and eye disease and, consequently, to reduce the cost to society. A comprehensive approach to diabetes prevention should combine population based primary prevention with programmes targeted at those who are at high risk. This approach should take account of the local circumstances and diversity within modern society (e.g. social inequalities). The challenge goes beyond the healthcare system. We need to encourage collaboration across many different sectors: education providers, non-governmental organisations, the food industry, the media, urban planners and politicians all have a very important role to play. Small changes in lifestyle will bring big changes in health. Through joint efforts, more people will be reached. The time to act is now.