Assessing the Accuracy of Estimated Lipoprotein(a) Cholesterol and Lipoprotein(a)‐Free Low‐Density Lipoprotein Cholesterol

Background Accurate measurement of the cholesterol within lipoprotein(a) (Lp[a]‐C) and its contribution to low‐density lipoprotein cholesterol (LDL‐C) has important implications for risk assessment, diagnosis, and treatment of atherosclerotic cardiovascular disease, as well as in familial hypercholesterolemia. A method for estimating Lp(a)‐C from particle number using fixed conversion factors has been proposed (Lp[a]‐C from particle number divided by 2.4 for Lp(a) mass, multiplied by 30% for Lp[a]‐C). The accuracy of this method, which theoretically can isolate “Lp(a)‐free LDL‐C,” has not been validated. Methods and Results In 177 875 patients from the VLDbL (Very Large Database of Lipids), we compared estimated Lp(a)‐C and Lp(a)‐free LDL‐C with measured values and quantified absolute and percent error. We compared findings with an analogous data set from the Mayo Clinic Laboratory. Error in estimated Lp(a)‐C and Lp(a)‐free LDL‐C increased with higher Lp(a)‐C values. Median error for estimated Lp(a)‐C <10 mg/dL was −1.9 mg/dL (interquartile range, −4.0 to 0.2); this error increased linearly, overestimating by +30.8 mg/dL (interquartile range, 26.1–36.5) for estimated Lp(a)‐C ≥50 mg/dL. This error relationship persisted after stratification by overall high‐density lipoprotein cholesterol and high‐density lipoprotein cholesterol subtypes. Similar findings were observed in the Mayo cohort. Absolute error for Lp(a)‐free LDL‐C was +2.4 (interquartile range, −0.6 to 5.3) for Lp(a)‐C<10 mg/dL and −31.8 (interquartile range, −37.8 to −26.5) mg/dL for Lp(a)‐C≥50 mg/dL. Conclusions Lp(a)‐C estimations using fixed conversion factors overestimated Lp(a)‐C and subsequently underestimated Lp(a)‐free LDL‐C, especially at clinically relevant Lp(a) values. Application of inaccurate Lp(a)‐C estimations to correct LDL‐C may lead to undertreatment of high‐risk patients.

Adjuvant Capecitabine for Early Breast Cancer: 15-Year Overall Survival Results From a Randomized Trial

PURPOSE Few data are available regarding the influence of adjuvant capecitabine on long-term survival of patients with early breast cancer. METHODS The Finland Capecitabine Trial (FinXX) is a randomized, open-label, multicenter trial that evaluates integration of capecitabine to an adjuvant chemotherapy regimen containing a taxane and an anthracycline for the treatment of early breast cancer. Between January 27, 2004, and May 29, 2007, 1,500 patients with axillary node-positive or high-risk node-negative early breast cancer were accrued. The patients were randomly allocated to either TX-CEX, consisting of three cycles of docetaxel (T) plus capecitabine (X) followed by three cycles of cyclophosphamide, epirubicin, and capecitabine (CEX, 753 patients), or to T-CEF, consisting of three cycles of docetaxel followed by three cycles of cyclophosphamide, epirubicin, and fluorouracil (CEF, 747 patients). We performed a protocol-scheduled analysis of overall survival on the basis of approximately 15-year follow-up of the patients. RESULTS The data collection was locked on December 31, 2020. By this date, the median follow-up time of the patients alive was 15.3 years (interquartile range, 14.5-16.1 years) in the TX-CEX group and 15.4 years (interquartile range, 14.8-16.0 years) in the T-CEF group. Patients assigned to TX-CEX survived longer than those assigned to T-CEF (hazard ratio 0.81; 95% CI, 0.66 to 0.99; P = .037). The 15-year survival rate was 77.6% in the TX-CEX group and 73.3% in the T-CEF group. In exploratory subgroup analyses, patients with estrogen receptor–negative cancer and those with triple-negative cancer treated with TX-CEX tended to live longer than those treated with T-CEF. CONCLUSION Addition of capecitabine to a chemotherapy regimen that contained docetaxel, epirubicin, and cyclophosphamide prolonged the survival of patients with early breast cancer.

Patient-Reported Outcome-Based Symptom Management Versus Usual Care After Lung Cancer Surgery: A Multicenter Randomized Controlled Trial

PURPOSE We aimed to evaluate the efficacy and feasibility of patient-reported outcome (PRO)-based symptom management in the early period after lung cancer surgery. METHODS Before surgery, patients with clinically diagnosed lung cancer were randomly assigned 1:1 to receive postoperative PRO-based symptom management or usual care. All patients reported symptoms on MD Anderson Symptom Inventory-Lung Cancer presurgery, daily postsurgery, and twice a week after discharge for up to 4 weeks via an electronic PRO system. In the intervention group, treating surgeons responded to overthreshold electronic alerts driven by any of the five target symptom scores (score ≥ 4 on a 0-10 scale for pain, fatigue, disturbed sleep, shortness of breath, and coughing). The control group patients received usual care and no alerts were generated. The primary outcome was the number of symptom threshold events (any target symptom with a score of ≥ 4) at discharge. Per-protocol analyses were conducted. RESULTS Of the 166 participants, 83 were randomly allocated to each group. At discharge, the intervention group reported fewer symptom threshold events than the control group (median [interquartile range], 0 [0-2] v 2 [0-3]; P = .007). At 4 weeks postdischarge, this difference was maintained between the intervention and control groups (median [interquartile range], 0 [0-0] v 0 [0-1]; P = .018). The intervention group had a lower complication rate than the control group (21.5% v 40.6%; P = .019). Surgeons spent a median of 3 minutes managing an alert. CONCLUSION PRO-based symptom management after lung cancer surgery showed lower symptom burden and fewer complications than usual care for up to 4 weeks postdischarge.

Sex Differences in Factors Associated With Progression of Aortic Valve Calcification in the General Population

Background: Guidelines recommend measurement of the aortic valve calcification (AVC) score to help differentiate between severe and nonsevere aortic stenosis, but a paucity exists in data about AVC in the general population. The aim of this study was to describe the natural history of AVC progression in the general population and to identify potential sex differences in factors associated with this progression rate. Methods: Noncontrast cardiac computed tomography was performed in 1298 randomly selected women and men aged 65 to 74 years who participated in the DANCAVAS trial (Danish Cardiovascular Screening). Participants were invited to attend a reexamination after 4 years. The AVC score was measured at the computed tomography, and AVC progression (ΔAVC) was defined as the difference between AVC scores at baseline and follow-up. Multivariable regression analyses were performed to identify factors associated with ΔAVC. Results: Among the 1298 invited citizens, 823 accepted to participate in the follow-up examination. The mean age at follow-up was 73 years. Men had significantly higher AVC scores at baseline (median AVC score 13 Agatston Units [AU; interquartile range, 0–94 AU] versus 1 AU [interquartile range, 0–22 AU], P <0.001) and a higher ΔAVC (median 26 AU [interquartile range, 0–101 AU] versus 4 AU [interquartile range, 0–37 AU], P <0.001) than women. In the fully adjusted model, the most important factor associated with ΔAVC was the baseline AVC score. However, hypertension was associated with ΔAVC in women (incidence rate ratios, 1.58 [95% CI, 1.06–2.34], P =0.024) but not in men, whereas dyslipidemia was associated with ΔAVC in men (incidence rate ratio: 1.66 [95% CI, 1.18–2.34], P =0.004) but not in women. Conclusions: The magnitude of the AVC score was the most important marker of AVC progression. However, sex differences were significant; hence, dyslipidemia was associated with AVC progression only among men; hypertension with AVC progression only among women. REGISTRATION: URL: https://www.isrctn.com ; Unique identifier: ISRCTN12157806.

LYMPHEDEMA DURATION AS A PREDICTIVE FACTOR OF EFFICACY OF COMPLETE DECONGESTIVE THERAPY

Lymphedema is a common condition with global impact and a multitude of complications, however, only a few professionals specialize in its management. A retrospective analysis of 105 subjects with unilateral lymphedema upper or lower limb was performed to investigate whether the duration of lymphedema constitutes an important factor associated with the efficacy of complete decongestive therapy (CDT). Subjects were classified into two groups according to the duration of lymphedema, prior to CDT: group A (≤1 year) and group B (>1 year). Both groups were treated daily according to the same CDT protocol for four weeks. The CDT efficacy was determined based on the percent reduction of excess volume (PREV) measurements. Lymphedema was significantly reduced in both groups of subjects, but significantly more in group A (p<0.001). In subjects with upper limb lymphedema, median value of PREV was 80.8% (interquartile range, 79.1-105.0%) in group A and 62.0% (interquartile range, 56.7-66.5%) in group B (p<0.001). In subjects with lower limb lymphedema PREV was 80.7% (interquartile range, 74.9-85.2%) and 64.5% (interquartile range, 56.0-68.1%) for groups A and B, respectively (p<0.001). Duration of lymphedema was found to be a strong predictive factor that may significantly impact CDT efficacy. Therapeutic effects were increased in subjects who were detected and treated earlier for lymphedema.

Preoperative serum C-reactive protein concentration can be used to detect gallbladder rupture in dogs with gallbladder mucocele

OBJECTIVE To determine whether serum C-reactive protein (CRP) concentration could be used to detect gallbladder rupture (GBR) prior to surgery in dogs undergoing cholecystectomy for treatment of gallbladder mucocele (GBM). ANIMALS 45 dogs that underwent cholecystectomy because of GBM at a companion animal referral hospital from 2017 to 2020. PROCEDURES Electronic medical records were reviewed, and dogs were included if serum CRP concentration had been measured within 24 hours prior to cholecystectomy. Dogs were grouped as to whether the gallbladder was found to be ruptured or intact during surgery. Accuracy of using preoperative CRP concentration to predict GBR was compared with accuracy of abdominal ultrasonography and other preoperative blood tests. RESULTS GBR was present in 15 dogs at the time of surgery. Median preoperative CRP concentration was significantly higher in dogs with GBR (15.1 mg/dL; interquartile range, 7.4 to 16.8 mg/dL) than in dogs with an intact gallbladder (2.65 mg/dL; interquartile range, 0.97 to 13.4 mg/dL). Sensitivity, specificity, and accuracy of using preoperative CRP concentration to predict GBR were 100%, 67%, and 78%, respectively. CLINICAL RELEVANCE Measurement of preoperative CRP concentration provided excellent sensitivity and moderate specificity for detection of GBR in dogs undergoing cholecystectomy because of GBM. Accuracy of using preoperative CRP concentration for detection of GBR was not superior to the accuracy of preoperative abdominal ultrasonography. However, when CRP concentration was combined with results of ultrasonography, the sensitivity, specificity, and accuracy for detection of GBR were 100%, 93%, and 96%, respectively.

Safety of immediate use of totally implantable venous access ports in adult patients with cancer: a retrospective single-center study

Purpose: Totally implantable venous access ports (TIVAPs) can be used long-term for safe administration of intravenous drugs. TIVAP complications include catheter-related infections, venous thrombosis, extravasation, TIVAP migration, and pain. The relationship between the timing of the first chemotherapy administration after port implantation and complications is controversial. This study aimed to investigate the safety of immediate use of TIVAPs and the associated risk factors for complications.Methods: Between January 2016 and December 2018, 305 patients (median age, 53 years; 256 women) who underwent TIVAP placement at our institution were included. Chemotherapy was administered within 2 days of implantation. A retrospective analysis of patients’ clinical data was performed to investigate catheter days and complications of TIVAPs.Results: Overall, 305 patients were evaluated over 57,324 catheter days (median, 168 catheter days; interquartile range, 105). The median interval between placement and first use of TIVAPs was 0.98 days. The overall morbidity rate was 2.95%. Nine complications occurred in nine patients, including TIVAP-related infection (4), pain (2), port occlusion (1), thrombosis (1), and scar disunion (1), of which five required port removal (1.64%). The median number of catheter days before complications occurred was 61 (range, 10–457 days; interquartile range, 51). No complications occurred within 7 days of implantation. Body mass index was an independent risk factor for TIVAP-related complications in the Cox proportional hazards model (multivariable analysis: hazard ratio, 1.221; 95% confidence interval, 1.054–1.414; P = 0.008).Conclusion: This study suggests the safe long-term use of TIVAPs following their immediate chemotherapy administration within 2 days of implantation.

Surgery Versus Radiofrequency Ablation for Small Hepatocellular Carcinoma: a Randomized Controlled Trial (SURF-Trial)

Introduction: It remains unclear which of surgery or radiofrequency ablation (RFA) is the more effective treatment for small hepatocellular carcinoma (HCC). We aimed to compare survival between patients undergoing surgery (surgery group) and patients undergoing RFA (RFA group). Methods: We conducted a randomized controlled trial involving 49 institutions in Japan. Patients with Child-Pugh scores ≤ 7, largest HCC diameter ≤ 3 cm, and ≤ 3 HCC nodules were considered eligible. The co-primary endpoints were recurrence-free survival (RFS) and overall survival (OS). The current study reports the final result of RFS, and the follow-up of OS is still ongoing. Results: During 2009–2015, 308 patients were registered. After excluding ineligible patients, the surgery and RFA groups included 150 and 151 patients, respectively. Baseline factors did not differ significantly between the groups. In both groups, 90% of patients had solitary HCC. The median largest HCC diameter was 1.8 cm (interquartile range, 1.5–2.2 cm) in the surgery group and 1.8 cm (interquartile range, 1.5–2.3 cm) in the RFA group. The median procedure duration (274 versus 40 minutes, P<0.01) and the median duration of hospital stay (17 days versus 10 days, P<0.01) were longer in the surgery group than in the RFA group. RFS did not differ significantly between the groups as the median RFS was 3.5 (95% confidence interval [CI], 2.6–5.1) years in the surgery group and 3.0 (95% CI, 2.4–5.6) years in the RFA group (hazard ratio, 0.92; 95% CI, 0.67–1.25; P=0.58). Discussion/Conclusion: Our study did not show which of surgery or RFA is the better treatment option for small HCC.

Georeferencing of COVID-19 Positive Nasopharyngeal Swabs to Support Emergency Management in an Area of Northern Italy

Spatial distribution heterogeneity of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has been observed in several countries. While previous studies have covered vast geographic areas, detailed analyses on smaller territories are not available to date. The aim of our study was to understand the spatial spread of SARS-CoV-2 in a province of Northern Italy through the analysis of positive nasopharyngeal (NP) swabs. The study was conducted on subjects who lived in the province of Alessandria with at least one positive NP swab between 2 March and 22 December 2020. To investigate if clustering occurred, the proportion of SARS-CoV-2 positive subjects over the total number of residents in each small administrative subregion was calculated and then mapped. A total of 17,260 subjects with at least one positive NP swab were included; the median age was 54 years (Interquartile range 38–72) and 54.9% (n = 9478) of our study population were female. Among the 192 towns scanned, 26 showed a prevalence between 5% and 7.5%, one between 7.5% and 10% and two with more than 10% positive swabs. The territories with a higher prevalence of positive subjects were located in areas with at least one nursing home and potential clusters were observed within these structures. The maps produced may be considered a useful and important monitoring system to identify areas with a significant and relevant diffusion of SARS-CoV-2.

The Diet of Children Attending a Holiday Programme in the UK: Adherence to UK Food-Based Dietary Guidelines and School Food Standards

Child poverty rates are rising, particularly in London, putting more children at risk of experiencing food insecurity. Holiday programmes in the UK provide children who receive free schools meals during term time with access to free/low-cost holiday clubs offering nutritious food and enriching activities during the school holidays. This study aimed to investigate whether children’s dietary intake was more adherent to the UK Eatwell Guide throughout the day and meets School Food Standards (SFS) for the lunchtime meal on a club attendance versus a non-attendance day. A repeated measures design was used to assess data on the food and drink intake of children (n = 57) aged 7–16 years old using a 24 h recall method on two separate occasions: once based on an attending club day and once based on a non-attending club day. The results showed children’s diet quality improved (p = 0.007) on an attending club day (mean: 58.0 ± SD 12.6) versus a non-attending club day (51.8 ± 15.0). Children also more closely adhered to the SFS (p = 0.001) on an attending club day (median = 9, interquartile range = 8–9) versus a non-attending club day (median = 7, interquartile range = 6–8). This suggests that holiday programmes targeting children who receive free school meals during term time have the potential to improve children’s dietary behaviours during the school holidays, underlining the importance of holiday programmes to support food security.