Prevalence of High-Risk Human Papillomavirus Infections before and after Cervical Lesion Treatment, among Women Living with HIV

Even when receiving combination antiretroviral therapy, women living with HIV are at high risk of human papillomavirus (HPV) infection and/or cervical lesions, including cancer. Using data from the PapilloV prospective cohort, we evaluated the prevalence of high-risk HPV (HR-HPV) infections after cervical lesion treatment and investigated factors associated with their carriage. Women were followed up for three years with annual Pap smear and HPV genotyping. We offered treatment to women presenting either a Pap smear with high-grade squamous intraepithelial lesion or higher, and/or a biopsy showing cervical intraepithelial neoplasia II or III. We compared the prevalence of HR-HPV infection at the time of first treatment indication and at the end of follow-up among women who received treatment and those who did not. Overall, 46 women had treatment indication. HR-HPV prevalence significantly decreased from 67% to 27% (p value = 0.001) in the 30 women who received treatment, while it did not significantly decrease (from 56% to 38%) in the 16 women who did not (p value = 0.257). Due to lack of statistical power, the 40% relative difference in HR-HPV carriage between treated and untreated women was not significant. In women living with HIV, the treatment of a cervical lesion may be beneficial for clearing HR-HPV infections.

Prognostic factors in postoperative radiotherapy for prostate cancer – tertiary center experience

Background The aim of the study was to analyse the prognostic factors in postoperative prostate cancer irradiation and develop a nomogram for disease-free survival (DFS). Patients and methods This retrospective study included 236 consecutive prostate cancer patients who had radical prostatectomy followed by radiotherapy (RT) at a single tertiary institution between 2009 and 2014. The main outcome was DFS analysed through uni- and multivariable analysis, Kaplan-Meier curves, log-rank testing, recursive partitioning analysis, and nomogram development. Results The median follow up was 62.3 (interquartile range [IQR] 38.1–79) months. The independent clinical factors associated with increased risk of recurrence or progression in the multivariate analysis (MVA) were prostate-specific antigen (PSA) level before RT, pT3 characteristic, and local failure as salvage indication. The value of PSA nadir had a significant impact on the risk of biochemical failure. Biochemical control and DFS were significantly different depending on treatment indication (p < 0.0001). The recursive partitioning analysis highlighted the importance of the PSA level before RT, Gleason Grade Group, PSA nadir, and local failure as a treatment indication. Finally, the nomogram for DFS was developed and is available online at https://apps.konsta.com.pl/app/prostate-salvage-dfs/. Conclusions The Pre-RT PSA level, pT3 characteristic and local failure as salvage indication are pivotal prognostic factors associated with increased risk of recurrence or progression. The Gleason grade group of 4–5 and PSA nadir value allow for further risk stratification. The treatment outcomes in postoperative prostate cancer irradiation are significantly different depending on treatment indication. An online nomogram comprising of both pre-treatment and current data was developed allowing for visualization of changes in prognosis depending on clinical data.

Temporal Changes in Secondary Prevention and Cardiovascular Outcomes after Revascularization for Peripheral Arterial Disease in Denmark: A Nationwide Cohort Study

Background: Patients with peripheral arterial disease (PAD) are at increased risk of cardiovascular morbidity and mortality. Medical prevention with antithrombotic and statin therapies is a mainstay of treatment to prevent adverse outcomes; nevertheless, patients with PAD are often undertreated. This study described the temporal changes in medical prevention and adverse outcomes in a national cohort of patients with symptomatic PAD after revascularization. Methods: We identified all patients with a first open surgical or endovascular revascularization procedure in the lower extremities or abdomen in Denmark, from 2000 to 2016. We examined temporal changes in the use of aspirin, clopidogrel, and statins and one-year cause-specific hazard ratios (HR) for adverse clinical outcomes, after adjusting for procedure type, treatment indication, age, sex and cardiovascular risk factors. The analyses were performed overall, and within strata of index procedure (endovascular vs. surgical), treatment indication, age, sex, and high-risk comorbidities. Results: Between 2000 and 2016, we identified 32,911 patients that underwent revascularization for symptomatic PAD. The mean age was 69 years and increased over time as did the burden of comorbidity. The cumulative incidence of medication use increased between 2000-2004 and 2013-2016, respectively, from 57.3% to 64.3% for aspirin, 3.6% to 24.8% for clopidogrel, and from 36.2% to 77.1% for statins. Concurrently, the one-year outcome rates declined. Compared with 2000-2004, the adjusted HRs in 2013-2016 were 0.73 (95% CI 0.62-0.84) for major adverse cardiovascular events, 0.92 (95% CI 0.85-1.00) for major adverse limb events, 0.60 (95% CI 0.48-0.74) for myocardial infarction, 0.94 (95% CI 0.75-1.18) for ischemic stroke, 0.92 (95% CI 0.75-1.12) for major bleeding, 0.54 (95% CI 0.39-0.76) for cardiovascular death, and 0.80 (95% CI 0.72-0.88) for all cause death. These improvements in prognosis were most prominent from 2000-2004 to 2005-2008, and occurred in all strata of index procedure, treatment indication, sex, age and comorbidity. In contrast, the adjusted HR for major amputations was 1.00 (95% CI 0.90-1.11), when comparing 2013-2016 to 2000-2004. Conclusions: Medical prevention of adverse events has increased considerably over time in patients that underwent revascularization for symptomatic PAD. This increase was accompanied by reductions in all adverse outcomes, except major amputations.

Favorable Outcome in CLL Patients Not Treated Despite Presenting Iwcll Criteria: A Retrospective Analysis of the Brazilian CLL Group

Introduction: Some patients with CLL will require treatment at diagnosis, but many other will remain untreated under observation for several years. In 2008, the International Workshop on Chronic Lymphocytic Leukemia(IWCLL) defined the criteria for treatment indications, which have been widely used in daily practice and in clinical trials. We have observed that many patients tolerate several of these clinical manifestations without treatment need, especially in public hospitals were resources and treatment options are scarce. We identified 5 reference centers for CLL that share the same profile of being more conservative in indicating treatment for CLL patients. We decided to analyze if more conservative local criteria for treatment indication impacts on patients' outcomes. Objective: To describe the outcomes of a series of CLL patients treated according to locally defined more conservative criteria for initiating treatment. Methods: The Brazilian Registry of CLL was started in 2004 as a prospective observational data collection tool. Inclusion criteria for enrollment followed the IWCLL guidelines. We retrospectively evaluated all patients with CLL in the Brazilian Registry of CLL who were followed between January 2013 and April 2020 at the 5 reference centers (3 public and 2 private). The following local criteria were used for treatment indications to all patients included: 1) persistent and progressive symptomatic cytopenias (no predefined minimum levels), 2) Massive or symptomatic lymphadenopathy, 3) Massive or symptomatic splenomegaly, 4) Disease-related symptoms, only if persistent and if other causes were excluded, and 5) Autoimmune complications including anemia or thrombocytopenia non-responsive to steroids. Progressive lymphocytosis and extranodal manifestations were not considered for treatment indication. Results: A total of 581 patients were followed during the observation period of 7 years (median follow-up was 40 months (range: 3-86). Median age was 65 years (range: 32-98) and most patients were male (57%). Binet stage was A in 67%, B in 14% and C in 19% of cases. FISH, performed in only 199 patients (34%), was normal in 47%, and showed del13q in 22%, trisomy 12 in 17%, del11q in 8% and del17p in 7%. According to IWCLL criteria, 257 (44%) presented indication for treatment over the time: 140 (55%) at diagnosis and 117 (45%) during follow-up. Based on the local criteria, 148 (25%) patients met criteria for indication of treatment. Therefore, 109 patients with IWCLL indication were not treated to date according to the local criteria. The IWCLL indications for these untreated patients were: cytopenias in 50 patients (48%), constitutional symptoms in 37 patients (35%), progressive lymphocytosis in 9 (9%), and lymphadenopathy or splenomegaly in 8 (8%). The median observation time for these untreated patients from the time of indication of treatment by IWCLL until the analysis was closed was 39 months, ranging from 3 to 86 months. Of the 109 untreated patients, 12 (13%) died during follow-up: 4 from infections probably unrelated to CLL (all patients were elderly, Binet A, non-neutropenic and non-hypoglobulinemic), 2 from cardiac causes, 1 from a car accident and 5 of unknown causes (lost follow-up after at least 2 years). No deaths were attributable to LLC. Overall survival at 4 years was 90% for the patients who were treated versus 89% for the patients who were not treated (P=0.85). Conclusion: Our data suggest that it is feasible and safe to adopt more conservative criteria to indicate treatment in a CLL patient. A more restrict approach may not only reflect in a significant financial impact to the health care system but also avoid premature exposition to prolonged and/or potentially toxic treatments. This finding might be of special interest to low-income countries. Disclosures No relevant conflicts of interest to declare.

Multinational comparison of new antidepressant use in older adults: a cohort study

ObjectivesWe used an international pharmacosurveillance network to estimate the rate and characteristics of antidepressant use in older adults in countries with more conservative (UK) and liberal depression guidelines (Canada, USA).SettingElectronic health records and population-based administrative data from six jurisdictions in four countries (UK, Taiwan, USA and Canada).ParticipantsA historical cohort of older adults (≥65 years) who had a new episode of antidepressant use between 2009 and 2014.Outcome measuresThe age and sex-standardised cumulative incidence of new episodes of antidepressant use in older adults was measured. Descriptive statistics were used to compare the proportion of new users by the antidepressant prescribed, therapeutic class, potential treatment indication and country, as well as the characteristics of the first treatment episode (standardised daily doses, duration and changes).ResultsThe incidence of antidepressant use between 2009 and 2014 varied from 4.7% (Montreal and Quebec City) to 18.6% (Taiwan). Tricyclic antidepressants (TCAs) were the most commonly used class in the UK (48.8%) and Taiwan (52.4%) compared with selective serotonin reuptake inhibitors (SSRIs) in North American jurisdictions (42.3%–53.3%). Chronic pain was the most common potential treatment indication (41.2%–68.2%). Among users with chronic pain, TCAs were used most frequently in the UK and Taiwan (55.2%–60.4%), whereas SSRIs were used most frequently in North America (33.5%–46.4%). Treatment was longer (252–525 vs 169–437 days), standardised doses were higher (0.7–1.3 vs 0.5–1.0) and treatment was more likely to be changed (31%–46% vs 21%–34%) among patients with depression (9.1%–43%) than those with chronic pain.ConclusionAntidepressant use in older adults varied 24-fold by country, with the UK, which has the most conservative treatment guidelines, being among the lowest. Chronic pain was the most common potential treatment indication. Evaluation of real-world risks of TCAs is a priority for future research, given high rates of use and the potential for increased toxicity in older adults because of potent anticholinergic effects.