Genetic testing in severe aplastic anemia is required for optimal hematopoietic cell transplant outcomes.

Patients with severe aplastic anemia (SAA) can have an unrecognized inherited bone marrow failure syndrome (IBMFS) because of phenotypic heterogeneity. We curated germline genetic variants in 104 IBMFS-associated genes from exome sequencing performed on 732 patients who underwent hematopoietic cell transplant (HCT) between 1989 and 2015 for acquired SAA. Patients with pathogenic or likely pathogenic (P/LP) variants fitting known disease zygosity patterns were deemed unrecognized IBMFS. Carriers were defined as patients with a single P/LP variant in an autosomal recessive gene or females with an X-linked recessive P/LP variant. Cox proportional hazard models were used for survival analysis with follow-up until 2017. We identified 113 P/LP single-nucleotide variants or small insertions/deletions and 10 copy number variants across 42 genes in 121 patients. Ninety-one patients had 105 in silico predicted deleterious variants of uncertain significance (dVUS). Forty-eight patients (6.6%) had an unrecognized IBMFS (33% adults), and 73 (10%) were carriers. No survival difference between dVUS and acquired SAA was noted. Compared with acquired SAA (no P/LP variants), patients with unrecognized IBMFS, but not carriers, had worse survival after HCT (IBMFS hazard ratio [HR], 2.13; 95% confidence interval[CI], 1.40-3.24; P = .0004; carriers HR, 0.96; 95% CI, 0.62-1.50; P = .86). Results were similar in analyses restricted to patients receiving reduced-intensity conditioning (n = 448; HR IBMFS = 2.39; P = .01). The excess mortality risk in unrecognized IBMFS attributed to death from organ failure (HR = 4.88; P < .0001). Genetic testing should be part of the diagnostic evaluation for all patients with SAA to tailor therapeutic regimens. Carriers of a pathogenic variant in an IBMFS gene can follow HCT regimens for acquired SAA.

Effectiveness trial of an online self-help intervention for sexual problems after cancer.

Sexual dysfunction affects over 60% of cancer survivors. Internet interventions have improved sexual function, but with considerable clinician guidance, restricting scalability. This pragmatic trial evaluated an online, self-help intervention. As with many unguided digital interventions, attrition was high. Given low numbers in other groups, this paper focuses on 30% of female patient participants who completed 3-month questionnaires and visited the intervention site (N = 60). Benefits included increased sexually active individuals at follow-up (p < 0.001, Effect size = 0.54), improved sexual function (p < 0.001, Effect size = -0.76, N = 41), and increased use of sexual aids (p = 0.01, Effect size=-0.14, N = 58). The intervention has been revised to improve patient engagement.

Understanding Long-Term Cancer Survivors' Preferences for Ongoing Medical Care.

BACKGROUND: Due to risk for treatment-related late effects and concerns about cancer recurrence, long-term cancer survivors have unique medical needs. Survivors' preferences for care may influence adherence and care utilization. OBJECTIVE: To describe survivors' preferences for care and factors associated with preferred and actual care. DESIGN: Cross-sectional analysis of participants in a longitudinal study using mailed questionnaires. PARTICIPANTS: Survivors of ten common cancers (n = 2,107, mean years from diagnosis 8.9). MAIN MEASURES: (1) Survivors' preferences for primary care physician (PCP) and oncologist responsibilities across four types of care: cancer follow-up, cancer screening, preventive health, and comorbid conditions. (2) Survivor-reported visits to PCPs and oncologists. KEY RESULTS: The response rate was 42.1%. Most long-term survivors preferred PCPs and oncologists share care for cancer follow-up (63%) and subsequent screening (65%), while preferring PCP-led preventive health (77%) and comorbid condition (83%) care. Most survivors (88%) preferred oncologists involved in cancer follow-up care, but only 60% reported an oncologist visit in the previous 4 years, and 96% reported a PCP visit in the previous 4 years. In multivariable regressions, those with higher fear of cancer recurrence were less likely to prefer PCP-led cancer follow-up care (OR = 0.96, CI = 0.93-0.98), as did survivors with advanced cancer stage (OR = 0.56, CI = 0.39-0.79). Those with higher fear of recurrence (OR = 1.03, CI = 1.01-1.04) or who preferred oncologist-led cancer follow-up care (OR = 2.08, CI = 1.63-2.65) had greater odds of seeing an oncologist in the last 4 years. CONCLUSIONS: Most cancer survivors preferred PCPs and oncologists share care for cancer follow-up and screening, yet many had not seen an oncologist recently. Survivors preferred PCP-led care for other preventive services and management of comorbid conditions. These findings highlight the important role PCPs could play in survivor care, suggesting the need for PCP-oriented education and health system policies that support high-quality PCP-led survivor care.

Epidemiology of Hospitalizations Associated with Invasive Candidiasis, United States, 2002-20121.

Invasive candidiasis is a major nosocomial fungal disease in the United States associated with high rates of illness and death. We analyzed inpatient hospitalization records from the Healthcare Cost and Utilization Project to estimate incidence of invasive candidiasis-associated hospitalizations in the United States. We extracted data for 33 states for 2002-2012 by using codes from the International Classification of Diseases, 9th Revision, Clinical Modification, for invasive candidiasis; we excluded neonatal cases. The overall age-adjusted average annual rate was 5.3 hospitalizations/100,000 population. Highest risk was for adults >65 years of age, particularly men. Median length of hospitalization was 21 days; 22% of patients died during hospitalization. Median unadjusted associated cost for inpatient care was $46,684. Age-adjusted annual rates decreased during 2005-2012 for men (annual change -3.9%) and women (annual change -4.5%) and across nearly all age groups. We report a high mortality rate and decreasing incidence of hospitalizations for this disease.

Association between Smoking Cannabis and Quitting Cigarettes in a Large American Cancer Society Cohort.

BACKGROUND: Cannabis use is increasing, including among smokers, an at-risk population for cancer. Research is equivocal on whether using cannabis inhibits quitting cigarettes. The current longitudinal study investigated associations between smoking cannabis and subsequently quitting cigarettes. METHODS: Participants were 4,535 adult cigarette smokers from a cohort enrolled in the American Cancer Society's Cancer Prevention Study-3 in 2009-2013. Cigarette quitting was assessed on a follow-up survey in 2015-2017, an average of 3.1 years later. Rates of quitting cigarettes at follow-up were examined by retrospectively assessed baseline cannabis smoking status (never, former, recent), and by frequency of cannabis smoking among recent cannabis smokers (low: ≤3 days/month; medium: 4-19 days/month; high: ≥20 days/month). Logistic regression models adjusted for sociodemographic factors, smoking- and health-related behaviors, and time between baseline and follow-up. RESULTS: Adjusted cigarette quitting rates at follow-up did not differ significantly by baseline cannabis smoking status [never 36.2%, 95% confidence interval (CI), 34.5-37.8; former 34.1%, CI, 31.4-37.0; recent 33.6%, CI, 30.1-37.3], nor by frequency of cannabis smoking (low 31.4%, CI, 25.6-37.3; moderate 36.7%, CI, 30.7-42.3; high 34.4%, CI, 28.3-40.2) among recent baseline cannabis smokers. In cross-sectional analyses conducted at follow-up, the proportion of cigarette smokers intending to quit smoking cigarettes in the next 30 days did not differ by cannabis smoking status (P = 0.83). CONCLUSIONS: Results do not support the hypothesis that cannabis smoking inhibits quitting cigarette smoking among adults. IMPACT: Future longitudinal research should include follow-ups of >1 year, and assess effects of intensity/frequency of cannabis use and motivation to quit on smoking cessation.

Cancer-related problems, sleep quality, and sleep disturbance among long-term cancer survivors at 9-years post diagnosis.

OBJECTIVE: To estimate the prevalence of sleep difficulties in a large cohort of long-term cancer survivors (>5 years) and examine associations with four domains of cancer-related problems. METHODS: This study analyzed a nationwide sample (N = 1903) of cancer survivors (31% Breast; 20% prostate) at nine years (m = 8.9 sd = 0.6) post-diagnosis with a mean age of 64.5 years. Sleep quality and sleep disturbance were assessed by the Pittsburgh Sleep Quality Index. Multivariable logistic regression models examined associations between cancer-related problems (physical distress, emotional distress, economic distress, and fear of recurrence) and sleep difficulty (poor vs. low sleep quality and high vs. low sleep disturbance). Odds ratios (OR) and 95% confidence intervals (CI) were estimated, adjusting for medico-demographics, behavioral factors, and sleep medication use. RESULTS: In sum, 20% percent of the sample reported poor sleep quality, 51% reported high sleep disturbance and 17% reported both. Sleep medication use was reported by 28% of the total sample. All four domains of cancer-related problems were significantly associated with poor sleep quality and high sleep disturbance. Above median cancer-related physical distress had the strongest association with both poor sleep quality (OR = 3.42; 95% CI = 2.44-4.79) and high sleep disturbance (OR = 4.06; 95% CI = 3.09-5.34). CONCLUSIONS: Among nine-year cancer survivors, multiple domains of cancer-related health problems were associated with sleep difficulties. Knowledge of the relationship between cancer-related problems and sleep may aid clinicians during the evaluation and treatment of sleep problems in long-term cancer survivors. Future research should utilize prospective data to better understand the causal nature of the associations.

Use of complementary/integrative methods: cancer survivors' misconceptions about recurrence prevention.

PURPOSE: Many cancer survivors use complementary and alternative health methods (CAM). Because we are unaware of high-level evidence supporting CAM for preventing cancer recurrence, we studied post-treatment survivors who use CAM to assess (1) the percentage who included preventing recurrence as a motive for using CAM, (2) characteristics of survivors who use CAM intended to prevent recurrence, and (3) CAM domains associated with use for recurrence prevention. METHODS: We studied participants in the American Cancer Society's Study of Cancer Survivors-I (nationwide study of adult survivors) who used CAM (excluding osteopathy, yoga, tai chi, or qi gong users, as well as anyone whose only reported CAM was prayer/meditation). Multivariable logistic regression was used to examine associations of independent variables with CAM use for recurrence prevention. RESULTS: Among 1220 survivors using CAM, 14.8% reported recurrence prevention as a reason for CAM use (although only 0.4% indicated this was their only reason). The following were independently associated with odds of CAM use to prevent recurrence: not being married/in a marriage-like relationship (OR = 1.53, 95% confidence interval [CI] 1.05-2.23), using mind-body (OR = 1.65, 95% CI 1.08-2.51) or biologically based (OR = 4.11, 95% CI 1.96-8.59) CAM and clinically relevant fear of recurrence (OR = 1.96, 95% CI 1.38-2.78). CONCLUSIONS: Approximately 1/7 of survivors who use CAM have unrealistic expectations about CAM reducing recurrence risk. This expectation is strongly associated with the use of biologically based CAM. IMPLICATIONS FOR CANCER SURVIVORS: Patient education should support informed decisions and realistic expectations regarding any complementary/integrative or mainstream/conventional clinical intervention.

Epidemiology of Norovirus Infection Among Immunocompromised Patients at a Tertiary Care Research Hospital, 2010-2013.

Background. Noroviruses are a major cause of infectious gastroenteritis worldwide, and viruses can establish persistent infection in immunocompromised individuals. Risk factors and transmission in this population are not fully understood. Methods. From 2010 through 2013, we conducted a retrospective review among immunocompromised patients (n = 268) enrolled in research studies at the National Institutes of Health Clinical Center and identified a subset of norovirus-positive patients (n = 18) who provided stool specimens for norovirus genotyping analysis. Results. Norovirus genome was identified by reverse-transcription quantitative polymerase chain reaction in stools of 35 (13%) of the 268 immunocompromised patients tested, and infection prevalence was 21% (11 of 53) in persons with primary immune deficiencies and 12% (20 of 166) among persons with solid tumors or hematologic malignancies. Among 18 patients with norovirus genotyping information, norovirus GII.4 was the most prevalent genotype (14 of 18, 78%). Persistent norovirus infection (≥6 months) was documented in 8 of 18 (44%) individuals. Phylogenetic analysis of the GII.4 capsid protein sequences identified at least 5 now-displaced GII.4 variant lineages, with no evidence of their nosocomial transmission in the Clinical Center. Conclusions. Norovirus was a leading enteric pathogen identified in this immunocompromised population. Both acute and chronic norovirus infections were observed, and these were likely community-acquired. Continued investigation will further define the role of noroviruses in these patients and inform efforts toward prevention and treatment.

The Burden of Pulmonary Nontuberculous Mycobacterial Disease in the United States.

RATIONALE: State-specific case numbers and costs are critical for quantifying the burden of pulmonary nontuberculous mycobacterial disease in the United States. OBJECTIVES: To estimate and project national and state annual cases of nontuberculous mycobacterial disease and associated direct medical costs. METHODS: Available direct cost estimates of nontuberculous mycobacterial disease medical encounters were applied to nontuberculous mycobacterial disease prevalence estimates derived from Medicare beneficiary data (2003-2007). Prevalence was adjusted for International Classification of Diseases, 9th Revision, undercoding and the inclusion of persons younger than 65 years of age. U.S. Census Bureau data identified 2010 and 2014 population counts and 2012 primary insurance-type distribution. Medical costs were reported in constant 2014 dollars. Projected 2014 estimates were adjusted for population growth and assumed a previously published 8% annual growth rate of nontuberculous mycobacterial disease prevalence. MEASUREMENTS AND MAIN RESULTS: In 2010, we estimated 86,244 national cases, totaling to $815 million, of which 87% were inpatient related ($709 million) and 13% were outpatient related ($106 million). Annual state estimates varied from 48 to 12,544 cases ($503,000-$111 million), with a median of 1,208 cases ($11.5 million). Oceanic coastline states and Gulf States comprised 70% of nontuberculous mycobacterial disease cases but 60% of the U.S. population. Medical encounters among individuals aged 65 years and older ($562 million) were twofold higher than those younger than 65 years of age ($253 million). Of all costs incurred, medications comprised 76% of nontuberculous mycobacterial disease expenditures. Projected 2014 estimates resulted in 181,037 national annual cases ($1.7 billion). CONCLUSIONS: For a relatively rare disease, the financial cost of nontuberculous mycobacterial disease is substantial, particularly among older adults. Better data on disease dynamics and more recent prevalence estimates will generate more robust estimates.