Learning and implementation of TransREctus sheath PrePeritoneal procedure for inguinal hernia repair.

PURPOSE: The TransREctus sheath PrePeritoneal procedure (TREPP) was introduced as an alternative open and preperitoneal technique for inguinal hernia mesh repair, demonstrating safety and efficacy in retro- and prospective studies. However, little is known about the technique's inherent learning curve. In this study, we aimed to determine TREPP learning curve effects after its implementation in high-volume surgical practice. METHODS: All primary, unilateral TREPP procedures performed in the first three years after implementation (between January 2016 and December 2018) were included out of a large preconstructed regional inguinal hernia database. Data were analyzed on outcome (i.e., surgical complications, hernia recurrences, postoperative pain). Learning curve effects were analyzed by assessing outcome in relation to surgeon experience. RESULTS: In total, 422 primary, unilateral TREPP procedures were performed in 419 patients. In three patients a unilateral TREPP procedure was performed on both sides separated in time. A total of 99 surgical complications were registered in 83 procedures (19.6% of all procedures), most commonly inguinal postoperative pain (8%) and bleeding complications (7%). Hernia recurrences were observed in 17 patients (4%). No statistically significant differences on outcome were found between different surgeon experience (< 40 procedures, 40-80 procedures, > 80 procedures). CONCLUSION: Implementation of TREPP seems not to be associated with a notable increase of adverse events. We were not able to detect a clear learning curve limit, potentially suggesting a relatively short learning curve among already experienced hernia surgeons compared to other guideline techniques.

High prevalence of peripheral neuropathy in multiple myeloma patients and the impact of vitamin D levels, a cross-sectional study.

PURPOSE: Peripheral neuropathy (PN) is common in patients with multiple myeloma (MM). We hypothesized that the relationship between hypovitaminosis D and PN described in diabetes mellitus patients may also be present in MM patients. METHODS: To study this potential association, we assessed the incidence of hypovitaminosis D (vitamin D < 75 nmol/L [= 30 ng/mL]) in smouldering and active MM patients in two Dutch hospitals. Furthermore, a validated questionnaire was used to distinguish different PN grades. RESULTS: Of the 120 patients included between January 2017 and August 2018, 84% had an inadequate vitamin D level (median vitamin D level 49.5 nmol/L [IQR 34-65 nmol/L]; mean age: 68 years [SD ± 7.7]; males: 58%). PN was reported by 69% of patients (n = 83); however, of these 83 patients, PN was not documented in the medical records of 52%. An association was found between lower vitamin D levels and higher incidence of PN in the total population (P = 0.035), and in the active MM patients (P = 0.016). CONCLUSION: This multi-centre cohort study showed that PN and hypovitaminosis D are common in MM patients, and addressing low vitamin D levels in the treatment of MM patients might be beneficial in reducing the risk of PN. More attention for PN is warranted, as PN is underreported by clinicians. Further research is needed to fully understand the implications of vitamin D in the development of PN in patients with MM. CLINICAL TRIAL REGISTRATION: Netherland Trial Register NL5835, date of registration July 28, 2016.

Transrectus sheath pre-peritoneal (TREPP) procedure versus totally extraperitoneal (TEP) procedure and Lichtenstein technique: a propensity-score-matched analysis in Dutch high-volume regional hospitals.

PURPOSE: Results of the most commonly used inguinal hernia repair techniques often originate from expert centers or from randomized controlled studies. In this study, we portray daily-practice results of a high-volume, regional surgical group in the Netherlands, comparing TREPP (open (posterior) transrectus sheath pre-peritoneal) with Lichtenstein (open anterior) and TEP (endoscopic (posterior) totally extraperitoneal). We hypothesize that the TREPP shows more favorable outcome compared to the current gold standard procedures: TEP and Lichtenstein. METHODS: Between January 2016 and December 2018, 3285 consecutive patients underwent surgical treatment and were included for analysis. The outcome measures were postoperative pain, recurrence rate and other surgical complications. Propensity-score matching was used to address potential selection bias. RESULTS: After propensity-score matching, there was no statistically significant difference in postoperative pain in the TREPP group compared to the Lichtenstein group (TREPP 7.3% versus Lichtenstein 6.3%; p = 0.67) nor in TREPP compared to TEP (TREPP 7.4% versus TEP 4.1%; p = 0.064). There was no statistically significant difference in recurrences in the TREPP group compared to Lichtenstein (3.8% vs 2.5%; p = 0.42), nor in the TREPP versus TEP comparison (3.9% vs 2.8%; p = 0.55) CONCLUSION: This study compares TREPP with Lichtenstein and TEP in the presence of postoperative pain, recurrences and other adverse outcomes. After propensity-score matching, no statistically significant difference in postoperative pain or recurrences remained between either TREPP compared to Lichtenstein, or TREPP compared to TEP. Based on these results, TREPP, Lichtenstein and TEP showed comparable results in postoperative pain, recurrences and other surgical site complications.

More precise dosing of acenocoumarol for better control in patients aged above 80 years, a randomised controlled pilot study.

INTRODUCTION: Many elderly patients are confined to treatment with vitamin K antagonists (VKA) instead of direct oral anticoagulants (DOACs). However, quality of VKA treatment declines with age. This might be caused by the lower dose requirements with increasing age, which result in relatively large day-by-day VKA dose differences. Therefore, more precise dosing with smaller dose increments might improve quality of VKA treatment in the elderly. METHODS: We randomised 80 elderly patients (≥80 years, using 0.5-2 mg acenocoumarol daily) to either conventional dosing with 1.0 mg acenocoumarol increments, or more precise dosing with 0.5 mg increments, to assess effect sizes and feasibility of a larger trial. We compared changes in the time in therapeutic range (TTR), INR variability and anticoagulation-related quality of life (measured with the PACT-Q) between treatment groups. RESULTS: Overall, baseline TTR was 61.3 ± 19.2. After six study months, TTR had improved to 69.5 ± 19.7 in the precise dosing group versus 67.7 ± 21.2 in the conventional dosing group (absolute difference 3.4 (95% CI -6.7 to 13.6)). The between-groups difference in INR variability was not assessed because of baseline differences. PACT-Q convenience declined slightly with more precise dosing, compared with conventional dosing: 2.1/100 (95% CI 0.5-3.7). Satisfaction decreased equally in both groups with -6.4 ± 8.6/100. Four dosing errors occurred: three with precise and one with conventional dosing. CONCLUSION: Although more precise dosing of acenocoumarol leads to a slightly higher TTR, this effect is too small to convey a relevant clinical benefit and could be abolished by the increased risk of medication errors.

Bridging the gap between the randomised clinical trial world and the real world by combination of population-based registry and electronic health record data: A case study in haemato-oncology.

Randomised clinical trials (RCTs) are considered the basis of evidence-based medicine. It is recognised more and more that application of RCT results in daily practice of clinical decision-making is limited because the RCT world does not correspond with the clinical real world. Recent strategies aiming at substitution of RCT databases by improved population-based registries (PBRs) or by improved electronic health record (EHR) systems to provide significant data for clinical science are discussed. A novel approach exemplified by the HemoBase haemato-oncology project is presented. In this approach, a PBR is combined with an advanced EHR, providing high-quality data for observational studies and support of best practice development. This PBR + EHR approach opens a perspective on randomised registry trials.

The impact of a male or female thrombotic family history on contraceptive counseling: a cohort study.

UNLABELLED: Essentials It is unknown if a male or female thrombotic family history influences risk in female relatives. We assessed thrombotic risk in female relatives of male and female patients with thrombosis. A hormonally related female thrombotic family history further increases risk in female relatives. This information could be important in counseling women on contraceptive options. Click to hear Prof. Rosendaal's perspective on venous thrombosis: etiology, pathogenesis, and prognosis SUMMARY: Background Women from thrombophilic families have increased risk of venous thromboembolism (VTE), which increases further during oral contraceptive (COC) use and pregnancy-postpartum. Whether this additional risk differs between relatives of male and female patients, or is different when that female patient had a hormonally related VTE (during COC use/pregnancy), is unknown. Methods One thousand five female relatives of consecutive patients with VTE from a family-based cohort were retrospectively followed for incident VTE from ages 15 to 50, first VTE, or study inclusion. Absolute and relative VTE risks adjusted for factors of patients (sex, age) and relatives (thrombophilia, COC use, pregnancy) were estimated in relatives of female and male patients and in relatives of female patients with and without hormonally related VTE. Results Absolute risk in relatives of female (0.32 [95% confidence interval [CI] 0.23-0.43]) vs. male patients (0.39 [95% CI 0.28-0.53]) was comparable. However, the heterogeneity analysis of risk estimates suggested that in relatives of female vs. male patients, the contribution of pregnancy-postpartum (hazard ratio [HR] 11.6 [95% CI 6.3-21.3] vs. HR6.6 [95% CI 2.8-15.2]) and, to a lesser extent, COC use (HR3.6 [95% CI 1.8-7.1] vs. HR2.7 [95% CI 1.5-5.0]) to the VTE risk differs. Absolute risk was significantly higher in relatives of female patients with hormonally related VTE (0.43 [95% CI 0.3-0.6]) vs. relatives of female patients without hormonally related VTE (0.13 [95% CI 0.05-0.27]), HR3.28 [95% CI 1.5-7.9]). The higher contribution of pregnancy-postpartum and COC use to the VTE risk was mainly observed in relatives of patients with hormonally related VTE. Conclusions These findings suggest that a family history from a female patient, especially when VTE was hormonally related, may further increase VTE risk in her female relatives. This information could be important in counseling women on contraceptive options.

¹8F-FDG PET/CT in inflammation of unknown origin: a cost-effectiveness pilot-study.

PURPOSE: Patients with increased inflammatory parameters, nonspecific signs and symptoms without fever and without a diagnosis after a variety of diagnostic procedures are a diagnostic dilemma and are referred to as having inflammation of unknown origin (IUO). The objective of this pilot study was to compare the cost-effectiveness of a diagnostic work-up/strategy with and without (18)F-FDG PET/CT in patients with IUO using a published dataset as a reference. METHODS: IUO patients without (18)F-FDG PET/CT (group A, 46 patients) and IUO patients referred for (18)F-FDG PET/CT (group B, 46 patients) were selected. IUO was defined as the combination of nonspecific signs and symptoms and a prolonged erythrocyte sedimentation rate (ESR), defined as ≥age/2 in men and ≥(age + 10)/2 in women (ESR in millimetres per hour and age in years), and/or C-reactive protein (CRP) ≥15 mg/l. The costs of all tests and procedures and the number of hospitalization days in each patient to reach a diagnosis were calculated using current Dutch tariffs. RESULTS: In group A a diagnosis was reached in 14 of the 46 patients. The mean cost per patient of all the diagnostic procedures was 2,051, and including the cost of hospitalization was 12,614. In group B a diagnosis was reached in 32 of the 46 patients. The mean cost per patient of all the diagnostic procedures was 1,821, significantly lower than in group A (p < 0.0002), and including the cost of hospitalization was 5,298. CONCLUSION: In IUO (18)F-FDG PET/CT has the potential to become a cost-effective routine imaging technique indicating the direction for further diagnostic decisions thereby allowing unnecessary, invasive and expensive diagnostic investigations to be avoided and possibly the duration of hospitalization to be reduced. However, a prospective multicentre "bottom-up microcosting" cost-effectiveness study is warranted before these preliminary data can be extrapolated to clinical practice.

Azacitidine results in comparable outcome in newly diagnosed AML patients with more or less than 30% bone marrow blasts.

The efficacy of azacitidine has been demonstrated in acute myeloid leukemia (AML) patients with 20-30% bone marrow (BM) blasts, but limited data is available on patients with ≥30% blasts. We analyzed 55 newly diagnosed AML patients, treated with azacitidine. The overall response rate was 42%. Median overall survival (OS) was 12.3 months. We confirmed poor-risk cytogenetics, therapy-related AML, performance score ≥2, and white blood cell count ≥15×10(9)/L as independent adverse predictors for OS. The BM blast percentage, however, had no impact on OS (P=0.55). In conclusion, administration of azacitidine is effective in AML patients with 20-30% and >30% BM blasts.

Insulin resistance and risk of venous thromboembolism: results of a population-based cohort study.

BACKGROUND: Obesity is an established risk factor for venous thromboembolism (VTE), but it is uncertain how this is mediated. Insulin resistance has a central role in the pathophysiology of the metabolic effects of obesity. OBJECTIVE: We aimed to investigate whether insulin resistance is a risk factor for VTE. METHODS: For this analysis we used the PREVEND prospective community-based observational cohort study. Insulin resistance was measured as HOMA-IR (homeostasis model assessment of insulin resistance) and fasting insulin. VTE was assessed using databases of the national registries of hospital discharge diagnoses, death certificates and the regional anticoagulation clinic. RESULTS: Out of 7393 subjects, 114 developed VTE during a median follow-up of 10.5 years. High HOMA-IR was associated with increased risk of VTE after adjustment for traditional cardiovascular risk factors, CRP and markers of endothelial dysfunction (hazard ratio [HR], 1.38; 95% confidence interval [95% CI], 1.09-1.75; P=0.007). When body mass index (BMI) was added to the model, BMI was a strong risk predictor for VTE (HR, 1.53; 95% CI, 1.24-1.88; P<0.001) whereas HOMA-IR no longer showed such an association (HR, 1.11; 95% CI, 0.85-1.43; P=0.45). Results were similar for fasting insulin. CONCLUSION: Our population-based cohort study shows an increased risk of VTE in subjects with increasing insulin resistance but not independently of BMI.

Fetal loss in women with hereditary thrombophilic defects and concomitance of other thrombophilic defects: a retrospective family study.

OBJECTIVE: To assess the absolute risk of fetal loss associated with hereditary deficiencies of antithrombin (AT), protein C (PC) and protein S (PS), and the contribution of additional thrombophilic defects to this risk. DESIGN: A retrospective family cohort study. SETTING: A tertiary referral teaching hospital. POPULATION: Women from families with hereditary deficiencies of AT, PC and PS, and their non-deficient relatives. METHODS: We assessed the absolute risk of fetal loss, comparing deficient women with non-deficient female relatives. MAIN OUTCOME MEASURES: Early, late and total fetal loss rates; odds ratios of fetal loss. RESULTS: We evaluated 289 women, who had 860 pregnancies. The total fetal loss rates were 23% (AT deficient), 26% (PC deficient), 11% (type-I PS deficient) and 15% (type-III PS deficient), compared with 11, 18, 12 and 13% in non-deficient women, respectively. Odds ratios were 2.3 (95% CI 0.9-6.1), 2.1 (95% CI 0.9-4.7), 0.7 (95% CI 0.2-1.8) and 1.1 (95% CI 0.6-2.0), none of which reached statistical significance. Differences were mainly the result of higher late fetal loss rates in women deficient in AT (OR 11.3, 95% CI 3.0-42.0) and PC (OR 4.7, 95% CI 1.3-17.4). The concomitance of factor-V Leiden and prothrombin G20210A was observed in 19% of women, and did not increase the risk of fetal loss. CONCLUSIONS: Although absolute risks of fetal loss were high, odds ratios of total fetal loss were not statistically significant in deficient versus non-deficient women. However the higher absolute risks appeared to reflect higher late fetal loss rates as opposed to early fetal loss rates. An additional effect of concomitance of factor-V Leiden and prothrombin G20210A was not demonstrated, which may result from the exclusion of women at highest risk of venous thromboembolism, or from the small numbers sampled in the study.

B-type natriuretic peptide and interdialytic fluid retention are independent and incremental predictors of mortality in hemodialysis patients.

AIM: Management of fluid homeostasis remains a major challenge in hemodialysis patients. We aimed to establish whether the cardiac strain marker B-type natriuretic peptide (BNP) could help to identify hypervolemic patients at increased risk of death. METHODS: BNP levels were determined before dialysis in the entire HD population at our institution (n = 57). IDWG and BNP were stratified above or below 1.5 kg or the median value, respectively. All patients were prospectively followed for 35 months. The influence of IDWG and BNP on mortality was assessed with a Cox proportional hazards model, adjusted for each other, as well as for demographics, comorbidities, cardiac function, residual diuresis, dialysis duration and efficiency and complications of renal failure. RESULTS: Median BNP was 303 (135 - 692) and 21 (36%) patients displayed an average IDWG below 1.5 kg. During follow up a total of 25 (44%) patients died, 5 (26%) in the low IDWG group and 20 (53%) in the high IDWG group (adjusted hazard ratio (adjusted HR) 5.31 95% CI (1.47 - 19.1), p = 0.011). In the low BNP group 7 (25%) patients died and in the high BNP Group 18 (62%) patients died (adjusted HR 3.53 95 CI (1.37 - 9.09), p = 0.009). When both factors were considered simultaneously, patients with low BNP and low IDWG had an 11 times lower risk of death compared to patients with high BNP and high IDWG (HR. 0.08 95% CI (0.01 - 0.6129, p = 0.015). CONCLUSIONS: BNP and IDWG are independent and incremental predictors of mortality in HD patients. These findings suggest that BNP guided fluid management could improve survival in these patients.

Fixed versus variable dose of prothrombin complex concentrate for counteracting vitamin K antagonist therapy.

BACKGROUND: Although prothrombin complex concentrate (PCC) is often used to counteract vitamin K antagonist (VKA) therapy, evidence regarding the optimal dose for this indication is lacking. In Dutch hospitals, either a variable dose, based on body weight, target INR (international normalised ratio) and initial INR, or a fixed dose is used. AIM/OBJECTIVES: In this observational, pilot study, the efficacy and feasibility of the fixed dose strategy compared to the variable dosing regimen, is investigated. MATERIALS AND METHODS: Consecutive patients receiving PCC (Cofact®, Sanquin, Amsterdam) for VKA reversal because of a major non-cranial bleed or an invasive procedure were enrolled in two cohorts. Data were collected prospectively in the fixed dose group, cohort 1, and retrospectively in the variable dose regimen, cohort 2. Study endpoints were proportion of patients reaching target INR and successful clinical outcome. RESULTS: Cohort 1 consisted of 35 and cohort 2 of 32 patients. Target INR was reached in 70% of patients in cohort 1 versus 81% in cohort 2 (P = 0·37). Successful clinical outcome was seen in 91% of patients in cohort 1 versus 94% in cohort 2 (P = 1·00). Median INR decreased from 4·7 to 1·8 with a median dosage of 1040 IU factor IX (F IX) in cohort 1 and from 4·7 to 1·6 with a median dosage of 1580 IU F IX in cohort 2. CONCLUSION: This study suggests that a fixed dose of 1040 IU of F IX may be an effective way to rapidly counteract VKA therapy in our patient population and provides a basis for future research.

Transfused stored platelets have the same haemostatic function as circulating native platelets.

BACKGROUND AND OBJECTIVES: As thrombelastography (TEG) measures haemostasis in whole blood, we used this instrument to study whether transfused platelets (PLTs) have the same haemostatic function compared to native circulating PLTs. Further, we studied the effect of storage time on the haemostatic potential of platelet concentrates (PCs). MATERIALS AND METHODS: During the decrease in PLT count after chemotherapy, TEG parameters were measured serially until the transfusion trigger was reached in 92 patients. TEG parameters for different ranges of native circulating PLTs could be assessed, which were compared to ranges obtained in the thrombocytopenic period in which the patient received PLT transfusions. Finally, we compared the haemostatic potential of fresh PCs (1-3 days) with PCs with longer storage time (4-5 days). RESULTS: No differences could be found in haemostatic potential between native PLTs and transfused stored PLTs (all P-values > or = 0.1). The transfusion of fresh PLTs demonstrated better haemostatic effects than longer stored PLTs, measured 1 h after transfusion. Both the time until a fixed level of clot firmness was reached (K-time) and the rate of clot growth (alpha angle) were superior for fresh PCs. CONCLUSION: TEG is able to monitor the haemostatic effects of PLT transfusion, with comparable haemostatic properties of native circulating and transfused stored-PLTs. Further, our data suggest that limited storage time is associated with a better haemostatic capacity. However, before TEG can be applied as a qualitative test in PLT transfusion, further research is needed with focus on clinical outcomes like bleeding episodes.

A prospective cohort study on the absolute risks of venous thromboembolism and predictive value of screening asymptomatic relatives of patients with hereditary deficiencies of protein S, protein C or antithrombin.

BACKGROUND: Absolute risks of venous thromboembolism (VTE) in protein S-, protein C-, or antithrombin-deficient subjects are mainly based on retrospective data. Screening asymptomatic relatives of these patients is disputed, though studies addressing this issue have yet to be conducted. METHODS: We prospectively followed 382 relatives of 84 probands. Participants were assessed for other thrombophilic defects and occurrence of exogenous risk factors (i.e. surgery/trauma/immobilization, malignancies, use of systemic estrogens, and pregnancy/puerperium). After screening, deficient subjects were advised to use thromboprophylaxis during exogenous risk factors; use of oral contraceptives was discouraged. RESULTS: Overall annual incidence of VTE was 1.53% (95% CI, 1.00-2.34) in deficient vs. 0.29% (0.13-0.64) in non-deficient relatives; adjusted hazard ratio, 7.0 (95% CI, 2.7-18.0). Annual incidence of unprovoked VTE was 0.95% in deficient vs. 0.05% in non-deficient subjects; age-adjusted hazard ratio, 22.3 (P = 0.003). In contrast, annual incidence of provoked VTE was 0.58% vs. 0.24%; age-adjusted hazard ratio, 2.8 (P = 0.08). Fifty-five (37%) deficient and 80 (34%) non-deficient subjects experienced 91 and 143 exogenous risk factors, respectively, during which six vs. five VTEs (6.6% vs 3.5% per risk-period) occurred, despite the higher compliance with recommended thromboprophylaxis use in deficient (51%) vs. non-deficient (22%) subjects. In deficient subjects all provoked VTEs occurred when thromboprophylaxis was not used. CONCLUSIONS: Protein S, protein C or antithrombin deficiencies confer high absolute risk of VTE. Screening and subsequent augmentation of thromboprophylaxis use may result in reduction of provoked VTE, whereas risk of unprovoked VTE could not be affected by screening.

[Value of basic and intensive management of patients with heart failure; results of a randomised controlled clinical trial]. / Waarde van lichte en intensieve begeleiding van patiënten met hartfalen; resultaten van het COACH-onderzoek.

OBJECTIVE: To determine the efficacy of 2 nurse-directed programmes of different intensity for the counselling and follow-up of patients hospitalised for heart failure, compared with standard care by a cardiologist. DESIGN: Multicentre randomised clinical trial (www.trialregister.nl: NCT 98675639). METHOD: A total of 1023 patients were randomized after hospitalisation for heart failure to 1 of 3 treatment strategies: standard care provided by a cardiologist, follow-up care from a cardiologist with basic counselling and support by a nurse specialising in heart failure, or follow-up care from a cardiologist with intensive counselling and support by a nurse specialising in heart failure. Primary end points were the time to rehospitalisation due to heart failure or death and the number of days lost to rehospitalisation or death during the 18-month study period. Data were analysed on an intent-to-treat basis. RESULTS: Mean patient age was 71 years, 38% were women, 50% had mild heart failure and 50% had severe heart failure. During the study, 411 patients (40%) were rehospitalised due to heart failure or died from any cause: 42% in the control group, and 41% and 38% in the basic and intensive support groups, respectively (differences not significant). The time to rehospitalisation or death was similar in the 3 groups: hazard ratios for the basic and intensive support groups versus the control group were 0.96 (95% CI: 0.76-1.21; p = 0.73) and 0.93 (95% CI: 0.73-1.17; p = 0.53), respectively. The number of days lost to rehospitalisation or death was 39,960 in the control group; this number was 15% less in the intervention groups, but the difference was not significant. However, there was a trend toward lower mortality in the intervention groups. In all 3 groups, more visits occurred than planned, which may have had a considerable effect on care, notably in the control group. CONCLUSION: The results of this study indicated that the provision of additional counselling and support by a nurse specialising in heart failure as an adjuvant to intensive follow-up care provided by a cardiologist does not always lead to a reduction in rehospitalisation frequency.