Comparing comprehensibility of standard and enhanced prescription medicine labels: a randomized simulation.

OBJECTIVES: The objective of this study is to develop and user-test the comparative effectiveness of two enhanced label designs to improve comprehension of patients with low English proficiency versus a standard label representative of the pharmacist-affixed medicine labels currently used in practice. METHODS: Using a randomized two-group study design, 66 participants from Sydney, Australia were allocated to view a set of standard labels followed by a set of enhanced labels named 'linguistically enhanced labels' or 'linguistically and graphically enhanced labels'. Each set of labels depicted medicine directions of three levels of complexity, which participants viewed consecutively. The 'enhanced labels' incorporated several features documented in the literature as improving understanding of low-health-literate/linguistically compromised individuals such as translated directions in a language the person is more proficient in, numeric presentations of numbers/counts, carriage returns and graphic depiction of directions. A user-testing questionnaire relating to comprehensibility was conducted after each label was viewed. Differences in comprehensibility were assessed using a generalized linear model, Cochran-Mantel-Haenszel test for trend and a chi-square test. KEY FINDINGS: Results indicated significant improvements in comprehensibility with both types of enhanced labels compared with standard labels (P < 0.0001). The 'linguistically and graphically enhanced label' improved comprehensibility of the most complex directions to a greater extent than the 'linguistically enhanced label' (P < 0.0001). CONCLUSIONS: This study has highlighted the scope for improvement of existing pharmacist-affixed prescription medicine labels to ensure better understanding by individuals with low English proficiency. The enhanced labels trialled presented a means with which this may be achieved through the incorporation of key design elements, such as simpler, translated and graphically supported directions.

Efficiency of Detecting New Primary Melanoma Among Individuals Treated in a High-risk Clinic for Skin Surveillance.

Importance: A previous single-center study observed fewer excisions, lower health care costs, thinner melanomas, and better quality of life when surveillance of high-risk patients was conducted in a melanoma dermatology clinic with a structured surveillance protocol involving full-body examinations every 6 months aided by total-body photography (TBP) and sequential digital dermoscopy imaging (SDDI). Objective: To examine longer-term sustainability and expansion of the surveillance program to numerous practices, including a primary care skin cancer clinic setting. Design, Setting, and Participants: This prospective cohort study recruited 593 participants assessed from 2012 to 2018 as having very high risk of melanoma, with a median of 2.9 years of follow-up (interquartile range, 1.9-3.3 years), from 4 melanoma high-risk clinics (3 dermatology clinics and 1 primary care skin cancer clinic) in New South Wales, Australia. Data analyses were conducted from February to September 2020. Exposures: Six-month full-body examination with the aid of TBP and SDDI. For equivocal lesions, the clinician performed SDDI at 3 or 6 months. Main Outcomes and Measures: All suspect monitored or excised lesions were recorded, and pathology reports obtained. Outcomes included the incidence and characteristics of new lesions and the association of diagnostic aids with rates of new melanoma detection. Results: Among 593 participants, 340 (57.3%) were men, and the median age at baseline was 58 years (interquartile range, 47-66 years). There were 1513 lesions excised during follow-up, including 171 primary melanomas. The overall benign to malignant excision ratio, including keratinocyte carcinomas, was 0.8:1.0; the benign melanocytic to melanoma excision ratio was 2.4:1.0; and the melanoma in situ to invasive melanoma ratio was 2.2:1.0. The excision ratios were similar across the 4 centers. The risk of developing a new melanoma was 9.0% annually in the first 2 years and increased with time, particularly for those with multiple primary melanomas. The thicker melanomas (>1-mm Breslow thickness; 7 of 171 melanomas [4.1%]) were mostly desmoplastic or nodular (4 of 7), self-detected (2 of 7), or clinician detected without the aid of TBP (3 of 7). Overall, new melanomas were most likely to be detected by a clinician with the aid of TBP (54 of 171 [31.6%]) followed by digital dermoscopy monitoring (50 of 171 [29.2%]). Conclusions and Relevance: The structured surveillance program for high-risk patients may be implemented at a larger scale given the present cohort study findings suggesting the sustainability and replication of results in numerous settings, including a primary care skin cancer clinic.

Sustained fall in inpatient MRSA prevalence after a video-reflexive ethnography project; an observational study.

BACKGROUND: Maintaining optimal infection prevention and control (IPC) in a busy, clinical environment is challenging. Video-reflexive ethnography (VRE) is a collaborative, interventionist approach to practice improvement. We hypothesised that giving clinicians opportunities to view and reflect on video footage of everyday ward activities would raise awareness of, and suggest strategies to reduce, pathogen transmission risks. We undertook a VRE project, between March and September 2013, in two tertiary hospital surgical wards, with persistently high methicillin resistant Staphylococcus aureus (MRSA) endemicity, despite previous IPC interventions. METHODS: This study was a retrospective/prospective observational study, using interrupted time-series analyses, to assess the effects of the VRE project on hand hygiene compliance, inpatient MRSA infections (newly infected patients, per 1000 occupied bed days) and inpatient MRSA colonisation prevalence, measured by serial point prevalence surveys. Follow-up continued until June 2016. RESULTS: The VRE project was associated with changes in IPC behaviour and outcomes. Hand hygiene compliance increased (from 62% to 75%; p < 0.0001) and MRSA colonisation prevalence decreased significantly, in both wards (baseline 42%; average post-VRE 12%; p=<0.0001), MRSA infection rate decreased in one ward. Interpretation of results was complicated by a potential confounding effect of unplanned environmental hydrogen peroxide decontamination (HPD). Improved hand hygiene compliance was a predicted outcome of VRE, but also a potential contributor to reduced MRSA transmission. CONCLUSION: Separate contributions of VRE (the intervention), HPD and hand hygiene compliance were uncertain, but their combined effect was significantly reduced MRSA endemicity, which previously had been resistant to attempted IPC interventions.

A Retrospective Study Using the String of Pearls Tibial Plateau Levelling Osteotomy Locking Plate for the Treatment of Cranial Cruciate Ligament Disease.

OBJECTIVE: The aim of this study was to describe the use of String of Pearls (SOP) tibial plateau levelling osteotomy (TPLO) locking plates for the treatment of cranial cruciate ligament disease and retrospectively assess osteotomy healing, tibial plateau angle (TPA) change (c) and overall complication rates. METHODS: Medical records and radiographic studies of 170 SOP TPLO surgical procedures were analysed. Radiographic measurement of TPAc and osteotomy union was determined 6 to 8 weeks postoperatively. Intra- and postoperative major and minor complications were identified. Factors influencing TPAc, osteotomy union and complications were assessed. RESULTS: Mean (standard deviation) TPAc was 1.3° (1.61) and median osteotomy union was graded as 2 (26-50%) union. Improved osteotomy union was associated with retention of the antirotational pin (odds ratio [OR]: 2.3; 95% confidence interval [CI]: 1.3-4; p = 0.005) and reduced TPAc (OR: 0.8; 95%CI: 0.66-0.97; p = 0.02). Complications occurred in 42 (24.7%) procedures with 11 (6.5%) considered major and 31 (18.2%) minor. CLINICAL SIGNIFICANCE: The use of the SOP TPLO plating system resulted in a median grade 2 (26-50%) radiographic osteotomy union score at 6 to 8 weeks' follow-up, less than previous TPLO locking plate studies. Osteotomy union was associated with retention of the antirotational pin and reduced TPAc. Major and minor complication rates were marginally greater than recent locking plate studies with fibular fracture and screw loosening common complications. The use of SOP TPLO plates is cautioned and further study is warranted.

Distress, uncertainty, and positive experiences associated with receiving information on personal genomic risk of melanoma.

The aim of this research was to understand how genomics-based personal melanoma risk information impacts psychological and emotional health outcomes in the general population. In a pilot randomized controlled trial, participants (n = 103) completed the Multidimensional Impact of Cancer Risk Assessment (MICRA) questionnaire, 3 months after receiving personal melanoma genomic risk information. Mean scores for MICRA items and subscales were stratified by genomic risk group (low, average, high), gender, education, age, and family history of melanoma. P values were obtained from t-tests and analysis of variance tests. We found that overall, participants (mean age: 53 years, range: 21-69; 52% female) had a total MICRA mean score of 18.6 (standard deviation: 11.1, range: 1-70; possible range: 0-105). The high genomic risk group had higher mean scores for the total (24.2, F2,100 = 6.7, P = 0.0019), distress (3.3, F2,100 = 9.4, P = 0.0002) and uncertainty (8.5, F2,100 = 6.5, P = 0.0021) subscales compared with average (17.6, 1.1, and 4.5, respectively) and low-risk groups (14.1, 0.5, and 2.5, respectively). Positive experiences scores were consistent across risk groups. In conclusion, MICRA scores for the total, distress and uncertainty subscales in our study were relatively low overall, but people who receive a high genomic risk result may benefit from increased support following testing.

Delineating the trajectories of social and occupational functioning of young people attending early intervention mental health services in Australia: a longitudinal study.

OBJECTIVES: Mental disorders typically emerge during adolescence and young adulthood and put young people at risk for prolonged socioeconomic difficulties. This study describes the longitudinal course of social and occupational functioning of young people attending primary care-based, early intervention services. DESIGN: A longitudinal study of young people receiving mental healthcare. SETTING: Data were collected between January 2005 and August 2017 from a designated primary care-based mental health service. PARTICIPANTS: 554 young people (54% women) aged 12-32 years. MEASURES: A systematic medical file audit collected clinical and functional information at predetermined time intervals (ie, 3 months to 5+ years) using a clinical pro forma. Group-based trajectory modelling (GBTM) was used to identify distinct trajectories of social and occupational functioning over time (median number of observations per person=4; median follow-up time=23 months). RESULTS: Between first clinical contact and time last seen, 15% of young people had reliably deteriorated, 23% improved and 62% did not demonstrate substantive change in function. Of the whole cohort, 69% had functional scores less than 70 at time last seen, indicative of ongoing and substantive impairment. GBTM identified six distinct functional trajectories whereby over 60% had moderate-to-serious functional impairment at entry and remained chronically impaired over time; 7% entered with serious impairment and deteriorated further; a quarter were mildly impaired at entry and functionally recovered and only a small minority (4%) presented with serious impairments and functionally improved over time. Not being in education, employment or training, previous hospitalisation and a younger age at baseline emerged as significant predictors of these functional trajectories. CONCLUSION: Young people with emerging mental disorders have significant functional impairment at presentation for care, and for the majority, it persists over the course of clinical care. In addition to providing clinical care earlier in the course of illness, these data suggest that more sophisticated and more intensive individual-level and organisational strategies may be required to achieve significant and sustained functional improvements.

Development and Evaluation of a Telephone Communication Protocol for the Delivery of Personalized Melanoma Genomic Risk to the General Population.

Communicating personalized genomic risk results for common diseases to the general population as a form of tailored prevention is novel and may require alternative genetic counseling service delivery models. We describe the development and evaluation of a communication protocol for disclosing melanoma genomic risk information to the asymptomatic general population and assess participants' satisfaction and acceptability. Participants (n = 117) were aged 22-69 years, living in New South Wales, Australia and unselected for family history. They provided a saliva sample and had genomic testing for melanoma for low to moderate penetrant melanoma susceptibility variants in 21 genes. Participants could choose to receive their results from a genetic counselor via telephone, followed by a mailed booklet or to receive their risk result via mailed booklet only with a follow-up call for those at high risk. A follow-up questionnaire was completed by 85% of participants 3-months later. Most participants (80%) elected to receive their result via telephone. Participants were highly satisfied with the delivery of results (mean 3.4 out of 4, standard deviation 0.5), and this did not differ by delivery mode, risk category, age or sex. On follow-up, 75% accurately recalled their risk category, 6% indicated a preference for a different delivery mode, either electronic or face-to-face. The process of disclosing genomic risk results to the general population over the telephone with accompanying written material was feasible and acceptable, and may be useful for communicating polygenic risk for common diseases in the context of increasing demands for genomic testing.

Cardiac iron load and function in transfused patients treated with deferasirox (the MILE study).

OBJECTIVES: To assess the effect of iron chelation therapy with deferasirox on cardiac iron and function in patients with transfusion-dependent thalassemia major, sickle cell disease (SCD), and myelodysplastic syndromes (MDS). METHODS: This phase IV, single-arm, open-label study over 53 wk evaluated the change in cardiac and liver iron load with deferasirox (up to 40 mg/kg/d), measured by magnetic resonance imaging (MRI). RESULTS: Cardiac iron load (myocardial T2*) significantly improved (P = 0.002) overall (n = 46; n = 36 thalassemia major, n = 4 SCD, n = 6 MDS). Results were significant for patients with normal and moderate baseline cardiac iron (P = 0.017 and P = 0.015, respectively), but not in the five patients with severe cardiac iron load. Liver iron concentration (LIC) significantly decreased overall [mean LIC 10.4 to 8.2 mg Fe/g dry tissue (dw); P = 0.024], particularly in those with baseline LIC >7 mg Fe/g dw (19.9 to 15.6 mg Fe/g dw; P = 0.002). Furthermore, myocardial T2* significantly increased in patients with LIC <7 mg Fe/g dw, but not in those with a higher LIC. Safety was consistent with previous reports. CONCLUSIONS: Once-daily deferasirox over 1 yr significantly increased myocardial T2* and reduced LIC. This confirms that single-agent deferasirox is effective in the management of cardiac iron, especially for patients with myocardial T2* >10 ms (Clinicaltrials.gov identifier: NCT00673608).

A prospective trial assessing the safety and efficacy of collecting up to 840 mL of plasma in conjunction with saline infusion during plasmapheresis.

BACKGROUND: The demand for plasma for manufacturing intravenous immunoglobulin and other plasma derivatives is increasing. A prospective study was conducted to determine whether up to 840 mL of plasma could be safely and effectively collected in conjunction with saline infusion during plasmapheresis. STUDY DESIGN AND METHODS: Ninety-one plasma donors were enrolled in a modified 3 × 3 crossover study to assess the equivalence of three plasma collection methods: 750 mL of plasma with no saline (control, Method 1), 840 mL of plasma with a 250-mL saline infusion during and at the end of the donation (Method 2), and 800 mL of plasma with a 500-mL saline infusion at the end of the donation (Method 3). The primary efficacy endpoint was the total protein concentration of the collected plasma. Secondary efficacy endpoints were immunoglobulin (Ig)G and Factor (F)VIII plasma concentration and donors' acceptance of the new procedures. Safety was determined from the adverse event (AE) rate. RESULTS: The total protein, IgG, and FVIII concentrations in plasma collected under Methods 2 and 3 were significantly lower than those in plasma collected under Method 1 (p < 0.0001). These variables were also significantly lower in plasma collected under Method 2 compared to Method 3. During the study, 75 AEs were recorded, 73 of which were mild to moderate. Significantly more donors (31%) preferred Method 2 compared to Method 3 (p = 0.006). CONCLUSIONS: Saline infusion during plasmapheresis led to hemodilution of plasma proteins. However, the benefits to donor safety and satisfaction are compelling reasons to implement saline infusion during plasmapheresis.

Measuring change in prescription drug utilization in Australia.

PURPOSE: The National Prescribing Service Ltd (NPS) aims to improve prescribing and use of medicines consistent with evidence-based best practice. This report compares two statistical methods used to determine whether multiple educational interventions influenced antibiotic prescription in Australia. METHODS: Monthly data (July 1996 to June 2003) were obtained from a national claims database. The outcome measures were the median number of antibiotic prescriptions per 1000 consultations for each general practitioner (GP) each month, and the mean proportion (across GPs) of each subgroup of antibiotics (e.g. roxithromycin) out of nine antibiotics having primary use for upper respiratory tract infection. Two approaches were used to investigate shifts in prescribing: augmented regression, which included seasonality, autocorrelation and one intervention; and seasonally adjusted piecewise linear dynamic regression, which removed seasonality prior to modelling, included several interventions, GP participation and autocorrelated errors. Both methods are variations of piecewise linear regression modelling. RESULTS: Both approaches described a similar decrease in rates, with a non-significant change after the first intervention. The inclusion of more interventions and GP participation made no difference. Using roxithromycin as an example of the analyses of proportions, both approaches implied that after the first intervention the proportion decreased significantly. The statistical significance of this intervention disappears when other interventions are included. CONCLUSIONS: The two analyses provide results which agree regarding the possible impact of the NPS interventions, but raise questions about what is the best way to model drug utilization, particularly regarding whether to include all intervention terms when they belong to an extended roll-out of related interventions.

Attenuation of the colorectal tonic reflex in female patients with irritable bowel syndrome.

Alterations in normal intestinointestinal reflexes may be important contributors to the pathophysiology of irritable bowel syndrome (IBS). Our aims were to compare the rectal tonic responses to colonic distension in female IBS patients with predominant constipation (IBS-C) and with predominant diarrhea (IBS-D) to those in healthy females, both fasting and postprandially. Using a dual barostat assembly, 2-min colonic phasic distensions were performed during fasting and postprandially. Rectal tone was recorded before, during, and after the phasic distension. Colonic compliance and colonic sensitivity in response to the distension were also evaluated fasting and postprandially. Eight IBS-C patients, 8 IBS-D patients, and 8 age- and sex-matched healthy subjects (group N) participated. The fasting increments in rectal tone in response to colonic distension in both IBS-C (rectal balloon volume change -4.6 +/- 6.1 ml) and IBS-D (-7.9 +/- 4.9 ml) were significantly reduced compared with group N (-34 +/- 9.7 ml, P = 0.01). Similar findings were observed postprandially (P = 0.02). When adjusted for the colonic compliance of individual subjects, the degree of attenuation in the rectal tonic response in IBS compared with group N was maintained (fasting P = 0.007; postprandial P = 0.03). When adjusted for colonic sensitivity there was a trend for the attenuation in the rectal tonic response in IBS patients compared with group N to be maintained (fasting P = 0.07, postprandial P = 0.08). IBS patients display a definite attenuation of the normal increase in rectal tone in response to colonic distension (colorectal reflex), fasting and postprandially. Alterations in colonic compliance and sensitivity in IBS are not likely to contribute to such attenuation.

Modulatory influences on antegrade and retrograde tonic reflexes in the colon and rectum.

Tonic reflexes in the colon and rectum are likely to be important in health and in disorders of gastrointestinal function. The aim of this study was to evaluate the fasting and postprandial "colorectal" and "rectocolic" reflexes in response to 2-min isobaric distensions of the colon and rectum, accounting for enteric sensation, compliance, and distending balloon volume. In 14 healthy fasting subjects, a dual barostat assembly was positioned (descending colon and rectum). A 2-min phasic distension was performed in the colon and rectum in random order while the opposing balloon volume was recorded. Sensation (phasic distension) and compliance (ramp distension) were also determined. The experiment was repeated postprandially. Colonic distension resulted in significant rectal tonic contraction in the fasting (rectal volume change: -35.4 +/- 8.4 ml, P < 0.01) and postprandial (-22.2 +/- 8.4 ml, P < 0.01) states. After adjustment for colonic sensitivity, for compliance, and for distending balloon volume, the rectal volume change remained significant; the extent of the tonic response, however, correlated significantly with increasing pain score (P < 0.01). In contrast, rectal distension did not produce a significant tonic response in the colon (fasting: -6.5 +/- 7.3 ml; postprandial: 2.7 +/- 7.3 ml), either unadjusted or adjusted for rectal sensitivity, compliance, and distending balloon volume. In conclusion, the colorectal reflex, but not the rectocolic reflex, can be readily demonstrated both before and after a meal in response to a 2-min isobaric distension in the colon and rectum, respectively. Although the presence of the colorectal reflex does not depend on colonic sensitivity or the volume of the distending colonic balloon, these factors modulate the reflex, especially in the fasting state.