Pulmonary Hypertension in Children with Down Syndrome: Results from the Pediatric Pulmonary Hypertension Network Registry.

OBJECTIVE: To characterize distinct comorbidities, outcomes, and treatment patterns in children with Down syndrome and pulmonary hypertension in a large, multicenter pediatric pulmonary hypertension registry. STUDY DESIGN: We analyzed data from the Pediatric Pulmonary Hypertension Network (PPHNet) Registry, comparing demographic and clinical characteristics of children with Down syndrome and children without Down syndrome. We examined factors associated with pulmonary hypertension resolution and a composite outcome of pulmonary hypertension severity in the cohort with Down syndrome. RESULTS: Of 1475 pediatric patients with pulmonary hypertension, 158 (11%) had Down syndrome. The median age at diagnosis of pulmonary hypertension in patients with Down syndrome was 0.49 year (IQR, 0.21-1.77 years), similar to that in patients without Down syndrome. There was no difference in rates of cardiac catheterization and prescribed pulmonary hypertension medications in children with Down syndrome and those without Down syndrome. Comorbidities in Down syndrome included congenital heart disease (95%; repaired in 68%), sleep apnea (56%), prematurity (49%), recurrent respiratory exacerbations (35%), gastroesophageal reflux (38%), and aspiration (31%). Pulmonary hypertension resolved in 43% after 3 years, associated with a diagnosis of pulmonary hypertension at age <6 months (54% vs 29%; P = .002) and a pretricuspid shunt (65% vs 38%; P = .02). Five-year transplantation-free survival was 88% (95% CI, 80%-97%). Tracheostomy (hazard ratio [HR], 3.29; 95% CI, 1.61-6.69) and reflux medication use (HR, 2.08; 95% CI, 1.11-3.90) were independently associated with a composite outcome of severe pulmonary hypertension. CONCLUSIONS: Despite high rates of cardiac and respiratory comorbidities that influence the severity of pulmonary hypertension, children with Down syndrome-associated pulmonary hypertension generally have a survival rate similar to that of children with non-Down syndrome-associated pulmonary hypertension. Resolution of pulmonary hypertension is common but reduced in children with complicated respiratory comorbidities.

A rare homozygous missense GDF2 (BMP9) mutation causing PAH in siblings: Does BMP10 status contribute?

Pulmonary arterial hypertension (PAH) is a disease characterized by pathological remodeling of the pulmonary vasculature causing elevated pulmonary artery pressures and ultimately, right ventricular failure from chronic pressure overload. Heterozygous pathogenic GDF2 (encoding bone morphogenetic protein 9 (BMP9)) variants account for some (>1%) adult PAH cases. Only three pediatric PAH cases, harboring homozygous or compound heterozygous variants, are reported to date. Ultra-rare pathogenic GDF2 variants are reported in hereditary hemorrhagic telangiectasia and overlapping disorders characterized by telangiectasias and arteriovenous malformations (AVMs). Here, we present two siblings with PAH homozygous for a GDF2 mutation that impairs BMP9 proprotein processing and reduces growth factor domain availability. We confirm an absence of measurable plasma BMP9 whereas BMP10 levels are detectable and serum-dependent endothelial BMP activity is evident. This contrasts with the absence of activity which we reported in two children with homozygous pathogenic GDF2 nonsense variants, one with PAH and one with pulmonary AVMs, both with telangiectasias, suggesting loss of BMP10 and endothelial BMP activity in the latter may precipitate telangiectasia development. An absence of phenotype in related heterozygous GDF2 variant carriers suggests incomplete penetrance in PAH and AVM-related diseases, indicating that additional somatic and/or genetic modifiers may be necessary for disease precipitation.

Ventricular assist device support following pediatric heart transplantation.

BACKGROUND: VAD support for early graft failure after HTx is a rare event in pediatrics. METHODS: We retrospectively describe our single-center experience with post-HTx VAD support in a cohort of patients transplanted between 01/05 and 12/20. RESULTS: Nine patients underwent VAD insertion in the early post-HTx period [median age 6.1 years (Range 0.3-20.3), median weight 17.6 kg (Range 3.5-65.0), and congenital heart disease (67%)]. Of the nine patients with early graft failure, almost half (44%) were implanted after 2015 and all of these patients had a pre-HTx plan for possible post-transplant VAD insertion. Time to VAD implant was a median of 0 day (Range 0-11). Total time on VAD support was a median of 12 days (Range 3.0-478.0). Two-thirds (n = 6; 67%) of the patients were weaned from support, retransplanted (11%) and two patients died (22%). In all of the patients where post-HTx VAD was anticipated there was 100% survival. CONCLUSIONS: In this small patient series, post-HTx VAD was a useful measure in selected patients especially with pre-HTx planning. However, more shared experiences to verify these findings are needed.

Virus detection in critically ill children with acute respiratory disease: a new profile in view of new technology.

AIM: To describe the epidemiology of critically ill children admitted to a paediatric intensive care unit (PICU) with acute respiratory disease. The association with intubation was analysed for the three most prevalent viruses and in those with and without viral co-infection. METHODS: Patients admitted to the PICU (2004-2014) with acute respiratory disease were included. Analyses were performed utilising each respiratory viral infection or multiple viral infections as an exposure. RESULTS: There were 1766 admissions with acute respiratory disease of which 1372 had respiratory virus testing and 748 had one or more viruses detected. The risk of intubation before or during the PICU stay was higher if parainfluenza virus was detected compared to respiratory syncytial virus (RSV) (OR: 2.20; 95% CI: 1.06-4.56). Sixty-three admissions had two or more viruses detected, and the combination of RSV and Rhinovirus/enterovirus was the most common. No significant difference was observed in the risk of intubation between patients with multiple and single viral infections. CONCLUSION: Higher risk of intubation was found in patients with parainfluenza as compared to RSV. The risk of intubation comparing parainfluenza virus to other viruses and for patients with multiple versus single virus needs to be further studied.

Actigraphy methodology in the Kids Mod PAH trial: Physical activity as a functional endpoint in pediatric clinical trials.

Pulmonary vasodilator treatment can improve hemodynamics, right ventricular function, symptoms, and survival in pediatric pulmonary hypertension (PH). However, clinical trial data are lacking due to many constraints. One major limitation is the lack of relevant trial endpoints reflective of hemodynamics or functional status in patients in whom standard exercise testing is impractical, unreliable, or not reproducible. The Kids Mod PAH trial (Mono- vs. Duo Therapy for Pediatric Pulmonary Arterial Hypertension) is an ongoing multicenter, Phase III, randomized, open-label, pragmatic trial to compare the safety and efficacy of first-line combination therapy (sildenafil and bosentan) to first-line monotherapy (sildenafil alone) in 100 pediatric patients with PH across North America. Investigators will measure participants' physical activity with a research-grade, wrist-worn actigraphy device at multiple time points as an exploratory secondary outcome. Vector magnitude counts per minute and activity intensity will be compared between the treatment arms. By directly and noninvasively measuring physical activity in the ambulatory setting, we aim to identify a novel, simple, inexpensive, and highly reproducible approach for quantitative assessment of exercise tolerance in pediatric PH. These data will increase the field's understanding of the effect of pulmonary vasodilator treatment on daily activity - a quantitative measure of functional status and wellbeing in pediatric PH and a potential primary outcome for future clinical trials in children with cardiopulmonary disorders.

A North American, single-center experience implanting fenestrated atrial devices and atrial flow regulators into a heterogeneous group of pediatric pulmonary hypertension patients.

Introduction: The clinical deterioration commonly experienced by pediatric patients with pulmonary arterial hypertension (PAH) has motivated a shift in the treatment of pulmonary hypertension (PH) through innovations in surgical salvage interventions. The Occlutech fenestrated atrial septal defect (FASD) Occluder and the atrial flow regulator (AFR), which provides a protective, atrial-level shunt during hypertensive crises, have found an important role in treating pediatric patients with PAH. Other groups of pediatric patients with PH may also benefit from a similar protective physiology. The primary aim of this work is to present a single center's experience with AFR and FASD devices for managing a heterogeneous group of pediatric PH patients. A secondary goal is to identify hemodynamic changes and complications following device implantation. Materials and Methods: We performed a retrospective review of all pediatric PH patients who, after being found suitable, either successfully or unsuccessfully received an FASD or AFR device between January 2015 and December 2021 at the Stollery Children's Hospital in Edmonton, Canada. Results: Fourteen patients (eight female) with a median age of 4.6 (range 0.3-17.9) years and a median body mass index of 15.1 (Q1 = 13.8, Q3 = 16.8) kg/m2 underwent device implantation: five received FASDs, eight received AFRs, and one was ultimately unable to receive an implant due to thrombosed iliac vessels and required surgical intervention. Of the fourteen patients, seven were in group 1 (PAH), one was in group 3 (lung disease), and six were in group 5 (primarily pulmonary hypertension vascular disease) under the World Symposium PH classification. All patients were on mono-, dual-, or triple-drug PH therapy. Device stabilization was not possible for two patients, who then required a repeat catheterization. Of the group 1 patients, three AFR and three FASD implants were successful, while one FASD implant was unsuccessful due to thrombosed vessels. At a six-month clinical assessment, all group 1 patients had patent devices and improved WHO FCs. Conclusion: This work presents a single center's experience with AFR and FASD implants in a heterogeneous group of fourteen pediatric patients with severe PH. This treatment strategy is novel in the pediatric population and so this work provides momentum for future studies of interventional cardiac catheterization procedures for pediatric patients with PH. Further collaborations are required to develop criteria to identify ideal pediatric candidates and optimally time interventions in order to maximize the benefits of this treatment.

A Canadian, retrospective, multicenter experience with selexipag for a heterogeneous group of pediatric pulmonary hypertension patients.

Introduction: Selexipag, an oral nonprostanoid prostaglandin receptor agonist, has led to reduced morbidity and mortality in adults with pulmonary arterial hypertension (PAH). While the adult literature has been extrapolated to suggest selexipag as an oral treatment for severe pediatric pulmonary hypertension (PH), longitudinal, multicenter data on the benefits of selexipag in this population are lacking. The purpose of this study is to present a longitudinal, multicentre experience with selexipag in a relatively large cohort of pediatric PH patients and add to the existing selexipag literature. Materials and methods: We performed a retrospective, multicenter review describing the clinical outcomes of pediatric PH patients receiving selexipag in addition to standard oral pulmonary vasodilator therapy across three Canadian centers between January 2005 and June 2021. Results: Twenty-four pediatric patients (fifteen female) with a mean age of 9.7 (range 2.0-15.5) years were included. Of this cohort, eighteen (75.0%) were in group 1, one (4.2%) was in group 2, four (16.7%) were in group 3, and one (4.2%) was in group 4. Twenty-two (91.7%) patients were on dual PH therapy after six months. Dosing was targeted to achieve 20-30 mcg/kg/dose orally every twelve hours. Median dose after twelve months was 30 mcg/kg/dose. Twelve months following selexipag initiation, median decreases of 0.2 cm in tricuspid annular plane systolic excursion, 3.5 mmHg in right-ventricular systolic pressure, and 6.1 mmHg in mean pulmonary arterial pressure were observed; none of these changes were statistically significant. Three patients died, one clinically deteriorated and required admission to a pediatric intensive care unit, ten had gastrointestinal symptoms, and three had flushing. Conclusion: Selexipag appears to be a safe and effective adjunctive therapy for pediatric PH patients and has a tolerable adverse effect profile aside from gastrointestinal disturbances. Additional prospective studies of changes in hemodynamics and functional classification over a longer period and with a larger sample are needed. Future research should aim to identify subgroups that stand to benefit from the addition of selexipag as well as optimal timing and dosing for the pediatric population.

Multicenter review of a tadalafil suspension formulation for infants and children with pulmonary hypertension: A North American experience.

Introduction: Phosphodiesterase type 5 (PDE5) inhibitors, with sildenafil the earliest among them, are widely used in the management of pediatric pulmonary arterial hypertension (PAH). Tadalafil is a PDE5 inhibitor with a long half life (16 h), stable pharmacokinetics and pharmacodynamics, and minimal adverse effects. However, the utility of tadalafil suspensions in this setting has not been widely explored due to a lack of clinical experience. We present a multicenter experience that details the safety and tolerability of a tadalafil suspension, either alone or in combination with another vasodilator, for the management of pediatric pulmonary hypertension (PH). Methods and materials: This is a retrospective chart review of infants and children at Children's Wisconsin and the Stollery Children's Hospital enrolled in pediatric PH programs between December 2013 and April 2022 managed with a tadalafil suspension. Patients aged six years of age and under who were treated with a tadalafil suspension were included. Demographics, clinical information, echocardiographic and hemodynamic measurements, and laboratory data were collected before and six months after tadalafil initiation. Results: Over the study period, 154 children with a median age of 1.0 (range 0.0-6.9) years were treated with tadalafil therapy. Of these, 39 (25.3%) were in group 1 (PAH), 79 (51.3%) were in group 3 (lung disease), and 33 (21.4%) were in group 5 (pulmonary hypertensive vascular disease). The median initial dose of tadalafil was 1.0 mg/kg once daily. Eleven (7.1%) patients in the cohort were established on tadalafil therapy de novo. The suspension formulation was necessary for 103 (66.9%) patients due to an inability to take enteral tablets and for 49 (31.8%) due to a need for feeding via gastric or jejunal tubes. We observed a statistically significant increase in tricuspid annular plane systolic excursion as well as significant decreases in right-ventricular systolic pressure and NT-proBNP. Tadalafil therapy was well tolerated over the six-month period: at six months, no adverse effects were reported aside from gastrointestinal disturbances by 2 (1.3%) patients. Conclusion: Tadalafil, a long-acting PDE5 inhibitor, when administered in a suspension formulation, has a safe and tolerable adverse effect profile. Following six months of therapy, our cohort showed improvements in clinical parameters, echocardiographic measurements, and laboratory results. Patient compliance was good and adverse effects were rare, minor, and manageable with nonpharmacological means.

Kids Mod PAH trial: A multicenter trial comparing mono- versus duo-therapy for initial treatment of pediatric pulmonary hypertension.

Pulmonary hypertension (PH) is a significant health problem that contributes to high morbidity and mortality in diverse cardiac, pulmonary, and systemic diseases in children. Evidence-based advances in PH care have been challenged by a paucity of quality endpoints for assessing clinical course and the lack of robust clinical trial data to guide pharmacologic therapies in children. While the landmark adult AMBITION trial demonstrated the benefit of up-front combination PH therapy with ambrisentan and tadalafil, it remains unknown whether upfront combination therapy leads to more rapid and sustained clinical benefits in children with various categories of PH. In this article, we describe the inception of the Kids Mod PAH Trial, a multicenter Phase III trial, to address whether upfront combination therapy (sildenafil and bosentan vs. sildenafil alone) improves PH outcomes in children, recognizing that marked differences between the etiology and therapeutic response between adults and children exist. The primary endpoint of this study is WHO functional class (FC) 12 months after initiation of study drug therapy. In addition to the primary outcome, secondary endpoints are being assessed, including a composite measure of time to clinical worsening, WHO FC at 24 months, echocardiographic assessment of PH and quantitative assessment of right ventricular function, 6-min walk distance, and NT-proBNP levels. Exploratory endpoints include selected biomarkers, actigraphy, and assessments of quality of life. This study is designed to pave the way for additional clinical trials by establishing a robust infrastructure through the development of a PPHNet Clinical Trials Network.

Building a dedicated pediatric pulmonary hypertension program: A consensus statement from the pediatric pulmonary hypertension network.

Pediatric pulmonary hypertension (PH) is a severe, life-threatening disease associated with diverse cardiac, pulmonary, and systemic disorders, which generally requires expertise from multiple disciplines for management. Unfortunately, expert centers are limited, often due to inadequate resources or unfamiliarity with needed components for success. The Pediatric Pulmonary Hypertension Network (PPHNet) includes expert centers in North America specifically dedicated to advancing the field of pediatric PH through research and excellent clinical care. PPHNet member sites were queried for valuable program components and these findings were discussed for consensus. Here we provide a collective overview of key elements of an optimal pediatric PH program: team composition, access to services, and commitment to education. It is our intention that this document will assist newer and/or smaller programs identify avenues and resources for growth and provide avenues for collaboration.

Cardiac Catheterization and Hemodynamics in a Multicenter Cohort of Children with Pulmonary Hypertension.

Rationale: Hemodynamic assessments direct care among children with pulmonary hypertension, yet the use of cardiac catheterization is highly variable, which could impact patient care and research. Objectives: We analyzed hemodynamic findings from right heart catheterization (RHC) and left heart catheterization and acute vasodilator testing (AVT) and the safety of catheterization in children with World Symposium on Pulmonary Hypertension (WSPH) group 1 and 3 subtypes in a large multicenter North American cohort. Methods: Of 1,475 children enrolled in the Pediatric Pulmonary Hypertension Network Registry (2014-2020), there were 1,383 group 1 and 3 patients, of whom 671 (48.5%) underwent RHC at diagnosis and were included for analysis. Results: Compared with those without diagnostic RHC, these children were older, less likely to be an infant or preterm, more often female, treated with targeted pulmonary hypertension medications at diagnosis, and had advanced World Health Organization functional class. Catheterization was performed without a difference in complication rates between WSPH groups. Pulmonary capillary wedge pressure was well correlated with left ventricular end-diastolic pressure and left atrial pressures. Results of AVT using three different methods were comparable; positive AVT results were observed in 8.0-11.8% of subjects, did not differ between WSPH groups 1 and 3, and were not associated with freedom from the composite endpoint of lung transplantation or death during follow-up. Conclusions: In a large pediatric pulmonary hypertension cohort, diagnostic RHC with or without left heart catheterization in WSPH group 1 and 3 patients was performed safely at experienced pediatric pulmonary hypertension centers. Hemodynamic differences were noted between group 1 and 3 subjects. Higher mean pulmonary arterial pressure and mean pulmonary arterial pressure/mean systemic arterial pressure ratio were associated with a higher risk of death/transplantation. Findings suggest overall safety and potential value of RHC as a standard diagnostic approach to guide pulmonary hypertension management in children.

Congenital diaphragmatic hernia and occupational therapy: a case report.

This case report describes occupational therapy (OT) intervention in an outpatient setting and outcomes for a child diagnosed with congenital diaphragmatic hernia (CDH) from 4 to 28 months of age. There is little information on therapy intervention and outcomes of children who have survived. The patient is a white male, born at 35 weeks gestation with a diagnosis of left CDH that required a patch repair. He also had a Nissen fundoplication, gastrostomy tube and spent the first 100 days of his life in the hospital. He received outpatient OT for 2 years. The process of service provision is described using the "Occupational therapy practice framework: Domain and process, 2nd edition" (American Occupational Therapy Association, 2008 , American Journal of Occupational Therapy, 62(6), 625-683). The focus of intervention, description of the intervention process, and timeline for achievement of skills is provided. Outcomes and assessment tools used included the Canadian Occupational Performance Measure and Peabody Developmental Motor Scales-Second Edition.

Bivalirudin Experience in a Heterogeneous Ventricular Assist Device Population.

Ventricular assist devices (VADs) are an increasingly common therapy for end-stage heart failure across all ages as a bridge to recovery or transplant and more recently as destination therapy. With increasing experience and difficulties with establishing therapeutic heparin levels, we have begun to explore the effectiveness of direct thrombin inhibitors in this patient population. This is a retrospective review of all long-term VAD patients, both adult and pediatric, who were anticoagulated with bivalirudin between January 2009 and January 2016. The starting dose was 0.3 mg/kg/hr, and dose was titrated for a goal partial thromboplastin time (PTT) of 70-100. There were 14 patients (13 males, 5 ≤18 years) with 17 episodes of bivalirudin therapy. The median age on initiation was 45 years (range, 15 days-67 years) with 10 episodes associated with a HeartWare HVAD, five a HeartMate II, and two with a Berlin Heart EXCOR. The predominant indication of bivalirudin therapy was suspected pump thrombosis (13/17). The median time from VAD insertion to initiation of bivalirudin was 116 days (range, 3-1,870) with the median duration of therapy being 21 days (range, 3-113). In patients with pump thrombosis, the mean baseline lactate dehydrogenase (LDH) was 229 ± 64 U/L, peak 690 ± 380 U/L, and decreased to 330 ± 243 U/L when bivalirudin was stopped. The outcomes following suspected pump thrombosis included: transitioned to warfarin (n = 7), death in two destination therapy patients who did not undergo pump exchange, transplantation (n = 2), and pump exchange (n = 2). A major bleeding complication occurred in only one patient. Our experience highlights the potential use of bivalirudin in a heterogenous VAD population. Although these initial results suggest some potential role for direct thrombin inhibitors for use in long-term VADs, larger prospective studies are required to support these preliminary observations and to determine who may benefit from direct thrombin inhibitors (DTIs) and the side effect profile in this patient population.

Driveline Site Is Not a Predictor of Infection After Ventricular Assist Device Implantation.

Driveline infections (DLIs) remain a major source of morbidity for patients requiring long-term ventricular assist device (VAD) support. We aimed to assess whether VAD driveline exit site (DLES) (abdomen versus chest wall) is associated with DLI. All adult patients who underwent insertion of a HeartWare HVAD or HeartMate II (HMII) between 2009 and 2016 were included. Driveline infection was defined as clinical evidence of DLI accompanied by a positive bacterial swab and need for antibiotics. Competing risks analysis was used to assess the association between patient characteristics and DLI. Ninety-two devices (59 HMII) were implanted in 85 patients (72 men; median age 57.4 years) for bridge to transplant or destination therapy. VAD DLES was chest in 28 (30.4%) devices. Median time on VAD support was 347.5 days (IQR 145.5, 757.5), with 28 transplants and 29 deaths (27 on device). DLI occurred in 24 patients (25 devices) at a median of 140 days (IQR 67, 314) from implant. Staphylococcus aureus accounted for 15 infections (60%). Freedom from infection was 72.8% (95% confidence interval [CI] 53.1-78.0%) at 1 year and 41.9% (95% CI 21.1-61.5%) at 3 years. In competing risks regression, abdominal DLES was not predictive of DLI (hazard ratio, HR 1.65 [95% CI 0.63, 4.29]), but body mass index (BMI) >30 kg/m was (HR 2.72 [95% CI 1.25, 5.92]). In conclusion, risk of DLI is high among patients on long-term VAD support, and a nonabdominal DLES does not reduce this risk. The only predictor of DLI in this series was an elevated BMI.

Perioperative antibiotics in pediatric cardiac surgery: protocol for a systematic review.

BACKGROUND: Post-operative infections in pediatric cardiac surgery are an ongoing clinical challenge, with rates between 1 and 20%. Perioperative antibiotics remain the standard for prevention of surgical-site infections, but the type of antibiotic and duration of administration remain poorly defined. Current levels of practice variation through informal surveys are very high. Rates of antibiotic-resistant organisms are increasing steadily around the world. METHODS/DESIGN: We will identify all controlled observational studies and randomized controlled trials examining prophylactic antibiotic use in pediatric cardiac surgery. Data sources will include MEDLINE, EMBASE, CENTRAL, and proceedings from recent relevant scientific meetings. For each included study, we will conduct duplicate independent data extraction, risk of bias assessment, and evaluation of quality of evidence using the GRADE approach. DISCUSSION: We will report the results of this review in agreement with the PRISMA statement and disseminate our findings at relevant critical care and cardiology conferences and through publication in peer-reviewed journals. We will use this systematic review to inform clinical guidelines, which will be disseminated in a separate stand-alone publication. STUDY REGISTRATION NUMBER: PROSPERO CRD42016052978C.

Factors related to thumb pain in physiotherapists.

The aim of this study was to determine whether differences exist between physiotherapists with work-related thumb pain and physiotherapists without thumb pain. Twenty-four physiotherapists with work-related thumb pain (Pain Group) and 20 physiotherapists without thumb or wrist pain (Non-pain Group), who were working at least 20 hours per week in an outpatient musculoskeletal setting, were compared on a number of attributes: generalised joint laxity, hand and thumb strength, height, weight, working environment, hand position and force applied during mobilisation, mobility at individual thumb joints, extent of osteoarthritis at the thumb and radial-sided wrist joints, and demographic data including age, gender and years of experience. All physiotherapists in the Pain Group reported their thumb pain was related to and initially caused by the performance of manual techniques, and 88% had altered their manual techniques because of pain in the thumb. There was extreme variability in hand position and force applied during mobilisation, and a slightly high prevalence of osteoarthritis (22.7%) considering the mean age of the total sample (38.6 years). Statistically significant differences between groups included increased right carpometacarpal joint laxity (6.4%, 95% CI 0.19 to 12.6), decreased right tip pinch strength (0.84 kg, 95% CI 0.01 to 1.68), and lower body mass index (2.0, 95% CI 0.11 to 3.9) for the Pain Group. Other factors were not statistically different between groups. These results indicate that work-related thumb pain affects physiotherapists ability to administer manual treatments, and suggest that decreased stability and strength of the thumb may be associated with work-related thumb pain.