Clinicoradiological outcomes after radical radiotherapy for lung cancer in patients with interstitial lung disease.

Objective: Interstitial lung disease (ILD) is relatively common in patients with lung cancer with an incidence of 7.5%. Historically pre-existing ILD was a contraindication to radical radiotherapy owing to increased radiation pneumonitis rates, worsened fibrosis and poorer survival compared with non-ILD cohorts. Herein, the clinical and radiological toxicity outcomes of a contemporaneous cohort are described. Methods: Patients with ILD treated with radical radiotherapy for lung cancer at a regional cancer centre were collected prospectively. Radiotherapy planning, tumour characteristics, and pre- and post-treatment functional and radiological parameters were recorded. Cross-sectional images were independently assessed by two Consultant Thoracic Radiologists. Results: Twenty-seven patients with co-existing ILD received radical radiotherapy from February 2009 to April 2019, with predominance of usual interstitial pneumonia subtype (52%). According to ILD-GAP scores, most patients were Stage I. After radiotherapy, localised (41%) or extensive (41%) progressive interstitial changes were noted for most patients yet dyspnoea scores (n = 15 available) and spirometry (n = 10 available) were stable. One-third of patients with ILD went on to receive long-term oxygen therapy, which was significantly more than the non-ILD cohort. Median survival trended towards being worse compared with non-ILD cases (17.8 vs 24.0 months, p = 0.834). Conclusion: Radiological progression of ILD and reduced survival were observed post-radiotherapy in this small cohort receiving lung cancer radiotherapy, although a matched functional decline was frequently absent. Although there is an excess of early deaths, long-term disease control is achievable. Advances in knowledge: For selected patients with ILD, long-term lung cancer control without severely impacting respiratory function may be possible with radical radiotherapy, albeit with a slightly higher risk of death.

Polypharmacy Management in Older Patients.

Medications to treat disease and extend life in our patients often amass in quantities, resulting in what has been termed "polypharmacy." This imprecise label usually describes the accumulation of 5, and often more, medications. Polypharmacy in advancing age frequently results in drug therapy problems related to interactions, drug toxicity, falls with injury, delirium, and nonadherence. Polypharmacy is associated with resulting increased hospitalizations and higher costs of care for individuals and health care systems. To reduce polypharmacy, we delineate a systematic, consultative approach to identify highest-risk medications and drug-therapy problems. We address strategic reductions (deprescribing) of medications in palliative care, long-term care, and ambulatory older adults. Best practices for reducing opioids, benzodiazepines, and other high-risk medications include education about risk and agreement by patients and their families, advocates, and care teams. Addressing deprescribing should be within the framework of patients' health status as their care and goals transition from longevity to a plan of maintaining alertness, comfort, and satisfaction of quality of life. A team approach to address polypharmacy and avoidance of high-risk therapy is optimal within long-term care. Patients with terminal illnesses or those moving toward a comfort-care emphasis benefit from medication adjustments that are recognized beneficially within each patient's care goals. In caring for older adults, the acknowledgement that complicated regimens and high-risk medications requires a care plan to reduce or prevent medication-related problems and costs that are associated with polypharmacy.

Prediction of Risk of Death for Patients Starting Dialysis: A Systematic Review and Meta-Analysis.

BACKGROUND AND OBJECTIVES: Dialysis is a preference-sensitive decision where prognosis may play an important role. Although patients desire risk prediction, nephrologists are wary of sharing this information. We reviewed the performance of prognostic indices for patients starting dialysis to facilitate bedside translation. DESIGN, SETTING, PARTICIPANTS, & MEASUREMENTS: Systematic review and meta-analysis following the PRISMA guidelines. We searched Ovid MEDLINE, Ovid Embase, Ovid Central Register of Controlled Trials, Ovid Cochrane Database of Systematic Reviews, and Scopus for eligible studies of patients starting dialysis published from inception to December 31, 2018. SELECTION CRITERIA: Articles describing validated prognostic indices predicting mortality at the start of dialysis. We excluded studies limited to prevalent dialysis patients, AKI and studies excluding mortality in the first 1-3 months. Two reviewers independently screened abstracts, performed full text assessment of inclusion criteria and extracted: study design, setting, population demographics, index performance and risk of bias. Pre-planned random effects meta-analysis was performed stratified by index and predictive window to reduce heterogeneity. RESULTS: Of 12,132 articles screened and 214 reviewed in full text, 36 studies were included describing 32 prognostic indices. Predictive windows ranged from 3 months to 10 years, cohort sizes from 46 to 52,796. Meta-analysis showed discrimination area under the curve (AUC) of 0.71 (95% confidence interval, 0.69 to 073) with high heterogeneity (I2=99.12). Meta-analysis by index showed highest AUC for The Obi, Ivory, and Charlson comorbidity index (CCI)=0.74, also CCI was the most commonly used (ten studies). Other commonly used indices were Kahn-Wright index (eight studies, AUC 0.68), Hemmelgarn modification of the CCI (six studies, AUC 0.66) and REIN index (five studies, AUC 0.69). Of the indices, ten have been validated externally, 16 internally and nine were pre-existing validated indices. Limitations include heterogeneity and exclusion of large cohort studies in prevalent patients. CONCLUSIONS: Several well validated indices with good discrimination are available for predicting survival at dialysis start.

Transcranial magnetic stimulation maintenance as a substitute for maintenance electroconvulsive therapy: a case series.

BACKGROUND: Transcranial magnetic stimulation (TMS) is an efficacious, well-tolerated, noninvasive brain stimulation treatment for major depressive disorder. Electroconvulsive therapy (ECT) is an effective maintenance treatment for depression but is not tolerated by some patients and declined by others. OBJECTIVE: We evaluated the effectiveness of TMS as a substitution strategy for successful maintenance ECT. METHODS: A consecutive clinical case series (n = 6) of maintenance ECT patients were transitioned to maintenance TMS because of adverse effects from ECT or because of specific patient request and preference. Patients were in either full remission or had clinical response to ECT at the time of transition. Primary outcome was the change in the Beck Depression Inventory (BDI) score from initiation of TMS maintenance sessions to the last observation time point. Relapse of depressive symptoms was also documented. RESULTS: Mean age of patients was 64 years, and most were female (n = 5). The majority (5 of 6) were diagnosed with major depressive disorder. Reasons for transition from ECT to TMS were, in order of frequency, cognitive adverse effects, fear of general anesthesia, time burden, lack of remission with ECT, and stigma associated with ECT. The mean frequency of TMS sessions was 1 every 3.5 weeks. Based on BDI scores, all patients maintained or improved their clinical status achieved with ECT at 3 and 6 months of TMS treatment. At last observation (range, 7-23 months), 4 patients maintained or improved their clinical status (total BDI score remained constant or decreased by 1-8 points). Two patients had a relapse after 8 and 9 months. Stimulation was well tolerated with adverse effects limited to headache and scalp discomfort. CONCLUSIONS: In this case series, TMS was effective and safe when used as a substitution strategy for successful maintenance ECT.

Bounds on spectral dispersion from Fermi-detected gamma ray bursts.

Data from four Fermi-detected gamma-ray bursts (GRBs) are used to set limits on spectral dispersion of electromagnetic radiation across the Universe. The analysis focuses on photons recorded above 1 GeV for Fermi-detected GRB 080916C, GRB 090510A, GRB 090902B, and GRB 090926A because these high-energy photons yield the tightest bounds on light dispersion. It is shown that significant photon bunches in GRB 090510A, possibly classic GRB pulses, are remarkably brief, an order of magnitude shorter in duration than any previously claimed temporal feature in this energy range. Although conceivably a>3σ fluctuation, when taken at face value, these pulses lead to an order of magnitude tightening of prior limits on photon dispersion. Bound of Δc/c<6.94×10(-21) is thus obtained. Given generic dispersion relations where the time delay is proportional to the photon energy to the first or second power, the most stringent limits on the dispersion strengths were k1<1.61×10(-5) sec Gpc(-1) GeV(-1) and k2<3.57×10(-7) sec Gpc(-1) GeV(-2), respectively. Such limits constrain dispersive effects created, for example, by the spacetime foam of quantum gravity. In the context of quantum gravity, our bounds set M1c(2) greater than 525 times the Planck mass, suggesting that spacetime is smooth at energies near and slightly above the Planck mass.

An ex vivo biomechanical comparison of a novel vertebral compression fracture treatment system to kyphoplasty.

BACKGROUND: Vertebral compression fracture repair aims to relieve pain and improve function by restoring vertebral structure and biomechanics, but is still associated with risks arising from polymethylmethacrylate cement extravasation. The Kiva® Vertebral Compression Fracture Treatment System, a stacked coil implant made of polyetheretherketone and delivered over a guide-wire, is a novel device designed to provide height restoration and mechanical stabilization, while improving cement containment and minimizing disruption of cancellous bone. The objective of this study was to determine whether the Kiva system is as effective as balloon kyphoplasty at restoring mechanical properties in osteoporotic vertebral compression fractures. METHODS: Wedge fractures were created in the middle vertebra of fourteen osteoporotic three-vertebra spine segments and then repaired with either the Kiva or kyphoplasty procedure. Height, stiffness and displacement under compression of the spine segments were measured for four conditions: intact, fractured, augmented, and post-cyclic eccentric loading (50,000cycles, 200-500N, 30mm anterior lever arm). FINDINGS: No significant differences were seen between the two procedures for height restoration, stiffness at high or low loads, or displacement under compression. However, the Kiva System required an average of 66% less cement than kyphoplasty to achieve these outcomes (mean 2.6 (SD 0.4) mL v. mean 7.5 (SD 0.8) mL 0; P<0.01). Extravasations and excessive posterior cement flow were also significantly lower with Kiva (0/7 v. 4/7; P<.05). INTERPRETATION: Kiva exhibits similar biomechanical performance to balloon kyphoplasty, but may reduce the risk of extravasation through the containment mechanism of the implant design and by reducing cement volume.