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Background: Deprescribing is an effective means to reduce polypharmacy in elderly patients. However, geriatric day care deprescribing services are challenging to implement in rural regions. In this study, we examined whether a subacute care unit of a rural hospital could deliver a comprehensive and multidisciplinary intervention to promote deprescribing in patients and whether this intervention would succeed in achieving significant and lasting deprescribing results. Methods: We conducted a cross-sectional analysis of a deprescribing program at a rural hospital in Eastern Ontario, Canada. Participants were 11 patients, aged 65 or older, who were admitted to the hospital’s medical/surgical unit or who presented to the emergency department. Clinicians followed a structured, comprehensive and multidisciplinary approach designed to facilitate deprescribing, which concluded with an outcome evaluation at discharge and follow-up phone calls. Outcomes included the frequency and total number of medications successfully removed, reduced, substituted and restarted after discharge and emergency department visits and hospitalizations 6 months before and after the intervention. Results: Of a total 57 deprescribed medications, 38 were eliminated, 8 were switched to a safer alternative, and 11 were dose reduced. Postdischarge deprescribing reversal occurred in only 5 of 57 deprescribed medications. Among the study population, a 59.2% reduction was observed in the combined number of emergency department visits and hospitalizations 6 months after deprescribing. Conclusions: This feasibility study was successful in showing the potential added value for offering a rehabilitative, subacute care, inpatient, comprehensive and multidisciplinary approach toward patients with complex deprescribing needs. It also showed proof of concept in reducing polypharmacy-induced adverse health outcomes. Can Pharm J (Ott) 2020:153:xx-xx.

BACKGROUND: The cardiac sodium channel (SCN5A) mutation, R222Q, neutralizes a positive charge in the domain I voltage sensor. Mutation carriers display very frequent ectopy and dilated cardiomyopathy (DCM). OBJECTIVES: To describe the effect of SCN5A R222Q on murine myocyte and Purkinje fiber electrophysiology, and identify underlying mechanisms. METHODS: We generated mice carrying humanized wild-type (H) and mutant (RQ) SCN5A channels. We characterized whole heart and isolated ventricular and Purkinje myocyte properties. RESULTS: RQ/RQ mice were not viable. I(Na) from RQ/H ventricular myocytes displayed increased “window current” and hyperpolarizing shifts in both inactivation and activation compared to H/H, as previously reported in heterologous expression systems. Surprisingly, action potentials were markedly abbreviated in RQ/H myocytes (APD90: 12.6±1.3 ms versus 29.1±1.0 ms in H/H, p

IntroductionUp to 30% of patients with Brugada Syndrome (BrS) carry loss-of-function (LoF) variants in the cardiac sodium channel geneSCN5A. Recent studies have suggested that theSCN5Aprotein product NaV1.5 can form dimers and exert dominant negative effects.MethodsWe identified 35 LoF variants (SCN5Avariants were studied in HEK293T cells alone or in heterozygous co-expression with WTSCN5Ausing automated patch clamp. To assess clinical risk, we compared the prevalence of dominant negative vs. putative haploinsufficient (frameshift/splice site) variants in a BrS case consortium and the gnomAD population database.ResultsIn heterozygous expression with WT, 32/35 LoF variants and 6/15 partial LoF showed reduction to Na, demonstrating a dominant negative effect. Carriers of dominant negative LoF missense variants had an enriched disease burden compared to putative haploinsufficient variant carriers (2.7-fold enrichment in BrS cases, p=0.019).ConclusionsMostSCN5Amissense LoF variants exert a dominant negative effect. Cohort analyses reveal that this class of variant confers an especially high burden of BrS.

Introduction: External loop recorders (ELRs) are recommended for the investigation of syncope and palpitations. This study aimed to compare rates of arrhythmia detection between primary care (PC) and hospital-based cardiac unit (HBCU) fitted ELRs. Methods: Data were captured from January to December 2015. Twenty-eight general practitioner practices and 1 hospital took part. Patients were divided into those with ELR fitted in PC or HBCU. All ELR data were analyzed by a cardiac physiologist. Results: A total of 560 ELR recordings were analyzed; 219 (PC) versus 341 (HBCU). There was no difference between the baseline characteristics (all Ps > .05). The predominant indication for ELR in each group were palpitations; between-group variation was observed for syncope ( P = .0004). There were no significant between-group differences in the number of recordings per patient; however, PC group wore the ELR for less time (median 7 days vs median 14 days; P < .0001). There were no differences in arrhythmia detection between PC- and HBCU-fitted ELRs (16.2% [n = 39] vs 21.7% [n = 74], respectively; P = .28). PC placement of ELRs was highest in very remote rural communities ( P = .005) and correlated with distance from HBCU ( r = 0.39; P = .04). Conclusions: This study showed no difference in detection of arrhythmias between PC and HBCU fitted ELRs. This suggests adequate ELR recording can be completed by suitably trained staff in PC. Furthermore, ELRs were fitted for less time in PC without an adverse effect on diagnostic yield. ELR usage increased with increasing distance from the specialist center and rurality suggesting improved local access to arrhythmia detection services.

RationalePartial or complete loss of function variants inSCN5Aare the most common genetic cause of the arrhythmia disorder Brugada Syndrome (BrS1). However, the pathogenicity ofSCN5Avariants is often unknown or disputed; 80% of the 1,390SCN5Amissense variants observed in at least one individual to date are variants of uncertain significance (VUS). The designation of VUS is a barrier to the use of sequence data in clinical care.ObjectiveWe selected 83 variants for study: 10 previously studied control variants, 10 suspected benign variants, and 63 suspected Brugada Syndrome-associated variants, selected on the basis of their frequency in the general population and in patients with Brugada Syndrome. We used high-throughput automated patch clamping to study the function of the 83 variants, with the goal of reclassifying variants with functional data.Methods and ResultsTen previously studied variants had functional properties concordant with published manual patch clamp data. All 10 suspected benign variants had wildtype-like function. 22 suspected BrS variants had loss of channel function (ConclusionsHigh-throughput automated patch clamping enabled the reclassification of the majority of tested VUS’s inSCN5A.

IntroductionA urinary catheter constitutes a one-point patient restraint, can induce deconditioning and may lead to patient mortality. An audit performed at Winchester District Memorial Hospital revealed that 20% of patients had a urinary catheter, of whom 31% did not meet the criteria for catheterisation. The main objective of this study was to use the Influencer Change Model and the Choosing Wisely Canada toolkit to create a bundle of interventions that would reduce the unnecessary use of urinary catheters in hospitalised patients.MethodsIn a rural teaching hospital, a time-series quasi-experiment was employed to decrease inappropriate use of urinary catheters. Both the Choosing Wisely Canada toolkit for appropriate use of urinary catheters and the Influencer change management approach were used to create effective interventions.ResultsThis study revealed that there was no improvement in appropriate urinary catheter use during Plan-Do-Study-Act (PDSA) cycle 1. There was gradual improvement during PDSA cycle 2, with the percentage of inappropriate urinary catheter use dropping from an initial 31% before any interventions to less than 5% by the end of this study.Discussion/conclusionThis study aimed to reduce the inappropriate use of urinary catheters in a rural hospital with limited resources. The findings indicate that by using a change model, such as the Influencer Change Model, it is possible to promote better patient care through empowering healthcare staff to implement accepted protocols more stringently and thereby to decrease the inappropriate use of urinary catheters to 0%.

Background: The calcium-activated chloride channel ANO1 is highly expressed in cancer. Results: Inhibition of ANO1 activity alone is not sufficient to inhibit cancer cell proliferation, suggesting a novel function of ANO1 protein in cancer. Conclusion: The ANO1 inhibitor CaCCinh-A01 inhibits cancer cell proliferation by facilitating degradation of ANO1. Significance: Our results may provide a new targeting approach for antitumor therapy in ANO1-amplified cancers., ANO1, a calcium-activated chloride channel, is highly expressed and amplified in human cancers and is a critical survival factor in these cancers. The ANO1 inhibitor CaCCinh-A01 decreases proliferation of ANO1-amplified cell lines; however, the mechanism of action remains elusive. We explored the mechanism behind the inhibitory effect of CaCCinh-A01 on cell proliferation using a combined experimental and in silico approach. We show that inhibition of ANO1 function is not sufficient to diminish proliferation of ANO1-dependent cancer cells. We report that CaCCinh-A01 reduces ANO1 protein levels by facilitating endoplasmic reticulum-associated, proteasomal turnover of ANO1. Washout of CaCCinh-A01 rescued ANO1 protein levels and resumed cell proliferation. Proliferation of newly derived CaCCinh-A01-resistant cell pools was not affected by CaCCinh-A01 as compared with the parental cells. Consistently, CaCCinh-A01 failed to reduce ANO1 protein levels in these cells, whereas ANO1 currents were still inhibited by CaCCinh-A01, indicating that CaCCinh-A01 inhibits cell proliferation by reducing ANO1 protein levels. Furthermore, we employed in silico methods to elucidate novel biological functions of ANO1 inhibitors. Specifically, we derived a pharmacophore model to describe inhibitors capable of promoting ANO1 degradation and report new inhibitors of ANO1-dependent cell proliferation. In summary, our data demonstrate that inhibition of the channel activity of ANO1 is not sufficient to inhibit ANO1-dependent cell proliferation, indicating that the role of ANO1 in cancer only partially depends on its function as a channel. Our results provide an impetus for gaining a deeper understanding of ANO1 modulation in cells and introduce a new targeting approach for antitumor therapy in ANO1-amplified cancers.

Background Genome‐wide association studies have implicated variants in SCN 10A , which encodes Nav1.8, as modulators of cardiac conduction. Follow‐up work has indicated the SCN 10A sequence includes an intronic enhancer for SCN 5A . Yet the role of the Nav1.8 protein in the myocardium itself is still unclear. To investigate this , we use homozygous knockout mice ( Scn10a −/− ) generated by disruption of exons 4 and 5, leaving the Scn5a enhancer intact. Methods and Results We previously reported that pharmacologic blockade of Nav1.8 in wild‐type animals blunts action potential prolongation by ATX ‐ II at slow drive rates (≤1 Hz). Here we present evidence of the same blunting in Scn10a −/− compared to wild‐type ventricular myocytes, supporting the conclusion that Nav1.8 contributes to late sodium current at slow rates. In contrast to earlier studies, we found no differences in electrocardiographic parameters between genotypes. Low‐dose ATX ‐ II exposure in lightly anesthetized animals and Langendorff‐perfused hearts prolonged QT c and generated arrhythmias to the same extent in wild‐type and Scn10a −/− . RNA sequencing failed to identify full‐length Scn10a transcripts in wild‐type or knockout isolated ventricular myocytes. However, loss of late current in Scn10a −/− myocytes was replicated independently in a blinded set of experiments. Conclusions While Scn10a transcripts are not detectible in ventricular cardiomyocytes, gene deletion results in reproducible loss of late sodium current under extreme experimental conditions. However, there are no identifiable consequences of this Scn10a deletion in the intact mouse heart at usual rates. These findings argue that common variants in SCN 10A that affect ventricular conduction do so by modulating SCN 5A .

The fossil pollen contents found in the charred dottle residue from 20 clay pipe bowls recovered from a cesspit at a house in Amsterdam, the Netherlands (which was owned and used by the artist Rembrandt Harmenszoon van Rijn), were collected and studied. The clay pipes date from approximately the same period when Rembrandt lived in the house and used the cesspit. We believe that some of the pollen in the dottle residue may have come from the tobacco, some possibly from airborne sources at Rembrandt's house and/or from debris in the cesspit in which the pipes were discarded. The results are compared with a similar study of pipe dottle from Native American clay pipes conducted more than 25 years ago. We also briefly review the origin and spread of domestic tobacco in an effort to determine potential sources of the tobacco imported and used in the Netherlands during the lifetime of Rembrandt and the period when he occupied the house. The pollen content of modern brands of commercial pipe tobacco is studied and the potential for using pollen found in tobacco products as evidence in forensic circumstances is reviewed.

Background— The D1275N SCN5A mutation has been associated with a range of unusual phenotypes, including conduction disease and dilated cardiomyopathy, as well as atrial and ventricular tachyarrhythmias. However, when D1275N is studied in heterologous expression systems, most studies show near-normal sodium channel function. Thus, the relationship of the variant to the clinical phenotypes remains uncertain. Methods and Results— We identified D1275N in a patient with atrial flutter, atrial standstill, conduction disease, and sinus node dysfunction. There was no major difference in biophysical properties between wild-type and D1275N channels expressed in Chinese hamster ovary cells or tsA201 cells in the absence or presence of β1 subunits. To determine D1275N function in vivo, the Scn5a locus was modified to knock out the mouse gene, and the full-length wild-type (H) or D1275N (DN) human SCN5A cDNAs were then inserted at the modified locus by recombinase mediated cassette exchange. Mice carrying the DN allele displayed slow conduction, heart block, atrial fibrillation, ventricular tachycardia, and a dilated cardiomyopathy phenotype, with no significant fibrosis or myocyte disarray on histological examination. The DN allele conferred gene-dose–dependent increases in SCN5A mRNA abundance but reduced sodium channel protein abundance and peak sodium current amplitudes (H/H, 41.0±2.9 pA/pF at −30 mV; DN/H, 19.2±3.1 pA/pF, P P Conclusions— Although D1275N produces near-normal currents in multiple heterologous expression experiments, our data establish this variant as a pathological mutation that generates conduction slowing, arrhythmias, and a dilated cardiomyopathy phenotype by reducing cardiac sodium current.

Background— The widely used macrolide antibiotic azithromycin increases risk of cardiovascular and sudden cardiac death, although the underlying mechanisms are unclear. Case reports, including the one we document here, demonstrate that azithromycin can cause rapid, polymorphic ventricular tachycardia in the absence of QT prolongation, indicating a novel proarrhythmic syndrome. We investigated the electrophysiological effects of azithromycin in vivo and in vitro using mice, cardiomyocytes, and human ion channels heterologously expressed in human embryonic kidney (HEK 293) and Chinese hamster ovary (CHO) cells. Methods and Results— In conscious telemetered mice, acute intraperitoneal and oral administration of azithromycin caused effects consistent with multi-ion channel block, with significant sinus slowing and increased PR, QRS, QT, and QTc intervals, as seen with azithromycin overdose. Similarly, in HL-1 cardiomyocytes, the drug slowed sinus automaticity, reduced phase 0 upstroke slope, and prolonged action potential duration. Acute exposure to azithromycin reduced peak SCN5A currents in HEK cells (IC 50 =110±3 μmol/L) and Na + current in mouse ventricular myocytes. However, with chronic (24 hour) exposure, azithromycin caused a ≈2-fold increase in both peak and late SCN5A currents, with findings confirmed for I Na in cardiomyocytes. Mild block occurred for K + currents representing I Kr (CHO cells expressing hERG; IC 50 =219±21 μmol/L) and I Ks (CHO cells expressing KCNQ1+KCNE1; IC 50 =184±12 μmol/L), whereas azithromycin suppressed L-type Ca ++ currents (rabbit ventricular myocytes, IC 50 =66.5±4 μmol/L) and I K1 (HEK cells expressing Kir2.1, IC 50 =44±3 μmol/L). Conclusions— Chronic exposure to azithromycin increases cardiac Na + current to promote intracellular Na + loading, providing a potential mechanistic basis for the novel form of proarrhythmia seen with this macrolide antibiotic.

CPSI deficiency is an inborn error of metabolism caused by mutations in the first, rate-determining enzyme of the urea cycle. Our mutation detection data from this disorder suggest that a significant number of mutant alleles cause RNA instability, most likely through the nonsense-mediated decay pathway. We identified 26 non-consanguinous CPSID patients with an available RNA source (liver tissue or cell line) and screened both genomic DNA and RNA for the identification and classification of mutations. Out of 52 total alleles screened from these patients, 21 (40%) have strong evidence for RNA processing mutations demonstrated by absent/minimal heterozygosity in patient cDNA sequences despite heterozygous genomic changes. These 21 alleles are a heterogenous group primarily composed of splicing defects and frameshifts that form premature termination codons which should subsequently elicit the nonsense-mediated decay pathway. This study provides evidence for the high prevalence of RNA instability mutations in genetic disease and underscores the importance of accounting for them in mutation-screening strategies.

This study evaluated current hospital-based palliative care programs using recommendations from the Center to Advance Palliative Care (CAPC) as a framework. Seven hospitals located in Buffalo, New York were included based on the existence of a hospital-based palliative care program. Data was collected from August through October of 2013 by means of key informant interviews with nine staff members from these hospitals using a guide comprised of questions based on CAPC’s recommendations. A gap analysis was conducted to analyze the current state of each hospital’s program based upon CAPC’s definition of a quality palliative care program. The findings identify challenges facing both existing/evolving palliative care programs, and establish a foundation for strategies to attain best practices not yet implemented. This study affirms the growing availability of palliative care services among these selected hospitals along with opportunities to improve the scope of services in line with national recommendations.

The purpose of this study is to examine the usefulness of Video Respite™ in reducing agitated behaviors and increasingpositive social behaviors in cognitively impairednursing home residents. Video RespiteTM is a series of 10 videotapes specifically designed to capture long term memory and maintain the attention ofpatients with dementia. Remembering when, a 21-minute Video Respite™ tape was utilized as the intervention. For this study, 36 residents in three nursing homes were observedpre-, during andpostintervention. Findings revealed that the video was not significantly effective in reducing agitation; however, it was significantly effective in increasing positive behaviors during the intervention. We offer suggestions to practitioners for use of this video in the context of nursing homes

Aims Female gender is a risk factor for long QT-related arrhythmias, but the underlying mechanisms remain uncertain. Here, we tested the hypothesis that gender-dependent function of the post-depolarization ‘late’ sodium current (INa-L) contributes. Methods and results Studies were conducted in mice in which the canonical cardiac sodium channel Scn5a locus was disrupted, and expression of human wild-type SCN5A cDNA substituted. Baseline QT intervals were similar in male and female mice, but exposure to the sodium channel opener anemone toxin ATX-II elicited polymorphic ventricular tachycardia in 0/9 males vs. 6/9 females. Ventricular INa-L and action potential durations were increased in myocytes isolated from female mice compared with those from males before and especially after treatment with ATX-II. Further, ATX-II elicited potentially arrhythmogenic early afterdepolarizations in myocytes from 0/5 male mice and 3/5 female mice. Conclusion These data identify variable late INa as a modulator of gender-dependent arrhythmia susceptibility.

Deficiency of carbamoyl phosphate synthetase I (CPSI) results in hyperammonemia ranging from neonatally lethal to environmentally induced adult-onset disease. Over 24 years, analysis of tissue and DNA samples from 205 unrelated individuals diagnosed with CPSI deficiency (CPSID) detected 192 unique CPS1 gene changes, of which 130 are reported here for the first time. Pooled with the already reported mutations, they constitute a total of 222 changes, including 136 missense, 15 nonsense, 50 changes of other types resulting in enzyme truncation, and 21 other changes causing in-frame alterations. Only ∼10% of the mutations recur in unrelated families, predominantly affecting CpG dinucleotides, further complicating the diagnosis because of the "private" nature of such mutations. Missense changes are unevenly distributed along the gene, highlighting the existence of CPSI regions having greater functional importance than other regions. We exploit the crystal structure of the CPSI allosteric domain to rationalize the effects of mutations affecting it. Comparative modeling is used to create a structural model for the remainder of the enzyme. Missense changes are found to directly correlate, respectively, with the one-residue evolutionary importance and inversely correlate with solvent accessibility of the mutated residue. This is the first large-scale report of CPS1 mutations spanning a wide variety of molecular defects highlighting important regions in this protein.

Objective The purpose of this study was to assess patient expectations of surgical outcome after preoperative counseling of surgical procedures in a randomized trial of 655 women in a comparison of the rectus fascial sling and Burch colposuspension. Study Design Women who selected surgery for treating stress incontinence and who consented to this randomized, surgical trial completed a preoperative questionnaire to assess expectations for the postsurgical effects of surgery on urinary incontinence-related symptoms, limitations, and emotions. Associations of expectations with a range of preoperative urinary incontinence measures were explored. Results The most frequent preoperative symptoms were urine leakage (98%), embarrassment (88%), frequency (74%), physical activity (72%), and urgency (70%). Sexual and social limitations were less frequent (≤44%). Treatment expectations were higher for women who reported more symptom bother. As expected, most women (98%) had an expectation that urine leakage would be completely or almost completely eliminated. However, most women (92%) who reported urgency or frequency (83%) expected significant improvement of these symptoms after surgery. Conclusion Patients who undergo stress incontinence surgery have high expectations regarding the outcome of incontinence surgery, which include the resolution of urgency and frequency.

Increased pulmonary artery pressure (PAP) can complicate the postoperative care of children undergoing surgical repair of congenital heart defects. Endogenous NO regulates PAP and is derived from arginine supplied by the urea cycle. The rate-limiting step in the urea cycle is catalyzed by a mitochondrial enzyme, carbamoyl-phosphate synthetase I (CPSI). A well-characterized polymorphism in the gene encoding CPSI (T1405N) has previously been implicated in neonatal pulmonary hypertension. A consecutive modeling cohort of children (N=131) with congenital heart defects requiring surgery was prospectively evaluated to determine key factors associated with increased postoperative PAP, defined as a mean PAP > 20mmHg for at least one hour during the 48 hours following surgery measured by an indwelling pulmonary artery catheter. Multiple Dimensionality Reduction (MDR) was used to both internally validate observations and develop optimal two-variable through five-variable models that were tested prospectively in a validation cohort (N= 41). Unconditional logistic regression analysis of the modeling cohort revealed that age (OR= 0.92, p=0.01), CPSI T1405N genotype (AC vs. AA: OR=4.08, p=0.04, CC vs. AA: OR=5.96, p=0.01), and Down syndrome (OR=5.25, p=0.04) were independent predictors of this complex phenotype. MDR predicted that the best two-variable model consisted of age and CPSI T1405N genotype (p

Hepatic veno-occlusive disease (HVOD) is a serious complication of hematopoietic stem cell transplantation (HSCT). Since the liver is a major site of iron deposition in HFE-associated hemochromatosis, and iron has oxidative toxicity, we hypothesized that HFE genotype might influence the risk of HVOD after myeloablative HSCT. We determined HFE genotypes in 166 HSCT recipients who were evaluated prospectively for HVOD. We also tested whether a common variant of the rate-limiting urea cycle enzyme, carbamyl-phosphate synthetase (CPS), previously observed to protect against HVOD in this cohort, modified the effect of HFE genotype. Risk of HVOD was significantly higher in carriers of at least one C282Y allele (RR=3.7, 95% CI 1.2–12.1) and increased progressively with C282Y allelic dose (RR=1.7, 95% CI 0.4–6.8 in heterozygotes; RR=8.6, 95% CI 1.5–48.5 in homozygotes). The CPS A allele, which encodes a more efficient urea cycle enzyme, reduced the risk of HVOD associated with HFE C282Y. We conclude that HFE C282Y is a risk factor for HVOD and that CPS polymorphisms may counteract its adverse effects. Knowledge of these genotypes and monitoring of iron stores may facilitate risk-stratification and testing of strategies to prevent HVOD, such as iron chelation and pharmacologic support of the urea cycle.

Carbamyl phosphate synthetase I (CPSI) determines the rate-limiting entry of free ammonia into the urea cycle. Disruption of CPSI affects the liver's ability to remove waste nitrogen and produce arginine, citrulline, and urea. Arginine is the necessary precursor for the critical biomolecule, nitric oxide (NO). We have studied the classic model of CPSI deficiency, which results in severe hyperammonemia, and identified a large number of molecular defects. A number of CPSI polymorphisms have been found that appear to result in functional consequences. We have examined the association of these polymorphisms with various environmental stress conditions and found that certain CPSI alleles are associated with clinical outcome. We refer to these associations as environmentally determined genetic expression (EDGE) affects. In addition to studies of classic CPSI deficiency, we have developed data for the EDGE concept in post-cardiac surgery-related pulmonary hypertension, hepatic veno-occlusive disease after bone marrow transplantation, and persistent pulmonary hypertension of the newborn. We have linked these outcomes and genotypes to the availability of the urea cycle intermediates, citrulline and arginine, and their role in NO synthesis. We hypothesize that these polymorphisms affect the functional efficiency of CPSI and thus the entire urea cycle and as such, the availability of the NO substrates. By piecing together the various functional aspects of the urea cycle changes we have seen, we can better understand the clinical vulnerabilities of patients in environmentally stressful situations. This knowledge should allow us to design intervention strategies to either predict or modify the associated adverse outcomes.

To understand the patient burden of study procedures/measures at completion of a randomized controlled trial (RCT) requiring extensive testing and follow-up visits. A survey sent after completing the 2-year visit of an RCT comparing Burch colposuspension and fascial retropubic sling to treat stress urinary incontinence assessed degree of bother for seven study procedures, eight study-related factors, and possible motivations to participate in the study. A total of 450 study participants (88%) returned the survey. Urodynamic testing was the most bothersome procedure, followed by 24-h pad test and Q-tip test. Self-administered questionnaires were the least bothersome. Main reasons to participate in the study were to help others, obtain better knowledge about the condition, and be guided by a committed team of investigators/study coordinators. At the end of a large multicenter RCT, we learned from a confidential patient survey that the most burdensome activities involved invasive procedures, frequent visits, and multiple forms to fill out.

16 parents of infants and toddlers (9 girls, 7 boys) with sickle cell disease reported normal speech and language development in their children but perceived slow physical development. Such perceptions may be related to the smaller physical size of children with this disease.