Objective-To evaluate patterns of antipsychotic use.Design, setting, and measurements-We used nationally representative data from the IMS Health National Disease and Therapeutic Index to describe outpatient antipsychotic use. The primary outcome was the volume of visits where antipsychotics were used for specific indications (treatment visits). We also quantified use without U.S. Food and Drug Administration approval (off-label use) and off-label use with compendium data suggesting an uncertain evidence base.Results-Antipsychotic use increased from 6.2 million (M) treatment visits (95% CI, 5.4-7.0) in 1995 to 16.7M visits (15.5-18.2) in 2006, then declined to 14.3M visits (13.0-15.6) by 2008. A shift occurred from typical agents in 1995 (84% of all antipsychotic visits) to atypical agents by 2008 (93%). As they declined, typical medications shifted towards use in schizophrenia (30% in 1995 to 48% 2008). In contrast, use of atypical agents expanded for bipolar affective disorder (10% to 34%), remained stable for depression (12% to 14%), and declined for schizophrenia (56% to 23%). Overall, antipsychotic use for indications without FDA approval increased from 4.4M visits in 1995 to 9.0M in 2008. The estimated cost associated with off-label use in 2008 was US $6.0 billion.Conclusions-Atypical use has grown far beyond substitution for the now infrequently used typical agents. Antipsychotics are increasingly used for conditions where FDA approval and associated clinical evidence is less certain. Despite the value of innovation, the benefits of widening atypical antipsychotic use should be weighed against their cost, regulatory status, and incomplete nature of available evidence.

Background In April 2005, the US Food and Drug Administration (FDA) issued an advisory and subsequent black box warning regarding the risks of atypical anti-psychotic use among elderly patients with dementia. The impact of these warnings on atypical drug use is unknown. Methods We used quasi-experimental, interrupted time-series analyses to examine nationally representative data from IMS Health’s National Disease and Therapeutic Index from January 2003 through December 2008. The primary measurement from this audit of office-based physicians was the use of an atypical antipsychotic agent. We quantified the impact of the advisory on atypical anti-psychotic use among all individuals and those 65 years or older with dementia. Results From January 2003 to March 2005, mentions of total atypical antipsychotic drugs increased at an annual rate of 34%, and among patients with dementia, 16%. In the year prior to the FDA advisory, there were approximately 13.6 million atypical drug mentions, including 0.8 million among those with dementia. In the year following the advisory, atypical drug mentions fell 2% overall and 19% among those with dementia. In 2004, 19% (0.8 of 4.1 million) of drug mentions for dementia were for an atypical agent. By 2008, this proportion decreased to 9% (0.4 of 4.3 million). Atypical drug use slowed for both FDA-approved and off-label indications and declined through 2008 for all populations examined. Conclusion The FDA advisory was associated with decreases in the use of atypical antipsychotics, especially among elderly patients with dementia.

Background To investigate the prognostic significance of positron emission tomography (PET) parameters from F-18 fluorodeoxyglucose (FDG) PET scans performed pre- and post- chemo-radiotherapy (CRT) for squamous cell carcinoma of the anal canal (AC). Methods From January 2013 to January 2017, 19 patients with non-metastatic AC enrolled on a prospective trial underwent FDG-PET/CT imaging before and 12 weeks following CRT. A computer-generated volume of interest (VOI) was snapped around the primary tumour using six different standard uptake value (SUV) thresholds and the following parameters were extracted: SUV max, mean, median, standard deviation and peak as well as metabolic tumour volume (MTV) and total lesion glycolysis. Exact logistic regression and ROC AUC analyses were performed for each metric at each timepoint. Results With a median follow up of 15.8 months, 3/19 patients had a local recurrence and 5/19 had any recurrence. On post-CRT PET, the median SUV within a VOI bounded by an SUV of 3 correlated with local recurrence ( p < 0.01) and demonstrated excellent discrimination (ROC AUC 1.00, perfect separation was achieved at a median SUV of 3.38). The mean SUV at this threshold did not quite reach significance for prediction of local recurrence ( p = 0.06) but demonstrated excellent discrimination (ROC AUC 0.91). The MTV bounded by a threshold of 41% SUVmax on the pre-CRT PET predicted for any recurrence ( p = 0.03) and showed excellent discrimination (ROC AUC 0.89). Conclusions FDG-PET parameters are predictive of recurrence in AC. FDG-PET may represent a valuable tool for prognostication and response assessment in AC. Trial registration ANZCTR, ACTRN12614001219673 . Registered 19 November 2014 - Retrospectively registered.

BackgroundThe use of gold fiducial markers (FM) for prostate image-guided radiotherapy (IGRT) is standard practice. Published literature suggests low rates of serious infection following this procedure of 0-1.3%, but this may be an underestimate. We aim to report on the infection incidence and severity associated with the use of transrectally implanted intraprostatic gold FM.MethodsThree hundred and fifty-nine patients who underwent transrectal FM insertion between January 2012 and December 2013 were assessed retrospectively via a self-reported questionnaire. All had standard oral fluoroquinolone antibiotic prophylaxis. The patients were asked about infective symptoms and the treatment received including antibiotics and/or related hospital admissions. Potential infective events were confirmed through medical records.Results285 patients (79.4%) completed the questionnaire. 77 (27.0%) patients experienced increased urinary frequency and dysuria, and 33 patients (11.6%) reported episodes of chills and fevers after the procedure. 22 patients (7.7%) reported receiving antibiotics for urinary infection and eight patients (2.8%) reported hospital admission for urosepsis related to the procedure.ConclusionThe overall rate of symptomatic infection with FM implantation in this study is 7.7%, with one third requiring hospital admission. This exceeds the reported rates in other FM implantation series, but is in keeping with the larger prostate biopsy literature. Given the higher than expected complication rate, a risk-adaptive approach may be helpful. Where higher accuracy is important such as stereotactic prostate radiotherapy, the benefits of FM may still outweigh the risks. For others, a non-invasive approach for prostate IGRT such as cone-beam CT could be considered.Electronic supplementary materialThe online version of this article (doi:10.1186/s13014-015-0347-2) contains supplementary material, which is available to authorized users.

Objectives: To report feasibility, early toxicity, and PSA kinetics following gantry-based, stereotactic radiotherapy (SBRT) boost within a prospective, phase 2, multicenter study (PROMETHEUS: ACTRN12615000223538). Methods: Patients were treated with gantry-based SBRT, 19–20 Gy in two fractions delivered 1 week apart, followed by conventionally fractionated IMRT (46 Gy in 23 fractions). The study mandated MRI fusion for RT planning, rectal displacement, and intrafraction image guidance. Toxicity was prospectively graded using the Common Terminology Criteria for Adverse Events version 4.0 (CTCAE v4). Results: Between March 2014 and July 2018, 135 patients (76% intermediate, 24% high-risk) with a median age of 70 years (range 53–81) were treated across five centers. Short course (≤6 months) androgen deprivation therapy (ADT) was used in 36% and long course in 18%. Rectal displacement method was SpaceOAR in 59% and Rectafix in 41%. Forty-two and ninety-three patients were treated at the 19 Gy and 20 Gy dose levels, respectively. Median follow-up was 24 months. Acute grade 2 gastrointestinal (GI) and urinary toxicity occurred in 4.4 and 26.6% with no acute grade 3 toxicity. At 6, 12, 18, 24, and 36 months post-treatment the prevalence of late grade ≥2 gastrointestinal toxicity was 1.6, 3.7, 2.2, 0, and 0%, respectively, and the prevalence of late grade ≥2 urinary toxicity was 0.8, 11, 12, 7.1, and 6.3%, respectively. Three patients experienced grade 3 late toxicity at 12 to 18 months which subsequently resolved to grade 2 or less. For patients not receiving ADT the median PSA value pre-treatment was 7.6 ug/L (1.1–20) and at 12, 24, and 36 months post-treatment was 0.86, 0.36, and 0.20 ug/L. Conclusions: Delivery of a gantry-based SBRT boost is feasible in a multicenter setting, is well-tolerated with low rates of early toxicity and is associated with promising PSA responses. A second transient peak in urinary toxicity was observed at 18 months which subsequently resolved. Follow-up is ongoing to document late toxicity, long-term patient reported outcomes, and tumor control with this approach.