Psychostimulants: Influence on Body Mass Index and Height in a Pediatric Population with Attention-Deficit/Hyperactivity Disorder?

Objectives: Attention-deficit/hyperactivity disorder (ADHD) is often treated with psychostimulants. Psychostimulants' adverse effects on body mass index standard deviation score (BMI-sds) and height in children/adolescents with ADHD have been reported. However, literature is inconsistent, and it is unclear whether the observed effects are dosage- and/or BMI-dependent. Therefore, the aim of this retrospective observational study is to evaluate the influence of psychostimulants on BMI-sds and height-sds in a pediatric cohort with ADHD from an outpatient clinic, and to study the correlation between psychostimulant dosage and BMI-sds and height-sds change.Method: Participants ≤18 years of age diagnosed with ADHD who started with psychostimulants (methylphenidate) were studied. Changes in BMI-sds and height-sds over an 18-month treatment period were assessed in subgroups according to baseline BMI-sds, gender, and age. Furthermore, correlations between BMI-sds, height-sds, and psychostimulant dose were studied.Results: In total, 298 participants [median age 9.8 years, height-sds 0.0, BMI-sds 0.5, psychostimulant dosage 0.5 (0.2–1.4) mg/kg/day] were analyzed, with an underweight, overweight, and obesity prevalence of 5%, 21%, and 7%, respectively. After 18 months of treatment a significant decline in BMI-sds (−0.4) and height-sds (−0.2) was observed. These effects were consistent in all subgroups except for no change in BMI-sds in the underweight subgroup and no change in height-sds in the overweight subgroup. Medication dosage was weakly correlated with change in BMI-sds [r = −0.3 (−0.9 to +0.5); p r = −0.2 (−0.4 to −0.1); p = 0.01].Conclusion: After 18 months of psychostimulant treatment, a significant decline in BMI-sds and height-sds was observed. However, the correlation with psychostimulant dosage was weak, and the decline was not observed in all subgroups. Therefore, further studies on the etiology of BMI-change are warranted, particularly with regard to the ADHD symptoms.Pharmacolog

Differential metabolic host response to pathogens associated with community-acquired pneumonia

BACKGROUND\nMETHOD\nRESULTS\nCONCLUSIONS\nMetabolic changes induced by the host immune response to pathogens found in patients with community-acquired pneumonia (CAP) may provide insight into its pathogenesis. In this study, we characterized differences in the host metabolic response to common CAP-associated pathogens.\nTargeted metabolomic profiling was performed on serum samples obtained from hospitalized CAP patients (n = 119) at admission. We quantified 347 unique metabolites across multiple biochemical classes, including amines, acylcarnitines, and signaling lipids. We evaluated if unique associations between metabolite levels and specific CAP-associated pathogens could be identified.\nSeveral acylcarnitines were found to be elevated in C. burnetii and herpes simplex virus and lowered in M. pneumoniae as compared to other pathogens. Phenylalanine and kynurenine were found elevated in L. pneumophila as compared to other pathogens. S-methylcysteine was elevated in patients with M. pneumoniae, and these patients also showed lowered cortisol levels in comparison to almost all other pathogens. For the herpes simplex virus, we observed a unique elevation of eicosanoids and several amines. Many lysophosphatidylcholines showed an altered profile in C. burnetii versus S. pneumoniae, L. pneumophila, and respiratory syncytial virus. Finally, phosphatidylcholines were negatively affected by the influenza virus in comparison to S. pneumoniae.\nIn this exploratory analysis, metabolites from different biochemical classes were found to be altered in serum samples from patients with different CAP-associated pathogens, which may be used for hypothesis generation in studies on differences in pathogen host response and pathogenesis of CAP.Pharmacolog

Randomized Controlled Trial on the Influence of Intraoperative Remifentanil versus Fentanyl on Acute and Chronic Pain after Cardiac Surgery

Remifentanil has been associated with increased acute and potentially chronic postoperative pain. The objective of this prospective randomized controlled trial was to investigate the influence of intraoperative remifentanil on acute and chronic postoperative pain after cardiac surgery.\nPatients (N = 126) receiving standardized anesthesia with propofol and intermittent intravenous fentanyl at predetermined times for cardiac surgery were randomized to intraoperatively receive either a continuous remifentanil infusion or additional intermittent intraoperative fentanyl as needed. The primary endpoint was chronic thoracic pain at 12 months after surgery. Secondary endpoints were pain at 3 and 6 months after surgery and analgesic requirements and pain levels in the first 72 hours.\nThere was no significant difference in incidence of chronic thoracic pain between the remifentanil and fentanyl groups, respectively (20% vs. 18%; P = 0.817). At 3 months, however, significantly more patients in the remifentanil group reported chronic thoracic pain (51% vs. 33%; P = 0.047). This effect was more pronounced in younger patients and in patients receiving a higher dose of remifentanil (both P < 0.05). The first 24 and 48 hours postoperatively, morphine consumption in the remifentanil group was significantly higher than in the fentanyl group (34.3 mg [interquartile range (IQR) 25.3 to 48.2] vs. 30.2 mg [IQR 19.2 to 38.1], P = 0.028; and 46.8 mg [IQR 33.8 to 59.2] vs. 39.0 mg [IQR 6.2 to 51.4], P = 0.047, respectively).\nIntraoperative use of remifentanil during cardiac surgery does not impact chronic postoperative pain 1 year after surgery. Nevertheless, remifentanil increases analgesic requirements and thoracic pain until 3 months after surgery, and its use is therefore less favorable during cardiac surgery.\nBACKGROUND\nMETHODS\nRESULTS\nCONCLUSIONSPharmacolog

Recommendations for antibacterial therapy in adults with COVID-19-an evidence based guideline

Scope: The Dutch Working Party on Antibiotic Policy constituted a multidisciplinary expert committee to provide evidence-based recommendation for the use of antibacterial therapy in hospitalized adults with a respiratory infection and suspected or proven 2019 Coronavirus disease (COVID-19).Methods: We performed a literature search to answer four key questions. The committee graded the evidence and developed recommendations by using Grading of Recommendations Assessment, Development, and Evaluation methodology.Questions addressed by the guideline and Recommendations: We assessed evidence on the risk of bacterial infections in hospitalized COVID-19 patients, the associated bacterial pathogens, how to diagnose bacterial infections and how to treat bacterial infections. Bacterial co-infection upon admission was reported in 3.5% of COVID-19 patients, while bacterial secondary infections during hospitalization occurred up to 15%. No or very low quality evidence was found to answer the other key clinical questions. Although the evidence base on bacterial infections in COVID-19 is currently limited, available evidence supports restrictive antibiotic use from an antibiotic stewardship perspective, especially upon admission. To support restrictive antibiotic use, maximum efforts should be undertaken to obtain sputum and blood culture samples as well as pneumococcal urinary antigen testing. We suggest to stop antibiotics in patients who started antibiotic treatment upon admission when representative cultures as well as urinary antigen tests show no signs of involvement of bacterial pathogens after 48 hours. For patients with secondary bacterial respiratory infection we recommend to follow other guideline recommendations on antibacterial treatment for patients with hospital-acquired and ventilator-associated pneumonia. An antibiotic treatment duration of five days in patients with COVID-19 and suspected bacterial respiratory infection is recommended upon improvement of signs, symptoms and inflammatory markers. Larger, prospective studies about the epidemiology of bacterial infections in COVID-19 are urgently needed to confirm our conclusions and ultimately prevent unnecessary antibiotic use during the COVID-19 pandemic. (C) 2020 The Author(s). Published by Elsevier Ltd on behalf of European Society of Clinical Microbiology and Infectious Diseases.Immunogenetics and cellular immunology of bacterial infectious disease

Burden and risk factors for Pseudomonas aeruginosa community-acquired pneumonia:a Multinational Point Prevalence Study of Hospitalised Patients

Pseudornonas aeruginosa is a challenging bacterium to treat due to its intrinsic resistance to the antibiotics used most frequently in patients with community-acquired pneumonia (CAP). Data about the global burden and risk factors associated with P. aeruginosa-CAP are limited. We assessed the multinational burden and specific risk factors associated with P. aeruginosa-CAP. We enrolled 3193 patients in 54 countries with confirmed diagnosis of CAP who underwent microbiological testing at admission. Prevalence was calculated according to the identification of P. aeruginosa. Logistic regression analysis was used to identify risk factors for antibiotic-susceptible and antibiotic-resistant P. aeruginosa-CAP. The prevalence of P. aeruginosa and antibiotic-resistant P. aeruginosa-CAP was 4.2% and 2.0%, respectively. The rate of P. aeruginosa CAP in patients with prior infection/colonisation due to P. aeruginosa and at least one of the three independently associated chronic lung diseases (i.e. tracheostomy, bronchiectasis and/or very severe chronic obstructive pulmonary disease) was 67%. In contrast, the rate of P. aeruginosa-CAP was 2% in patients without prior P. aeruginosa infection/colonisation and none of the selected chronic lung diseases. The multinational prevalence of P. aeruginosa-CAP is low. The risk factors identified in this study may guide healthcare professionals in deciding empirical antibiotic coverage for CAP patients

Drug effects on the risk and prognosis of community-acquired pneumonia

This thesis presents a series of studies exploring the hypothesis that both ACE-inhibitors and statins, besides their intended effects, reduce the risk of acquiring pneumonia. Furthermore, as the burden of pneumonia is not only determined by its incidence but also by a high mortality, another widely prescribed class of drugs, antibiotics, is evaluated in relation to the prognosis of pneumonia. In chapter 2 of the thesis the predictive value of antibiotic use prior to hospital admission for pneumonia is examined regarding microbial etiology and clinical outcome. Initial outpatient treatment with beta-lactam antibiotics increased the change of finding atypical pathogens threefold and decreased the probability of pneumococcal pneumonia to a similar degree, whereas, outpatient macrolide treatment was associated with an increased probability of viral pneumonia. Additionally, the possibility that non-responsiveness to outpatient treatment compromises outcome was studied. Prior outpatient therapy showed no association with length of hospital stay nor in-hospital mortality, except for a subgroup of patients with heart failure. These patients had a decreased change of survival after prior outpatient treatment. The use of ACE-inhibitors was examined in patients with diabetes and was associated with a significant dose-dependent protection against pneumonia. The effect was strongest in patients with a recent history of stroke. The latter supports the proposed mechanism of action that ACE-inhibitors prevent aspiration of oropharyngeal flora through improvement of the cough reflex. Additional study showed that the identified ACE insertion/deletion polymorphism is not associated with the risk neither outcome of community-acquired pneumonia. This in contrast with previous findings in Asian populations. reporting the ACE D allele as an independent risk factor for pneumonia. Possibly, the ACE I/D polymorphism is not a functional polymorphism but rather a marker for the true polymorphism for which the linkage differs among ethnic groups. Regarding ACE as a biomarker, serum ACE activity was studied during hospital stay in patients with pneumonia and appeared significantly decreased during the acute phase of pneumonia with return to control level at recovery. Serum ACE activity showed a significant inverse correlation with disease severity as quantified using Acute Physiology Score. The diagnostic and prognostic value of decreased serum ACE activity needs to be further established. Statin use was associated with a significant 50% reduction in pneumonia risk in patients with diabetes. The association was similar for all sorts of statins and independent of trends in prescribing. Regarding this association, the possibility of residual confounding due to selective prescribing of statins to patients with longer life-expectancy could not be excluded. The findings from this thesis were confirmed in four other studies published recently. The last chapter of this thesis focused on the accuracy of International Classification of Diseases codes for identifying patients with pneumonia in administrative databases. The sensitivity for detecting patients with pneumonia in Dutch hospital databases was modest (72%) and dependent on duration of hospital stay. This implies that patients with prolonged and probably complicated hospital-stay are underrepresented in hospital databases. The positive predictive value for coded hospital discharge records as a marker for pneumonia was high (88%)

Host-response biomarkers for the diagnosis of bacterial respiratory tract infections

Appropriate antibiotic treatment for respiratory tract infections (RTIs) necessitates rapid and accurate diagnosis of microbial etiology, which remains challenging despite recent innovations. Several host response-based biomarkers due to infection have been suggested to allow discrimination of bacterial and non-bacterial microbial RTI etiology. This review provides an overview of clinical studies that investigated the diagnostic performance of host-response proteomic biomarkers to identify RTI microbial etiology. Procalcitonin and C-reactive protein have been studied most extensively; whereof procalcitonin has demonstrated the strongest diagnostic performance compared to other biomarkers. Proadrenomedullin, soluble triggering receptor expressed on myeloid cells-1, neopterin and pentraxin-3 need more studies to confirm their diagnostic value. For syndecan-4 and lipocalin-2 currently insufficient evidence exists. Common limitations in several of the studies were the relatively small scale setting, heterogeneous patient population and the absence of statistical power calculation.Pharmacolog

Beperkte gezondheidsvaardigheden vormen risico bij ziekenhuisopname: Ruim helft patiënten heeft moeite met complexe gezondheidsbeslissingen

Patiënten die in het ziekenhuis worden opgenomen kunnen door beperkte gezondheidsvaardigheden problemen hebben met instructies. Zorg-op-maat kan het risico op (geneesmiddelgerelateerde) problemen tijdens (en na) opname verminderen. Voor zorgverleners is het daarom van belang inzicht te hebben in de gezondheidsvaardigheden van een patiënt