Can we increase the cervical cancer screening interval with an HPV test for women living with HIV? Results of a cohort study from Maharashtra,India

We are reporting (a) updated incidence of cervical intraepithelial neoplasia (CIN) among women who did not have colposcopic or histopathological disease at baseline and (b) disease outcomes among women treated for CIN and their follow-up HPV status; in a cohort of women living with HIV (WHIV). The median overall follow-up was 3.5 years (IQR 2.8-4.3). The incidence of any CIN and that of CIN 2 or worse disease was 16.7 and 7.0 per 1000 person-years of observation (PYO), respectively. Compared with women who were HPV negative at baseline, women who cleared HPV infection had 23.95 times increased risk of incident CIN 2 or worse lesions (95% CI 2.40-661.07). Women with persistent HPV infection had 138.18 times increased risk of CIN 2 or worse lesions (95% CI 20.30-3300.22). Complete disease regression was observed in 65.6% of the HPV positive women with high-grade CIN and were treated with thermal ablation but HPV persistence was seen in 44.8% of those with high-grade disease. Among those who did not have any disease at baseline and were also HPV negative, about 87% (95% CI 83.79-89.48) women remained HPV negative during consecutive HPV test/s with the median interval of 3.5 years. Long-term surveillance of WHIV treated for any CIN is necessary for the prevention of cervical cancer among them. Our study provides an early indication that the currently recommended screening interval of 3 to 5 years among WHIV may be extended to at least 5 years among HPV negative women. Increasing the screening interval can be cost saving and improve scalability among WHIV to support WHO's cervical cancer elimination initiative.     

Canakinumab: Promises and Future in Cardiometabolic Diseases and Malignancy

Inflammation has proven in multiple studies to be responsible for the progression of cardiometabolic diseases and malignancies. The interleukin family has been critically associated with progression of atherosclerosis, insulin resistance, and various malignancies. Given the advent of pharmacologic interleukin-1 (IL-1) inhibition, this pathway can potentially be targeted to improve outcomes. In the recently concluded Canakinumab Anti-inflammatory Thrombosis Outcomes Study (CANTOS) trial, investigators looked at the potential role of IL-1 (especially IL-1β) inhibition in halting the progression of atherosclerosis. In the subset analysis of the data from this trial, IL-1β inhibition with canakinumab was found to have beneficial effects in other cardiometabolic diseases characterized by inflammation, like diabetes, stroke, and chronic kidney disease, and also in patients with lung cancer. In this article, we will try to review the current literature on the role of canakinumab in the treatment of cardiometabolic diseases and malignancies.     

Medicare's hospital readmissions reduction program and the rise in observation stays

Objective

To evaluate whether Medicare's Hospital Readmissions Reduction Program (HRRP) is associated with increased observation stay use.

Data Sources and Study Setting

A nationally representative sample of fee-for-service Medicare claims, January 2009–September 2016.

Study Design

Using a difference-in-difference (DID) design, we modeled changes in observation stays as a proportion of total hospitalizations, separately comparing the initial (acute myocardial infarction, pneumonia, heart failure) and subsequent (chronic obstructive pulmonary disease) target conditions with a control group of nontarget conditions. Each model used 3 time periods: baseline (15 months before program announcement), an intervening period between announcement and implementation, and a 2-year post-implementation period, with specific dates defined by HRRP policies.

Data Collection/Extraction Methods

We derived a 20% random sample of all hospitalizations for beneficiaries continuously enrolled for 12 months before hospitalization (N = 7,162,189).

Principal Findings

Observation stays increased similarly for the initial HRRP target and nontarget conditions in the intervening period (0.01% points per month [95% CI −0.01, 0.3]). Post-implementation, observation stays increased significantly more for target versus nontarget conditions, but the difference is quite small (0.02% points per month [95% CI 0.002, 0.04]). Results for the COPD analysis were statistically insignificant in both policy periods.

Conclusions

The increase in observation stays is likely due to other factors, including audit activity and clinical advances.     

Radiotherapy-specific interprofessional learning through simulation

IntroductionInterprofessional learning (IPL) is a vital aspect of training in radiation oncology professions, yet is rarely delivered to those professionals who work most closely together in clinical practice. Scenario-based learning using simulation facilities provides a unique opportunity to facilitate this learning and this project aimed to determine the impact and value of this initiative.MethodsSmall groups comprising post-graduate diploma pre-registration therapeutic radiographers, medical physics trainees and radiation oncology registrars were challenged with 4 plausible and challenging radiotherapy scenarios within an academic simulation centre. Pre- and post-event completion of the “Readiness for Interprofessional Learning Scale” measured impact and a Likert-style survey gathered feedback from participants.ResultsThe session increased participants' teamwork and collaboration skills as well as strengthening professional identities. Participants reported high levels of enjoyment related to collaborative working, communication and observing other professionals deploying their technical skills and specialist knowledge.ConclusionAlthough beneficial, simulated scenarios offering equal opportunities for engagement across the professions are challenging to plan and timetabling issues between the 3 groups present significant difficulties. The safe environment and unique opportunity for these groups to learn together was particularly well received and future oncology-specific simulated scenario sessions are planned with larger cohorts.Implications for practiceSimulated scenario training can be used to improve team working across the radiotherapy interprofessional team and may have wider use in other specialist interdisciplinary team development.     

A perivascular niche in the bone marrow hosts quiescent and proliferating tumorigenic colorectal cancer cells

Disseminated tumor cells (dTCs) can frequently be detected in the bone marrow (BM) of colorectal cancer (CRC) patients, raising the possibility that the BM serves as a reservoir for metastatic tumor cells. Identification of dTCs in BM aspirates harbors the potential of assessing therapeutic outcome and directing therapy intensity with limited risk and effort. Still, the functional and prognostic relevance of dTCs is not fully established. We have previously shown that CRC cell clones can be traced to the BM of mice carrying patient-derived xenografts. However, cellular interactions, proliferative state and tumorigenicity of dTCs remain largely unknown. Here, we applied a coculture system modeling the microvascular niche and used immunofluorescence imaging of the murine BM to show that primary CRC cells migrate toward endothelial tubes. dTCs in the BM were rare, but detectable in mice with xenografts from most patient samples (8/10) predominantly at perivascular sites. Comparable to primary tumors, a substantial fraction of proliferating dTCs was detected in the BM. However, most dTCs were found as isolated cells, indicating that dividing dTCs rather separate than aggregate to metastatic clones—a phenomenon frequently observed in the microvascular niche model. Clonal tracking identified subsets of self-renewing tumor-initiating cells in the BM that formed tumors out of BM transplants, including one subset that did not drive primary tumor growth. Our results indicate an important role of the perivascular BM niche for CRC cell dissemination and show that dTCs can be a potential source for tumor relapse and tumor heterogeneity.     

Biochanin A impedes STAT3 activation by upregulating p38δ MAPK phosphorylation in IL-6-stimulated macrophages

Inflammation Research - IL-6-induced STAT3 activation is associated with various chronic inflammatory diseases. In this study, we investigated the anti-STAT3 mechanism of the dietary polyphenol,...     

Effects of deep sedation on sleep in critically ill medical patients on mechanical ventilation

Atypical EEG patterns not consistent with standard sleep staging criteria have been observed in medical intensive care unit (ICU) patients. Our aim was to examine the relationship between sleep architecture and sedation in critically ill mechanically ventilated patients pre‐ and post‐extubation. We performed a prospective observational repeated measures study where 50 mechanically ventilated patients with 31 paired analyses were examined at an academic medical centre. The sleep efficiency was 58.3 ± 25.4% for intubated patients and 45.6 ± 25.4% for extubated patients (p = .02). Intubated patients spent 76.33 ± 3.34% of time in non‐rapid eye movement (NREM) sleep compared to 64.66 ± 4.06% of time for extubated patients (p = .02). REM sleep constituted 1.36 ± 0.67% of total sleep time in intubated patients and 2.06 ± 1.09% in extubated patients (p = .58). Relative sleep atypia was higher in intubated patients compared to extubated patients (3.38 ± 0.87 versus 2.79 ± 0.42; p < .001). Eleven patients were sedated with propofol only, 18 patients with fentanyl only, 11 patients with fentanyl and propofol, and 10 patients had no sedation. The mean sleep times on “propofol”, “fentanyl”, “propofol and fentanyl,” and “no sedation” were 6.54 ± 0.64, 4.88 ± 0.75, 6.20 ± 0.75 and 4.02 ± 0.62 hr, respectively. The sigma/alpha values for patients on “propofol”, “fentanyl”, “propofol and fentanyl” and “no sedation” were 0.69 ± 0.04, 0.54 ± 0.01, 0.62 ± 0.02 and 0.57 ± 0.02, respectively. Sedated patients on mechanical ventilation had higher sleep efficiency and more atypia compared to the same patients following extubation. Propofol was associated with higher sleep duration and less disrupted sleep architecture compared to fentanyl, propofol and fentanyl, or no sedation.