Individuals diagnosed with cystic fibrosis (CF) as adults represent a growing subpopulation of CF cases, but there are limited studies describing their characteristics and prognosis.
The objectives ...of this study were to describe the clinical characteristics of individuals with adult-diagnosed CF, estimate survival rates in this population, and identify clinical predictors of reduced survival at baseline.
The Canadian CF Patient Registry was used to identify patients with CF who were ≥18 years of age at diagnosis and received a diagnosis between 1990 and 2014. Clinical characteristics were described and the Kaplan-Meier method was used to estimate lung-transplant-free survival. Multivariable Cox regression analysis and adjusted survival curves were employed to identify important predictors of reduced survival at the time of diagnosis (i.e., baseline) and to produce adjusted effects.
A total of 362 adults were diagnosed with CF during the study period. The median follow-up time was 7.7 years and 48 individuals experienced an event (15 transplants, 33 deaths without transplant). The median age at diagnosis was 34.3 years, with the majority of individuals presenting with pulmonary and/or gastrointestinal symptoms (71%). Lung-transplant-free survival was 88% at 10 years and 86% at 15 years. Age at diagnosis (hazard ratio HR, 1.24 per 5-year increase, 95% confidence interval CI, 1.09-1.43), diabetes (HR, 4.19; 95% CI, 1.35-13.01), and lung function (HR, 1.35 per 5% decrease in forced expiratory volume in 1 second % predicted; 95% CI, 1.24-1.48) at baseline were important predictors of reduced survival.
CF care providers can use this information to inform individuals who received a diagnosis of CF as adults about their prognosis and to guide the necessity of treatments, specifically with regard to those who are at high risk for a worse prognosis.
Most reports of active surveillance (AS) of small renal masses (SRMs) lack biopsy confirmation, and therefore include benign tumors and different subtypes of renal cell carcinoma (RCC).
We compared ...the growth rates and progression of different histologic subtypes of RCC SRMs (SRMRCC) in the largest cohort of patients with biopsy-characterized SRMs on AS.
Data from patients in a multicenter Canadian trial and a Princess Margaret cohort were combined to include 136 biopsy-proven SRMRCC lesions managed by AS, with treatment deferred until progression or patient/surgeon decision.
Growth curves were estimated from serial tumor size measures. Tumor progression was defined by sustained size ≥4 cm or volume doubling within 1 yr.
Median follow-up for patients who remained on AS was 5.8 yr (interquartile range 3.4–7.5 yr). Clear cell RCC SRMs (SRMccRCC) grew faster than papillary type 1 SRMs (0.25 and 0.02 cm/yr on average, respectively, p = 0.0003). Overall, 60 SRMRCC lesions progressed: 49 (82%) by rapid growth (volume doubling), seven (12%) increasing to ≥4 cm, and four (6.7%) by both criteria. Six patients developed metastases, and all were of clear cell RCC histology. Limitations include the use of different imaging modalities and a lack of central imaging review.
Tumor growth varies between histologic subtypes of SRMRCC and among SRMccRCC, which likely reflects individual host and tumor biology. Without validated biomarkers that predict this variation, initial follow-up of histologically characterized SRMs can inform personalized treatment for patients on AS.
Many small kidney cancers are suitable for surveillance and can be monitored over time for change. We demonstrate that different types of kidney cancers grow at different rates and are at different risks of progression. These results may guide better personalized treatment.
Tumor growth varies within and between histological subtypes of small renal masses (renal cell carcinomas), which likely reflects individual host and tumor biology. Histology-specific growth rates and initial monitoring of small renal masses can inform personalized treatment for patients on active surveillance.
•Adults with CF have smaller thigh muscles, compared to healthy controls.•Adults with CF have lower handgrip strength than healthy controls.•A subgroup of adults with CF has lower quadriceps strength ...than healthy controls.•Lower handgrip strength is associated with lower lung function in adults with CF.•Females with CF has lower handgrip strength than males with CF.
There is conflicting evidence regarding the presence of limb muscle impairments in adults with cystic fibrosis (CF), and the factors associated with these muscle impairments. The objectives of this study were to compare limb muscle size and function between adults with CF and healthy controls; and to examine their associations with demographic and clinical variables in adults with CF.
The systematic review was performed using PRISMA guidelines. Studies were included if they measured any aspect of limb muscle size or function in adults with CF. Meta-analyses were performed to compare muscle variables between CF and healthy controls; and to examine their associations with demographic and clinical variables.
Twenty-eight studies were included, with 747 adults with CF. The meta-analyses showed that adults with CF have smaller thigh muscles standardized mean difference (SMD) = 0.57, p<.0011, I2=0%, and lower handgrip strength (SMD = 0.89, p=.0034, I2=74.03%), which was weakly correlated with forced expiratory volume in one second (FEV1) (r=0.24, p=.035, I2=0%) and lower in females with CF (SMD = 2.05, p<.0001, I2=0%). There is no significant difference between adults with CF and controls in knee extensor strength (SMD = 0.25, p=.095, I2=42.79%).
Leg muscle atrophy and lower handgrip strength were noted. There may be a subgroup of adults with CF with knee extensor (quadriceps) weakness. Future studies are needed to better understand muscle impairments in people with CF; to explore the factors that can predict these muscle impairments; and to investigate their clinical significance in people with CF.
France implemented a high emergency lung transplantation (HELT) programme nationally in 2007. A similar programme does not exist in Canada. The objectives of our study were to compare health outcomes ...within France as well as between Canada and France before and after the HELT programme in a population with cystic fibrosis (CF).
This population-based cohort study utilised data from the French and Canadian CF registries. A cumulative incidence curve assessed time to transplant with death without transplant as competing risks. The Kaplan-Meier method was used to estimate post-transplant survival.
Between 2002 and 2016, there were 1075 (13.0%) people with CF in France and 555 (10.2%) people with CF in Canada who underwent lung transplantation. The proportion of lung transplants increased in France after the HELT programme was initiated (4.5%
10.1%), whereas deaths pre-transplant decreased from 85.3% in the pre-HELT period to 57.1% in the post-HELT period. Between 2008 and 2016, people in France were significantly more likely to receive a transplant (hazard ratio (HR) 1.56, 95% CI 1.37-1.77; p<0.001) than die (HR 0.55, 95% CI 0.46-0.66; p<0.001) compared with Canada. Post-transplant survival was similar between the countries, and there was no difference in survival when comparing pre- and post-HELT periods in France.
Following the implementation of the HELT programme, people living with CF in France were more likely to receive a transplant than die. Post-transplant survival in the post-HELT period in France did not change compared with the pre-HELT period, despite potentially sicker patients being transplanted, and was comparable to Canada.
Understanding how health outcomes differ for patients with advanced cystic fibrosis (CF) lung disease living in the United States compared with Canada has health policy implications.
What are rates ...of lung transplant (LTx) and rates of death without LTx in the United States and Canada among individuals with FEV
< 40% predicted?
This was a retrospective population-based cohort study, 2005 to 2016, using the US CF Foundation, United Network for Organ Sharing, and Canadian CF registries. Individuals with CF and at least two FEV
measurements < 40% predicted within a 5-year period, age ≥ 6 years, without prior LTx were included. Multivariable competing risk regression for time to death without LTx (LTx as a competing risk) and time to LTx (death as a competing risk) was performed.
There were 5,899 patients (53% male) and 905 patients (54% male) with CF with FEV
< 40% predicted living in the United States and Canada, respectively. Multivariable competing risk regression models identified an increased risk of death without LTx (hazard ratio HR, 1.79; 95% CI, 1.52-2.1) and decreased LTx (HR, 0.66; 95% CI, 0.58-0.74) among individuals in the United States compared with Canada. More pronounced differences were seen in the patients in the United States with Medicaid/Medicare insurance compared with Canadians (multivariable HR for death without LTx, 2.24 95% CI, 1.89-2.64; multivariable HR for LTx, 0.54 95% CI, 0.47-0.61). Patients of nonwhite race were also disadvantaged (multivariable HR for death without LTx, 1.56 95% CI, 1.32-1.84; multivariable HR for LTx, 0.47 95% CI, 0.36-0.62).
There are lower rates of LTx and an increased risk of death without LTx for US patients with CF with FEV
< 40% predicted compared with Canadian patients. Findings are more striking among US patients with CF with Medicaid/Medicare health insurance, and nonwhite patients in both countries, raising concerns about underuse of LTx among vulnerable populations.
We aimed to develop a clinical tool for predicting 1- and 2-year risk of death for patients with cystic fibrosis (CF). The model considers patients' overall health status as well as risk of ...intermittent shock events in calculating the risk of death.
Canadian CF Registry data from 1982 to 2015 were used to develop a predictive risk model using threshold regression. A 2-year risk of death estimated conditional probability of surviving the second year given survival for the first year. UK CF Registry data from 2007 to 2013 were used to externally validate the model.
The combined effect of CF chronic health status and CF intermittent shock risk provided a simple clinical scoring tool for assessing 1-year and 2-year risk of death for an individual CF patient. At a threshold risk of death of ≥20%, the 1-year model had a sensitivity of 74% and specificity of 96%. The area under the receiver operating curve (AUC) for the 2-year mortality model was significantly greater than the AUC for a model that predicted survival based on forced expiratory volume in 1 s <30% predicted (AUC 0.95
0.68 respectively, p<0.001). The Canadian-derived model validated well with the UK data and correctly identified 79% of deaths and 95% of survivors in a single year in the UK.
The prediction models provide an accurate risk of death over a 1- and 2-year time horizon. The models performed equally well when validated in an independent UK CF population.
Malnutrition is prevalent in gastrointestinal (GI) cancer patients, possibly due to inflammation and altered fatty acids (FA). There is a lack of research describing nutritional decline in these ...patients during chemotherapy. We described changes in nutritional, inflammatory, and FA status over time and factors relating to change in nutritional status according to tumor presence in 41 GI cancer patients undergoing first-line treatment over four chemotherapy visits, using linear mixed effects models. At baseline, 53% of patients were malnourished. Over time, there was a decrease in the proportion of malnourished vs. well-nourished individuals (β= −0.564, p < 0.01). Median concentrations of plasma linoleic acid, arachidonic acid, eicosapentaenoic acid, docosahexaenoic acid, total n-3, total n-6 and total plasma phospholipid FA increased over time. Changes over time in nutritional status based on weight (p < 0.001), fat free mass (FFM) measured by bioelectrical impedance analysis (BIA, p = 0.02), and skinfold anthropometry (FSA, p = 0.04) were significantly dependent on tumor presence. There were positive associations between weight and total n-3 (β = 0.02, p < 0.01), FFM and IL-6 (BIA, β = 0.028, p = 0.02; FSA, β = 0.03, p = 0.02), and FFM and total n-6 (BIA, β = 0.003, p = 0.01). Changes in nutritional status during chemotherapy were negatively impacted by tumor presence, and were associated with increasing concentrations of cytokines and FA.
Introduction and Aims
Even though individuals with substance‐use disorders have a high prevalence of tobacco smoking, surprisingly little is known about smoking‐related mortality in these ...populations. The current retrospective cohort study aims to address this gap.
Design and Methods
The study sample included cohorts of individuals hospitalised in California between 1990 and 2005 with alcohol‐ (n = 509 422), cocaine‐ (n = 35 276), opioid‐ (n = 53 172), marijuana‐ (n = 15 995) or methamphetamine‐use (n = 36 717) disorders. Death records were linked to inpatient data. Age‐, race‐ and sex‐adjusted standardised mortality ratios (SMR) were generated for 19 smoking‐related causes of death.
Results
Smoking‐related conditions comprised 49% (79 188/163 191) of total deaths in the alcohol, 40% (1412/3570) in the cocaine, 39% (4285/11 091) in the opioid, 42% (554/1332) in the methamphetamine and 36% (1122/3095) in the marijuana cohorts. The SMRs for all smoking‐linked diseases were: alcohol, 3.57 (95% confidence interval CI = 3.55 to 3.58); cocaine, 2.40 (95% CI = 2.39 to 2.41); opioid, 4.26 (95% CI = 4.24 to 4.27); marijuana, 3.73 (95% CI = 3.71 to 3.74); and methamphetamine, 2.58 (95% CI = 2.57 to 2.59). The SMRs for almost all of the 19 cause‐specific smoking‐related outcomes were elevated across cohorts.
Discussion and Conclusions
Given the current findings, addressing tobacco smoking among persons with substance‐use disorders should be a critical concern, especially given the heavy smoking‐related mortality burden and the currently limited attention devoted to smoking in these populations. Callaghan RC, Gatley JM, Sykes J, Taylor L. The prominence of smoking‐related mortality among individuals with alcohol‐ or drug‐use disorders. Drug Alcohol Rev 2018;37:97–105
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