The efficacy and toxicity of immune checkpoint inhibitors in a real-world older patient population

ImportanceImmunotherapy has emerged as an effective treatment option for the management of advanced cancers. The effects of these immune checkpoint inhibitors in the older patient population has not been adequately assessed.ObjectiveTo understand the impact of aging on CTLA-4 and PDL-1 inhibitors efficacy and immune-related adverse events (irAE) in the context of real-world management of advanced solid cancers.Design, Setting, and ParticipantsThis retrospective study involved all non-study patients with histologically-confirmed metastatic or inoperable solid cancers receiving immunotherapy at Kingston Health Sciences Centre. We defined ‘older patient’ as age ≥ 75. All statistical analyses were conducted under SPSS IBM for Windows version 24.0.Main Outcomes and MeasuresStudy outcomes included immunotherapy treatment response, survival, as well as number, type, and severity of irAEs.ResultsOur study (N = 78) had 29 (37%) patients age <65, 26 (33%) patients age 65–74, and 23 (30%) patients age ≥75. Melanoma, non-small cell lung cancer, and renal cell carcinoma accounted for 70%, 22%, and 8% of the study population, respectively. Distributions of ipilimumab (32%), nivolumab (33%), and pembrolizumab (35%) were similar in the study. The response rates were 28%, 27%, and 39% in the age <65, age 64–74, age ≥75 groups, respectively (P = 0.585). Kaplan-Meier curve showed a median survival of 28 months (12.28–43.9, 95% CI) and 17 months (0–36.9, 95% CI) in the age <65 and age 64–74 groups, respectively; the estimated survival probability did not reach 50% in the age ≥75 group (P = 0.319). There were no statistically significant differences found in terms of irAEs, multiple irAEs, severity of grade 3 or higher, types of irAEs, and irAEs resolution status when comparing between different age groups.Conclusion and RelevanceOur results suggest that patients age ≥75 are able to gain as much benefit from immunotherapy as younger patients, without excess toxicity. Our findings suggest that single agent immunotherapy is generally well-tolerated across different age groups with no significant difference in the type, frequency or severity of irAEs. Future studies evaluating aging and combination immunotherapy are warranted.     

A hypothesis for reactivation of pulmonary tuberculosis: How thoracic wall shape affects the epidemiology of tuberculosis

This study was aimed at determining the cause for the high incidence of tuberculosis (TB) reactivation occurring in males with a low body mass index (BMI). Current thinking about pulmonary TB describes infection in the lung apex resulting in cavitation after reactivation. A different hypothesis is put forward for TB infection, suggesting that this occurs in subclinical apical cavities caused by increased pleural stress due to a low BMI body habitus. A finite element analysis (FEA) model of a lung was constructed including indentations for the first rib guided by paramedian sagittal CT reconstructions, and simulations were conducted with varying antero‐posterior (AP) diameters to mimic chests with a different thoracic index (ratio of AP to the transverse chest diameters). A Pubmed search was conducted about gender and thoracic index, and the effects of BMI on TB. FEA modeling revealed a tenfold increase in stress levels at the lung apex in low BMI chests, and a four‐fold increase with a low thoracic index, r² = 0.9748 P < 0.001. Low thoracic index was related to BMI, P = 0.001. The mean thoracic index was statistically significantly lower in males, P = 0.001, and increased with age in both genders. This article is the first to suggest a possible mechanism linking pulmonary TB reactivation to low BMI due to the flattened thoracic wall shape of young male adults. The low thoracic index in young males may promote TB reactivation due to tissue destruction in the lung apex from high pleural stress levels. Clin. Anat. 28:614–620, 2015. © 2015 Wiley Periodicals, Inc.     

Injury as a Global Phenomenon of Concern in Nursing Science

PURPOSE: To discuss injury research as a phenomenon of concern in nursing science. ORGANIZING CONSTRUCT: Injury is defined as the physical damage that results when the human body is briefly subjected to intolerable levels of energy. It is the leading cause of death in the first 4 decades of life in high-income nations and is second only to infectious diseases as a leading cause of death in low- and middle-income nations. METHODS: Review and discussion of relevant scientific and theoretical literature in both injury and nursing science. FINDINGS: Nurse scientists can apply unique perspectives to increase understanding of injury and its consequences. Fertile areas for nursing inquiry include identifying people at risk, developing models to explain the association between risk-taking and injury, testing interventions to prevent and limit injury, and creating and refining interventions that are culturally relevant to subpopulations most at risk for injury. CONCLUSIONS: The mandate to improve global heath should lead to nursing inquiry about this phenomenon, including developing and testing interventions to prevent and reduce injury.     

Short-term complications and resource utilization in matched subjects after on-pump or off-pump primary isolated coronary artery bypass.

BACKGROUND: Studies suggest that patients who undergo off-pump coronary artery bypass grafting (OPCABG) have fewer short-term complications and use fewer inpatient resources than do patients who undergo standard coronary artery bypass grafting (CABG) with extracorporeal circulation. However, dissimilarity between groups in risk factors for complications has hindered interpretation of results. OBJECTIVES: To compare the prevalence of selected complications (atrial fibrillation, stroke, reoperation, and bleeding) and inpatient resource utilization (length of stay, discharge disposition, total charges) between subjects undergoing primary isolated CABG or OPCABG who were matched with respect to key risk factors. METHODS: Retrospective, causal-comparative survey conducted in 1 center for 18 months. Patients who underwent primary isolated CABG or OPCABG were matched for sex, age (within 2 years), left ventricular ejection fraction (within 0.05), and graft-patient ratio (exact match) and compared for prevalence of new-onset atrial fibrillation, stroke, reoperation within 24 hours, and bleeding. Statistical analysis included Wilcoxon and t tests for paired comparisons. RESULTS: The sample (107 matched pairs) was 63% male, with a mean age of 66 (SD 9.5) years, a mean left ventricular ejection fraction of 0.51 (SD 0.13), and a mean graft-patient ratio of 3.41 (SD 0.74). The 2 groups did not differ significantly in New York Heart Association class (P = .43), Acute Physiology and Chronic Health Evaluation III score (P = .22), postoperative beta-blocker use (P = .73), or comorbid conditions. None of the complications examined differed significantly between pairs. CONCLUSION: Patients with comparable risk profiles have similar prevalences of selected complications after CABG and OPCABG.     

Indwelling Versus Intermittent Feeding Tubes in Premature Neonates

Objective: To determine the effect of indwelling versus intermittent feeding tube placement on weight gain, apnea, and bradycardia in premature neonates.
Design: Eligible subjects were assigned randomly to either feeding tube method. Each subject was followed for 6 days.
Setting: The study was conducted in a secondary level neonatal intensive-care unit (NICU), a tertiary level NICU in a perinatal center, and a tertiary level NICU in a referral center.
Patients/Participants: Neonates who were 24–34 weeks gestational age, developmentally appropriate for gestational age, medically stable, on full enteral feedings through an orogastric or a nasogastric tube, and not fluid restricted. Ninety-three neonates were enrolled-49 in the indwelling group and 44 in the intermittent group. Nine neonates did not complete the study.
Interventions: Nasogastric indwelling feeding tubes were placed and left in site for up to 3 days. Orogastric intermittent feeding tubes were placed for each feeding and removed at completion of the feeding.
Main outcome measures: Weight gain, apnea, and bradycardia. Results: Members of both groups had similar demographic characteristics, clinical problems, and nutritional intake. No statistical differences were found between the two groups in weight gain or episodes of apnea and bradycardia.
Conclusions: There were no statistically or clinically significant differences between the two groups. The intermittent method of feeding is more expensive. Because no clinical differences were found, the type of tube placement chosen for feeding the premature infant may be based on economics.