Risk Assessment and Prevention of Falls in Older Community-Dwelling Adults: A Review.

Importance: Falls are reported by more than 14 million US adults aged 65 years or older annually and can result in substantial morbidity, mortality, and health care expenditures. Observations: Falls result from age-related physiologic changes compounded by multiple intrinsic and extrinsic risk factors. Major modifiable risk factors among community-dwelling older adults include gait and balance disorders, orthostatic hypotension, sensory impairment, medications, and environmental hazards. Guidelines recommend that individuals who report a fall in the prior year, have concerns about falling, or have gait speed less than 0.8 to 1 m/s should receive fall prevention interventions. In a meta-analysis of 59 randomized clinical trials (RCTs) in average-risk to high-risk populations, exercise interventions to reduce falls were associated with 655 falls per 1000 patient-years in intervention groups vs 850 falls per 1000 patient-years in nonexercise control groups (rate ratio [RR] for falls, 0.77; 95% CI, 0.71-0.83; risk ratio for number of people who fall, 0.85; 95% CI, 0.81-0.89; risk difference, 7.2%; 95% CI, 5.2%-9.1%), with most trials assessing balance and functional exercises. In a meta-analysis of 43 RCTs of interventions that systematically assessed and addressed multiple risk factors among individuals at high risk, multifactorial interventions were associated with 1784 falls per 1000 patient-years in intervention groups vs 2317 falls per 1000 patient-years in control groups (RR, 0.77; 95% CI, 0.67-0.87) without a significant difference in the number of individuals who fell. Other interventions associated with decreased falls in meta-analysis of RCTs and quasi-randomized trials include surgery to remove cataracts (8 studies with 1834 patients; risk ratio [RR], 0.68; 95% CI, 0.48-0.96), multicomponent podiatry interventions (3 studies with 1358 patients; RR, 0.77; 95% CI, 0.61-0.99), and environmental modifications for individuals at high risk (12 studies with 5293 patients; RR, 0.74; 95% CI, 0.61-0.91). Meta-analysis of RCTs of programs to stop medications associated with falls have not found a significant reduction, although deprescribing is a component of many successful multifactorial interventions. Conclusions and Relevance: More than 25% of older adults fall each year, and falls are the leading cause of injury-related death in persons aged 65 years or older. Functional exercises to improve leg strength and balance are recommended for fall prevention in average-risk to high-risk populations. Multifactorial risk reduction based on a systematic clinical assessment for modifiable risk factors may reduce fall rates among those at high risk.

Aging is not an Illness: Exploring Geriatricians' Resistance to Serious Illness Conversations.

CONTEXT: Serious illness conversations help clinicians align medical decisions with patients' goals, values, and priorities and are considered an essential component of shared decision-making. Yet geriatricians at our institution have expressed reluctance about the serious illness care program. OBJECTIVES: We sought to explore geriatricians' perspectives on serious illness conversations. METHODS: We conducted focus groups with interprofessional stakeholders in geriatrics. RESULTS: Three key themes emerged that help explain the reluctance of clinicians caring for older patients to have or document serious illness conversations: 1) aging in itself is not a serious illness; 2) geriatricians often focus on positive adaptation and social determinants of health and in this context, the label of "serious illness conversations" is perceived as limiting; and 3) because aging is not synonymous with illness, important goals-of-care conversations are not necessarily documented as serious illness conversations until an acute illness presents itself. CONCLUSION: As institutions work to create system-wide processes for documenting conversations about patients' goals and values, the unique communication preferences of older patients and geriatricians should be specifically considered.

Discontinuation of beta-blockers among nursing home residents at end of life.

BACKGROUND: Given limited life expectancy of nursing home (NH) residents, harms of continuing beta-blockers (BBs) may outweigh clinical benefits. Our objective was to describe beta-blocker discontinuation for NH residents during the last year of life, and identify characteristics associated with earlier discontinuation. METHODS: This was a retrospective cohort study that included all long-stay residents in fee-for-service Medicare who died in 2016 and were prescribed oral BBs 1 year before death. Beta-blocker discontinuation was defined as a gap in medication on hand for ≥45 days per Medicare Part D claims, measured from the last date drug was on hand. Comorbidities were obtained from Chronic Condition Warehouse, and other characteristics from the Minimum Data Set. Kaplan-Meier curves were used to describe time to first discontinuation. Findings were stratified by cardiac diagnoses, perceived life expectancy of <6 months, or elevated mortality index. RESULTS: Eighty-eight thousand two hundred and eighty-four residents were prescribed ≥1 daily BB 12 months before death. Mean age was 84.1 years and 69.2% were female. Of these, 60,573 residents (68.6%) remained on a BB in the last 45 days of life, and 57,880 residents (65.6%) had ≥1 cardiac diagnosis. Only 5239 residents (5.9%) had elevated mortality index, whereas 16,798 residents (19.0%) had perceived poor prognosis. In the last year of life, there was no difference in beta-blocker discontinuation pattern between residents with and without cardiac diagnoses. Residents with perceived poor prognosis and elevated mortality index discontinued BBs earlier. For example, mean time until discontinuation among residents with poor perceived prognosis was 245 versus 279 days in residents without such prognosis (p < 0.0001). CONCLUSIONS: BBs are commonly prescribed to NH residents in the final year of life. Overall, discontinuation occurs earlier in residents for whom clinicians perceive limited life expectancy, suggesting that improved prognostication may offer an important opportunity to reduce polypharmacy toward end of life.

Radioluminescent nanoparticles for radiation-controlled release of drugs.

The present work demonstrates a novel concept for intratumoral chemo-radio combination therapy for locally advanced solid tumors. For some locally advanced tumors, chemoradiation is currently standard of care. This combination treatment can cause acute and long term toxicity that can limit its use in older patients or those with multiple medical comorbidities. Intratumoral chemotherapy has the potential to address the problem of systemic toxicity that conventional chemotherapy suffers, and may, in our view, be a better strategy for treating certain locally advanced tumors. The present study proposes how intratumoral chemoradiation can be best implemented. The enabling concept is the use of a new chemotherapeutic formulation in which chemotherapy drugs (e.g., paclitaxel (PTX)) are co-encapsulated with radioluminecsnt nanoparticles (e.g., CaWO4 (CWO) nanoparticles (NPs)) within protective capsules formed by biocompatible/biodegradable polymers (e.g., poly(ethylene glycol)-poly(lactic acid) or PEG-PLA). This drug-loaded polymer-encapsulated radioluminescent nanoparticle system can be locally injected in solution form into the patient's tumor before the patient receives normal radiotherapy (e.g., 30-40 fractions of 2-3 Gy daily X-ray dose delivered over several weeks for locally advanced head and neck tumors). Under X-ray irradiation, the radioluminescent nanoparticles produce UV-A light that has a radio-sensitizing effect. These co-encapsulated radioluminescent nanoparticles also enable radiation-triggered release of chemo drugs from the polymer coating layer. The non-toxic nature (absence of dark toxicity) of this drug-loaded polymer-encapsulated radioluminescent nanoparticle ("PEG-PLA/CWO/PTX") formulation was confirmed by the MTT assay in cancer cell cultures. A clonogenic cell survival assay confirmed that these drug-loaded polymer-encapsulated radioluminescent nanoparticles significantly enhance the cancer cell killing effect of radiation therapy. In vivo study validated the efficacy of PEG-PLA/CWO/PTX-based intratumoral chemo-radio therapy in mouse tumor xenografts (in terms of tumor response and mouse survival). Results of a small-scale NP biodistribution (BD) study demonstrate that PEG-PLA/CWO/PTX NPs remained at the tumor sites for a long period of time (> 1 month) following direct intratumoral administration. A multi-compartmental pharmacokinetic model (with rate constants estimated from in vitro experiments) predicts that this radiation-controlled drug release technology enables significant improvements in the level and duration of drug availability within the tumor (throughout the typical length of radiation treatment, i.e., > 1 month) over conventional delivery systems (e.g., PEG-PLA micelles with no co-encapsulated CaWO4, or an organic liquid, e.g., a 50:50 mixture of Cremophor EL and ethanol, as in Taxol), while it is capable of maintaining the systemic level of the chemo drug far below the toxic threshold limit over the entire treatment period. This technology thus has the potential to offer a new therapeutic option that has not previously been available for patients excluded from conventional chemoradiation protocols.

Biomechanical evaluation of transfacet screw fixation for stabilization of multilevel cervical corpectomies.

STUDY DESIGN: Cadaveric biomechanical investigation. OBJECTIVES: To test the feasibility of transfacet screws as a minimally invasive posterior fixation device for the cervical spine by comparing the biomechanical stability of transfacet screws to lateral mass screws and rods in a multilevel cervical corpectomy model. SUMMARY OF BACKGROUND DATA: Minimally invasive surgery (MIS) of the spine has gained increasing acceptance and popularity. However, a minimally invasive means of instrumenting the posterior cervical spine has yet to be discovered. Posterior transfacet screws have been described as a means of posterior fixation. In addition, they have the potential of being placed percutaneously through stab incisions. However, validation of transfacet screws in an unstable cervical model in which posterior instrumentation may be necessary has not been carried out till date. METHODS: Sixteen cadaveric cervical spines were randomized to transfacet or lateral mass instrumentation groups. The spines were tested in the following conditions: (a) intact, (b) after multilevel corpectomies with strut graft placement with stand-alone posterior fixation, and (c) with an additional anterior plate over the strut graft. Corpectomy site loading was measured with a custom-designed strut graft. Data were collected for spinal stiffness, range of motion, and strut graft loading, and was analyzed using 2-way analysis of variance (P<0.05). RESULTS: Stand-alone transfacet screw fixation was found to provide inferior spinal stability and resulted in increased spinal motion and graft loading compared with the other constructs (P<0.05 for all). CONCLUSIONS: It is unclear what kind of mechanical stiffness is necessary to stabilize the cervical spine and obtain solid fusion. However, decreased stability and increased graft loading suggest that transfacet screws may not be the ideal method of posterior fixation to supplement multilevel anterior cervical corpectomies and fusions despite their potential as a minimally invasive method for posterior cervical instrumentation.

Tissue-like phantoms for near-infrared fluorescence imaging system assessment and the training of surgeons.

We demonstrate how to construct calibrated, stable, and inexpensive tissue-like phantoms for near-IR (NIR) fluorescence imaging applications. The bulk phantom material is composed of gelatin, intralipid, hemoglobin, and indocyanine green (ICG). Absorbance, scatter, background fluorescence, and texture can be tuned as desired. NIR fluorescent inclusions are comprised of ICG-labeled polystyrene divinylbenzene beads and Pam78-labeled hydroxyapatite crystals. The former mimic tumor masses of controllable size and contrast agent concentration, and the latter mimic microcalcifications in breast cancer. NIR-fluorescent inclusions can be positioned precisely in phantoms, with one or more regions having different optical properties, and their position can be verified independently using microcomputed tomography. We demonstrate how these phantoms can be used to calibrate and compare imaging systems, and to train surgeons to operate under NIR fluorescence image guidance.