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BackgroundThe influence of selective serotonin reuptake inhibitors (SSRIs) on blood pressure is poorly understood. We hypothesized that if SSRIs have an influence on blood pressure, this might become manifest in changes in intraoperative blood pressure. We aimed to study the association between perioperative use of SSRIs and changes in intraoperative blood pressure by measuring the occurrence of intraoperative hyper- and hypotension.MethodsWe conducted a retrospective observational follow-up study among patients who underwent elective primary total hip arthroplasty. The index group included users of SSRIs. The reference group included a random sample (ratio 1:3) of nonusers of an antidepressant agent. The outcome was the occurrence of intraoperative hypo- and hypertensive episodes (number, mean and total duration, and area under the curve (AUC)). The outcome was adjusted for confounding factors using regression techniques.ResultsThe index group included 20 users of an SSRI. The reference group included 60 nonusers. Users of SSRIs showed fewer intraoperative hypotensive episodes, a shorter mean and total duration, and a smaller AUC when compared to the reference group. After adjustment for confounders, SSRI use was associated with a significantly shorter total duration of hypotension: mean difference of −29.4 min (95% confidence interval (CI) −50.4 to −8.3). Two users of an SSRI and two patients in the reference group had a hypertensive episode.ConclusionsContinuation of treatment with SSRIs before surgery was associated with a briefer duration of intraoperative hypotension.American Journal of Hypertension (2012). doi:10.1038/ajh.2011.194 [ABSTRACT FROM AUTHOR]

Context: A biomarker for discriminating mechanisms of chemotherapy-induced thrombocytopenia (CIT) (i.e. increased platelet destruction and decreased platelet production) would be valuable in managing treatment. Objective: We explored the discriminating value of platelet size indices for this purpose in a population of adult oncology patients. Materials and methods: Mean platelet volume (MPV) and platelet distribution width (PDW) were compared between patients with (i) thrombocytopenia possibly due to increased platelet destruction; (ii) thrombocytopenia possibly due to decreased platelet destruction; and (iii) no thrombocytopenia. Results and conclusions: We obtained negative results, suggesting that these indices are not useful for discriminating different CIT mechanisms. [ABSTRACT FROM AUTHOR]

Background and objective: Atrial fibrillation is an indication for oral anticoagulation treatment. Maintaining the International Normalized Ratio (INR) within the therapeutic range minimises thromboembolic and bleeding complications. We have investigated whether cognitive capacity affects control of anticoagulation in elderly patients with atrial fibrillation. Patients and methods: A retrospective study was conducted to investigate the association between cognitive impairment and control of anticoagulation. Patients ≥70 years of age with atrial fibrillation using acenocoumarol (nicoumalone) as anticoagulant were included. All patients were monitored by the Anticoagulation Clinic in the Midden-Brabant region in the Netherlands. The cognitive function of all patients was assessed using the Mini-Mental State Examination (MMSE) on the index date. INR values were obtained from the year preceding the index date. Patients with an MMSE score <23 were defined as cognitively impaired. The primary outcome of the study was the incidence of an INR value within the therapeutic range of 2.0–3.4 during ≤70% of treatment time in the year prior to the cognitive function assessment. The secondary endpoint was the number of patients with an INR <2.0 or ≥6.0 at least once during this year. Logistic regression analysis was used to evaluate the association between cognitive function and control of anticoagulation. Results: A total of 152 patients were included in the study. An MMSE score <23 was associated with an inadequate INR control (odds ratio [OR] 2.77; 95% CI 1.13, 6.74). After correction for hospital admission and change of possibly interacting medication (both also associated with inadequate INR control), this association remained statistically significant. Significantly more patients with an MMSE score <23 had one or more INR values of six or higher (OR 3.06; 95% CI 1.14, 8.18). Conclusion: In elderly people with atrial fibrillation using oral anticoagulation, an MMSE score <23 is independently associated with an inadequate INR control, mainly because of an increased number of supratherapeutic INR values. This finding should be taken into account when making decisions about use of oral anticoagulants in the elderly. [ABSTRACT FROM AUTHOR]

Background: Persistence with lipid-lowering drug use is important in order for patients to gain full treatment benefit. The withdrawal of cerivastatin from the market may have affected persistence due to the fear of serious adverse effects.Objective: To assess failure of patients to continue lipid-lowering drug use following the withdrawal of cerivastatin.Methods: A cohort study including 3.5 months follow-up after the withdrawal of cerivastatin in August 2001 was conducted using data from community pharmacies in The Netherlands, covering a population of approximately 600,000 subjects. Patients selected for inclusion in the index group were current users of cerivastatin on August 10, 2001 (the date that cerivastatin was withdrawn from the market). Reference patients were gender, age and pharmacy or region matched patients who were using any HMG-CoA reductase inhibitor other than cerivastatin on the same date. The main outcome measure was discontinuation of lipid-lowering drug use. To assess whether discontinuation had increased in the reference group, discontinuation rates were compared with discontinuation rates in the previous year. Data on these rates in 2000 were obtained from the population-based PHARMO record linkage system.Results: A total of 31 pharmacies of the research network (response rate 86.1%) provided medication histories of 234 current users of cerivastatin and 431 matched patients using any other HMG-CoA reductase inhibitor. In addition, 352 current users of cerivastatin and 704 matched patients using any other HMG-CoA reductase inhibitor were obtained from the PHARMO database. Overall, 13.7% of subjects in the cerivastatin group (n=586) and 9.5% in the reference group (n=1135) discontinued lipid-lowering medication (adjusted odds ratio [OR] 1.44; 95% CI 1.04-2.00). The rate of discontinuation in the reference group was comparable to this rate in the previous year. Discontinuation was more prevalent in women who had been taking cerivastatin (adjusted OR 1.74; 95% CI 1.09-2.78), those receiving low doses of cerivastatin (adjusted OR 2.45; 95% CI 1.20-4.97), those who received their last cerivastatin prescription from a specialist (adjusted OR 1.92; 95% CI 1.02-3.60) and those who had recently started using cerivastatin (adjusted OR 2.80; 95% CI 0.98-7.98), although the latter was not statistically significant.Conclusions: Failure to continue lipid-lowering drug use was higher in patients using cerivastatin than in users of other HMG-CoA reductase inhibitors, especially in women, those using low doses of HMG-CoA reductase inhibitors and recent starters of lipid-lowering medication. The prevention of unwarranted discontinuation of drugs due to market withdrawal should be a joint task of healthcare providers, industry and regulatory bodies. [ABSTRACT FROM AUTHOR]

• Exposure to drugs with anticholinergic effects before ICU admission increases the risk of developing delirium. • The effect is more pronounced in the first days of the ICU admission. • Advanced age and septic shock increases the risk for delirium in ICU patients. • The ADS scale can be effectively used to measure anticholinergic load in ICU patients. Anticholinergic drugs may increase the risk of delirium in non-critically ill patients, but it is unclear whether exposure to these drugs is also a risk factor for Intensive Care Unit (ICU) delirium. In this study the hypothesis was tested that anticholinergic drug exposure at ICU admission increases the risk to develop delirium during ICU stay, particularly in patients with advanced age and severe sepsis. A prospective cohort study was performed in the mixed 32-bed medical-surgical ICU of the University Medical Center Utrecht, the Netherlands in the period from January 2011 till June 2013. Included were nonneurological patients that were consecutively admitted for more than 24 hours. The presence of delirium was evaluated each day using a validated algorithm based on the Confusion Assessment Method for the ICU (CAM-ICU), the initiation of delirium treatment as well as chart review by researchers. Anticholinergic drug exposure at ICU admission was assessed using the Anticholinergic Drug Scale (ADS). To evaluate the association between anticholinergic drug exposure at ICU admission and the risk of developing delirium, we performed multivariable competing risk Cox proportional hazard analysis corrected for confounding factors. Approximately half (47%, n=513) of the 1090 included patients developed delirium during ICU admission. The absolute risk for delirium development increased with more anticholinergic drug exposure: 42% in patients with ADS score=0, 49% in patients with ADS score=1, and 53% in patients with ADS higher than 1. Taking competing events (death and discharge) and potential confounding factors into account, the subdistribution hazard ratio (SHR) was 1.13 (95% CI: 0.91-1.40) for ADS score=1 point and 1.35 (95% CI: 1.09-1.68) for ADS ≥2 compared with an ADS score=0 (no anticholinergic drug exposure). The effect was strongest during the first days of ICU admittance and was strongest in patients above 65 year without severe sepsis and/or septic shock (SHR 2.15, 95% CI 1.43-3.25). Anticholinergic drug exposure at ICU admission increases the risk of delirium in critically ill patients. This effect was most pronounced in patients older than 65 years without severe sepsis and/or septic shock, and declining over time. [ABSTRACT FROM AUTHOR]

Presents a study on the early detection of known and unknown adverse drug reactions. Incidence of patient and doctor reporting of drug side effects; Impact on pharmacovigilance.

• Impulse control disorders can result in devastating psychosocial consequences. • Dopamine receptor agonists, psychostimulants, and dopaminergic antidepressants are associated with disproportionally frequent reporting of impulse control disorders. • Impulse control disorders may resemble symptoms of the underlying condition and may not be recognised as side effects. • Monitoring for impulse control disorders is recommended when prescribing dopaminergic drugs. Dopamine receptor agonist drugs, which are used, for example, to treat Parkinson's disease (PD), increase the risk for impulse control disorders (ICDs), potentially resulting in devastating psychosocial consequences. It is unknown whether other drugs with dopaminergic properties also increase the risk for ICDs. This study assesses the disproportionality of reporting ICDs between drugs with dopaminergic properties and selected non-dopaminergic drugs. A case/non-case disproportionality analysis was performed, using data from VigiBase (1968–2020). Reports on ICDs as suspected adverse drug reactions (ADRs) were cases (n=852) , and those with ADRs other than ICDs were non-cases (n =281,720). Relative reporting frequencies were expressed as adjusted reporting odds ratios (aRORs). Within the dopamine receptor agonists, the relationship between reporting odds ratios and dopamine receptor occupancy was explored. A high disproportionality was found for reporting ICDs for all dopaminergic drugs (aROR 20.4 [95% CI 17.4–24.1]) compared to non-dopaminergic drugs. In pharmacotherapeutic subgroups, a high disproportionality was found for primary dopaminergic agents used in PD (aROR 52.1 [95% CI 44.1–61.5]), and to a lesser extent for ADHD psychostimulants and antidepressants (aROR 5.8 [95% 4.1–8.3] and aROR 3.9 [95% CI 2.9–5.6], respectively). There was no difference in reporting by consumers and healthcare professionals. The highest disproportionality was found for the dopamine receptor agonists pramipexole and ropinirole. A signal of disproportion in ICD occurrence was found among all investigated drugs with dopaminergic properties, highlighting the importance of counselling and monitoring for ICDs when prescribing dopaminergic drugs. [ABSTRACT FROM AUTHOR]

Highlights: [•] Knowledge of prognostic factors on intractability facilitates patient management. [•] Several prognosticators seem relevant to predict medically intractable epilepsy. [•] Prognostic value of genetic, neurobiological and immunological factors yet unclear. [Copyright &y& Elsevier]

Abstract: Aim: Both tricyclic antidepressants (TCAs) and selective serotonin reuptake inhibitors (SSRIs) have been associated with an increased risk of fractures. The serotonin transporter (5-HTT) has been located in the bone and may play a role in bone physiology. We assessed the association between antidepressant drug use, categorized in a therapeutical-based way and on basis of their affinity for the 5-HTT, and the risk of both osteoporotic and non-osteoporotic fractures. Methods: A case–control study was conducted using the PHARMO RLS. Cases were patients with a first hospital admission for a fracture during the study period. Up to four controls were matched to each case on gender, age, geographical area, and index date. Results: We identified 16,717 cases, of whom 59.5% had an osteoporotic fracture, and 61,517 controls. Compared to no use, current use of SSRIs was associated with a statistically significant increased risk of osteoporotic fractures (OR 1.95, 95% CI 1.69–2.26), as was current use of TCAs and non-SSRI/non-TCA antidepressant drugs (ORs 1.37, 95% CI 1.16–1.63 and 1.40, 95% CI 1.06–1.85, respectively). The risk of an osteoporotic fracture was statistically significantly higher for antidepressants with a high affinity for the 5-HTT (OR 1.86, 95% CI 1.63–2.13) compared to antidepressants with a medium or low affinity (OR 1.43, 95% CI 1.19–1.72 (medium) and OR 1.32 95% CI 0.98–1.79 (low) (p<0.05 for trend). The risk of non-osteoporotic fractures did not show the same trend. Conclusions: The extent of affinity for the 5-HTT may contribute to the increased risk of osteoporotic fractures related to antidepressant drug use. The pharmacological mechanism-based classification could to be an appropriate alternative for traditional classification to study the association between the use of antidepressants and the risk of fractures. [ABSTRACT FROM AUTHOR]

Background: In view of the high rates of off-label and unlicensed prescribing of drugs in children, the US Food and Drug Administration and the European Union have implemented legislative regulations for the pharmaceutical industry to increase the number of drugs with approved pediatric labeling. However, the extent to which the effects of pharmaceutical technologic aspects of pediatric oral drugs (eg, taste, route and frequency of administration, user instructions) on patient-related outcomes (eg, efficacy, tolerability, preference, adherence) can be based on clinical evidence from the available literature is unknown. Objective: This systematic literature review aimed to identify the nature, volume, and quality of comparative studies that have assessed the effects of pharmaceutical technologic aspects of oral pediatric drugs on patient-related outcomes. Methods: The Cochrane, EMBASE, and MEDLINE databases were searched from their start through December 31, 2009. Studies were eligible for inclusion if they were published in English; included search terms for child, study design, medicine, formulation aspects, dosage form, routes of administration, patient acceptance, adherence, side effects and tolerability, and/or efficacy; reported on ≥10 children aged 0 to <18 years; and described the effects of ≥1 of 3 pharmaceutical technologic aspects of an oral pediatric drug (formulation and dosage form; route and frequency of administration; and/or packaging, administration device, and user instruction) on ≥1 of 6 patient-related outcomes (clinical efficacy, side effects and tolerability, patient preference, patient acceptance, administration errors, and/or adherence). Studies were excluded if they concerned a nonallopathic drug (ie, homeopathic remedy, anthroposophic drug, herbal supplement, or food supplement); related to asthma (because modern asthma treatment protocols strongly favor the use of drug inhalation above oral medication); and/or related to analgesics. The characteristics of each of the included publications were assessed with respect to pharmaceutical technologic aspect studied; patient-related outcomes studied; pharmacotherapeutic indication; year of publication; geographic location; number and age of the included subjects; and sponsorship by industry and/or author affiliation with the pharmaceutical industry. The electronic search was supplemented with a manual search of the cited references. Results: Ninety-four publications were identified as eligible for inclusion. These publications reported on 176 assessments of the effects of ≥1 pharmaceutical technologic aspect on ≥1 patient-related outcome. Fiftyfive percent of the studies were conducted in children aged 2 or 3 years, and 69% in children aged 4 or 5 years. Forty-three percent of the publications included ≥100 patients. Fifty-one percent of the studies were conducted in the United States or Canada, and 29% in Europe. Antibacterials for systemic use were the subject of 30% of the included publications. Two of the 94 publications were of appropriate méthodologie quality (Jadad score ≥4). Forty-nine percent of the studies were sponsored by the pharmaceutical industry or were written by ≥1 author affiliated with the industry. Sixty-eight percent of the included studies had Jadad scores of 0 or 1 (poor quality). The proportion of industry-sponsored or industryauthored studies with a Jadad score ≥2 or in ≥100 children was not significantly different from that of non-industry-sponsored or-authored studies. The proportion of industry-sponsored or industry-authored studies conducted in the United States/Canada (48 [51%]) was not significantly different from that of studies conducted elsewhere (46 [49%]). The distribution of technologic aspects assessed in the included studies were formulation and dosage form, 48%; route and frequency of administration, 44%; and packaging, administration device, and user instruction, 8%. Seventy-six assessments included ≥100 patients. Twenty-one of these assessments addressed patient acceptance or patient preference; 17, clinical efficacy; and 14, side effects and tolerability. Conclusions: This systematic review identified 94 articles on oral drugs for use in children and adolescents, which reported on a total 176 assessments of the effects of 3 pharmaceutical technologic aspects (formulation and dosage form; route and frequency of administration; and packaging, administration device, and user instruction) on 6 patient-related outcomes (clinical efficacy, side effects and tolerability, patient preference, patient acceptance, administration errors, and adherence). Only 2 of the 94 publications were of appropriate methodologic quality. These results suggest that published clinical evidence to support pharmaceutical development programs is limited. [Copyright &y& Elsevier]

Objective: The aim of the study was to assess monitoring of adverse drug reaction (ADR)-related parameters in children, youth, and young adults treated with second-generation antipsychotic drugs (SGAs) prescribed by general practitioners (GPs). Methods: This retrospective follow-up study included children, youth, and young adults aged 0 - 24 years, who had an initial prescription of an SGA recorded in the Clinical Practice Research Datalink between 2000 and 2017, and who were prescribed an SGA more than once for a duration of at least 6 months. It included an assessment of which ADR-related physical parameters (weight, height, body-mass index, waist circumference, pulse, blood pressure, and heart examination) and laboratory parameters (glucose, HbA1c, lipids, and prolactin) were monitored in children, youth, and young adults at least once every 6-month period, stratified by sex, age categories, and calendar years. Results: In total, 7006 patients were included and the mean duration of follow-up was 1.6 years. Monitoring frequencies of all parameters were below 25%. Blood pressure and weight were monitored in 23.6% and 23.4%, respectively, of all children, youth, and young adults during the first half year; waist circumference was monitored in 0.2%. Females were monitored more often than males, some differences between age categories were observed, and monitoring frequencies increased after 2000, but did not exceed 35% in any year. Conclusion: Monitoring frequencies of ADR-related parameters in children, youth, and young adults treated with SGAs prescribed by a GP were low. Monitoring in primary care should be improved to enable a better evaluation of the benefit-risk balance during antipsychotic drug therapy. [ABSTRACT FROM AUTHOR]

The availability of ready-to-administer (RTA) syringes for intravenous (IV) drugs facilitates rapid and safe administration in emergency and intensive care situations. Hospital pharmacies can prepare RTA syringes through aseptic batchwise filling. Due to excess production of these RTA syringes for sufficient availability for patient care and their limited (microbiological) shelf-life, waste is unavoidable, which contributes to environmental pollution. RTA prefilled sterilized syringes (PFSSs) have much longer shelf-lives than aseptically prepared RTA syringes and might contribute to reducing drug waste. This study aimed to evaluate the difference in drug waste between RTA syringes that were prepared through aseptic batchwise filling and RTA PFSSs in the Intensive Care Unit (ICU). We measured drug waste of RTA syringes over an 8-year time period from August 2015 to May 2023 in the 32-bed ICU of the University Medical Center Utrecht. We distinguished between RTA syringes prepared through aseptic batchwise filling by our hospital pharmacy (" RTA aseptic syringes", shelf-life of 31 days) and RTA PFSSs (shelf-life of 18 months). An intervention group of three drug products that were replaced by PFSSs was compared to a control group of five drug products that were not replaced by PFSSs during the study period. We then defined four different periods within the total study period, based on quarantine time of the RTA aseptic syringes and time of PFSS introduction: 1) no quarantine, 2) 3-day quarantine, 3) 7-day quarantine and 4) PFSS introduction. Our primary endpoint was the number of RTA syringes that was wasted, expressed as the percentage of the total number of syringes dispensed to the ICU in each of these four periods. We used a Kruskall-Wallis test to test if waste percentages differed between time periods in the control and intervention groups, with a post-hoc Dunn's test for pairwise comparisons. Furthermore, we applied two interrupted time series (ITS) analyses to visualize and test the effect of introducing different quarantine times and the PFSSs on waste percentage. Introduction of PFSSs significantly decreased drug waste of RTA syringes irrespective of drug type in the intervention group, from 31% during the 7-day quarantine period to 5% after introduction of the PFSS (p <0.001). The control group showed no significant decrease in drug waste over the same time periods (from 20% to 16%; p =0.726). We observed a significant difference in the total drug waste of RTA aseptic syringes between time periods, which may be attributed to the implementation of different quality control quarantine procedures. The ITS model of the intervention group showed a direct decrease of 17.7% in waste percentage after the introduction of PFSSs (p =0.083). Drug waste of RTA syringes for the ICU can be significantly decreased by introducing PFSSs, supporting hospitals to enhance environmental sustainability. Furthermore, the waste percentage of RTA syringes prepared through aseptic batchwise filling is significantly impacted by duration of quarantine time. [Display omitted] [ABSTRACT FROM AUTHOR]

Background: Psychotropic drugs are prescribed to approximately 30-40% of adults with intellectual disability (ID) and challenging behaviour, despite the limited evidence of effectiveness and the potential of adverse events.Aims: To assess the prevalence of adverse events in association with psychotropic drug use in adults with ID and challenging behaviour and to examine the relation of these adverse events with the person's quality of life.Method: The presence of adverse events was measured with a questionnaire that had to be filled in by the physicians of the participants. Movement disorders were measured separately with a standardised protocol. The strength of the association between adverse events and Intellectual Disability Quality of Life-16 (IDQOL-16), and daily functioning was investigated using linear regression analyses, taking into account the severity of disease (CGI-S) as potential confounder.Results: Virtually all of 103 adults with ID and challenging behaviour had at least one adverse event (84.4%) and almost half had ≥3 adverse events (45.6%) across different subclasses. Using psychotropic drugs increased the prevalence of adverse events significantly. Respectively 13% of the patients without psychotropic drugs and 61% of the patients with ≥2 psychotropic drugs had ≥3 adverse events. Having adverse events had a significantly negative influence on the quality of life.Conclusions: A large majority of all patients had at least one adverse event associated with psychotropic drug use. More attention is needed for these adverse events and their negative influence on the quality of life of these patients, taking into account the lack of evidence of effectiveness of psychotropic drugs for challenging behaviour. [ABSTRACT FROM AUTHOR]

Introduction Children may be unable or unwilling to swallow medicines. In order to avoid or accommodate any such problems, parents may decide to administer medicines other than intended. The aim of this study was to investigate how parents administered four oral placebo formulations to infants and preschool children and how the applied methods correlated with child acceptability. Methods Parents were asked to administer a 4 mm mini-tablet, powder, suspension and syrup to their child twice on one day and to report the child characteristics and administration details in a participant diary. Results A 151 children were included. The tablet, syrup and suspension were mostly given on their own, whereas the powder was commonly given with food or drink. Generally, the higher the child acceptability (VAS-score) of the first administration of a specific formulation, the less frequently its method of administration was changed. A change in the method of administration of the same formulation involving (a larger quantity of) food or drink generally resulted in a higher VAS-score. Conclusions The joint administration of medicines with food or drink is an effective strategy to ensure swallowing. This study supports earlier findings that 4 mm mini-tablets are a suitable dosage form from infant age. [ABSTRACT FROM AUTHOR]

Abstract: Purpose: The purpose of this study was to determine whether homecare workers can detect signs and symptoms indicative of potential adverse drug reactions (ADRs) in homecare patients, using a standardized observation list. Methods: This observational study involved 115 patients cared for by 2 homecare organizations in The Netherlands between April 2011 and August 2011. During routine home visits, homecare workers filled out a standardized observation list of signs and symptoms indicative of potential ADRs, namely, gastrointestinal and other bleedings, electrolyte disturbances, renal and heart failure, digoxin intoxication, constipation, disturbances of diabetic control, and falls. Their observations were compared against the medications that the patients were using and their known side effects, by a panel of clinical pharmacology experts. Sensitivity, specificity, and positive and negative predicted values of the standardized observations were calculated. Results: In total, 234 signs and symptoms indicative of potential ADRs were observed by the homecare workers, 116 (49.6%) of which were considered drug related. More than one-half of the observed signs of gastrointestinal bleeding could be considered as drug related. Observed dizziness (64.1%) and drowsiness (53.3%) could be drug related in most cases, as could most cases (71.4%) of fainting spells (indicative of renal or heart failure). Seventeen of 20 observed falls could be drug related. The specificity of the standardized observation list was high, varying from 0.70 (confidence interval 0.62–0.77) to 0.97 (confidence interval 0.95–0.98). Conclusions: Signs and symptoms indicative of potential ADRs recorded by homecare workers using a standardized observation list can aid in the early recognition of ADRs in homecare patients. [Copyright &y& Elsevier]

Highlights: [•] High prevalence of psychotropic drug use in institutionalized children with mild ID. [•] Boys with behavioral problems have a higher risk of psychotropic drug use. [•] Worrisome high prevalence given unclear efficacy and adverse drugs reactions. [Copyright &y& Elsevier]

Abstract: The severity of complications of allogeneic hematopoietic stem cell transplantation (HSCT) is governed mainly by the status of immune reconstitution. In this study, we investigated differences in immune reconstitution with different cell sources and the association between the kinetics of immune reconstitution and mortality. Immunophenotyping was performed every 2 weeks in children who had undergone HSCT between 2004 and 2008 at University Medical Center Utrecht. Lymphocyte reconstitution in the first 90 days after HSCT was studied in relation to mortality in 3 HSCT groups: matched sibling bone marrow (BM) recipients (35 patients), unrelated BM recipients (32 patients), and unrelated cord blood recipients (36 patients). The median age of recipients was 5.9 years (range, 0.1-21 years). The nature and speed of T cell, B cell, and natural killer (NK) cell reconstitution were highly dependent on the cell source. In the first 90 days after HSCT, faster B cell and NK cell reconstitution and delayed T cell reconstitution were shown in unrelated cord blood recipients compared with matched sibling BM and unrelated BM recipients. Of the lymphocyte subsets investigated, a large number of NK cells and a more rapid CD4+ immune reconstitution over time, resulting in sustained higher CD4+ counts, were the only predictors of a lower mortality risk in all cell sources. The final model showed that during the first 90 days, patients with an area under the CD4+ cell receiver- operating curve of >4,300 cells/day and no peak in CD4+ cell counts had the highest likelihood of survival (hazard ratio for mortality, 0.2; 95% confidence interval, 0.06-0.5). Our data indicate that CD4+ kinetics may be used to identify patients at greatest risk for mortality early after HSCT. [Copyright &y& Elsevier]