Development of a multivariable prognostic PREdiction model for 1-year risk of FALLing in a cohort of community-dwelling older adults aged 75 years and above (PREFALL)

Abstract Background Falls are the leading cause of fatal and non-fatal injuries in older adults, and attention to falls prevention is imperative. Prognostic models identifying high-risk individuals could guide fall-preventive interventions in the rapidly growing older population. We aimed to develop a prognostic prediction model on falls rate in community-dwelling older adults. Methods Design: prospective cohort study with 12 months follow-up and participants recruited from June 14, 2018, to July 18, 2019. Setting: general population. Subjects: community-dwelling older adults aged 75+ years, without dementia or acute illness, and able to stand unsupported for one minute. Outcome: fall rate for 12 months. Statistical methods: candidate predictors were physical and cognitive tests along with self-report questionnaires. We developed a Poisson model using least absolute shrinkage and selection operator penalization, leave-one-out cross-validation, and bootstrap resampling with 1000 iterations. Results Sample size at study start and end was 241 and 198 (82%), respectively. The number of fallers was 87 (36%), and the fall rate was 0.94 falls per person-year. Predictors included in the final model were educational level, dizziness, alcohol consumption, prior falls, self-perceived falls risk, disability, and depressive symptoms. Mean absolute error (95% CI) was 0.88 falls (0.71–1.16). Conclusion We developed a falls prediction model for community-dwelling older adults in a general population setting. The model was developed by selecting predictors from among physical and cognitive tests along with self-report questionnaires. The final model included only the questionnaire-based predictors, and its predictions had an average imprecision of less than one fall, thereby making it appropriate for clinical practice. Future external validation is needed. Trial registration Clinicaltrials.gov ( NCT03608709 )

Incidence and time trends of second primary malignancies after non-Hodgkin lymphoma:a Swedish population-based study

Considering treatment changes and an improved prognosis of non-Hodgkin lymphoma (NHL) over time, knowledge regarding long-term health outcomes, including late effects of treatment, has become increasingly important. We report on time trends of second primary malignancies (SPMs) in Swedish NHL patients, encompassing the years before as well as after the introduction of anti-CD20 antibody therapy. We identified NHL patients in the Swedish Cancer Register 1993 to 2014 and matched comparators from the Swedish Total Population Register. The matched cohort was followed through 2017. By linking to the Swedish Lymphoma Register, subcohort analyses by NHL subtype were performed. Flexible parametric survival models were used to estimate hazard ratios (HRs) with 95% confidence intervals (CIs) of SPM among patients and comparators. Among 32 100 NHL patients, 3619 solid tumors and 217 myelodysplastic syndrome (MDS)/acute myeloid leukemia (AML) cases were observed, corresponding to a 40% higher rate of solid tumors (HR(solid tumors) = 1.4; 95% CI, 1.4-1.5) and a 5-fold higher rate of MDS/AML (HR(MDS/AML )= 5.2; 95% CI, 4.4-6.2) than for comparators. Overall, the observed excess risks for solid tumors or MDS/AML remained stable over the study period, except for follicular lymphoma, where the excess rate of MDS/AML attenuated with time (P for trend = .012). We conclude that NHL survivors have an increased risk of both solid tumors and hematologic malignancies, in particular MDS/AML. Stable excess risks over time indicate that contemporary treatment standards are not associated with modified SPM risk. Encouragingly, decreasing rates of MDS/AML were noted among patients with follicular lymphoma, possibly due to the increasing use of nonchemotherapy-based treatments

A randomized trial of alendronate as prophylaxis against loss in bone mineral density following lymphoma treatment

Lymphoma patients often receive high glucocorticoid doses as part of standard therapy. Observational studies have shown a substantial risk of glucocorticoid-induced osteoporosis (GIO) with associated fractures. The aim of the SIESTA trial was to determine if oral alendronate (ALN) is a safe and effective prophylaxis against GIO in lymphoma. SIESTA was a single-center, randomized, double-blinded, phase 2 study of lymphoma patients planned for glucocorticoid-containing chemotherapy. After randomization, patients received weekly ALN 70 mg or placebo for a total of 52 weeks. Bone mineral density (BMD) was assessed at baseline, after completion of chemotherapy (end of treatment [EOT]) (4 to 6 months), and at the end of the study (EOS) (12 months). Vertebral fracture and biomarkers were assessed at baseline and EOS. Patients with baseline BMD assessment and at least 1 follow-up BMD assessment were analyzed for efficacy. The primary endpoint was a change in lumbar spine T-score from baseline to EOS. Of the 59 patients enrolled, 23 of 30 in the ALN arm and 24 of 29 in the placebo arm were analyzed for efficacy. The mean change in T-score from baseline to 12 months at the lumbar spine was +0.15 for ALN and -0.12 for placebo (P = .023). The difference in ΔT(EOS) between the ALN and placebo groups was larger among females (ALN 0.28; placebo -0.28; P = .01). Biomarker analyses confirmed reduced bone resorption in ALN-treated patients. In conclusion, ALN is a safe and effective primary prophylaxis against loss in BMD following glucocorticoid-containing chemotherapy. Despite reduced BMD loss in the ALN arm, the treatment did not influence fracture risk in this small cohort of patients

Risk of diabetes and the impact on preexisting diabetes in patients with lymphoma treated with steroid-containing immunochemotherapy

First-line treatments for lymphomas often include high doses of prednisolone, but the risks of new-onset diabetes mellitus (DM) or worsening of preexisting DM following treatment with cyclic high dose corticosteroids is unknown. This cohort study matched non-Hodgkin lymphoma (NHL) patients treated with steroid-containing immunochemotherapy (ie, R-CHOP[-like] and R-CVP) between 2002 and 2015 to individuals from the Danish population to investigate the risks of new-onset DM. For patients with preexisting DM, the risks of insulin dependency and anthracycline-associated cardiovascular diseases (CVDs) were assessed. In total, 5672 NHL patients and 28 360 matched comparators were included. Time-varying incidence rate ratios (IRRs) showed increased risk of DM in the first year after treatment compared with matched comparators, with the highest IRR being 2.7. The absolute risks were higher among patients in the first 2 years, but the difference was clinically insignificant. NHL patients with preexisting DM had increased risks of insulin prescriptions with 0.5-, 5-, and 10-year cumulative risk differences of insulin treatment of 15.3, 11.8, and 6.0 percentage units as compared with the DM comparators. In a landmark analysis at 1 year, DM patients with lymphoma had decreased risks of insulin dependency compared with comparators. Time-varying IRRs showed a higher CVD risk for NHL patients with DM as compared with comparators in the first year after treatment. NHL patients treated with steroid-containing immunochemotherapy regimens have a clinically insignificant increased risk of DM in the first year following treatment, and patients with preexisting DM have a temporary increased risk of insulin prescriptions and CVD