Growth and population structure of Lodoicea maldivica in natural stands in Seychelles.

We monitored leaf production in seedlings, trunkless juvenile, immature, and mature male and female plants of the dioecious palm, Lodoicea maldivica, and studied how internode length changed with trunk height. The fieldwork was conducted in closed forest on Praslin Island and degraded forest on Curieuse Island. Data on numbers of leaves produced and rates of leaf production were used to estimate plant age. On Praslin, the interval between successive leaves increased from 0.47/0.52 years in male/female plants to 4.2 years in seedlings, and on Curieuse from 0.41/0.49 to 2.3 years. Estimated leaf lifespan was 6.4-6.8 years in mature palms and much longer in seedlings and juveniles. On Praslin, internode length increased from the base of the trunk to a mean of 14 cm at leaf 21, before declining to 2.75 cm above leaf 100. Mean internode length of the smaller palms on Curieuse was 1.9 cm and varied little with height. Plants at the same development stage varied widely in age. On Praslin, median time to maturity was 77 (range: 32-209) and on Curieuse 83 (31-191) years. The tallest palms on Praslin (28.4 m trunk height) and Curieuse (8 m) were estimated at 442 and 232 years old, respectively. The ageing method was used to interpret height data of different populations. All showed a marked decline in regeneration in the 19th or early 20th centuries, probably caused by fires. We conclude that slow growth makes this species very vulnerable to disturbance, especially from fire.

Patients' Emotional Talk During Surveillance Cystoscopy for Non-muscle Invasive Bladder Cancer: Opportunities for Improving Communication.

OBJECTIVE: To examine the emotional communication that takes place between patients and health care providers during surveillance cystoscopy for non-muscle invasive bladder cancer (NMIBC). METHODS: Participants were 57 patients with a diagnosis of NMIBC attending for surveillance cystoscopy and 10 health care professionals (HCPs). Cystoscopy procedures were audio-recorded and transcribed verbatim. Two approaches to analysis of transcriptions were undertaken: (1) a template analysis and (2) Verona Coding Definitions of Emotional Sequences. RESULTS: Communication during cystoscopy generally comprised of "social/small talk," "results of the cystoscopy," and "providing instructions to the patient." Emotional talk was present in 41/57 consultations, with 129 emotional cues and concerns expressed by patients. Typically patients used hints to their emotions rather than stating explicit concerns. The majority (86%) of HCPs responses to the patient did not explicitly mention the patient's emotional concern or cue. Urology trainees were less likely than other HCPs to provide space for patients to explore their emotional concerns (t = -1.78, P <.05). CONCLUSION: Emotional communication was expressed by the majority of patients during cystoscopy. While all HCPs responded to patients' emotional communication, there were a number of missed opportunities to "pick-up" on patients' emotional cues and improve communication. Urologists need to be aware of the nuances of patients' emotional communication. Learning to identify and respond appropriately to emotional cues may improve communication with patients.

Use of Ceftriaxone and Benzylpenicillin in Outpatient Parenteral Antimicrobial Therapy: Spectrum vs Cost.

Background: The application of antimicrobial stewardship (AMS) principles may entail increased cost to allow for narrower-spectrum therapy. Prescribing benzylpenicillin (BP) and ceftriaxone (CRO) for outpatient parenteral antimicrobial therapy (OPAT) demonstrates the complex challenge of this principle. The aim of this study is to analyze the use of BP and CRO in our OPAT program, including indications and relative cost. Methods: We analyzed all adult patients in our OPAT program who received intravenous BP or CRO over 1 year. We identified a "crossover group" of patients who could have received either agent. Economic comparison was based on acquisition cost of the therapy (drug, infuser, and preparation costs). Results: Of 105 eligible patients, 54 (51%) and 51 (49%) received BP and CRO, respectively. Forty (38%) patients were suitable for either agent; of these, the majority (n = 31, 78%) were treated with BP. Economic analysis demonstrated that the average daily cost of BP therapy was $93.76/d (AUD) vs $1.23/d for CRO. Thus, across our OPAT programs, we had an additional average cost of $92.53/patient/d to use BP instead of CRO. Program-wide the annual additional cost of using BP and thus applying this AMS strategy was $68 386.12. Conclusions: BP is often selected over CRO by clinicians, where possible, as recommended by the Australian guidelines; however, BP is associated with higher daily acquisition costs. More broadly, a number of narrower-spectrum agents may involve significantly higher costs than comparators; as such, the $92.53/d to prevent CRO exposure can be considered when applying other antimicrobial-substitution AMS interventions in an acute health care setting.

Healthcare Workers Beliefs about COVID-19; a Longitudinal, Mixed Methods Analysis.

The psychological impact of COVID-19 on Health Care Workers (HCWs) has been widely reported. Few studies have sought to examine HCWs personal models of COVID-19 utilising an established theoretical framework. We undertook a mixed methods study of beliefs about COVID-19 held by HCWs in the Mid-West and South of Ireland during the first and third waves of COVID-19. Template analysis was undertaken on the free text responses of 408 HCWs about their perceptions of the Cause of COVID-19 as assessed by the Brief Illness Perception Questionnaire (B-IPQ). Responses were re-examined in the same cohort for stability at 3 months follow-up (n = 100). This analytic template was subsequently examined in a new cohort (n = 253) of HCWs in the third wave. Female HCWs perceived greater emotional impact of COVID-19 than men (t = -4.31, df405, p < 0.01). Differences between occupational groups were evident in relation to Timeline (F4,401 = 3.47, p < 0.01), Treatment Control (F4,401 = 5.64, p < 0.001) and Concerns about COVID-19 (F4,401 = 3.68, p < 0.01). Administration staff believed that treatment would be significantly more helpful and that COVID-19 would last a shorter amount of time than medical/nursing staff and HSCP. However, administration staff were significantly more concerned than HSCP about COVID-19. Template analysis on 1059 responses to the Cause items of the B-IPQ identified ten higher order categories of perceived Cause of COVID-19. The top two Causes identified at both Waves were 'individual behavioural factors' and 'overseas travel'. This study has progressed our understanding of the models HCWs hold about COVID-19 over time, and has highlighted the utility of the template analysis approach in analysing free-text questionnaire data. We suggest that group and individual occupational identities of HCWs may be of importance in shaping HCWs responses to working through COVID-19.

Levonorgestrel-Releasing Intrauterine System Utilization in Patients with Developmental Delays.

INTRODUCTION: Adolescent females with developmental delays (DDs) experience unique physical and emotional challenges related to menstruation. Providers often recommend hormonal medication for menstrual management. The objective of our study was to describe the utilization and safety of the levonorgestrel-releasing intrauterine system (LNG-IUS) in adolescents with DDs. METHODS: We utilized the Pediatric Health Information System to identify females aged 10-25 with DDs who underwent an LNG-IUS insertion between 2011 and 2020. Using a gynecologic procedure and diagnosis codes, we assessed indications for and complications of LNG-IUS use. We also evaluated early LNG-IUS removal. RESULTS: One thousand five hundred and sixty female patients with DDs underwent LNG-IUS insertion. LNG-IUS insertion under anesthesia was most commonly performed in patients with autism and Down syndrome, and unspecified menstrual issues were documented for 40% of the cohort. Perforation was observed in 11 patients (1%), and mechanical complications (malpositioned IUS or lost threads) were observed in 23 patients (1%). DISCUSSION: This is the largest analysis of LNG-IUS use in patients with DDs to our knowledge and shows the utilization of LNG-IUS in patients with DDs. We provide descriptive information that providers can use to accurately advise their patients with DDs on the risks and benefits of LNG-IUS use for menstrual management.

A digital therapeutic for management of psychosocial aspects of psoriasis: A pre-post proof of concept study.

Background: Despite the psychosocial challenges of living with psoriasis many patients may not be able to access appropriate services to manage these challenges. Mobile health interventions may be helpful as a means to support patients in managing the impact of their condition. Objective: To conduct a preliminary examination of the feasibility and acceptability of a bespoke psoriasis-specific digital therapeutic solution (hereafter termed Allay), and to provide initial data on psychological changes pre-post. Methods: Phase one proof of concept pre-post study. Eligible patients were provided with Allay on their smartphone and assessed at baseline and at 12 weeks on a range of indices of well-being. Participants experiences on usability were collected by telephone interview at 4 weeks, 8 and 12 weeks. Results: Out of 66 participants recruited, 59 persisted in using Allay after the familiarisation phase, and 34 participants completed the 12 weeks programme. Participants showed a statistically significant improvement between induction and the end of the 12 weeks programme on Quality of life, Resilience, Perceptions of 'Overall impact' of psoriasis, and 'Emotional impact'. There was a significant change over the course of using Allay for symptoms of depression but not anxiety. While there was an interaction effect of changes in severity of psoriasis symptoms over the course of the study for dermatology-specific measures, there was no interaction between such changes in psoriasis symptoms and changes in depression, resilience or beliefs in emotional impact. Conclusions: Study results suggest that the use of Allay as an adjunct to medical management of psoriasis may help patients improve resilience, mood, beliefs about their condition and enhance their quality of life. Given that this is a phase one proof of concept study, and our rates of attrition further research is necessary to examine comparative effectiveness and stability of these findings.

Explaining the complex impact of the Covid-19 pandemic on children with overweight and obesity: a comparative ecological analysis of parents' perceptions in three countries.

BACKGROUND: The Covid-19 pandemic has changed children's eating and physical activity behaviours. These changes have been positive for some households and negative for others, revealing health inequalities that have ramifications for childhood obesity. This study investigates the pandemic's impact on families of children aged 2-6 years with overweight or obesity. METHODS: Drawing on interviews conducted as part of a randomised controlled trial (RCT) for childhood obesity, thematic analysis was used to examine how parents of pre-schoolers perceived changes in their eating, screentime and physical activity behaviours between the first and second waves of Covid-19. Parents (n = 70, representing 68 families) were interviewed twice during a period of 6 months in three countries with markedly different pandemic policies - Sweden, Romania, and Spain. The analysis is informed by Bronfenbrenner's ecological systems theory, which embeds home- and school-based influences within societal and policy contexts. RESULTS: The findings show that, although all participants were recruited from an RCT for families of children with excess weight, they reported different responses to the pandemic's second wave, with some children engaging in healthier eating and physical activity, and others engaging in comfort eating and a more sedentary lifestyle. Differences in children's obesity-related behaviours were closely related to differences in parents' practices, which were, in turn, linked to their emotional and social wellbeing. Notably, across all sites, parents' feeding and physical activity facilitation practices, as well as their emotional and social wellbeing, were embedded in household resilience. In resilient households, where parents had secure housing and employment, they were better able to adapt to the challenges posed by the pandemic, whereas parents who experienced household insecurity found it more difficult to cope. CONCLUSIONS: As the Covid-19 pandemic is turning into a long-term public health challenge, studies that address household resilience are crucial for developing effective prevention and treatment responses to childhood obesity.

Patient reported psychosocial functioning following successful ptosis surgery.

BACKGROUND: Ptosis may result in increased anxiety, appearance-related distress and social avoidance, and impacts visual function. Previous work demonstrates the benefits of ptosis surgery for health-related quality of life, but there is a paucity of research comparing such outcomes before and after surgery. The aim of this study was to determine potential patient benefits in health-related quality of life, social dysfunction and anxiety following successful ptosis surgery using validated measures. METHODS: Adult ptosis correction surgery patients completed validated measures of appearance-related social anxiety and avoidance, anxiety and depression, and fear of negative evaluation pre-surgery. Following successful surgery, these measures were repeated post-discharge in addition to another health-related quality of life measure. RESULTS: Of 61 patients recruited, follow-up measures were sent to 33 and completed by 23. Paired samples t-tests demonstrated positive significant changes in appearance-related social distress pre-op m = 30.94, post-op m = 23.67 (t(17) = 3.46, 95% CI 2.84-11.72, p = 0.003), anxiety pre-op m = 7.6, post-op m = 4.9 (t(19) = 4.27, 95% CI 1.38-4.02, p < 0.001) and fear of negative evaluation pre-op m = 34.79, post-op m = 31.26 (t(18) = 2.47, 95% CI 0.52-6.53, p = 0.024). There was no significant difference in depression scores pre-op m = 3.6; post-op m = 3.2 (t(19) = 0.672, 65% CL -0.85 to 1.65, p = 0.510). In total, 85% of patients reported positive benefit to well-being following surgery. CONCLUSION: Increasingly, evidence suggests ptosis surgery may benefit patient's well-being, appearance-related social anxiety and avoidance, as well as improving visual function. These psychosocial benefits should be considered alongside functional benefits in the provision of ptosis surgery.

Electronic collection of patient-reported outcomes following discharge after surgery: systematic review.

BACKGROUND: Little is known about the electronic collection and clinical feedback of patient-reported outcomes (ePROs) following surgical discharge. This systematic review summarized the evidence on the collection and uses of electronic systems to collect PROs after discharge from hospital after surgery. METHOD: Systematic searches of MEDLINE, Embase, PsycINFO, CINAHL and Cochrane Central were undertaken from database inception to July 2019 using terms for 'patient reported outcomes', 'electronic', 'surgery' and 'at home'. Primary research of all study designs was included if they used electronic systems to collect PRO data in adults after hospital discharge following surgery. Data were collected on the settings, patient groups and specialties, ePRO systems (including features and functions), PRO data collected, and integration with health records. RESULTS: Fourteen studies were included from 9474 records, including two RCTs and six orthopaedic surgery studies. Most studies (9 of 14) used commercial ePRO systems. Six reported types of electronic device were used: tablets or other portable devices (3 studies), smartphones (2), combination of smartphones, tablets, portable devices and computers (1). Systems had limited features and functions such as real-time clinical feedback (6 studies) and messaging service for patients with care teams (3). No study described ePRO system integration with electronic health records to support clinical feedback. CONCLUSION: There is limited reporting of ePRO systems in the surgical literature, and ePRO systems lack integration with hospital clinical systems. Future research should describe the ePRO system and ePRO questionnaires used, and challenges encountered during the study, to support efficient upscaling of ePRO systems using tried and tested approaches.

Patient experiences of an electronic PRO tailored feedback system for symptom management following upper gastrointestinal cancer surgery.

PURPOSE: Complications following upper gastrointestinal (UGI) surgery are common. Symptom-monitoring following discharge is not standardized. An electronic patient-reported outcome (ePRO) system providing feedback to patients and clinicians could support patients and improve outcomes. Little is known about patients' experiences of using such systems. This qualitative sub-study explored patients' perspectives of the benefits of using a novel ePRO system, developed as part of the mixed methods eRAPID pilot study, to support recovery following discharge after UGI surgery. METHODS: Patients completed the online ePRO symptom-report system post-discharge. Weekly interviews explored patients' experiences of using ePRO, the acceptability of feedback generated and its value for supporting their recovery. Interviews were audio-recorded and targeted transcriptions were thematically analysed. RESULTS: Thirty-five interviews with 16 participants (11 men, mean age 63 years) were analysed. Two main themes were identified: (1) reassurance and (2) empowerment. Feelings of isolation were common; many patients felt uninformed regarding their expectations of recovery and whether their symptoms warranted clinical investigation. Participants were reassured by tailored feedback advising them to contact their care team, alleviating their anxiety. Patients reported feeling empowered by the ePRO system and in control of their symptoms and recovery. CONCLUSION: Patients recovering at home following major cancer surgery regarded electronic symptom-monitoring and feedback as acceptable and beneficial. Patients perceived that the system enhanced information provision and provided a direct link to their care team. Patients felt that the system provided reassurance at a time of uncertainty and isolation, enabling them to feel in control of their symptoms and recovery.

A real-time electronic symptom monitoring system for patients after discharge following surgery: a pilot study in cancer-related surgery.

BACKGROUND: Advances in peri-operative care of surgical oncology patients result in shorter hospital stays. Earlier discharge may bring benefits, but complications can occur while patients are recovering at home. Electronic patient-reported outcome (ePRO) systems may enhance remote, real-time symptom monitoring and detection of complications after hospital discharge, thereby improving patient safety and outcomes. Evidence of the effectiveness of ePRO systems in surgical oncology is lacking. This pilot study evaluated the feasibility of a real-time electronic symptom monitoring system for patients after discharge following cancer-related upper gastrointestinal surgery. METHODS: A pilot study in two UK hospitals included patients who had undergone cancer-related upper gastrointestinal surgery. Participants completed the ePRO symptom-report at discharge, twice in the first week and weekly post-discharge. Symptom-report completeness, system actions, barriers to using the ePRO system and technical performance were examined. The ePRO surgery system is an online symptom-report that allows clinicians to view patient symptom-reports within hospital electronic health records and was developed as part of the eRAPID project. Clinically derived algorithms provide patients with tailored self-management advice, prompts to contact a clinician or automated clinician alerts depending on symptom severity. Interviews with participants and clinicians determined the acceptability of the ePRO system to support patients and their clinical management during recovery. RESULTS: Ninety-one patients were approached, of which 40 consented to participate (27 male, mean age 64 years). Symptom-report response rates were high (range 63-100%). Of 197 ePRO completions analysed, 76 (39%) triggered self-management advice, 72 (36%) trigged advice to contact a clinician, 9 (5%) triggered a clinician alert and 40 (20%) did not require advice. Participants found the ePRO system reassuring, providing timely information and advice relevant to supporting their recovery. Clinicians regarded the system as a useful adjunct to usual care, by signposting patients to seek appropriate help and enhancing their understanding of patients' experiences during recovery. CONCLUSION: Use of the ePRO system for the real-time, remote monitoring of symptoms in patients recovering from cancer-related upper gastrointestinal surgery is feasible and acceptable. A definitive randomised controlled trial is needed to evaluate the impact of the system on patients' wellbeing after hospital discharge.

A laminated energetic electrostatic analyzer for 0-5 keV charged particles.

A compact electrostatic energy bandpass filter based on a laminated analyzer design has been developed to measure charged particle fluxes at energies ranging from 0 to 5 keV. The sensor head has been successfully tested against a low energy magnetically filtered plasma source and an ion beam source capable of producing energetic ions in the range of 100-1250 eV. Additionally, the instrument has demonstrated the ability to accurately measure negative spacecraft frame charging using a low Earth orbit plasma simulator. The effects of the spacecraft frame charging on the measured energy distribution measurements and the impact regarding the derived charged particle density and temperature parameters are also examined.

Spinal radiographic progression over 2 years in ankylosing spondylitis patients treated with secukinumab: a historical cohort comparison.

OBJECTIVE: The aim of this study was to compare radiographic progression in patients with ankylosing spondylitis (AS) treated for up to 2 years with secukinumab (MEASURE 1) with a historical cohort of biologic-naïve patients treated with NSAIDs (ENRADAS). METHODS: Baseline and 2-year lateral cervical and lumbar spine radiographs were independently evaluated using mSASSS by two readers, who were blinded to the chronology and cohort of the radiographs. The primary endpoint was the proportion of patients with no radiographic progression (mSASSS change ≤ 0 from baseline to year 2). The Primary Analysis Set included patients with baseline (≤ day 30) and post-baseline day 31-743 radiographs. Sensitivity analyses were performed to assess the robustness of the comparison between the two cohorts, as follows: Sensitivity Analysis Set 1 included all patients with baseline (≤ day 30) and year 2 (days 640-819) radiographs; Sensitivity Analysis Set 2 included all patients with baseline and post-baseline (> day 30) radiographs. RESULTS: A total of 168 patients (84%) from the MEASURE 1 cohort and 69 (57%) from the ENRADAS cohort qualified for the Primary Analysis Set. Over 2 years, the LS (SE) mean change from baseline in mSASSS for the primary analysis was 0.55 (0.139) for MEASURE 1 vs 0.89 (0.216) for ENRADAS (p = 0.1852). Mean changes from baseline in mSASSS were lower in MEASURE 1 vs ENRADAS for the primary and sensitivity analyses. The proportion of patients with no radiographic progression was consistently higher in the MEASURE 1 vs ENRADAS cohort across all cutoffs for no radiographic progression (change in mSASSS from baseline to year 2 of ≤ 0, ≤ 0.5, ≤ 1, and ≤ 2), but the differences were not statistically significant. CONCLUSION: Secukinumab-treated patients demonstrated a numerical, but statistically non-significant, higher proportion of non-progressors and lower change in mSASSS over 2 years versus a cohort of biologic-naïve patients treated with NSAIDs.

Secukinumab after anti-tumour necrosis factor-α therapy: a phase III study in active rheumatoid arthritis.

OBJECTIVE: To assess the efficacy and safety of secukinumab in patients with rheumatoid arthritis (RA) who failed to respond to tumour necrosis factor- α (TNF-α) inhibitors. METHOD: This phase III double-blind, double-dummy, placebo-controlled study (NCT01770379) randomized (1:1:1) patients to subcutaneous secukinumab 150 mg, secukinumab 75 mg, or placebo at baseline, weeks 1, 2, 3, and 4, and then every 4 weeks. American College of Rheumatology (ACR) 20 response at week 24 was the primary endpoint. Secondary outcomes included the 28-joint Disease Activity Score using C-reactive protein (DAS28-CRP), Health Assessment Questionnaire Disability Index (HAQ-DI), and ACR50 at week 24. Long-term treatment was planned for 5 years. RESULTS: ACR20 response rates at week 24 for the secukinumab 150 mg and 75 mg groups were not statistically superior to placebo. None of the secondary endpoints was met for either secukinumab dose. Although not statistically significant, compared with placebo, numerically greater differences in least squares mean changes from baseline in HAQ-DI score and numerically higher ACR50 response rates were observed at week 24 in both secukinumab treatment groups. No new or unexpected adverse events were observed in this study compared with the large secukinumab safety database across psoriasis, psoriatic arthritis, ankylosing spondylitis, and other RA studies. CONCLUSIONS: Given that other second-line therapies have demonstrated efficacy in RA patients who failed to respond to TNF-α inhibitors, these findings may suggest that interleukin-17A inhibition with secukinumab does not provide additional benefit to these patients. This study further confirms the well-characterized safety profile of secukinumab.

Secukinumab and Sustained Improvement in Signs and Symptoms of Patients With Active Ankylosing Spondylitis Through Two Years: Results From a Phase III Study.

OBJECTIVE: Secukinumab improved the signs and symptoms of ankylosing spondylitis (AS) over 52 weeks in the phase III MEASURE 2 study. Here, we report longer-term (104 weeks) efficacy and safety results. METHODS: Patients with active AS were randomized to subcutaneous secukinumab 150 mg, 75 mg, or placebo at baseline; weeks 1, 2, and 3; and every 4 weeks from week 4. The primary end point was the Assessment of SpondyloArthritis international Society criteria for 20% improvement (ASAS20) response rate at week 16. Other end points included ASAS40, high-sensitivity C-reactive protein, ASAS5/6, Bath Ankylosing Spondylitis Disease Activity Index, Short Form 36 health survey physical component summary, ASAS partial remission, EuroQol 5-domain measure, and Functional Assessment of Chronic Illness Therapy fatigue subscale. End points were assessed through week 104, with multiple imputation for binary variables and a mixed-effects model repeated measures for continuous variables. RESULTS: Of 219 randomized patients, 60 of 72 (83.3%) and 57 of 73 (78.1%) patients completed 104 weeks of treatment with secukinumab 150 mg and 75 mg, respectively; ASAS20/ASAS40 response rates at week 104 were 71.5% and 47.5% with both secukinumab doses, respectively. Clinical improvements with secukinumab were sustained through week 104 across all secondary end points. Across the entire treatment period (mean secukinumab exposure 735.6 days), exposure-adjusted incidence rates for serious infections and infestations, Crohn's disease, malignant or unspecified tumors, and major adverse cardiac events with secukinumab were 1.2, 0.7, 0.5, and 0.7 per 100 patient-years, respectively. No cases of tuberculosis reactivation, opportunistic infections, or suicidal ideation were reported. CONCLUSION: Secukinumab provided sustained improvement through 2 years in the signs and symptoms of AS, with a safety profile consistent with previous reports.

Single- and multiple-dose pharmacokinetic studies of tramadol immediate-release tablets in children and adolescents.

In these combined analyzes from 3 open-label, phase-1 studies, the pharmacokinetic profile of tramadol and its metabolite (M1) following administration of tramadol immediate-release (IR) tablets in children and adolescents, 7-16 years old (studies 1 and 2: n = 38; study 3: n = 21) with painful conditions following single oral dose of tramadol IR (25-100 mg) (studies 1 and 2) or multiple oral doses of tramadol IR tablets every 6 hours for 3 days (study 3) were compared with that of healthy adults following similar treatment. Area under the curve of tramadol and its metabolite M1 in children and adolescents was lower compared with adults (Dose-normalized [DN] AUC, h ng/mL: tramadol: 1316.87 [children]; 1418.02 [adolescents];1838.29 [adults]; M1: 342.56 [children]; 475.4 [adolescents]; 636.13 [adults]) while the Cmax remained similar (DN Cmax , ng/mL: tramadol: 203.75 [children]; 165.35 [adolescents]; 226.92 [adults]; M1: 34.93 [children]; 38.42 [adolescents]; 52.14 [adults]). The DN AUC was further lower in children and adolescents with a lower body weight (<50 kg). The weight normalized oral clearance of tramadol was higher in children and adolescents compared with adults (CL/F, mL/min/kg: 12.66 [children]; 11.75 [adolescents]; 9.06 [adults]). No new safety findings emerged. Tramadol was generally safe and well-tolerated by children and adolescents with painful conditions.