Understanding The Number Needed to Treat.

The number needed to treat (NNT) is the inverse of the absolute risk difference, which is used as a secondary outcome to clinical trials as a measure relevant to a positive trial, supplementing statistical significance. The NNT requires dichotomous outcomes and is influenced by the baseline disease or symptom severity, the particular population, the type and intensity of the interventional, the duration of treatment, the time period to assessment of response, and the comparator response. Confidence intervals should always accompany NNT for the precision of its estimate. In this review, three meta-analyses are reviewed, which included the NNT in the analysis of response.

Radiation Therapy in the Last Month of Life: Association With Aggressive Care at the End of Life.

CONTEXT: Half of the patients with cancer who undergo radiation therapy do so with palliative intent. OBJECTIVES: To determine the proportion of undergoing radiation in the last month of life, patient characteristics, cancer course, the type and duration of radiation, whether palliative care was involved, and the of radiation with aggressive cancer care metrics. METHODS: One thousand seven hundred twenty-seven patients who died of cancer between January 1, 2018, and December 31, 2019, were included. Demographics, cancer stage, palliative care referral, advance directives, use of home health care, radiation timing, and survival were collected. Type of radiation, course, and intent were reviewed. Chi-square analysis was utilized for categorical variables, and Kruskal-Wallis tests for continuous variables. A stepwise selection was used to build a Cox proportional hazard model. RESULTS: Two hundred thirty-three patients underwent radiation in the last month of life. Younger patients underwent radiation 67.3 years (SD 11.52) versus 69.2 years (SD 11.96). 42.6% had radiation within two weeks of death. The average fraction number was 5.5. Individuals undergoing radiation were more likely to start chemotherapy within the last 30 days of life, continue chemotherapy within two weeks of death, be admitted to the ICU, and have two or more hospitalizations or emergency room visits. Survival measured from the date of diagnosis was shorter for those undergoing radiation, 122 days (IQR 58-462) versus 474 days (IQR 225-1150). Palliative care consultations occurred later in those undergoing radiation therapy. CONCLUSION: Radiation therapy in the last month of life occurs in younger patients with rapidly progressive cancer, who are subject to more aggressive cancer care, and have late palliative care consults.

Validation of the Surprise Question and the Development of a Multivariable Model.

CONTEXT: The Surprise Question (SQ) (would you be surprised if this patient died within a year?) is a prognostic variable explored in chronic illnesses. Validation is limited to sensitivity, specificity, and predictive values. OBJECTIVES: Our objective is to validate the SQ in cancer patients and develop a predictive model with additional variables. METHODS: A prospective cohort study of adult (age>18) cancer patients seen between October 1, 2019, through March 31, 2021, undergoing systemic therapies had the SQ completed by oncologists prior to each change in systemic therapy. The primary outcome was survival for one year. Secondary outcomes were predictions of survival at three, six, and nine months. Patients were grouped into negative SQ (not surprised) and positive SQ (surprised). Sensitivity, specificity, predictive values, and likelihood ratios (LR) were calculated for the SQ. Additional prognostic variables were age, gender, cancer stage, line of therapy, Charleson Comorbid Index (CCI), palliative care consultation (prior to, after the SQ, or not at all), and healthcare utilization (outpatient, inpatient, and emergency department (ED). Logistic regression and receiver operating characteristics (ROC) were used for discrimination and modeling. Akaike information criterion (AIC) was used to compare the model fit as each predictor. RESULTS: 1366 patients had 1 SQ; 784 died within a year. The SQ predicted survival at one year (P = 0.008), with a positive LR of 1.459 (95%CI 1.316-1.602) and a c-statistic of 0.565 (95%CI 0.530-0.600). Additional variables increased the c-statistic to 0.648 (95% CI 0.608-0.686). The total model best predicted survival at three months, c-statistic of 0.663 (95% CI 0.616-0.706). However, the total model c-statistic remained <0.70. CONCLUSIONS: The SQ, as a single factor, poorly predicts survival and should not be used to alter therapies. Adding additional objective variables improved prognostication, but further refinement and external validation are needed.

The Financial Impact of Palliative Care and Aggressive Cancer Care on End-of-Life Health Care Costs.

BACKGROUND: Medicare cancer expenditures in the last month of life have increased. Aggressive cancer care at the end-of-life (ACEOL) is considered poor quality care. We used Geisinger Health Plan (GHP) last month's costs for cancer patients who died in 2018 and 2019 to determine the costs of and influence of Palliative Care (PC) on ACEOL. METHOD: Patients with GHP ages 18-99 who died in 2018 and 2019 were included. Demographic, clinical characteristics, and Charlson Comorbid Index were compared across care groups defined as no ACEOL indicator, 1 or more than 1 indicator. Differences between groups were compared with Kruskal-Wallis tests and one-way ANOVA for 3 groups. Median two-sample tests and independent t-tests compared groups of 2. A P-value 1. There were incremental cost increases with each additional ACEOL indicator (p = < .0001). Palliative Care <90 days before death was associated with increased costs while consultations >90 days before death lowered cost (P < .0001) due to reduced chemotherapy in the last month. Completed ADs reduced cost by $4000. DISCUSSION: ACEOL indicators multiply costs during the last month of life. Palliative care instituted >90 days before death reduces chemotherapy in the last month of life and AD reduces health care costs. CONCLUSION: Cancer health care costs increase with indicators of ACEOL. Palliative care consultations >90 days before death; ADs reduce cancer health care costs.

Is Weight Loss During Chemotherapy for Pancreatic Cancer Prognostic?

BACKGROUND: Predicting poor survival outcomes early in palliative chemotherapy is important to the timing of palliative care. Weight loss during chemotherapy if prognostic would lead to early palliative care. METHOD: We collected demographics, stage, chemotherapy, chemotherapy cycles, weight, healthcare utilization, comorbidities (Charleson Comorbid Index), tumor markers, and weight changes over 60 days. We defined 3 groups of patients: 1. Weight gain to <.5% weight loss, 2. Weight loss< 2% and 3. Weight loss of >2%. A Chi-square test assessed differences in weight during treatment. Time-to-event analysis was expressed in a Kaplan Meier curve. RESULTS: 93 individuals died of pancreatic cancer in 2018 and 2019. The median age was 71.2 years. Forty-three had stage I and II, 40 stages III and IV cancers, and 10 had unknown stages. Most received FOLFIRINOX and gemcitabine/nab-paclitaxel chemotherapy. Thirty-six gained to lost < .5% during chemotherapy,8 lost < 2% and 49 patients lost > 2% of their weight. Mortality was available in 55 of 93 patients. Median survival was 16.6 months in those with weight gain to < .5% weight loss, 17.28 months for those with < 2% weight loss, and 20.5 months for those with > 2% weight loss (P = .42). DISCUSSION: Weight loss over 60 days did not predict a poor prognosis in this small retrospective study; larger prospective studies may clarify the prognostic importance of weight loss during chemotherapy. CONCLUSION: In this small retrospective study, weight loss over 60 days did not predict poor survival.

Use of a chatbot to increase uptake of cascade genetic testing.

Successful proband-mediated family communication and subsequent cascade genetic testing uptake requires interventions that present information clearly, in sufficient detail, and with medical authority. To facilitate family communication for patients receiving clinically actionable results via the MyCode® Community Health Initiative, a Family Sharing Tool (FST) and a cascade chatbot were developed. FST is an electronic mechanism allowing patients to share genetic test results with relatives via chatbot. The cascade chatbot describes the proband's result, associated disease risks, and recommended management and captures whether the user is a blood relative or caregiver, sex, and relationship to the proband. FST and cascade chatbot uptake among MyCode® probands and relatives was tracked from August 2018 through February 2020. Cascade genetic testing uptake was collected from testing laboratories as number of cascades per proband. Fifty-eight percent (316/543) of probands consented to FST; 42% (227/543) declined. Receipt preferences were patient electronic health record (EHR) portal (52%), email (29%), and text (19%). Patient EHR portal users (p < 0.001) and younger patients were more likely to consent (p < 0.001). FST was deployed to 308 probands. Fifty-nine percent (183/308) opened; of those, 56% (102/183) used FST to send a cascade chatbot to relatives. These 102 probands shared a cascade chatbot with 377 relatives. Sixty-two percent (235/377) of relatives opened; of these, 69% (161/235) started, and of these, 57% (92/161) completed the cascade chatbot. Cascade genetic testing uptake was significantly greater among relatives of probands who consented to the FST (M = 2.34 cascades, SD = 2.10) than relatives of probands who declined (M = 1.40 cascades, SD = 0.82, p < 0.001). Proband age was not a significant predictor of cascade genetic testing uptake. Further work is needed to better understand factors impacting proband use of FST and relative use of cascade chatbots.

When does early palliative care influence aggressive care at the end of life?

BACKGROUND: Early palliative care improves patient quality of life and influences cancer care. The time frame of early has not been established. Eight quality measures reflect aggressive care at the end of life. We retrospectively reviewed patients who died with cancer between January 1, 2018, through December 31, 2019, and compared the timing of palliative care consultation, advance directives (AD), and home palliative care with aggressive care at the end of life (ACEOL). METHODS: Patients without ACEOL indicators were compared to patients with one or more than one indicator of ACEOL. The proportion of patients who received palliative care, completed AD, and the timing of palliative care and AD (less than 30 days, 30-90 days, and greater than 90 days prior to death) was compared for patients who had ACEOL versus those who did not. Chi-square analysis was used for categorical data, one-way ANOVA for continuous variables, and odds ratio (OR) with confidence intervals (CI) was reported as a measure of effect size. A p value ≤ 0.05 was considered significant. RESULTS: 1727 patients died, 46% were female, and the mean age was 69 (SD 11.91). Seventy-one percent had a palliative care consult, 26% completed AD, and 888 (51.4%) had at least one indicator of ACEOL. The most common indicator of ACEOL was new chemotherapy within 30 days of death, in 571 of 888 (64%) of patients experiencing ACEOL. ADs completed at any time reduced ACEOL (OR 0.80, 95%CI 0.64-0.99). Palliative care initiated at 30 days was associated with a greater risk of ACEOL (OR 5.32, 95% CI 3.94-7.18) and initiated between 30 and 90 days (OR 1.39, 95% CI 1.07-1.80) compared to no palliative care but was associated with reduced chemotherapy as an indicator of ACEOL when > 90 days (OR 0.46, 95% CI 0.38-0.57) before death. DISCUSSION: Completed ADs were associated with reduced chemotherapy in the last 30 days of life and reduced ICU admissions. This may reflect goals of care and end-of-life discussions and transition of care to comfort measures. Palliative care paradoxically when initiated within 90 days before death was associated with greater ACEOL compared to no palliative care. This may be due to consultation late in the course of illness with a focus on crisis management in patients frequently utilizing the health care system. There is an associated reduction in the use of chemotherapy in the last 30 days of life if palliative care is consulted 90 days prior to death. CONCLUSIONS: An initial palliative care consult greater than 90 days before death and ADs completed at any time during the disease trajectory was associated only with reduced chemotherapy in the last 30 days of life compared with no palliative care among the 7 ACEOL indicators. ADs were associated with reduced ICU admissions. Most palliative care consults occurred within 90 days of death and a palliative care consult within 90 days of death is not an optimal utilization of services.

Outcomes of Patients Undergoing Cardiac Catheterization After a Three-Day Holiday Weekend Versus a Two-Day Weekend.

OBJECTIVES: The study aim is to determine whether invasive cardiac procedures following a 3-day (holiday) weekend have worse outcomes compared with procedures following a 2-day (normal) weekend. BACKGROUND: Catheterization laboratory schedules after 3-day holiday weekends tend to be overloaded with urgent procedures for patients who have waited up to 3 days. We hypothesized that this would be reflected by more procedural complications in patients undergoing procedures after a 3-day weekend. METHODS: Invasive cardiac procedures that occurred after a weekend at Geisinger Medical Center from July 2012 to December 2019 were included. Baseline characteristics, presentation, periprocedural variables, adverse events, and clinical outcomes were compared between catheterizations on the day following a 2-day weekend and catheterizations following a 3-day weekend. Independent correlates of adverse events were identified by logistic regression analysis. RESULTS: We identified 13,704 invasive cardiac procedures performed after a weekend, of which 722 occurred after a 3-day (holiday) weekend. Baseline demographics, presentation, and case volumes were similar between the 2 groups. Procedures after a 3-day weekend were not associated with any differences in in-hospital mortality, myocardial infarction, or stroke compared with those after a standard 2-day weekend. By univariate analysis, procedural complications were more frequent after a 3-day weekend (15.1% vs 12.3%; P=.03), but this difference was not significant on multivariate analysis (odds ratio, 1.22; P=.30). CONCLUSIONS: Cardiac catheterization procedures performed after a 3-day weekend were not associated with differences in in-patient mortality, myocardial infarction, stroke, or procedural complications.

Clinical Outcomes of Selective Versus Nonselective His Bundle Pacing.

OBJECTIVES: The aim of the study was to evaluate the clinical outcomes of nonselective (NS) His bundle pacing (HBP) compared with selective (S) HBP. BACKGROUND: HBP is the most physiologic form of ventricular pacing. NS-HBP results in right ventricular septal pre-excitation due to fusion with myocardial capture in addition to His bundle capture resulting in widened QRS duration compared with S-HBP wherein there is exclusive His bundle capture and conduction. METHODS: The Geisinger and Rush University HBP registries comprise 640 patients who underwent successful HBP. Our study population included 350 consecutive patients treated with HBP for bradyarrhythmic indications who demonstrated ≥20% ventricular pacing burden 3 months post-implantation. Patients were categorized into S-HBP or NS-HBP based on QRS morphology (NS-HBP n = 232; S-HBP n = 118) at the programmed output at the 3-month follow-up. The primary analysis outcome was a combined endpoint of all-cause mortality or heart failure hospitalization. RESULTS: The NS-HBP group had a higher number of men (64% vs. 50%; p = 0.01), higher incidence of infranodal atrioventricular block (40% vs. 9%; p < 0.01), ischemic cardiomyopathy (24% vs. 14%; p = 0.03), and permanent atrial fibrillation (18% vs. 8%; p = 0.01). The primary endpoint occurred in 81 of 232 patients (35%) in the NS-HBP group compared with 23 of 118 patients (19%) in the S-HBP group (hazard ratio: 1.38; 95% confidence interval: 0.87 to 2.20; p = 0.17). Subgroup analyses of patients at greatest risk (higher pacing burden or lower left ventricular ejection fraction) revealed no incremental risk with NS-HBP. CONCLUSIONS: NS-HBP was associated with similar outcomes of death or heart failure hospitalization when compared with S-HBP. Multicenter risk-matched clinical studies are needed to confirm these findings.