Tele‐Health Followup Strategy for Tight Control of Disease Activity in Rheumatoid Arthritis: Results of a Randomized Controlled Trial

Objective

To test the effect of patient‐reported outcome (PRO)–based tele‐health followup for tight control of disease activity in patients with rheumatoid arthritis (RA), and the differences between tele‐health followup performed by rheumatologists or rheumatology nurses.

Methods

A total of 294 patients were randomized (1:1:1) to either PRO‐based tele‐health followup carried out by a nurse (PRO‐TN) or a rheumatologist (PRO‐TR), or conventional outpatient followup by physicians. The primary outcome was a change in the Disease Activity Score in 28 joints (DAS28) after week 52. Secondary outcomes were physical function, quality of life, and self‐efficacy. The noninferiority margin was a DAS28 score change of 0.6. Mean differences were estimated following per protocol, intent‐to‐treat (ITT), and multivariate imputation analysis.

Results

Overall, patients had low disease activity at baseline and end followup. Demographics and baseline characteristics were similar between groups. Noninferiority was established for the DAS28. In the ITT analysis, mean differences in the DAS28 score between PRO‐TR versus control were ?0.10 (90% confidence interval [90% CI] ?0.30, 0.13) and ?0.19 (90% CI ?0.41, 0.02) between PRO‐TN versus control. When including 1 yearly visit to the outpatient clinic, patients in PRO‐TN had mean ± SD 1.72 ± 1.03 visits/year, PRO‐TR had 1.75 ± 1.03 visits/year, and controls had 4.15 ± 1.0 visits/year. This included extra visits due to inflammatory flare.

Conclusion

Among RA patients with low disease activity or remission, a PRO‐based tele‐health followup for tight control of disease activity in RA can achieve similar disease control as conventional outpatient followup. The degree of disease control did not differ between patients seen by rheumatologists or rheumatology nurses.

     

Serial pulmonary function tests in patients treated with low-dose amiodarone.

Problems with pulmonary toxicity have emerged as a potentially limiting factor for amiodarone use. We studied 24 consecutive patients receiving low-dose (i.e., less than or equal to 400 mg/day) amiodarone for refractory tachyarrhythmias. Serial pulmonary function test results were correlated with daily dose, serum concentration, cumulated dose, and duration of amiodarone treatment to determine the effect of the drug on pulmonary function. The mean follow-up period for the 24 patients, who completed baseline and follow-up evaluations, was 47 months (range 31 to 75 months). In 22 of the 24 patients a reduction in total diffusion capacity (TLCO) was noted after treatment; for all 24 patients the mean reduction in TLCO was 12.9% of the predicted value (SD 9.6% predicted) (p less than 0.02). The decrease in TLCO was found to be significantly related to an increasing cumulated dose of amiodarone (p = 0.007), whereas the reduction in TLCO was found to be unrelated to sex, age, underlying heart disease, arrhythmia, daily dose of amiodarone, duration of treatment, plasma concentration of amiodarone and desethylamiodarone, and pretreatment pulmonary function abnormalities. Seven (29%) of the patients had asymptomatic pulmonary toxicity with a decrease in TLCO greater than or equal to 20% of the predicted value. In conclusion, long-term treatment with low-dose amiodarone was associated with a substantial decrease in TLCO, a higher cumulative dose of the drug was related to an increasing reduction in TLCO, and pretreatment pulmonary function abnormalities were not predictive for development of subclinical pulmonary toxicity.     

Is dermatome shaving a potential treatment for actinic keratosis in organ transplant recipients? A cross-sectional study

Background

Non-melanoma skin cancer (NMSC) is correlated with high morbidity and mortality in solid-organ transplant recipients (OTR) and it appears after a mean interval of 8 to 10 years. Prophylactic treatments are still required to prevent the development of NMSC. This study aims to investigate whether dermatome shaving reduced the occurrence of keratotic skin lesions in OTRs.

Methods

A retrospective study was conducted. One thousand and twenty-four patients who had a split-thickness skin graft due to NMSC excision were identified in the Central Denmark Region and the Region of Southern Denmark between 1996 and 2011. Eleven of these patients were OTRs at the time of split-thickness skin grafting and were included in the study. The patients were examined for keratotic skin lesions, representing suspected premalignant lesions, on the donor area of the split-thickness skin graft, recipient area and two corresponding control areas. Epidemiological and medical parameters for each patient were registered via medical records and through patient interviews.

Results

The average time between split-thickness skin grafting and clinical examination was 6.2 years (1.1–16.8). The occurrence of keratotic skin lesions were lower in the donor area compared to both of the control areas (Wilcoxon matched-pairs signed-rank test, p?=?0.024, respectively, p?=?0.019).

Conclusions

Dermatome shaving reduced the occurrence of keratotic skin lesions in OTRs and might prevent the development of field cancerization and NMSC. Level of Evidence: Level III, therapeutic study.     

Traumatic distress symptoms in early breast cancer I: Acute response to diagnosis

In this study, the concept of ‘acute traumatic stress response’ was applied to breast cancer diagnosis. A total of 106 patients were studied before surgery, by means of a psychiatric interview and questionnaires (Impact of Event Scale, General Health Questionnaire and Clinical Global Impression Scale). The traumatic stress response was related to age, marital status, occurrence of breast cancer in first-degree relatives, previous physical and psychological health parameters, social support and life events during the last year. Of the patients, 44% reported a high level of intrusive symptoms (mean score 17.2) and 29% of avoidance symptoms (mean score 15.0). Younger age and being married were positively correlated with intrusive symptomology while patients with a first-degree relative with breast cancer had less intrusive distress. Previous physical and psychiatric health parameters showed no association to acute traumatic stress symptoms except for those who had experienced ‘a serious illness/accident/hospitalisation last year’ who had some more avoidant symptomology. Multiple regression showed a statistically significant effect for age only on intrusive symptoms when other factors were controlled for in this analysis.     

Traumatic distress symptoms in early breast cancer. II: Outcome six weeks post surgery

One hundred and six consecutive patients with a confirmed diagnosis of breast cancer were studied before and after surgery with a clinical psychiatric interview and questionnaires (Impact of Event Scale, General Health Questionnaire and Clinical Global Impression scale). The traumatic stress response after six weeks was related to sociodemographic factors, premorbid health problems, negative life events and clinical-oncological parameters. Symptoms of traumatic distress were significantly reduced post-surgery compared to acutely, and most so among patients with no premorbid health problems and negative life events according to pre-surgery interview and self-report data. Eighteen percent of the patients reported a high level (>19) of intrusive symptoms and 14%, avoidance symptoms. Patients with premorbid impairment in work, family and social functioning and patients who during the last year had experienced the death of a close relative or a serious illness other than cancer showed the greatest distress. Previous consultations for nervous problems, age, marital status, stage of disease, type of surgery (breast-conserving versus mastectomy) and adjuvant cytostatic treatment did not influence the traumaticstress response six weeks after surgery. The level of acute posttraumatic stress response to breast cancer surgery seems best predicted by premorbid variables.     

Tumor mutational burden and purity adjustment before and after treatment with temozolomide in 27 paired samples of glioblastoma: a prospective study

Treatment of glioblastoma (GBM) remains a challenging task, with limited treatment options, none offering a cure. Immune therapy has proven effective across different cancers with remarkable response rates. Tumor mutational burden (TMB) is a marker of response, but technical and methodological differences in TMB estimates have made a proper assessment and comparison challenging. Here, we analyzed a prospective collection of paired samples from 35 patients with newly diagnosed GBM, all of whom were wild‐type (WT) for isocitrate dehydrogenase, before and after treatment with radiotherapy and temozolomide. Seven patients (20%) had O6‐methylguanine‐DNA methyltransferase‐methylated tumors. Six patients (17%) had two relapse surgeries, and tissue from all three surgeries was collected. We found that accurate evaluation of TMB was confounded by high variability in the cancer cell fraction of relapse samples. To ameliorate this, we developed a model to adjust for tumor purity based on the relative density distribution of variant allele frequencies in each primary–relapse pair. Additionally, we examined the mutation spectra of shared and private mutations. After tumor purity adjustment, we found TMB comparison reliable in tumors with tumor purity between 15% and 40%, resulting in 27/35 patients (77.1%). TMB remained unchanged from 0.65 mutations per megabase (Mb) to 0.67/Mb before and after treatment, respectively. Examination of the mutation spectra revealed a dominance of C > T transitions at CpG sites in both shared and relapse‐private mutations, consistent with cytosine deamination and the clock‐like mutational signature 1. We present and apply a cellularity correction approach that enables more accurate assessment of TMB in paired tumor samples. We did not find a significant increase in TMB after correcting for cancer cell fraction. Our study raises significant concerns when determining TMB. Although a small sample size, corrected TMB can have a clinical significance when stratifying patients to experimental treatment, for example, immune checkpoint therapy.