Making decisions for follow-up chemotherapy based on digital patient reported outcomes data in patients with multiple myeloma and other M protein diseases - A mixed method study.

OBJECTIVES: To test if Patient Reported Outcomes (PRO) data can replace physical on-site consultation in determining if patients with multiple myeloma, AL amyloidosis, or plasma cell leukemia are ready for their next bortezomib treatment without dose reduction. METHODS: We developed an online questionnaire addressing common side effects to bortezomib and an algorithm stratifying patients according to their responses and asked them to complete the questionnaire the day before attending the clinic. Applying a mixed-method study design of PRO data, time registrations, and interviews with patients and healthcare professionals, we tested the usability of electronic PRO data forming the basis of decision-making on whether patients are physically fit for the next treatment with an unchanged dose. RESULTS: The questionnaire and the associated algorithm were able to identify patients who were physically fit for treatment without need for further consultation, with a positive predictive value of 98 %. The method proved to be feasible for all groups of patients regardless of age and educational level. Patients and healthcare professionals found the online questionnaire to be advantageous and flexible. CONCLUSION: The use of PRO data to evaluate patients prior to bortezomib treatment is safe and feasible. Patients prefer to report their side effects themselves as it provides them with more freedom during their treatment.

Translation and Cross-Cultural Validation of the Danish Version of the Family Health Scale-Long Form: A Psychometric Study.

OBJECTIVES: The Family Health Scale is a new instrument for evaluating family health. The instrument is reported as valid and reliable in investigating family health among different types of adult family members. This study aimed to translate the Family Health Scale into Danish and investigate its validity and reliability in families with a family member affected by chronic or serious illness. DATA SOURCES: Translation was performed through forward and backward bilingual practice consisting of 10 steps. A cross-sectional study included 406 participants, of whom 94 also participated in a follow-up study within 3 weeks for the test-retest. Content validity was examined by conducting cognitive interviews with nine family members. Internal consistency reliability was assessed using Cronbach α. The test-retest reliability was evaluated using intraclass correlation coefficients. Model fit was assessed using confirmatory factor analysis. CONCLUSION: The Family Health Scale demonstrated good content validity and a moderate model fit. Both Internal consistency reliability and test-retest reliability were satisfying. Cronbach α ranged from 0.73 to 0.89, while the intraclass correlation coefficient value was 0.88. The confirmatory factor analysis estimated a satisfying model fit, with an acceptable root-mean-square error of 0.076 and a moderate comparative fit index of 0.794. IMPLICATION FOR NURSING PRACTICE: The Family Health Scale instrument has the potential to identify vulnerable families or families affected by chronic or serious illnesses, such as cancer. The assessment tool can consequently be used to target interventions to promote family health and improve the health of both the individual and his/her family.

HPV Test as Test of Cure After Conization for CIN2+: A Nationwide Register-Based Cohort Study.

OBJECTIVE: The purpose of this study was to assess if cytology can be omitted in the follow-up after treatment for cervical intraepithelial neoplasia grade 2 or worse (CIN2+) and if human papillomavirus (HPV) test can be used alone as test of cure (TOC) after stratifying for resection margins. MATERIAL AND METHODS: In this retrospective register-based study, women who had a conization performed in Denmark between January 1 and December 31, 2013, were included. Histology, cytology, and HPV test results were obtained from The Danish Pathology Data Bank for a 3-year follow-up. RESULTS: A total of 5,174 women were included, of whom 6.1% (318/5,174) had histological residual/recurrent disease in the follow-up period. In the group with free margins, 2.6% (73/2,780) had residual/recurrent disease in contrast to 10.2% (245/2,394) in the group with involved margins. In the group with free resection margins and negative HPV test results, residual/recurrent disease was found in 0.5% (13/2,780) compared with 0.3% (9/2,780) in the group with negative HPV test results and normal cytology at 6 months' follow-up. Based on margin status and HPV test result as follow-up, the sensitivity, specificity, and positive and negative predictive values were 95.9%, 43.2%, 10.0%, and 99.4% respectively, and for combined testing (margin status, HPV, and cytology), 97.2%, 41.2%, 9.8%, and 99.6%, respectively. CONCLUSIONS: Using the HPV test at the first post-treatment control as TOC for cervical intraepithelial neoplasia grade 2 or worse after stratifying for resection margins in cone resections yields an equally high sensitivity and negative predictive value as cotesting with cytology. We suggest that women with free resection margins return to the routine screening program after negative HPV test result as TOC at 6 months.

Can National Registries Contribute to Predict the Risk of Cancer? The Cancer Risk Assessment Model (CRAM).

PURPOSE: To develop a predictive model based on Danish administrative registers to facilitate automated identification of individuals at risk of any type of cancer. METHODS: A nationwide register-based cohort study covering all individuals in Denmark aged +20 years. The outcome was all-type cancer during 2017 excluding nonmelanoma skin cancer. Diagnoses, medication, and contact with general practitioners in the exposure period (2007-2016) were considered for the predictive model. We applied backward selection to all variables by logistic regression to develop a risk model for cancer. We applied the models to the validation cohort, calculated the receiver operating characteristic curves, and estimated the corresponding areas under the curve (AUC). RESULTS: The study population consisted of 4.2 million persons; 32,447 (0.76%) were diagnosed with cancer in 2017. We identified 39 predictive risk factors in women and 42 in men, with age above 30 as the strongest predictor for cancer. Testing the model for cancer risk showed modest accuracy, with an AUC of 0.82 (95% CI 0.81-0.82) for men and 0.75 (95% CI 0.74-0.75) for women. CONCLUSION: We have developed and tested a model for identifying the individual risk of cancer through the use of administrative data. The models need to be further investigated before being applied to clinical practice.

Outcomes in patients with chronic leg wounds in Denmark: A nationwide register-based cohort study.

This study aimed to investigate incidence and predictors of wound healing, relapse, major amputation, and/or death among patients with chronic leg wounds who were referred to specialist treatment at hospital for their condition. A nationwide register-based cohort study design was applied with 5 years of follow-up. All patients with diagnoses of chronic leg wounds in Denmark between 2007 and 2012 were included (n = 8394). Clinical, social, and demographic individual-level linked data from several Danish national registries were retrieved. Incidence rate per 1000 person-years (PY) was calculated. Predictors were investigated using Cox proportional hazards regression analysis. Incidence rates of having a healed wound was 236 per 1000 PY. For relapse, the incidence rate was 75 per 1000 PY, for amputation 16 per 1000 PY, and for death 100 per 1000 PY. Diabetes, peripheral arteria disease, or other comorbidities were associated with decreased chance of wound healing and increased risk of relapse, major amputation, and death. Regional differences in all four outcomes were detected. Basic or vocational education independently predicted risk of amputation and death. This study provides epidemiological data that may help identify patients at particular risk of poor outcomes. It also elucidates social inequality in outcomes.

Association of Socioeconomic Status With Dementia Diagnosis Among Older Adults in Denmark.

Importance: Low socioeconomic status (SES) has been identified as a risk factor for the development of dementia. However, few studies have focused on the association between SES and dementia diagnostic evaluation on a population level. Objective: To investigate whether household income (HHI) is associated with dementia diagnosis and cognitive severity at the time of diagnosis. Design, Setting, and Participants: This population- and register-based cross-sectional study analyzed health, social, and economic data obtained from various Danish national registers. The study population comprised individuals who received a first-time referral for a diagnostic evaluation for dementia to the secondary health care sector of Denmark between January 1, 2017, and December 17, 2018. Dementia-related health data were retrieved from the Danish Quality Database for Dementia. Data analysis was conducted from October 2019 to December 2020. Exposures: Annual HHI (used as a proxy for SES) for 2015 and 2016 was obtained from Statistics Denmark and categorized into upper, middle, and lower tertiles within 5-year interval age groups. Main Outcomes and Measures: Dementia diagnoses (Alzheimer disease, vascular dementia, mixed dementia, dementia with Lewy bodies, Parkinson disease dementia, or other) and cognitive stages at diagnosis (cognitively intact; mild cognitive impairment but not dementia; or mild, moderate, or severe dementia) were retrieved from the database. Univariable and multivariable logistic and linear regressions adjusted for age group, sex, region of residence, household type, period (2017 and 2018), medication type, and medical conditions were analyzed for a possible association between HHI and receipt of dementia diagnosis. Results: Among the 10 191 individuals (mean [SD] age, 75 [10] years; 5476 women [53.7%]) included in the study, 8844 (86.8%) were diagnosed with dementia. Individuals with HHI in the upper tertile compared with those with lower-tertile HHI were less likely to receive a dementia diagnosis after referral (odds ratio, 0.65; 95% CI, 0.55-0.78) and, if diagnosed with dementia, had less severe cognitive stage (ß, -0.16; 95% CI, -0.21 to -0.10). Individuals with middle-tertile HHI did not significantly differ from those with lower-tertile HHI in terms of dementia diagnosis (odds ratio, 0.92; 95% CI, 0.77-1.09) and cognitive stage at diagnosis (ß, 0.01; 95% CI, -0.04 to 0.06). Conclusions and Relevance: The results of this study revealed a social inequality in dementia diagnostic evaluation: in Denmark, people with higher income seem to receive an earlier diagnosis. Public health strategies should target people with lower SES for earlier dementia detection and intervention.

Validation of the Fracture Risk Evaluation Model (FREM) in predicting major osteoporotic fractures and hip fractures using administrative health data.

BACKGROUND: Prevention of osteoporotic fractures remains largely insufficient, and effective means to identify patients at high, short-term fracture risk are needed. The FREM tool is available for automated case finding of men and women aged 45 years or older at high imminent (1-year) risk of osteoporotic fractures, based on administrative health data with a 15-year look-back. The aim of this study was to validate the performance of FREM, and the effect of applying a shorter look-back period. We also evaluated FREM for 5-year fracture risk prediction. METHODS: Using Danish national health registers we generated consecutive general population cohorts for the years 2014 through 2018. Within each year and across the full time period we estimated the individual fracture risk scores and determined the actual occurrence of major osteoporotic fractures (MOF) and hip fractures. Risk scores were calculated with 15- and 5-year look-back periods. The discriminative ability was evaluated by area under the receiver operating curve (AUC), and negative predictive value (NPV) and positive predictive value (PPV) were estimated applying a calculated risk cut-off of 2% for MOF and 0.3% for hip fractures. RESULTS: Applying a 15-year look-back, AUC was around 0.75-0.76 for MOF and 0.84-0.87 for hip fractures in 2014, with minor decreases in the subsequent fracture cohorts (2015 to 2018). Applying a 5-year look-back generated similar results, with only marginally lower AUC. In the 5-year risk prediction setting, AUC-values were 0.70-0.72 for MOF and 0.81-0.84 for hip fractures. Generally, PPVs were low, while NPVs were very high. CONCLUSION: FREM predicts the 1- and 5-year risk of MOF and hip fractures with acceptable vs excellent discriminative power, respectively, when applying both a 15- and a 5-year look-back. Hence, the FREM tool may be applied to improve identification of individuals at high imminent risk of fractures using administrative health data.

The effect of compression therapy on post-surgical swelling and pain after total knee arthroplasty.

BACKGROUND: We hypothesized that the use of a graduated medical elastic thigh compression stocking for 14 days after total knee arthroplasty would reduce swelling by 2 cm and reduce pain among patients with a BMI ≥30 kg/m2. The aim of this pilot study was to provide preliminary data and information about feasibility. The specified objectives were to investigate: 1) the level of post-surgical swelling and, 2) the level of post-surgical pain, 14 days after surgery. METHODS: In a randomized controlled pilot study, 44 patients were allocated to a graduated medical elastic thigh compression stocking or standard treatment for 14 days after total knee arthroplasty. Outcome measures were knee, calf, and ankle swelling and pain. Study feasibility included acceptable rates of written consent and compliance with the use of the compression stocking. Data was analyzed using two-sample t-test for equality of mean. RESULTS: Overall, 68.8% of eligible patients gave written consent to participate in the study and 41.2% complied with use of the graduated medical elastic thigh compression stocking for 14 days post-surgery. No significant difference was found between the groups regarding knee, calf and ankle swelling or pain. INTERPRETATION: Knee swelling was reduced in both groups after 14 days, but was slightly more in the intervention group. The result is not statistically significant but indicates that a graduated medical elastic thigh compression stocking may have a positive effect on reduction of swelling after total knee arthroplasty. Initiating a larger scale randomized controlled study to determine effectiveness requires a higher level of compliance.

Clinical Evaluation of Scar Quality Following the Use of Prophylactic Negative Pressure Wound Therapy in Obese Women Undergoing Cesarean Delivery: A Trial-Based Scar Evaluation.

OBJECTIVE: To evaluate the cosmetic result of using incisional negative-pressure wound therapy (iNPWT) compared with standard postsurgical dressings in obese women undergoing cesarean delivery (CD). METHODS: Postcesarean scars were objectively evaluated 6 and 12 months postsurgery by a plastic surgeon using the Manchester Scar Scale and the Stony Brook Scar Evaluation Scale. Subjective scar evaluation and health-related quality of life were assessed using the Patient Scar Assessment Scale and the EQ-5D-5L instrument, respectively. Main outcome measures were the cosmetic and functional outcome of treating a standardized surgical wound with iNPWT compared with standard dressings, changes in scar rating over time, and testing different scar scales for cosmetic evaluation. RESULTS: The study found no difference in long-term cosmetic outcomes between iNPWT and standard dressings. The study demonstrated a statistically significant positive change in scar rating from surgery to 12 months postsurgery. A strong association was found between the scar scales with a high correlation between the objective scar scales (R approximately 0.80) and a moderate correlation between the subjective scale and each objective scale (R approximately 0.50). CONCLUSIONS: Prophylactic iNPWT has been found to reduce the risk of surgical site infection following CD. Conversely, this study was not able to detect a difference in the long-term cosmetic result after CD when compared with standard dressings.

Differences in Current Procedures for Handling of Expressed Mother's Milk in Danish Neonatal Care Units.

BACKGROUND: Mother's own milk (MOM) is preferred when feeding preterm infants. When expressed mother's milk is stored and handled, there is a risk of bacterial contamination, decreased immunological activity, and less nutritional potential. PURPOSE: The aim of this study was to investigate current routines when handling MOM in Danish neonatal intensive care units (NICUs). METHODS: A survey was sent to all 17 NICUs in Denmark in which current practices regarding human milk handling, storage, and preparation were evaluated. Furthermore, one question sought to establish when mother's milk was believed to be colostrum. Respondents of the survey were neonatal nurses. RESULTS: All 17 units responded to the survey. Only 5 of 17 units answered that human colostrum was defined as milk from the first week after birth. Refrigerator storage time varied between 24 and 72 hours. In 6 of 17 units, parents were in charge of mixing milk and fortifier. Heating of human milk was done by using microwave ovens in 4 of 17 of the units. IMPLICATIONS FOR PRACTICE: This national survey established that there is significant variability in the way mother's milk is handled. Some of the procedures performed may affect the quality of the milk. It is important to implement evidence-based practice regarding storage and handling of expressed mother's milk to ensure that the quality of the milk is the best possible alternative for all preterm infants. IMPLICATIONS FOR RESEARCH: Prospective studies are needed to examine the association between handling of human milk and changes in composition and nutritional potential of the milk.

FortiColos - a multicentre study using bovine colostrum as a fortifier to human milk in very preterm infants: study protocol for a randomised controlled pilot trial.

BACKGROUND: Very preterm infants (< 32 weeks gestation) have a relatively high nutrient requirement for growth and development. The composition of human milk is often inadequate to ensure optimal growth so it is common to fortify human milk for very preterm infants with nutrient fortifiers based on bovine milk. However, there are concerns that bovine milk-based fortifiers may increase the risk of feeding intolerance, necrotizing enterocolitis and late-onset sepsis. We hypothesize that a bovine colostrum-based product is a suitable alternative to bovine milk-based products when used as a fortifier to human milk in very preterm infants. METHODS/DESIGN: In an open-label multicentre randomised controlled pilot trial, 200 very preterm infants (26 + 0 to 30 + 6 weeks gestation at birth) will be randomly allocated to a bovine colostrum-based or a bovine milk-based fortifier added to mother's own milk and/or human donor milk. Outcomes are growth rate, incidence of necrotizing enterocolitis and late-onset sepsis, a series of paraclinical endpoints, and practical feasibility of using the novel fortifier for very preterm infants. DISCUSSION: The optimal enteral diet and feeding regimen for very preterm infants remain debated; this clinical trial will document the feasibility, safety and preliminary efficacy of using bovine colostrum, rich in nutrients and bioactive factors, as a novel fortifier for human milk to very preterm infants. Data on infant growth, metabolism, gut function and immunity will be assessed from clinical data as well as blood and stool samples. TRIAL REGISTRATION: Registered retrospectively 25 May 2018 at ClinicalTrials.gov: NCT03537365 .

Impact of Early Exposure to Cefuroxime on the Composition of the Gut Microbiota in Infants Following Cesarean Delivery.

OBJECTIVES: To assess in mothers giving birth by cesarean delivery if prophylactic antibiotics administered either before skin incision or immediately after cutting the umbilical cord influences gut microbiota colonization and antibiotic susceptibility of the gut bacteria in the newborn. STUDY DESIGN: Forty-two pregnant women scheduled for elective cesarean delivery were recruited at Odense University Hospital, Denmark, and randomly assigned to receive cefuroxime either before skin incision or immediately after the umbilical cord was cut. Fecal samples were collected from all infants at age 10 days and 9 months. Composition of the gut microbiota was determined by 16S ribosomal RNA gene amplicon high-throughput sequencing. Gram-positive cocci and Enterobacteriaceae were isolated and identified before antimicrobial susceptibility tests were performed by disk diffusion. RESULTS: No clear difference in the composition of the gut microbiota was observed between infants whose mothers received cefuroxime before or after cesarean delivery at neither time point, though surprisingly at 9 months of age, but not at 10 days of age, the number of observed species was higher in infants where mothers received cefuroxime after cord clamping. No differences in antimicrobial susceptibility of Enterobacteriaceae, Enterococcus spp, and Staphylococcus spp were seen at 10 days. CONCLUSIONS: Timing of cefuroxime administration to mothers undergoing cesarean delivery does not have a major effect on the gut microbiota and bacterial antibiotic resistance traits in infants. TRIAL REGISTRATION: Clinicaltrials.gov: NCT02072798.

Correction to: Prevention of seroma following inguinal lymph node dissection with prophylactic, incisional, negative-pressure wound therapy (SEROMA trial): study protocol for a randomized controlled trial.

Following publication of the original article [1], the authors reported that one of the authors' names is spelled incorrectly. In this Correction the incorrect and correct author name are shown. The original publication of this article has been corrected.

Prevention of seroma following inguinal lymph node dissection with prophylactic, incisional, negative-pressure wound therapy (SEROMA trial): study protocol for a randomized controlled trial.

BACKGROUND: Radical inguinal lymphadenectomy (ILND) for metastatic melanoma is associated with a high complication rate. Seroma is often the first postoperative complication, followed by prolonged wound healing sometimes requiring reoperation, infection, multiple outpatient visits and re-hospitalization. Prevention of seroma may, therefore, lead to a reduction in many of the other complications. METHODS/DESIGN: The primary aim of this randomized study is to investigate whether fewer patients require treatment for seroma by immediate prophylactic application of incisional, Negative-pressure Wound Therapy (iNPWT) following ILND, compared to standard postoperative treatment. The secondary outcomes include surgical-site infection, dehiscence, hematoma, length of hospitalization, quality of life, safety, long-term assessment of lymphedema and non-inferiority oncological outcome. Data will be registered prospectively at check-ups after 7 and 14 days, 1 and 3 months and 2 years after inguinal lymphadenectomy using case report forms and questionnaires and stored in a secure online database. DISCUSSION: To our knowledge, this trial is the first randomized study evaluating negative-pressure wound therapy as a prophylactic intervention for complications following melanoma-related ILND. The results from this trial will hopefully determine the efficacy and safety of prophylactic iNPWT treatment in prevention of the clinical relevant short- and long-term postoperative complications following ILND and may provide an evidence base for the an improved postoperative regimen. TRIAL REGISTRATION: ClinicalTrials.gov, ID: NCT03433937 . Prospectively registered on 15 February 2018.