Estimation of adherence to urate-lowering therapy in people living with gout using Australia's Pharmaceutical Benefits Scheme and patient-reported dosing.

AIMS: The aim of this study was to estimate adherence to urate-lowering therapy (ULT), predominately allopurinol, from Australia's Pharmaceutical Benefits Scheme (PBS) claims database in association with (1) patient-reported doses and (2) World Health Organization's (WHO) defined daily doses (DDD), namely, allopurinol (400 mg/day) or febuxostat (80 mg/day). METHODS: Proportion of days covered (PDC) was calculated in 108 Gout App (Gout APP) trial participants with at least two recorded ULT dispensings in an approximately 12-month period before provision of intervention or control apps. Adherence was defined as PDC ≥80%. We measured the correlation between the two methods of calculating PDC using a Wilcoxon signed rank test. Agreement between ULT-taking status (self-reports) and ULT-dispensed status (PBS records) was tested with Cohen's kappa (κ), and positive and negative percent agreement. RESULTS: Allopurinol was prescribed in 93.5% of participants taking ULT. Their self-reported mean daily dose (SD) was 291 (167) mg/day. Mean PDC (SD) for allopurinol was 83% (21%) calculated using self-reported dose, and 63% (24%) using WHO's DDD. Sixty-three percent of allopurinol users were identified as adherent (PDC ≥80%) using self-reported dose. There was good agreement between self-reported ULT use and PBS dispensing claims (κ = 0.708, P < .001; positive percent agreement = 90%, negative percent agreement = 82%). CONCLUSIONS: Participant-reported allopurinol daily doses, in addition to PBS dispensing claims, may enhance confidence in estimating PDC and adherence compared to using DDD. This approach improves adherence estimations from pharmaceutical claims datasets for medications where daily doses vary between individuals or where there is a wide therapeutic dose range.

Neurodevelopmental outcomes in a cohort of Australian families with self-limited familial epilepsy of neonatal/infantile onset.

OBJECTIVES: To determine: i) seizure recurrence; ii) developmental disability; iii) co-morbidities and risk factors in self-limited familial neonatal and/or infantile epilepsy (SeLFE) in a multigenerational study. METHODS: Families were retrospectively recruited from epilepsy databases (2021-2022) in 2 paediatric hospitals, Sydney, Australia. Eligible families had 2 first degree relatives with seizures and underwent genetic testing. Demographics/clinical data were collected from interviews and medical records. Vineland Adaptive Behaviour Scales-Third Edition measured adaptive function. RESULTS: Fifteen families participated. Fourteen had a genetic diagnosis (93%): 11 pathogenic; PRRT2 (n=4), KCNQ2 (n=3), SCN2A (n=4), 3 likely pathogenic; KCNQ2 (n=1), SCN8A (n=2). Seizures affected 73 individuals (ages 1-76 years); 30 children and 20 adults had in-depth phenotyping. Ten of 50 individuals (20%) had seizure recurrence, aged 8-65 years. Median time from last neonatal/infantile seizure was 11.8/12.8 years. Predictors of recurrence were high seizure number (p=0.05) and longer treatment duration (p=0.03). Seven children had global developmental delay (GDD): mild (n=4), moderate (n=1) and severe (n=2). Vineland-3 identified 3 had low-average and 3 had mild-moderately impaired functioning. The majority (82%) were average. GDD was associated with older age at last seizure (p=0.03), longer epilepsy duration (p=0.02), and higher number of anti-seizure medications (p=0.05). Four children had speech delay, 5 (10%) had Autism Spectrum Disorder. Paroxysmal kinesiogenic dyskinesia (n=5) occurred in 4 families and hemiplegic migraine (n=8) in 3 families. CONCLUSIONS: Individuals with SeLFE have a small risk of recurrent seizures (20%) and neurodevelopmental disability. Significant predictors are higher seizure number and longer epilepsy duration. Developmental surveillance is imperative.

Patient factors and health outcomes associated with illness perceptions in people with gout.

OBJECTIVE: Illness perceptions are views and beliefs formed in response to a health threat which may influence self-management behaviours and chronic disease outcomes. Despite effective medication, sub-optimal outcomes in gout are common. This study aimed to quantitatively investigate illness perceptions in gout to examine how illness perceptions relate to health outcomes. METHODS: Data were obtained from a randomised-controlled trial where people with gout (n = 493) completed surveys measuring illness perceptions (Brief Illness Perception Questionnaire (B-IPQ)), gout flares, medication adherence, health-related quality of life, healthcare utilisation and productivity, alongside serum urate blood tests at baseline, 6- and 12-month follow-ups. Multivariable linear regression identified patient factors independently associated with each B-IPQ item score. Logistic and linear regression, adjusted for age and sex, determined whether baseline B-IPQ items could predict current and future health outcomes. RESULTS: Younger individuals and those with severe gout were more likely to experience pessimistic illness perceptions at baseline. Optimistic illness perceptions were associated with lower odds of having at least one flare in the preceding 6 months. Every 1-point increase in B-IPQ treatment control, indicating the optimistic view that gout is treatable, decreased the odds of a recent flare prior to baseline by 33% (OR : 0.67; 95%CI : 0.53,0.85; p< 0.001) and prior to 12-month follow-up by 15% (OR : 0.85; 95%CI : 0.76,0.96; p= 0.01). Pessimistic illness perceptions also predicted poorer medication adherence, health-related quality of life and productivity but not serum urate levels. CONCLUSION: Modifying pessimistic illness perceptions, including, but not limited to, patient education, may promote prudent self-management behaviours and better outcomes in gout. TRIAL REGISTRATION: Australian New Zealand Clinical Trials Registry; https://www.anzctr.org.au/; ACTRN12616000455460.

Internet-Delivered Dialectical Behavioral Therapy Skills Training for Chronic Pain: Protocol for a Randomized Controlled Trial.

BACKGROUND: Emotion dysregulation is key to the development and maintenance of chronic pain, feeding into a cycle of worsening pain and disability. Dialectical behavioral therapy (DBT), an evidence-based treatment for complex transdiagnostic conditions presenting with high emotion dysregulation, may be beneficial to manage and mitigate the emotional and sensory aspects of chronic pain. Increasingly, DBT skills training as a key component of standard DBT is being delivered as a stand-alone intervention without concurrent therapy to help develop skills for effective emotion regulation. A previous repeated-measure single-case trial investigating a novel technologically driven DBT skills training, internet-delivered DBT skills training for chronic pain (iDBT-Pain), revealed promising findings to improve both emotion dysregulation and pain intensity. OBJECTIVE: This randomized controlled trial aims to examine the efficacy of iDBT-Pain in comparison with treatment as usual to reduce emotion dysregulation (primary outcome) for individuals with chronic pain after 9 weeks and at the 21-week follow-up. The secondary outcomes include pain intensity, pain interference, anxiety symptoms, depressive symptoms, perceived stress, posttraumatic stress, harm avoidance, social cognition, sleep quality, life satisfaction, and well-being. The trial also examines the acceptability of the iDBT-Pain intervention for future development and testing. METHODS: A total of 48 people with chronic pain will be randomly assigned to 1 of 2 conditions: treatment and treatment as usual. Participants in the treatment condition will receive iDBT-Pain, consisting of 6 live web-based group sessions led by a DBT skills trainer and supervised by a registered psychologist and the iDBT-Pain app. Participants in the treatment-as-usual condition will not receive iDBT-Pain but will still access their usual medication and health interventions. We predict that iDBT-Pain will improve the primary outcome of emotion dysregulation and the secondary outcomes of pain intensity, pain interference, anxiety symptoms, depressive symptoms, perceived stress, harm avoidance, social cognition, sleep quality, life satisfaction, and well-being. A linear mixed model with random effects of individuals will be conducted to investigate the differences between the baseline, 9-week (primary end point), and 21-week (follow-up) assessments as a function of experimental condition. RESULTS: Recruitment started in February 2023, and the clinical trial started in March 2023. Data collection for the final assessment is planned to be completed by July 2024. CONCLUSIONS: If our hypothesis is confirmed, our findings will contribute to the evidence for the efficacy and acceptability of a viable intervention that may be used by health care professionals for people with chronic pain. The results will add to the chronic pain literature to inform about the potential benefits of DBT skills training for chronic pain and will contribute evidence about technologically driven interventions. TRIAL REGISTRATION: Australian New Zealand Clinical Trials Registry ACTRN12622000113752; https://www.anzctr.org.au/Trial/Registration/TrialReview.aspx?id=383208&isReview=true. INTERNATIONAL REGISTERED REPORT IDENTIFIER (IRRID): PRR1-10.2196/41890.

Blink Rate Measured In Situ Decreases While Reading From Printed Text or Digital Devices, Regardless of Task Duration, Difficulty, or Viewing Distance.

Purpose: To compare blinking measured in situ during various tasks and examine relationships with ocular surface symptoms. The day-to-day repeatability of the blink rate and interblink interval was assessed. Methods: Twenty-four students (28.6 ± 6.3 years; 8 male and 16 female) completed six reading tasks (printed text, laptop, TV, smartphone, smartphone at 50% brightness, smartphone with complex text), and two nonreading tasks (conversation, walking) in a randomized cross-over study. Ocular surface symptoms and clinical signs were assessed. The blink rate and interblink interval were measured using a wearable eye tracking headset. Blink parameters were compared across tasks and time (linear mixed model and post hoc comparisons with Bonferroni correction). Associations between blinking, symptoms, ocular surface, and clinical signs were assessed (Spearman's correlation). The smartphone reading task was completed twice to determine the coefficient of repeatability. Results: The blink rate was lower (mean 10.7 ± 9.7 blinks/min) and the interblink interval longer (mean 9.6 ± 8.7 seconds) during all reading tasks compared with conversation (mean 32.4 ± 12.4 blinks/min; 1.5 ± 0.6 seconds) and walking (mean 31.3 ± 15.5 blinks/min; 1.9 ± 1.3s) (P < 0.001). There were no significant differences in blink parameters between any of the reading tasks or between conversation and walking. Changes in blinking occurred within 1 minute of starting the task. No associations were evident between blink rate or interblink interval and ocular surface symptoms or signs. The coefficient of repeatability was ±12.4 blinks/min for blink rate and ±18.8 seconds for interblink interval. Conclusions: Spontaneous blinking can be measured reliably in situ. The blink rate was decreased and the interblink interval increased during reading compared with conversation and walking. Changes in blinking were immediate, sustained, and not associated with ocular surface symptoms or signs.

Parent Training Adapted to the Needs of Children With Callous-Unemotional Traits: A Randomized Controlled Trial.

Callous-unemotional (CU) traits designate a distinct subgroup of children with early-starting, stable, and aggressive conduct problems. Critically, traditional parenting interventions often fail to normalize conduct problems among this subgroup. The aim of this study was to test whether parent-child interaction therapy (PCIT) adapted to target distinct deficits associated with CU traits (PCIT-CU) produced superior outcomes relative to standard PCIT. In this proof-of-concept trial, 43 families with a 3- to 7-year-old child (M age = 4.84 years, SD = 1.12, 84% male) with clinically significant conduct problems and elevated CU traits were randomized to receive standard PCIT (n = 21) or PCIT-CU (n = 22) at an urban university-based research clinic. Families completed five assessments measuring child conduct problems, CU traits, and empathy. Parents in both conditions reported good treatment acceptability and significantly improved conduct problems and CU traits during active treatment, with no between-group differences. However, linear mixed-effects models showed treatment gains in conduct problems deteriorated for children in standard PCIT relative to those in PCIT-CU during the 3-month follow-up period (ds = 0.4-0.7). PCIT-CU shows promise for sustaining improvements in conduct problems for young children with conduct problems and CU traits, but requires continued follow-up and refinement.

The No Worries Trial: Efficacy of Online Dialectical Behaviour Therapy Skills Training for Chronic Pain (iDBT-Pain) Using a Single Case Experimental Design.

Emotion dysregulation frequently co-occurs with chronic pain, which in turn leads to heightened emotional and physical suffering. This cycle of association has prompted a recommendation for psychological treatment of chronic pain to target mechanisms for emotion regulation. The current trial addressed this need by investigating a new internet-delivered treatment incorporating emotional skills training from dialectical behavioral therapy (DBT). Using a single-case experimental design that is suited to heterogeneous populations and can demonstrate efficacy with a small sample, three participants with chronic pain were recruited. Participants received four weeks of online DBT skills training (iDBT-Pain intervention) which incorporated one-on-one sessions over Zoom and a web app. Results revealed compelling evidence for the intervention on the primary outcome of emotion dysregulation and were promising for the secondary outcome of pain intensity. Improvement was also identified on pre-and post-measures of depression, coping behaviors, sleep problems, wellbeing, and harm avoidance, indicating that the intervention may positively influence other factors related to chronic pain. Overall, the trial provides preliminary efficacy for the intervention to improve chronic pain. However, we recommend further investigation of the iDBT-Pain intervention, either in single case trials, which when conducted with scientific rigor may be aggregated to derive nomothetic conclusions, or in a group-comparison trial to compare with usual modes of treatment. PERSPECTIVE: This trial advances understanding of emotion-focused treatment for chronic pain and provides evidence for a viable new technological treatment. Importantly, as an internet-delivered approach, the iDBT-Pain intervention is accessible to those with restricted mobility and remote communities where there are often limited psychological services for people with chronic pain.

Prognostic indicators of subacute combined degeneration from B12 deficiency: A systematic review.

OBJECTIVE: A systematic review was conducted on published data of subacute combined degeneration (SCD) from B12 deficiency to investigate potential prognostic indicators of final ambulatory function in affected patients. TYPE: Systematic review. LITERATURE SURVEY: Records published from 1999 through 2018 were searched on the electronic databases MEDLINE, PUBMED, and SCOPUS. The publication language was restricted to English and French. METHODOLOGY: Records that described cases of SCD from B12 deficiency in patients ≥16 years of age at onset were included. From a final total of 66 cases of SCD identified, ambulation scores were assigned based on the clinical descriptions reported. Patient characteristics, clinical manifestations, and ambulatory function were reported descriptively. Subanalyses on potential prognostic indicators were performed. SYNTHESIS: Greater ambulatory function at diagnosis was associated with recovery of normal ambulatory function at follow-up (P < .001). Nearly 90% of patients walking unsupported at diagnosis made a complete recovery regardless of etiology. For patients initially walking with support, 22% of cases from impaired B12 digestion/absorption made a complete recovery compared with ≥50% of cases from other etiologies. For patients initially requiring a wheelchair, 33% of cases from impaired digestion/absorption were able to walk with support compared with ≥50% of cases from other etiologies. The total B12 administered over the course of treatment was correlated with improved ambulation (P = .024) for all patients, with a higher B12 replacement regimen associated with better outcomes in patients who were unable to walk unsupported at diagnosis (number needed to treat = 4). CONCLUSIONS: Initial ambulatory function may be a useful clinical marker of the severity of spinal cord dysfunction and final functional outcome. Etiological risk factors influenced both clinical manifestations and final walking ability in SCD, suggesting a distinct pathophysiological mechanism among the causes. In addition, a more intensive B12 replacement regimen may improve ultimate ambulatory function in advanced cases of SCD.

TP53 Mutation Is a Prognostic Factor in Lower Grade Glioma and May Influence Chemotherapy Efficacy.

BACKGROUND: Identification of prognostic biomarkers in cancers is a crucial step to improve overall survival (OS). Although mutations in tumour protein 53 (TP53) is prevalent in astrocytoma, the prognostic effects of TP53 mutation are unclear. METHODS: In this retrospective study, we sequenced TP53 exons 1 to 10 in a cohort of 102 lower-grade glioma (LGG) subtypes and determined the prognostic effects of TP53 mutation in astrocytoma and oligodendroglioma. Publicly available datasets were analysed to confirm the findings. RESULTS: In astrocytoma, mutations in TP53 codon 273 were associated with a significantly increased OS compared to the TP53 wild-type (HR (95% CI): 0.169 (0.036-0.766), p = 0.021). Public datasets confirmed these findings. TP53 codon 273 mutant astrocytomas were significantly more chemosensitive than TP53 wild-type astrocytomas (HR (95% CI): 0.344 (0.13-0.88), p = 0.0148). Post-chemotherapy, a significant correlation between TP53 and YAP1 mRNA was found (p = 0.01). In O (6)-methylguanine methyltransferase (MGMT) unmethylated chemotherapy-treated astrocytoma, both TP53 codon 273 and YAP1 mRNA were significant prognostic markers. In oligodendroglioma, TP53 mutations were associated with significantly decreased OS. CONCLUSIONS: Based on these findings, we propose that certain TP53 mutant astrocytomas are chemosensitive through the involvement of YAP1, and we outline a potential mechanism. Thus, TP53 mutations may be key drivers of astrocytoma therapeutic efficacy and influence survival outcomes.

Multidisciplinary Tracheotomy Teams: An Analysis of Patient Outcomes and Resource Allocation.

We sought to establish the effect of introducing a multidisciplinary tracheotomy management team (MDT). Tracheotomies are high-cost interventions with potentially devastating complications. Multidisciplinary teams have been introduced in many hospitals with the aim of reducing complications, however, data supporting them are lacking. There is currently insufficient evidence to conclude MDTs reduce length of hospital or intensive care unit (ICU) stay, and there is little information on cost analysis. A chart review identified patients who had a tracheotomy inserted at a major metropolitan teaching hospital with an acute spinal medicine service 2 years before and after the MDT was implemented. The primary outcome was time to decannulation. Other outcomes included tracheotomy complications, the proportion of patients decannulated, length of ICU and hospital stay, and admission cost. Our search identified 174 (78 prior and 96 post-MDT) patients. Baseline demographics were similar between groups. There was no difference in time to decannulation, the decannulation rate, or the length of hospital or ICU stay. Complication rates were low in both groups. There was an increase in the proportion of patients who received speaking valves and a reduction in cost of admission in a subgroup of patients who did not undergo head and neck surgery. There is insufficient evidence to support the widespread introduction of tracheotomy MDTs. Institutions considering introducing a tracheotomy team should carefully consider their case-mix, volume, and available resources as well as the structure and responsibilities of the team, and the timing of its activities within the working week. The potential benefits of MDTs including teaching of staff, and collaboration of teams should be acknowledged. Given the potentially significant implications for cost to the health system, a randomized trial is needed to guide policy in this area.

A Randomized Controlled Trial of Brief Cognitive Behavioral Therapy for Regular Methamphetamine Use in Methadone Treatment.

This study evaluated the efficacy of brief cognitive behavioral therapy (BCBT) for regular methamphetamine use among methadone-maintained women. A randomized controlled trial was conducted in four methadone treatment services. Eligible women were assigned to receive either BCBT or drug education. Five questionnaires were used to assess the research hypotheses at weeks 0, 4, and 12. Urinalysis was used to verify self-reported methamphetamine use at week 0. Urinalyses were used for those participants who reported abstinence from methamphetamine at weeks 4 and 12. Overall, 120 women were enrolled. Sixteen participants were lost to follow-up. Compared with the control group, the treatment group showed significant reductions in frequency of methamphetamine use (p < 0.001), severity of methamphetamine dependence (p < 0.001), and number of days of methamphetamine use (p < 0.001) at weeks 4 and 12. Significant improvements in readiness to change (p < 0.001), psychological well-being (p < 0.001), and social functioning (p = 0.001) were found in the treatment group at weeks 4 and 12. Nineteen urine specimens (31.66%) in the treatment group were negative for methamphetamine use at post-treatment and follow-up, while no change was found in the control group (0.00%). The study supported the efficacy of BCBT for methamphetamine use and associated harms.

The ocular surface in children: A review of current knowledge and meta-analysis of tear film stability and tear secretion in children.

PURPOSE: A review of ocular surface and meta-analysis of tear stability (tear break up time, TBUT) and tear secretion (Schirmer test) values in healthy children was conducted. METHODS: Articles published between 1996 and 2017 indexed on MEDLINE, PubMed, Embase, Scopus and Google Scholar were retrieved using defined search terms. Statistical analysis (including sensitivity analysis and meta-regression) was performed. RESULTS: 23 studies were summarised (5,291 participants; neonates (0-29 days), infants (1 month - 1 year) or children (1-18 years) and a meta-analysis conducted using 15 eligible studies (1,077 participants). The combined mean TBUT in children was 14.64 seconds (s) (95% CI, 11.64, 17.64) and 21.76 s (95% CI, 20.43, 23.09) for sodium fluorescein TBUT and non-invasive TBUT respectively (NIBUT). The combined mean NIBUT was 32.5 s (95% CI, 31.78-33.22) in neonates. The combined mean Schirmer I with and without anesthesia were 16.26 mm/5 min (95% CI, 13.17, 19.36) and 29.30 mm/5 min (95% CI, 27.65, 30.96) in children and 9.36 mm/5 min (95% CI, 6.54, 12.18) and 17.63 mm/5 min (95% CI, 12.03, 23.23) in neonates. Meta-regression showed a significantly lower TBUT in children from studies conducted in Asia (p = 0.004). CONCLUSION: There is paucity of data on ocular surface variables in healthy children, making it difficult to draw valid comparisons with adult values.

Seminal plasma pro-inflammatory cytokines interferon-γ (IFNG) and C-X-C motif chemokine ligand 8 (CXCL8) fluctuate over time within men.

STUDY QUESTION: Do seminal plasma pro-inflammatory cytokines interferon-γ (IFNG) and C-X-C motif chemokine ligand 8 (CXCL8) vary within individual men over time? SUMMARY ANSWER: IFNG exhibits substantial variation that is independent of duration of abstinence but correlates with lipopolysaccharide (LPS) content, while CXCL8 varies moderately in association with duration of abstinence. WHAT IS KNOWN ALREADY: Pro-inflammatory cytokines IFNG and CXCL8 in seminal fluid can adversely impact male and female fertility. Other cytokines as well as sperm parameters fluctuate considerably within individuals over time, but whether IFNG and CXCL8 vary similarly, and the determinants of variance, are unknown. STUDY DESIGN, SIZE, DURATION: Between two and seven semen samples were collected from 14 proven fertile donors at 6-10 week intervals over the course of ~12 months, to assess variation over time in cytokines and LPS, and to investigate relationships with sperm parameters and possible regulatory factors. PARTICIPANTS/MATERIALS, SETTING, METHODS: The concentrations and total amounts per ejaculate of IFNG and CXCL8 were determined using commercial ELISA. Sperm parameters were assessed according to World Health Organization (WHO) IV standards and LPS was measured by limulus amebocyte lysate (LAL) assay. Mixed model analysis was utilized to determine the relative contribution of between- and within-individual factors in explaining variance. Relationships between cytokines, LPS and sperm parameters, as well as effect of age and duration of abstinence, were investigated by correlation analysis. MAIN RESULTS AND THE ROLE OF CHANCE: Within-individual variability contributed to total variance particularly for both IFNG, CXCL8 and LPS, and was a stronger determinant than between-individual variability for IFNG and LPS. Normal sperm motility correlated inversely with CXCL8, and sperm concentration correlated inversely with LPS. Duration of abstinence was a determinant of total CXCL8, but not IFNG or LPS. Associations between LPS, IFNG and CXCL8 suggest IFNG and perhaps CXCL8 are influenced by microbial populations. LIMITATIONS, REASONS FOR CAUTION: A limited number of donors from a single clinic were investigated. Clinical information on complete microbiology, BMI, nutrition, smoking and other lifestyle factors was unavailable. Further studies are required to determine whether the findings can be generalized to larger populations and different ethnicities. WIDER IMPLICATIONS OF THE FINDINGS: These data reveal substantial variation over time in pro-inflammatory seminal fluid cytokines and imply existence of microbial or other environmental regulatory factors. STUDY FUNDING/COMPETING INTEREST(S): This study was supported by grants from the National Health and Medical Research Council of Australia. The authors have no competing interests to disclose.

Seminal plasma transforming growth factor-ß, activin A and follistatin fluctuate within men over time.

STUDY QUESTION: Do seminal plasma transforming growth factor-ß (TGFB) cytokines vary within individuals over time, and does this relate to sperm parameters, age or prior abstinence? SUMMARY ANSWER: Activin A and follistatin, and to a lesser extent TGFB1, TGFB2 and TGFB3, vary within individuals over time, in association with duration of abstinence. WHAT IS ALREADY KNOWN: Seminal plasma TGFB cytokines can influence sperm function and reproductive success through interactions with the female reproductive tract after coitus. Over time, individual sperm parameters fluctuate considerably. Whether seminal fluid TGFB cytokines vary similarly, and the determinants of any variance, is unknown. STUDY DESIGN, SIZE, DURATION: Between two and seven semen samples were collected from each of 14 fertile donors at 6-10 week intervals over the course of 12 months, then seminal plasma cytokines and sperm parameters were measured. PARTICIPANTS/MATERIALS, SETTING AND METHOD: The concentrations and total amounts per ejaculate of TGFB1, TGFB2, TGFB3, activin A and follistatin were determined using commercial assays. Sperm parameters were assessed according to WHO IV standards. Mixed model analysis was utilised to determine the relative contribution of between- and within-individual factors to the variance. Relationships between cytokines and sperm parameters, as well as effect of age and duration of abstinence, were investigated by correlation analysis. MAIN RESULTS AND THE ROLE OF CHANCE: Within-individual variability contributed to the total variance for all cytokines and sperm parameters, and was a stronger determinant than between-individual variability for activin A and follistatin as well as for total sperm concentration and sperm motility. Positive correlations between each of the three TGFB isoforms, and activin and follistatin, suggest co-regulation of synthesis. Duration of abstinence influenced total content of TGFB1, TGFB2, activin A and follistatin. TGFB1 correlated inversely with age. LIMITATIONS, REASONS FOR CAUTION: A limited number of donors from a single clinic were investigated. Clinical information on BMI, nutrition, smoking and other lifestyle factors was unavailable. Further studies are required to determine whether the findings can be generalised to larger populations and different ethnicities. WIDER IMPLICATIONS OF THE FINDINGS: These data reveal substantial variation over time in seminal fluid cytokines and indicate that repeated analyses are required to gain precise representative data on an individual's status. Within-individual variation in seminal fluid components should be taken into account when investigating seminal fluid cytokines. STUDY FUNDING/COMPETING INTERESTS: This study was supported by grants from the National Health and Medical Research Council of Australia, ID453556 and APP1041332. The authors have no competing interests to disclose.

Early molecular response and female sex strongly predict stable undetectable BCR-ABL1, the criteria for imatinib discontinuation in patients with CML.

Recent studies have demonstrated that some patients with chronic myeloid leukemia (CML) can maintain remission after discontinuation of imatinib. A prerequisite is stable, undetectable BCR-ABL1. It is not known how many patients achieve this response or the factors associated with its achievement. We examined 423 de novo imatinib-treated patients to determine the cumulative incidence of achieving the discontinuation criteria as defined in the CML8 study (≥2 years of undetectable BCR-ABL1 [Stable MR(4.5)]), and predictive factors. After 8 years of imatinib, the cumulative incidence of Stable MR(4.5) was 36.5%. Therefore, 9% to 15% of first-line imatinib-treated patients would maintain remission after discontinuation. The BCR-ABL1 level at 3 months and factors at diagnosis were examined for association with Stable MR(4.5): Sokal risk, age, sex, and assigned imatinib dose. The only independent predictors were female sex (54.4% vs 27.2%; P = .018) and the 3-month BCR-ABL1 (P < .001). The highest cumulative incidence of Stable MR(4.5) after 8 years was 78.2% for patients with BCR-ABL1 ≤ 0.10%(IS) at 3 months (n = 38). Time to major molecular response (MMR) influenced the time to reach Stable MR(4.5) (P < .001), suggesting slower dynamics of response with a delayed MMR. The findings justify the focus on rapid reduction of BCR-ABL1 as a strategy to maximize potential suitability for imatinib discontinuation studies. The Iris trial was registered at http://www.clinicaltrials.gov as NCT00006343. The Tops trial was registered at http://www.clinicaltrials.gov as NCT00124748. The TIDEL I trial was registered at www.ANZCTR.org.au as ACTRN12607000614493. The TIDEL II trial was registered at www.ANZCTR.org.au as ACTRN12607000325404.

Helmets for snow sports: prevalence, trends, predictors and attitudes to use.

BACKGROUND: Traumatic head injury is the leading cause of mortality and serious morbidity in snow sports and is increasing in incidence. Helmet use in snow sports can reduce the incidence of head injury by up to 60%. Mandatory helmet use is not legislated in most recreational settings for snow sports. This study aimed to quantify the prevalence and trends of helmet use by skiers and snowboarders as well as to investigate predictors of helmet use and reasons why they are worn. METHODS: A cross-sectional study including observation of skiers and snowboarders allocated to adult and child groups (5,267 persons), retrospective review of ski patrol accident report forms recorded between 2003 and 2008 (3,984), and completion of specially designed questionnaires by randomly approached snow sport participants (1,029). RESULTS: In 2008, 16% of adults and 67% of children wore helmets. Helmet use increased for adult and child participants between 2003 and 2008. Children, men, and snowboarders were significantly more likely to wear a helmet than their respective counterparts. Significant predictors of helmet use were level of experience, past major crash requiring medical assistance, snow sport lessons, and location of activity. Key reasons for helmet use and disuse were identified. DISCUSSION: Child helmet use far exceeded adult helmet use. Rates of voluntary helmet use are increasing but many remain unprotected from the benefits of a helmet. Identification of the snow sport participants least likely to wear a helmet and their reasons for not doing so should allow targeted helmet promotion and injury prevention strategies to reduce serious head injuries in snow sports.

To teach or not to teach? A cost-benefit analysis of teaching in private general practice.

OBJECTIVE: To identify the financial costs and benefits associated with teaching in private general practice. DESIGN: Cost-benefit analysis of teaching in private general practice across three levels of training--undergraduate medical training, prevocational training and general practice vocational training--using data from a 2007 survey of general practitioners in South Australia. SETTING AND PARTICIPANTS: GPs and practices teaching in association with the Adelaide to Outback GP Training Program or the Discipline of General Practice at the University of Adelaide. MAIN OUTCOME MEASURE: Net financial outcome per week. RESULTS: The net financial outcome of teaching varied across the training levels. Practices incurred a net financial cost from teaching medical students that was statistically significantly different from zero. With respect to vocational training and teaching junior doctors, there were small net financial benefits to practices, although the mean estimates were not statistically significantly different from zero. CONCLUSIONS: This study shows a net financial cost for practices teaching medical students, while at the prevocational and vocational training levels, adequate levels of subsidies and income generated by the trainees help offset the costs of teaching. Our results suggest that a review of subsidies for undergraduate teaching is necessary, particularly as the demand for teaching practices will increase substantially over the next 5 years.

The cost-effectiveness of point of care testing in a general practice setting: results from a randomised controlled trial.

BACKGROUND: While point of care testing (PoCT) for general practitioners is becoming increasingly popular, few studies have investigated whether it represents value for money. This study aims to assess the relative cost-effectiveness of PoCT in general practice (GP) compared to usual testing practice through a pathology laboratory. METHODS: A cost-effectiveness analysis based on a randomized controlled trial with 4,968 patients followed up for 18 months and fifty-three general practices in urban, rural and remote locations across three states in Australia.The incremental costs and health outcomes associated with a clinical strategy of PoCT for INR, HbA1c, lipids, and ACR were compared to those from pathology laboratory testing. Costs were expressed in year 2006 Australian dollars. Non-parametric bootstrapping was used to generate 95% confidence intervals. RESULTS: The point estimate of the total direct costs per patient to the health care sector for PoCT was less for ACR than for pathology laboratory testing, but greater for INR, HbA1c and Lipids, although none of these differences was statistically significant. PoCT led to significant cost savings to patients and their families. When uncertainty around the point estimates was taken into account, the incremental cost-effectiveness ratio (ICER) for PoCT was found to be unfavourable for INR, but somewhat favourable for ACR, while substantial uncertainty still surrounds PoCT for HbA1c and Lipids. CONCLUSIONS: The decision whether to fund PoCT will depend on the price society is willing to pay for achievement of the non-standard intermediate outcome indicator. TRIAL REGISTRATION: Australian New Zealand Clinical Trial Registry ACTRN12605000272695.

Applicant characteristics and their influence on success: results from an analysis of applicants to the University of Adelaide Medical School, 2004-2007.

OBJECTIVE: To determine the applicant characteristics that influence success at each application stage for entry to the University of Adelaide Medical School. DESIGN, SETTING AND PARTICIPANTS: Retrospective analysis of characteristics associated with a successful outcome to an undergraduate-entry medical school for 6699 applicants from four cohorts (2004-2007). MAIN OUTCOME MEASURES: Offer of an interview, offer of a place, and acceptance of a place in the medical school. RESULTS: Female applicants were less likely to gain an interview (odds ratio [OR], 0.88; 95% CI, 0.78-0.99) but more likely to receive an offer of a place (OR, 1.33; 95% CI, 1.07-1.66). Older applicants were less likely than younger applicants (OR, 0.78; 95% CI, 0.71-0.86) and non-school leavers (applying after leaving school) were more likely than school leavers (applying while at school) (OR, 9.54; 95% CI, 6.16-14.78) to receive an offer of an interview. Applicants from areas of high socioeconomic status were more likely to gain an interview (quartile 1 v 4: OR, 0.55; 95% CI, 0.45-0.68). The more interviews an applicant had, the more likely he or she was to be offered a place (OR, 1.49; 95% CI, 1.34-1.66). CONCLUSION: This study indicates that some applicant characteristics have a significant influence on the success of an application at particular stages, but overall there does not appear to be a large or inherent systematic bias in the selection process at the University of Adelaide Medical School.

Prevalence, awareness, treatment, and control of hypertension in rural China: results from Shandong Province.

OBJECTIVES: Hypertension is an important public health problem in rural China with a rapidly increasing prevalence noted in recent years. This study estimates the prevalence, awareness, treatment and control of hypertension in a rural population in Shandong Province, China. METHODS: A cross-sectional study was conducted in rural Shandong Province, China, in April 2007 using multistage cluster sampling. A total of 16 364 rural residents aged 25 years and more were interviewed and examined. Two blood pressure (BP) measurements were obtained using a standardized mercury sphygmomanometer after a 5-min seated rest. Information on history of hypertension was obtained using a standard questionnaire. Hypertension was defined as mean systolic BP (SBP) at least 140 mmHg and/or diastolic BP (DBP) at least 90 mmHg, and/or self-reported current use of antihypertensive medication. RESULTS: Overall, 43.8% of the population had hypertension. Among hypertensive patients, only 26.2% were aware of their hypertension, 22.2% were currently undergoing antihypertensive treatment, and 3.9% achieved BP control (<140/90 mmHg). Lack of knowledge about hypertension and the importance of BP control were associated with poor compliance with nonpharmacological and pharmacological treatments. CONCLUSIONS: In the study population, the prevalence of hypertension is high, but levels of awareness, treatment and control are unacceptably low. There is an urgent need for comprehensive integrated strategies to improve prevention, detection and treatment of hypertension in rural areas in Shandong Province, China.