Attentional network deficits in children with autism spectrum disorder

Statement of purpose: Individuals with autism spectrum disorder (ASD) often demonstrate deficient attentional ability, but the specific nature of the deficit is unclear. The Attention Networks model provides a useful approach to deconstruct this attentional deficit into its component parts. Method: Fifty-two neurotypical (NT) children and 14 children with ASD performed the child version of the Attention Network Test (ANT). The latter requires participants to indicate the direction of a centre target stimulus, which is presented above/below fixation and sometimes flanked by either congruent or incongruent distractor stimuli. Results: Relative to NT children, those with ASD were: (1) slower to react to spatially cued trials and (2) more error prone on executive (conflict) attention trials. Conclusions: Young children with ASD have intact alerting attention, but less-efficient orienting and executive attention.     

Usefulness of prostate-specific antigen (PSA) rise as a marker of prostate cancer in men treated with dutasteride: lessons from the REDUCE study

Study Type – Prognostic (RCT) Level of Evidence 1b What's known on the subject? and What does the study add? Previous studies used the decrease in PSA after 6 months of dutasteride treatment as a new ‘baseline’ PSA value from which subsequent rises may serve as a warning for prostate cancer; however, PSA tends to continue to decrease as dutasteride treatment continues. By comparing positive biopsy rates in the REDUCE study using any rise from nadir in the dutasteride arm and standard PSA decision criteria (NCCN) in the placebo arm, we demonstrated that the ability to detect prostate cancer and high grade prostate cancer is maintained with dutasteride treatment.

OBJECTIVES

? To determine if dutasteride‐treated men can be monitored safely and adequately for prostate cancer based on data from the Reduction by Dutasteride in Prostate Cancer Events (REDUCE) study. ? To analyse whether the use of treatment‐specific criteria for repeat biopsy maintains the usefulness of prostate‐specific antigen (PSA) level for detecting high grade cancers.

PATIENTS AND METHODS

? The REDUCE study was a randomized, double‐blind, placebo‐controlled investigation of whether dutasteride (0.5 mg/day) reduced the risk of biopsy‐detectable prostate cancer in men with a previous negative biopsy. ? The usefulness of PSA was evaluated using biopsy thresholds defined by National Comprehensive Cancer Network guidelines in the placebo group and any rise in PSA from nadir (the lowest PSA level achieved while in the study) in the dutasteride group. ? The number of cancers detected on biopsy in the absence of increased/suspicious PSA level as well as sensitivity, specificity, positive predictive value and negative predictive value for high grade prostate cancer detection were analysed by treatment group. ? Prostate cancer pathological characteristics were compared between men who did and did not meet biopsy thresholds.

RESULTS

? Of 8231 men randomized, 3305 (dutasteride) and 3424 (placebo) underwent at least one prostate biopsy during the study and were included in the analysis. ? If only men meeting biopsy thresholds underwent biopsy, 25% (47/191) of Gleason 7 and 24% (7/29) of Gleason 8–10 cancers would have been missed in the dutasteride group, and 37% (78/209) of Gleason 7 and 22% (4/18) Gleason 8–10 cancers would have been missed in the placebo group. ? In both groups, the incidence of Gleason 7 and Gleason 8–10 cancers generally increased with greater rises in PSA. ? Sensitivity of PSA kinetics was higher and specificity was lower for the detection of Gleason 7–10 cancers in men treated with dutasteride vs placebo. ? Men with Gleason 7 and Gleason 8–10 cancer meeting biopsy thresholds had greater numbers of positive cores, percent core involvement, and biopsy cancer volume vs men not meeting thresholds.

CONCLUSION

? Using treatment‐specific biopsy thresholds, the present study shows that the ability of PSA kinetics to detect high grade prostate cancer is maintained with dutasteride compared with placebo in men with a previous negative biopsy. ? The sensitivity of PSA kinetics with dutasteride was similar to (Gleason 8–10) or higher than (Gleason 7–10) the placebo group; however, biopsy decisions based on a single increased PSA measurement from nadir in the dutasteride group resulted in a lower specificity compared with using a comparable biopsy threshold in the placebo group, indicating the importance of confirmation of PSA measurements.     

COVID-19 vaccine effectiveness by HIV status and history of injection drug use: a test-negative analysis

Introduction

People living with HIV (PLWH) and/or who inject drugs may experience lower vaccine effectiveness (VE) against SARS-CoV-2 infection.

Methods

A validated algorithm was applied to population-based, linked administrative datasets in the British Columbia COVID-19 Cohort (BCC19C) to ascertain HIV status and create a population of PLWH and matched HIV-negative individuals. The study population was limited to individuals who received an RT-PCR laboratory test for SARS-CoV-2 between 15 December 2020 and 21 November 2021 in BC, Canada. Any history of injection drug use (IDU) was ascertained using a validated administrative algorithm. We used a test-negative study design (modified case−control analysis) and multivariable logistic regression to estimate adjusted VE by HIV status and history of IDU.

Results

Our analysis included 2700 PLWH and a matched population of 375,043 HIV-negative individuals, among whom there were 351 and 103,049 SARS-CoV-2 cases, respectively. The proportion of people with IDU history was much higher among PLWH compared to HIV-negative individuals (40.7% vs. 4.3%). Overall VE during the first 6 months after second dose was lower among PLWH with IDU history (65.8%, 95% CI = 43.5–79.3) than PLWH with no IDU history (80.3%, 95% CI = 62.7–89.6), and VE was particularly low at 4–6 months (42.4%, 95% CI = −17.8 to 71.8 with IDU history vs. 64.0%; 95% CI = 15.7–84.7 without), although confidence intervals were wide. In contrast, overall VE was 88.6% (95% CI = 88.2–89.0) in the matched HIV-negative population with no history of IDU and remained relatively high at 4–6 months after second dose (84.6%, 95% CI = 83.8–85.4). Despite different patterns of vaccine protection by HIV status and IDU history, peak estimates were similar (≥88%) across all populations.

Conclusions

PLWH with a history of IDU may experience lower VE against COVID-19 infection, although findings were limited by a small sample size. The lower VE at 4–6 months may have implications for booster dose prioritization for PLWH and people who inject drugs. The immunocompromising effect of HIV, substance use and/or co-occurring comorbidities may partly explain these findings.     

Na+/H+ exchange inhibition and antioxidants lack additive protective effects after reperfusion injury in the working heterotopic rat heart isograft.

BACKGROUND: The utility of combining strategies of myocardial protection was studied in intact rat hearts subjected to 1 hour of ischemia and 40 minutes blood reperfusion. METHODS: Lewis rats (n = 48) were divided into 4 transplant groups. Twenty-four hearts were arrested by coronary perfusion with hypothermic Celsior solution at 60 mm Hg. The aortic valve was punctured to introduce volume into the left ventricle (LV), and the hearts were abdominally isografted. Animals were either given both the antioxidant probucol (300 mg/kg) and the sodium-hydrogen exchange inhibitor cariporide (5 mg/kg) (CP; n = 6), just cariporide (CAR; n = 6), just probucol (PROB; n = 6), or neither drug (CON; n = 6). After 40 minutes of blood reperfusion, transplanted hearts were rearrested. The control recipients' native hearts (native; n = 6) were also arrested. Postmortem LV compliance relations and myocardial water content (MWC) were measured. RESULTS: Grafts protected by probucol were significantly more compliant than controls and significantly less compliant than grafts protected by cariporide alone and with both cariporide and probucol (p = 0.0001, analysis of variance). Compliance relations for CP overlapped those for CAR. All grafts were less compliant than natives. MWC was significantly greater in controls and PROB than in natives. CONCLUSIONS: Pretreatment with cariporide in the setting of ischemia-reperfusion injury provides greater protection against the development of diastolic abnormalities than probucol when Celsior solution is used for both arrest and preservation. In this model, there is no advantage to combining the drugs, supporting the hypothesis that there is an overlapping mechanism of protection.     

RisedronatE and ALendronate Intervention over Three Years (REALITY): minimal differences in fracture risk reduction

Summary  The comparative effectiveness of alendronate and risedronate has received limited evaluation. Among 19,063 new users of bisphosphonates, risedronate users had a higher relative rate of hip fracture compared to alendronate users, but the difference in absolute fracture rate was small. We conclude that the agents have comparable efficacy. Introduction  Bisphosphonates differ in their in vitro potency, avidity for bone, and rapidity of onset in clinical trials. To address potential differences between bisphosphonates in comparative effectiveness, we compared new users of alendronate and risedronate to determine if there were differences in the risk of clinical fractures at 1 year and beyond. Methods  Using claims data from a U.S. health care organization, we identified new, adherent users of weekly alendronate or risedronate and assessed subsequent fractures. We calculated fracture incidence rate differences and ratios between the two agents. Results  There were no significant differences in fracture rates between alendronate users (n = 12,956) and risedronate users (n = 6,107) at 1 year. Using all available data, the rate of hip fracture was higher among risedronate users compared to alendronate users (absolute rate difference approximately five per 1,000 person-years). Risedronate users had a higher relative rate (RR) of hip fracture (RR = 1.77, 95% CI 1.15–2.74) and similar rates of clinical vertebral and nonvertebral fractures compared to alendronate users. Conclusions  The absolute rate of clinical fractures among alendronate and risedronate users was similar both at 1 year and beyond, suggesting comparable effectiveness between agents. Some of the investigators (JRC and KGS) receive salary support from the National Institutes of Health (AR053351, AR052361) and the Arthritis Foundation (JRC).     

Health Care Expenditures Associated With Skeletal Fractures Among Medicare Beneficiaries, 1999–2005

Fractures impose substantial burdens, in terms of both costs and health, on individuals and health care systems. This is particularly true for older Americans and the Medicare system. The objective of this study was to estimate the costs of care associated with selected fractures among Medicare beneficiaries. This was a retrospective, person‐level, pre/postfracture analysis using administrative data. The study used Medicare claims data from 1999 through 2005 for a 5% sample of Medicare beneficiaries. The subjects included Medicare beneficiaries, ≥65 yr of age, who had at least 13 mo of both Parts A and B coverage and not enrolled in Medicare Advantage and who experienced a closed fracture of the hip, femur, pelvis, tibia/fibula, ankle, distal forearm, nondistal radius/ulna, humerus, clavicle, spine, or wrist, or any fracture of the distal forearm or ankle during the years 2000 through 2005. The main outcome measures were incremental (greater than baseline) and attributable (directly associated) payments for Medicare‐covered services for the first 6 mo after incident fractures. Incremental payments ranged from $7788 (95% CI, $7550–$8025) for distal forearm fractures to $31,310 (95% CI, $31,073–$31,547) for open hip fractures; the attributable payments for distal forearm and hip fractures were $1856 and $18,734, respectively. Fractures are associated with substantial increases in health services utilization and costs among Medicare beneficiaries, but significant proportions of those costs are not directly attributable to fracture treatment. Further research is needed to ascertain other health conditions that are driving costs for Medicare beneficiaries after fractures.     

Are Coronary Angiograms of Value in the Risk Stratification of Patients Undergoing Coronary Artery Bypass Surgery?

INTRODUCTION

There are currently more than 20 risk-scoring systems that attempt to predict peri-operative mortality following coronary artery bypass surgery (CABG). All these scoring systems use objective criteria to assess operative risk. Angiographic data are currently not included in any of these systems. This pilot study assessed the value of coronary angiography in predicting peri-operative mortality following CABG.

PATIENTS AND METHODS

Fourteen patients who died following first-time isolated CABG surgery were identified. These were matched with 14 patients of similar age, sex, left ventricle function and European System for Cardiac Operative Risk Evaluation (EuroSCORE). A panel of 25 clinicians were given details of the patients'' age, sex, diabetic status, family history, smoking history, hypertensive status, lipid status, pre-operative symptoms, left ventricle ejection fraction and weight and shown the coronary angiograms of the patient. They were asked to predict the outcome following CABG for each patient.

RESULTS

Receiver operator characteristic curves were constructed and the area under the curves calculated and analysed using a commercially available statistical package (PRISM). The area under the curve for the group was 0.6820 for the group. Consultant clinicians achieved an area of 0.6789 versus their trainees 0.6844 (P = NS). The cardiologists achieved an area of 0.7063 versus the cardiothoracic surgeons 0.6491 (P = NS).

CONCLUSIONS

Despite the EuroSCORE predicting equal risk for the two groups of patients, it would appear that clinicians are able to identify individual higher risk patients by assessing pre-operatively the quality of the patient'' coronary vasculature. Although the clinicians were able to predict individual patient mortality better than the EuroSCORE, the area under the curve indicates that it is not a robust method and clinicians, with all the clinical information to hand, are only moderately good at predicting the outcome following coronary artery bypass surgery.     

Finasteride monotherapy maintains stable lower urinary tract symptoms in men with benign prostatic hyperplasia following cessation of alpha blockers

Objective

Our Canadian multicentre open-label study sought to evaluate, in patients with moderate/severe lower urinary symptoms (LUTS) secondary to benign prostatic hyperplasia, the effect on symptoms of 9 months of monotherapy with finasteride 5 mg following 9 months of combination treatment (finasteride with an α-blocker) as quantified according to the International Prostate Symptom Score (IPSS).

Methods

The primary outcome measure for efficacy was the maintenance of IPSS response after cessation of the α-blocker. Subjects were treated with a combination of finasteride and an α-blocker for 9 months and then with finasteride alone for 3 or 9 months.

Results

Results showed that the IPSS scores after 3 months of monotherapy were within the criteria for equivalence to those after 9 months of combination therapy. Symptom control equivalence was also found after 9 months of monotherapy. The IPSS response rate was also similar for combination and monotherapy. The safety profile was similar and as expected with these medications.

Conclusion

Control of LUTS associated with BPH thus appears to be maintained for at least 9 months with finasteride alone, following a 9-month course of combination therapy with finasteride and an α-blocker, with similar safety profiles.     

The Canadian Benign Prostatic Hyperplasia Audit Study (CanBas)

Objective

To determine the prevalence, diagnostic patterns and management of lower urinary tract symptoms (LUTS) associated with benign prostatic hyperplasia (BPH) in Canadian urology outpatient practice.

Methods

Representative urologists were randomly selected from lists provided by the Canadian and Quebec Urological Associations. Each patient identified with a BPH diagnosis during a typical 2-consecutive-week period during April, May or June 2007 was asked to complete a corresponding International Prostate Symptom Score (IPSS) questionnaire. Each day, the participant urologist completed an outpatient log and a detailed programmed chart review to transcribe demographics, investigations and treatments associated with each BPH patient.

Results

Eighty-six urologists were invited to participate. Thirty-eight (44.2%) agreed, and 27 of those (71.1%) submitted evaluable data for the audit. Of the 5616 patients seen in outpatient practice (average 208 per urologist), 4324 (77%) were male. A BPH diagnosis was identified in 19.6% of the men (n = 849; mean age 69.5, standard deviation [SD] 10, yr; age range 40–100 yr; mean duration of symptoms 4.8, SD 4.2, yr; mean IPSS score 12.3, SD 7.4; mean prostate specific antigen [PSA] 3.9, SD 3.9, ng/mL). Twenty-four percent of patients had prostates that were rated as large, 50% as medium and 26% as small. PSA level correlated positively with prostate volume. Twenty-two percent were initial consultations for LUTS and 78% were repeat visits. Diagnostic evaluation tended to follow those examinations and tests recommended by the Canadian BPH guidelines. Treatment choices tended to follow an evidence-based algorithm with respect to treatment choices for men in the various prostate-volume and PSA groups.

Conclusion

This prospective audit indicates that BPH remains a common condition managed by urologists in outpatient practice. Investigations and treatments confirm that Canadian urologists appear to be following Canadian BPH guidelines as well as the most recent evidence from the literature.