Economic Burden of Induced Laryngeal Obstruction in Adolescents and Children.

PURPOSE: Diagnosing pediatric induced laryngeal obstruction (ILO) requires equipment typically available in specialist settings, and patients often see multiple providers before a diagnosis is determined. This study examined the financial burden associated with the diagnosis and treatment of ILO in pediatric patients with reference to socioeconomic disadvantage. METHODS: Adolescents and children (<18 years of age) diagnosed with ILO were identified through the University of Madison Voice and Swallow Outcomes Database. Procedures, office visits, and prescribed medications were collected from the electronic medical record. Expenditures were calculated for two time periods (1) pre-diagnosis (first dyspnea-related visit to diagnosis), and (2) the first year following diagnosis. The Area Deprivation Index (ADI) was used to estimate patient socioeconomic status to determine if costs differed with neighborhood-level disadvantage. RESULTS: A total of 113 patients met inclusion criteria (13.9 years, 79% female). Total pre-diagnosis costs of ILO averaged $6486.93 (SD = $6604.14, median = $3845.66) and post-diagnosis costs averaged $2067.69 (SD = $2322.78; median = $1384.12). Patients underwent a mean of 3.01 (SD = 1.9; median = 2) procedures and 5.8 (SD = 4.7; median = 5) office visits prior to diagnosis. Pharmaceutical, procedure/office visit, and indirect costs significantly decreased following diagnosis. Patients living in neighborhoods with greater socioeconomic disadvantage underwent fewer procedures and were prescribed more medication than those from more affluent areas. However, total expenditures did not differ based on ADI. CONCLUSIONS: Pediatric ILO is associated with considerable financial costs. The source of these costs, however, differed according to socioeconomic advantage. Future work should determine how ILO diagnosis and management can be more efficient and equitable across all patients. Laryngoscope, 134:3384-3390, 2024.

Economic Burden Associated With Management of Paradoxical Vocal Fold Motion Disorder.

OBJECTIVES: Paradoxical vocal fold movement (PVFM) is often misdiagnosed as asthma and tends to have a prolonged time to diagnosis. Study aims were to estimate the time from dyspnea onset to PVFM diagnosis, to estimate associated pre- and postdiagnosis direct and indirect healthcare cost, and to compare the cost of postdiagnosis care among patients who did and did not undergo standard-of-care speech therapy. METHODS: Patients diagnosed with PVFM were identified retrospectively. Time from dyspnea symptom onset to diagnosis was measured. Direct costs consisting of office visits, procedures, and prescribed pharmaceuticals before and after diagnosis were calculated. Indirect costs associated with lost wages related to healthcare were also estimated. Costs for patients who initiated versus did not initiate speech therapy and who had successful versus unsuccessful therapy were compared. RESULTS: Among 110 patients, median time from dyspnea onset to PVFM diagnosis was 33 months (interquartile range [IQR] 5-60). Direct and indirect prediagnosis median costs were $8,625 (IQR $1,687-$35,812) and $736 (IQR $421-$1,579) while first year following dyspnea symptom onset median direct and indirect costs were $1,706 (IQR $427-$7,118) and $315 (IQR $131-$631). Median direct and indirect costs of care in the postdiagnosis year were $2,062 (IQR $760-$11,496) and $841 (IQR $631-$1,261). Pharmaceuticals were predominant cost drivers in all time periods. Of those who completed speech therapy, 85% had breathing symptom improvement while incurring significant cost savings compared to those whose symptoms persisted. CONCLUSION: Costs of care leading to diagnosis of PVFM are substantial. More efficient methods of identifying patients with PVFM are essential to reduce prolonged time to diagnosis and associated costs. LEVEL OF EVIDENCE: NA Laryngoscope, 132:142-147, 2022.

Identification and assessment of alleles in the promoter of the Cyc-B gene that modulate levels of ß-carotene in ripe tomato fruit.

Novel diversity may be mined from databases and de novo sequencing, but functional characterization remains a limiting step to identifying new alleles. Classical breeding approaches augmented by marker-assisted selection offer a means to rapidly assess the function of new variation in coding or regulatory regions to modulate traits. We used the Cyc-B gene (B) of tomato (Solanum lycopersicum L.) for a proof of concept because of its role in the production of ß-carotene, a provitamin A carotenoid with importance to human nutrition. We measured carotenoid content in vintage and contemporary varieties and the profiles had a range of ß-carotene from 0.2 to 4.06 mg 100 g-1 fresh weight. We characterized variation in B from 84 sequences recovered from public databases and from an additional 29 high ß-carotene tomato, S. galapagense S. C. Darwin & Peralta, and S. cheesmaniae (L. Riley) Fosberg accessions. Thirteen unique haplotypes across 1600 bp of sequence 5' to the first ATG were identified with 11 occurring in high ß-carotene accessions we sequenced, and additional haplotypes were identified in public data. Phylogenetic analysis suggested that the alleles in high ß-carotene varieties were derived from wild species. Association analysis suggested two single nucleotide polymorphisms (SNPs) as the most likely causes of high ß-carotene, presumably through their influence on transcription of B that is elevated in ripening fruit. A marker-assisted backcross breeding scheme leveraging SNPs for background genome selection was used to rapidly develop germplasm resources containing different alleles of B in a uniform genetic background. Evaluation demonstrated that distinct promoter haplotypes function as different alleles that can be used to modulate the levels of ß-carotene in tomato.

Safety and Costs of Endobronchial Ultrasound-Guided Nodal Aspiration and Mediastinoscopy.

BACKGROUND: There remains debate over the best invasive diagnostic modality for mediastinal nodal evaluation. Prior studies have limited generalizability and insufficient power to detect differences in rare adverse events. We compared the risks and costs of endobronchial ultrasound (EBUS)-guided nodal aspiration and mediastinoscopy performed for any indication in a large national cohort. METHODS: We conducted a retrospective study (2007-2015) with MarketScan, a claims database of individuals with employer-provided insurance in the United States. Patients who underwent multimodality mediastinal evaluation (n = 1,396) or same-day pulmonary resection (n = 2,130) were excluded. Regression models were used to evaluate associations between diagnostic modalities and risks and costs while adjusting for patient characteristics, year, concomitant bronchoscopic procedures, and lung cancer diagnosis. RESULTS: Among 30,570 patients, 49% underwent EBUS. Severe adverse events-pneumothorax, hemothorax, airway/vascular injuries, or death-were rare and invariant between EBUS and mediastinoscopy (0.3% vs 0.4%; P = .189). The rate of vocal cord paralysis was lower for EBUS (1.4% vs 2.2%; P < .001). EBUS was associated with a lower adjusted risk of severe adverse events (OR, 0.42; 95% CI, 0.32-0.55) and vocal cord paralysis (OR, 0.57; 95% CI, 0.54-0.60). The mean cost of EBUS was $2,211 less than mediastinoscopy ($6,816 vs $9,023; P < .001). After adjustment this difference decreased to $1,650 (95% CI, $1,525-$1,776). CONCLUSIONS: When performed as isolated procedures, EBUS is associated with lower risks and costs compared with mediastinoscopy. Future studies comparing the effectiveness of EBUS vs mediastinoscopy in the community at large will help determine which procedure is superior or if trade-offs exist.

Analysis of the Prader-Willi syndrome imprinting center using droplet digital PCR and next-generation whole-exome sequencing.

BACKGROUND: Detailed analysis of imprinting center (IC) defects in individuals with Prader-Willi syndrome (PWS) is not readily available beyond chromosomal microarray (MA) analysis, and such testing is important for a more accurate diagnosis and recurrence risks. This is the first feasibility study of newly developed droplet digital polymerase chain reaction (ddPCR) examining DNA copy number differences in the PWS IC region of those with IC defects. METHODS: The study cohort included 17 individuals without 15q11-q13 deletions or maternal disomy but with IC defects as determined by genotype analysis showing biparental inheritance. Seven sets of parents and two healthy, unrelated controls were also analyzed. RESULTS: Copy number differences were distinguished by comparing the number of positive droplets detected by IC probes to those from a chromosome 15 reference probe, GABRß3. The ddPCR findings were compared to results from other methods including MA, and whole-exome sequencing (WES) with 100% concordance. The study also estimated the frequency of IC microdeletions and identified gene variants by WES that may impact phenotypes including CPT2 and NTRK1 genes. CONCLUSION: Droplet digital polymerase chain reaction is a cost-effective method that can be used to confirm the presence of microdeletions in PWS with impact on genetic counseling and recurrence risks for families.

Clinical and cost utility of an intraoperative endoscopic second look in cholesteatoma surgery.

OBJECTIVE/HYPOTHESIS: This study aimed to determine the clinical and cost-effectiveness of endoscopes during cholesteatoma surgery. More specifically, this study hypothesized that endoscope use would reduce cholesteatoma recurrence rates and cost. STUDY DESIGN: Case series involving the prospective enrollment of 110 consecutive cholesteatoma patients over a 2-year period. METHODS: Patients underwent cholesteatoma surgery with microscopy. During dissection, the location of the cholesteatoma was assessed. At the end of dissection and before reconstruction, the same subunits were visualized with straight and angled endoscopes for residual cholesteatoma. Hearing was analyzed before surgery and at the last possible examination. Costs were analyzed using Medicare reimbursement rates from the Centers for Medicare and Medicaid Services. RESULTS: Intraoperative endoscopic surveillance was able to detect residual cholesteatoma in 18 patients. With a 0° endoscope, residual cholesteatoma was noted in the epitympanum (two patients), sinus tympani (one patient), and the supratubal air cells (one patient). With a 45° endoscope, residual cholesteatoma was noted in the epitympanum (three patients), sinus tympani (nine patients), the supratubal air cells (two patients), and the mesotympanum (two patients). From a cost analysis, endoscopic surveillance ($6110.36 per patient) are less expensive than second look surgeries ($11,829.83 per patient), observation ($7097.20 per patient), and observation with annual magnetic resonance imaging studies ($9891.95 per patient). The patients hearing improved after surgery, consistent with previous studies. No complications were noted from the use of endoscopes. CONCLUSIONS: Intraoperative endoscopic surveillance reduced recurrence in our series of 110 patients. Endoscopes are particularly useful in evaluating the epitympanum, mesotympanum, sinus tympani, and supratubal air cells. Moreover, endoscopic surveillance is cost-effective. LEVEL OF EVIDENCE: 4 Laryngoscope, 128:2867-2871, 2018.

Nationwide Variation in Rates of Thyroidectomy Among US Medicare Beneficiaries.

Importance: Research on variation in rates of procedures across otherwise similar geographic regions provides vital insight into practice patterns. It reveals the degree of consensus on how a particular condition is managed, shows areas where access to care may be inadequate, and other areas where the population may be receiving inappropriately high levels of care. Objective: To test the hypothesis that rates of thyroid surgery vary across US geographic regions. Design, Setting, and Participants: A cross-sectional analysis of Medicare data for 15 888 beneficiaries aged 65 years or older from 2014 was carried out. Main Outcome and Measures: Overall and hospital referral region-specific thyroidectomy rate per 100 000 Medicare beneficiaries. Results: In 2014, 15 888 thyroidectomies were performed on Medicare beneficiaries in the United States (partial n = 7506, total n = 8382), representing a national average rate of 60 per 100 000 beneficiaries (median, 59 per 100 000 beneficiaries; IQR, 43-70 per 100 000). A 6.2-fold difference in thyroidectomy rates was observed across US regions (range, 22-139 per 100 000 Medicare beneficiaries). Conclusions and Relevance: Thyroidectomy rates in the United States vary 6.2 fold, more than prostatectomy rates, which are usually held as the example of the procedure with the widest variation in the United States. This wide variation in thyroidectomy rates observed among Medicare beneficiaries suggests widely divergent local beliefs and practice patterns surrounding the management of thyroid nodules and cancer because rates appeared to be unrelated to health care availability, regional socioeconomic status, or surgeons per capita. A better understanding for the reasons underlying this variation is needed.

A Case Series of the Probability Density and Cumulative Distribution of Laryngeal Disease in a Tertiary Care Voice Center.

OBJECTIVE: To examine the distribution of clinic and operative pathology in a tertiary care laryngology practice. METHODS: Probability density and cumulative distribution analyses (Pareto analysis) was used to rank order laryngeal conditions seen in an outpatient tertiary care laryngology practice and those requiring surgical intervention during a 3-year period. RESULTS: Among 3783 new clinic consultations and 1380 operative procedures, voice disorders were the most common primary diagnostic category seen in clinic (n = 3223), followed by airway (n = 374) and swallowing (n = 186) disorders. Within the voice strata, the most common primary ICD-9 code used was dysphonia (41%), followed by unilateral vocal fold paralysis (UVFP) (9%) and cough (7%). Among new voice patients, 45% were found to have a structural abnormality. The most common surgical indications were laryngotracheal stenosis (37%), followed by recurrent respiratory papillomatosis (18%) and UVFP (17%). CONCLUSIONS: Nearly 55% of patients presenting to a tertiary referral laryngology practice did not have an identifiable structural abnormality in the larynx on direct or indirect examination. The distribution of ICD-9 codes requiring surgical intervention was disparate from that seen in clinic. Application of the Pareto principle may improve resource allocation in laryngology, but these initial results require confirmation across multiple institutions.

Surgeon Awareness of Operating Room Supply Costs.

BACKGROUND: The extent to which surgeons understand costs associated with expensive operative procedures remains unclear. The goal of the study was to better understand surgeon cost awareness of operating room supplies and implants. METHODS: This was a cross-sectional study of faculty (n = 24) and trainees (fellow and residents, n = 27) in the Department of Otolaryngology. Participants completed surveys to assess opinions on importance of cost and ease in accessing cost data and were asked to estimate the costs of operating room (OR) supplies and implants. Estimates within 20% of actual cost were considered correct. Analyses were stratified into faculty and trainee surgeons. RESULTS: Cost estimates varied widely, with a low percentage of correct estimations (25% for faculty, 12% for trainees). Surgeons tended to underestimate the cost of high-cost items (55%) and overestimate the cost of low-cost items (77%). Attending surgeons were more accurate at correctly estimating costs within their own subspecialty (33% vs 16%, P < .001). Self-rated cost knowledge and years in practice did not correlate with cost accuracy (P < .05). CONCLUSIONS: A majority of surgeons were unable to correctly estimate the costs of items/implants used in their OR. An opportunity exists to improve the mechanisms by which cost data are fed back to physicians to help promote value-based decision making.

Longitudinal study of the feasibility of using ecological momentary assessment to study teacher stress: Objective and self-reported measures.

There is a lack of comprehensive research on Ecological Momentary Assessment (EMA) feasibility to study occupational stress, especially its long-term sustainability. EMA application in education contexts has also been sparse. This study investigated the feasibility of using EMA to study teacher stress over 2 years using both objective compliance data and a self-reported feasibility survey. It also examined the influence of individual and school factors on EMA feasibility. Participants were 202 sixth through eighth grade teachers from 22 urban middle schools in the southern United States. EMA was implemented via an iPod-based Teacher Stress Diary (TSD). Teachers recorded demands, stress responses, and resources during 12 days (6 waves) over 2 years. Feasibility was assessed via compliance data generated by the TSD (e.g., entry completion) and an EMA Feasibility Survey of self-reported user-friendliness and EMA interference. The results showed high compliance regarding entry and item completion, and completion time, which was sustained over time. User-friendliness was appraised as very high and EMA interference as low. Initial difficulties regarding timing and length of assessments were addressed via EMA method refinement, resulting in improved feasibility. Teachers' ethnicity, age, marital status, grade/course taught, class size, class load, and daily workload impacted feasibility. The results supported the feasibility of using EMA to study work stress longitudinally and the value of continued feasibility monitoring. They also support EMA use to study teacher stress and inform EMA implementation in schools. Some teacher and school factors need to be taken into consideration when deciding on EMA implementation in education contexts. (PsycINFO Database Record

Assessment of patient experience with unilateral vocal fold immobility: a preliminary study.

OBJECTIVE: Systematically moving toward patient-centered care for unilateral vocal fold immobility (UVFI) requires comprehensive understanding of the variability of actual patient experiences. This rigorous qualitative study assesses UVFI-related disability and proposes a preliminary taxonomy of UVFI patient experience. STUDY DESIGN: (1) Semistructured interviews and (2) taxonomy development. METHODS: Consecutive UVFI patients presenting July to September, 2012, prospectively underwent open-ended interviews investigating how UVFI affected their quality of life (QOL) and had caused disability. Comments reported by >20% were synthesized into axes based on content similarity. Variables were arranged into a preliminary taxonomy of UVFI patient experience, which was evaluated for four attributes of face validity. RESULTS: The majority of 39 patients had "extensive" baseline voice use (56%) and an iatrogenic etiology (62%). Taxonomy of patient experience included three main axes of symptomatic classification: (1) voice, (2) swallowing, and (3) breathing-all with intrinsic (physical and emotional) and extrinsic (social) subaxes that describe major impacts on QOL. Voice complaints were 100% penetrant, whereas breathing and swallowing symptoms afflicted 76% and 66%, respectively, of interviewees. Of affected patients, solid and liquid dysphagia was experienced by 70% and 63%, respectively. Of dyspneic patients, shortness of breath existed with talking (97%) and exercise (72%). Persistent throat congestion (76%), weakened cough (62%), globus (62%), and dysfunctional valsalva (41%) were frequent. CONCLUSIONS: Patient experience with UVFI has been incompletely characterized. This qualitative assessment and preliminary taxonomy highlight several related patient experiences not well documented in the literature or incorporated into currently available metrics.

Epidemiology of vocal fold paralyses after total thyroidectomy for well-differentiated thyroid cancer in a Medicare population.

OBJECTIVES: The population-level incidence of vocal fold paralysis after thyroidectomy for well-differentiated thyroid carcinoma (WDTC) is not known. This study aimed to measure longitudinal incidence of postoperative vocal fold paralyses and need for directed interventions in the Medicare population undergoing total thyroidectomy for WDTC. STUDY DESIGN: Retrospective cohort study. SETTING: US population. SUBJECTS AND METHODS: Subjects were Medicare beneficiaries. SEER-Medicare data (1991-2009) were used to identify beneficiaries who underwent total thyroidectomy for WDTC. Incident vocal fold paralyses and directed interventions were identified. Multivariate analyses were used to determine factors associated with odds of developing these surgical complications. RESULTS: Of 5670 total thyroidectomies for WDTC, 9.5% were complicated by vocal fold paralysis (8.2% unilateral vocal fold paralysis [UVFP]; 1.3% bilateral vocal fold paralysis [BVFP]). Rate of paralyses decreased 5% annually from 1991 to 2009 (odds ratio 0.95; 95% confidence interval, 0.93-0.97; P < .001). Overall, 22% of patients with vocal fold paralysis required surgical intervention (UVFP 21%, BVFP 28%). Multivariate logistic regression revealed that the odds of postthyroidectomy paralysis increased with each additional year of age, with non-Caucasian race, with particular histologic types, with advanced stage, and in particular registry regions. CONCLUSION: Annual rates of postthyroidectomy vocal fold paralyses are decreasing among Medicare beneficiaries with WDTC. High incidence in this aged population is likely due to a preponderance of temporary paralyses, which is supported by the need for directed intervention in less than a quarter of affected patients. Further population-based studies are needed to refine the population incidence and risk factors for paralyses in the aging population.

Bench to trench: how evidence and guidelines shape health care policy and practice.

Clinical practice guidelines and performance measures are becoming increasingly pervasive. They epitomize the evidence-based movement, which recognizes that mere "clinical judgment" is often inadequate to synthesize all the important data to determine the best management for a particular patient. This movement has at its core the fundamental expectation that medical decisions be based on sound data rather than anecdote. Unfortunately, this concept rarely manifests in daily practices where significant variations in care still exist. Guidelines were designed to improve patient care, reduce unnecessary variation, and reduce attributed costs. Therefore, it is not surprising that associated recommendations are now being incorporated into health care legislation as part of the Patient Protection and Affordable Care Act. In this environment, there is growing urgency for otolaryngologists to participate in rigorous comparative effectiveness research that will direct our Academy's guideline developers and policy makers to make recommendations that optimize care for all our patients.

High economic burden of caring for patients with suspected extraesophageal reflux.

OBJECTIVES: Extraesophageal symptoms are common manifestations of gastroesophageal reflux disease (GERD). Lack of a definitive diagnostic or treatment standards complicate management, which often leads to multiple specialty consultations, procedures, pharmaceuticals and diagnostic tests. The aim of this study was to determine the economic burden associated with extraesophageal reflux (EER). METHODS: Direct costs of evaluation were estimated for patients referred with symptoms attributed to EER between 2007 and 2011. Medicare payment for evaluation and management and pharmaceutical prices was used to calculate first year and overall costs of evaluating and treating extraesophageal symptoms attributed to reflux. RESULTS: Overall, 281 patients were studied (cough (50%), hoarseness (23%), globus/post-nasal drainage (15%), asthma (9%), and sore throat (3%)). Over a median (interquartile range) of 32 (16-46) months follow-up, patients had a mean (95% confidence interval) of 10.1 (9.4-10.9) consultations with specialists and underwent 6.4 (3-9) diagnostic procedures. Overall, the mean initial year direct cost was $5,438 per patient being evaluated for EER. Medical and non-medical components contributed $5,154 and $283. Of the overall cost, 52% were attributable to the use of proton pump inhibitors. During the initial year, direct costs were 5.6 times higher than those reported for typical GERD ($971). A total of 54% of patients reported improvement of symptoms. Overall cost per improved patient was $13,700. CONCLUSIONS: EER contributes substantially to health-care expenditures. In this cohort, the cost for initial year's evaluation and treatment of EER symptoms was quintuple that of typical GERD. Prescription costs and, in particular, proton pump inhibitors were the single greatest contributor to the cost of EER management.

Fragile X-related element 2 methylation analysis may provide a suitable option for inclusion of fragile X syndrome and/or sex chromosome aneuploidy into newborn screening: a technical validation study.

PURPOSE: We show that a novel fragile X-related epigenetic element 2 FMR1 methylation test can be used along with a test for sex-determining region Y (SRY) to provide the option of combined fragile X syndrome and sex chromosome aneuploidy newborn screening. METHODS: Fragile X-related epigenetic element 2, SRY, and FMR1 CGG repeat analyses were performed on blood and saliva DNA, and in adult and newborn blood spots. The cohort consisted of 159 controls (CGG <40), 187 premutation (CGG 56-170), and 242 full-mutation (CGG ~200-2,000) males and females, 106 sex chromosome aneuploidy individuals, and 151 cytogenetically normal controls. RESULTS: At the 0.435 threshold, fragile X-related epigenetic element 2 analysis in males was robust on both blood DNA and newborn blood spots, with specificity and sensitivity of ~100% for full-mutation genotype. In females, the specificity was 99%, whereas half of full-mutation females were above the 0.435 threshold in both blood DNA and newborn blood spots. Furthermore, at this threshold, the test could not differentiate individuals with Klinefelter syndrome from female controls without using the SRY marker. When combined with SRY analysis, the test was consistent with most results for sex chromosome aneuploidies from karyotyping. CONCLUSION: Setting specific thresholds for fragile X-related epigenetic element 2 analysis and including the SRY marker provides the option to either include or exclude detection of sex chromosome aneuploidies as part of fragile X syndrome newborn screening.

Impact of surveillance on survival after laryngeal cancer in the medicare population.

OBJECTIVES/HYPOTHESIS: Routine surveillance is advocated to detect recurrent disease after treatment for laryngeal cancer. This aim of this study was to determine the 1- and 5-year postrecurrence mortality for laryngeal cancers and evaluate whether more intensive surveillance improved survival. STUDY DESIGN: Retrospective cohort study. METHODS: Patients with recurrent cancers (1992-1999) were identified in a national cancer clinical database. Multivariate analysis was used to evaluate the effect of surveillance on postrecurrence survival. RESULTS: Of 2,121 recurrent cancers identified, 913 were laryngeal. Patients with laryngeal cancer recurrence had 27% (P = .001) and 22% (P = .007) better odds of 1- and 5-year survival than other sites. The 1- and 5-year postrecurrence survival rates for laryngeal cancer patients were 72.4% and 41.3%, respectively. Glottic cancer cases had the best postrecurrence life expectancy. Multivariate regression revealed that clinical surveillance intensity had no independent impact on their survival (P < .05). However, patients with recurrent glottic cancer seen in surveillance had 23% improved odds of survival (P = .037). CONCLUSIONS: More frequent surveillance visits was not associated with a survival advantage in the overall population. Patients with glottic cancer had a postrecurrence survival advantage if seen during the surveillance period. Laryngeal cancer patients had better postrecurrence survival than other head and neck sites.

Financial considerations in the conduct of multi-centre randomised controlled trials: evidence from a qualitative study.

BACKGROUND: Securing and managing finances for multicentre randomised controlled trials is a highly complex activity which is rarely considered in the research literature. This paper describes the process of financial negotiation and the impact of financial considerations in four UK multicentre trials. These trials had met, or were on schedule to meet, recruitment targets agreed with their public-sector funders. The trials were considered within a larger study examining factors which might be associated with trial recruitment (STEPS). METHODS: In-depth semi-structured telephone interviews were conducted in 2003-04 with 45 individuals with various responsibilities to one of the four trials. Interviewees were recruited through purposive and then snowball sampling. Interview transcripts were analysed with the assistance of the qualitative package Atlas-ti. RESULTS: The data suggest that the UK system of dividing funds into research, treatment and NHS support costs brought the trial teams into complicated negotiations with multiple funders. The divisions were somewhat malleable and the funding system was used differently in each trial. The fact that all funders had the potential to influence and shape the trials considered here was an important issue as the perspectives of applicants and funders could diverge. The extent and range of industry involvement in non-industry-led trials was striking. Three broad periods of financial work (foundation, maintenance, and resourcing completion) were identified. From development to completion of a trial, the trialists had to be resourceful and flexible, adapting to changing internal and external circumstances. In each period, trialists and collaborators could face changing costs and challenges. Each trial extended the recruitment period; three required funding extensions from MRC or HTA. CONCLUSION: This study highlights complex financial aspects of planning and conducting trials, especially where multiple funders are involved. Recognition of the importance of financial stability and of the need for appropriate training in this area should be paralleled by further similar research with a broader range of trials, aimed at understanding and facilitating the conduct of clinical research.

What influences recruitment to randomised controlled trials? A review of trials funded by two UK funding agencies.

BACKGROUND: A commonly reported problem with the conduct of multicentre randomised controlled trials (RCTs) is that recruitment is often slower or more difficult than expected, with many trials failing to reach their planned sample size within the timescale and funding originally envisaged. The aim of this study was to explore factors that may have been associated with good and poor recruitment in a cohort of multicentre trials funded by two public bodies: the UK Medical Research Council (MRC) and the Health Technology Assessment (HTA) Programme. METHODS: The cohort of trials was identified from the administrative databases held by the two funding bodies. 114 trials that recruited participants between 1994 and 2002 met the inclusion criteria. The full scientific applications and subsequent trial reports submitted by the trial teams to the funders provided the principal data sources. Associations between trial characteristics and recruitment success were tested using the Chi-squared test, or Fisher's exact test where appropriate. RESULTS: Less than a third (31%) of the trials achieved their original recruitment target and half (53%) were awarded an extension. The proportion achieving targets did not appear to improve over time. The overall start to recruitment was delayed in 47 (41%) trials and early recruitment problems were identified in 77 (63%) trials. The inter-relationship between trial features and recruitment success was complex. A variety of strategies were employed to try to increase recruitment, but their success could not be assessed. CONCLUSION: Recruitment problems are complex and challenging. Many of the trials in the cohort experienced recruitment difficulties. Trials often required extended recruitment periods (sometimes supported by additional funds). While this is of continuing concern, success in addressing the trial question may be more important than recruitment alone.

Phonological processing and emergent literacy in Spanish-speaking preschool children.

Phonological awareness (PA), phonological memory (PM), and phonological access to lexical storage (also known as RAN), play important roles in acquiring literacy. We examined the convergent, discriminant, and predictive validity of these phonological processing abilities (PPAs) in 147 3-, 4-, and 5-year-old children whose native language was Spanish. Confirmatory factor analysis (CFA) supported the validity of each PPA as separate from general cognitive ability and separate from each other. Moreover, structural equation modeling found RAN uniquely associated with knowledge of Spanish letter names and Spanish letter sounds. PA was found the best predictor of children's ability to distinguish alphabetic text from nonalphabetic text. Finally, general cognitive ability was only indirectly associated with emergent literacy skills via PPAs. These results highlight the importance of PPAs in the early literacy development of native Spanish speaking preschool children.

Evidence-based assessment of learning disabilities in children and adolescents.

The reliability and validity of 4 approaches to the assessment of children and adolescents with learning disabilities (LD) are reviewed, including models based on (a) aptitude-achievement discrepancies, (b) low achievement, (c) intra-individual differences, and (d) response to intervention (RTI). We identify serious psychometric problems that affect the reliability of models based on aptitude-achievement discrepancies and low achievement. There are also significant validity problems for models based on aptitude-achievement discrepancies and intra-individual differences. Models that incorporate RTI have considerable potential for addressing both the reliability and validity issues but cannot represent the sole criterion for LD identification. We suggest that models incorporating both low achievement and RTI concepts have the strongest evidence base and the most direct relation to treatment. The assessment of children for LD must reflect a stronger underlying classification that takes into account relations with other childhood disorders as well as the reliability and validity of the underlying classification and resultant assessment and identification system. The implications of this type of model for clinical assessments of children for whom LD is a concern are discussed.