[Physical Therapy for Chemotherapy-induced Peripheral Neuropathy in Pediatric Oncology]. / Physiotherapie bei Chemotherapie-assoziierter peripherer Neuropathie in der pädiatrischen Onkologie ­ Eine Literaturrecherche.

Background: Chemotherapy-induced peripheral neuropathy is a frequent side-effect of drugs that are used in the treatment of cancer. Affected individuals can suffer from motor, sensory or autonomy nerve damage. Further medication is used for the treatment of CIPN which can cause further side-effects. Patients should be offered physical therapy treatment to relieve the symptoms. Objective: The aim of this article is to give an overview of available literature investigating physical therapy in CIPN in pediatric oncology. Methods: To determine relevant literature, a systematic review was conducted in the databases CINAHL, The Cochrane Library, ERIC, MEDPILOT, PEDro, PsycARTICLES, PsycINFO, PubMed and DIMDI. Besides the methodological quality of the identified literature is supposed to be reviewed. Results: There is no current literature regarding the subject of this article, so no evaluation of the quality could be carried out. Although several publications concerning adults could be identified and transfer could be established for pediatrics. Conclusion: Acupuncture appeared to be effective in the treatment of CIPN in adults. Good results appeared especially regarding pain. Sensorimotor training, balance training, electrotherapy and alternative methods like Reiki and Yoga showed good results for patients symptoms. These treatment methods give a future prospect how CIPN in children can be treated successfully - but further pediatric research is necessary.

Performance of risk scores in predicting major bleeding in left ventricular assist device recipients: a comparative external validation.

Background: Implantation of a left ventricular assist device (LVAD) is a crucial therapeutic option for selected end-stage heart failure patients. However, major bleeding (MB) complications postimplantation are a significant concern. Objectives: We evaluated current risk scores' predictive accuracy for MB in LVAD recipients. Methods: We conducted an observational, single-center study of LVAD recipients (HeartWare or HeartMate-3, November 2010-December 2022) in the Netherlands. The primary outcome was the first post-LVAD MB (according to the International Society on Thrombosis and Haemostasis [ISTH] and Interagency Registry for Mechanically Assisted Circulatory Support [INTERMACS], and INTERMACS combined with intracranial bleeding [INTERMACS+] criteria). Mortality prior to MB was considered a competing event. Discrimination (C-statistic) and calibration were evaluated for the Hypertension, Abnormal Renal/Liver Function, Stroke, Bleeding History or Predisposition, Labile INR, Elderly, Drugs/Alcohol Concomitantly score, Hepatic or Renal Disease, Ethanol Abuse, Malignancy, Older Age, Reduced Platelet Count or Function, Re-Bleeding, Hypertension, Anemia, Genetic Factors, Excessive Fall Risk and Stroke score, Anticoagulation and Risk Factors in Atrial Fibrillation score, Outpatient Bleeding Risk Index, venous thromboembolism score, atrial fibrillation score, and Utah Bleeding Risk Score (UBRS). Results: One hundred four patients were included (median age, 64 years; female, 20.2%; HeartWare, 90.4%; HeartMate-3, 9.6%). The cumulative MB incidence was 75.7% (95% CI 65.5%-85.9%) by ISTH and INTERMACS+ criteria and 67.0% (95% CI 56.0%-78.0%) per INTERMACS criteria over a median event-free follow-up time of 1916 days (range, 59-4521). All scores had poor discriminative ability on their intended prediction timeframe. Cumulative area under the receiving operator characteristic curve ranged from 0.49 (95% CI 0.35-0.63, venous thromboembolism-BLEED) to 0.56 (95% CI 0.47-0.65, UBRS) according to ISTH and INTERMACS+ criteria and from 0.48 (95% CI 0.40-0.56, Anticoagulation and Risk Factors in Atrial Fibrillation) to 0.56 (95% CI 0.47-0.65, UBRS) per INTERMACS criteria. All models showed poor calibration, largely underestimating MB risk. Conclusion: Current bleeding risk scores exhibit inadequate predictive accuracy for LVAD recipients. There is a need for an accurate risk score to identify LVAD patients at high risk of MB who may benefit from patient-tailored antithrombotic therapy.

Inappropriate prescriptions of direct oral anticoagulants (DOACs) in hospitalized patients: A narrative review.

Direct oral anticoagulants (DOACs) have become the cornerstone for prevention of thromboembolic events in patients with atrial fibrillation and patients with a history of venous thromboembolism. However, studies show that DOAC prescriptions are commonly inconsistent with guideline recommendations. DOAC dosing in the acutely ill patient could impose an even greater challenge. In this review, we describe the prevalence of inappropriate inpatient prescribing of DOACs and the associated rationales, predictors and clinical consequences. With the aim of promoting appropriate prescriptions of DOACs to hospitalized patients, we further outline DOAC dose reduction criteria justified by various guidelines, illustrating the complexities of appropriate dosing, especially in acutely ill patients. Moreover, we will discuss the impact of anticoagulant stewardship programs and the vital role that pharmacists may play in optimizing inpatient DOAC treatment.

Relationship between neighborhood socioeconomic status and venous thromboembolism: results from a population-based study.

Essentials Literature on socioeconomic status (SES) and incidence of venous thromboembolism (VTE) is scarce. We assessed neighborhood SES with VTE risk in a population of over 1.4 million inhabitants. Higher neighborhood SES was associated with lower incidence of VTE. These findings are helpful to inform policy and resource allocation in health systems. SUMMARY: Background The association between socioeconomic status and arterial cardiovascular disease is well established. However, despite its high burden of disability-adjusted life years, little research has been carried out to determine whether socioeconomic status is associated with venous thromboembolism. Objective To determine if neighborhood socioeconomic status is associated with venous thromboembolism in a population-based study from the Netherlands. Methods We identified all patients aged 15 years and older with a first event of venous thromboembolism from inhabitants who lived in the urban districts of The Hague, Leiden and Utrecht in the Netherlands in 2008-2012. Neighborhood socioeconomic status was based on the status score, which combines educational level, income and unemployment on a four-digit postal code level. Incidence rate ratios of venous thromboembolism were calculated for different levels of neighborhood socioeconomic status, with adjustments for age and sex. Results A total of 7373 patients with a first venous thromboembolism (median age 61 years; 50% deep vein thrombosis) were identified among more than 1.4 million inhabitants. Higher neighborhood SES was associated with lower incidence of VTE. In the two highest status score groups (i.e. the 95-99th and > 99th percentile), the adjusted incidence rate ratios were 0.91 (95% confidence interval [CI], 0.84-1.00) and 0.80 (95% CI, 0.69-0.93), respectively, compared with the reference status score group (i.e. 30-70th percentile). Conclusions High neighborhood socioeconomic status is associated with a lower risk of first venous thromboembolism.

Major bleeding risks of different low-molecular-weight heparin agents: a cohort study in 12 934 patients treated for acute venous thrombosis.

Essentials Low-molecular-weight-heparins (LMWH) kinetics differ which may result in different bleeding risks. A cohort of 12 934 venous thrombosis patients on LMWH was followed until major bleeding. The absolute major bleeding risk was low among patients registered at the anticoagulation clinic. Once-daily dosing was associated with a lower bleeding risk as compared with twice-daily. SUMMARY: Background Low-molecular-weight heparins (LMWHs) are considered members of a class of drugs with similar anticoagulant properties. However, pharmacodynamics and pharmacokinetics between LMWHs differ, which may result in different bleeding risks. As these agents are used by many patients, small differences may lead to a large effect on numbers of major bleeding events. Objectives To determine major bleeding risks for different LMWH agents and dosing schedules. Methods A cohort of acute venous thrombosis patients from four anticoagulation clinics who used an LMWH and a vitamin K antagonist were followed until they ceased LMWH treatment or until major bleeding. Exposures were classified according to different types of LMWHs and for b.i.d. and o.d. use. Cumulative incidences for major bleeding per 1000 patients and risk ratios were calculated and adjusted for study center. Results The study comprised 12 934 patients with a mean age of 59 years; 6218 (48%) were men. The cumulative incidence of major bleeding was 2.5 per 1000 patients (95% confidence interval [CI], 1.7-3.5). Enoxaparin b.i.d. or o.d. was associated with a relative bleeding risk of 1.7 (95% CI, 0.2-17.5) compared with nadroparin o.d. In addition, a nadroparin b.i.d. dosing schedule was associated with a 2.0-fold increased major bleeding risk (95% CI, 0.8-5.1) as compared with a nadroparin o.d. dosing schedule. Conclusions Absolute major bleeding rates were low for all LMWH agents and dosing schedules in a large unselected cohort. Nevertheless, twice-daily dosing with nadroparin appeared to be associated with an increased major bleeding risk as compared with once-daily dosing, as also suggested in a meta-analysis of controlled clinical trials.

Increased risk of major bleeding after a minor bleed during treatment with vitamin K antagonists is determined by fixed common risk factors.

UNLABELLED: Essentials Minor bleeding is associated with subsequent major bleeding in patients treated with vitamin K antagonists. This study confirms that patients with minor bleeds have a 2.5-fold increased risk of major bleeds. A case-crossover analysis revealed that the increased risk is due to fixed underlying risk factors. Future research may unveil these unknown fixed risk factors and improve major bleeding risk scores. SUMMARY: Background Patients who have a minor bleed during treatment with vitamin K antagonists (VKAs) have a 3-fold increased risk of subsequent major bleeding. The nature of the underlying risk factors is largely unknown. Objectives To indicate why patients with minor bleeds are at increased risk of subsequent major bleeds (e.g. are risk factors of a transient or a fixed nature). Methods Patients who started VKA treatment between 2003 and 2013 were included. Exposure was from the minor bleed until 3 months later. We used two analyses: a Cox model which we adjusted for several known risk factors, and a case-crossover (CCO) design, which corrects for all fixed risk factors (such as chronic diseases and genes) as patients are compared with themselves. The combination of both analyses gives insight into whether the association of minor with major bleeds is a result of fixed or transient risk factors. Results Out of 26 130 patients who were included and followed for '61 672 patient years', 7194 experienced a minor bleed and 913 a major bleed. The Cox model indicated that patients with minor bleeds had a 2.5-fold increased risk of experiencing subsequent major bleeding after adjustment for known risk factors, whereas the CCO gave risk estimates around unity (odds ratio, 0.9; 95% confidence interval, 0.5-1.5). Conclusions The combination of both analyses indicates that minor bleeds are markers for fixed and currently unknown risk factors for major bleeding events.

Impact of point-of-care international normalized ratio monitoring on quality of treatment with vitamin K antagonists in non-self-monitoring patients: a cohort study.

BACKGROUND: Point-of-care (POC) international normalized ratio (INR) monitoring by healthcare professionals could eliminate the need for venous blood sampling in non-self-monitoring (NSM) patients on vitamin K antagonists (VKA). However, few studies have investigated the impact of POC INR monitoring on the quality of treatment in these patients and real-world data on this issue are lacking. OBJECTIVES: To investigate the safety, efficacy and quality of anticoagulant control during POC INR monitoring as compared with laboratory INR monitoring in NSM patients. METHODS: We performed a retrospective cohort study using data from the anticoagulation clinic of the Star-Medical Diagnostic Center (Rotterdam, the Netherlands). Patients who received treatment with VKA between 29 May 2012 and 29 May 2014 were eligible. Percentage of time in therapeutic range (TTR) and incidence rates of major clinical events (all-cause mortality, hospitalization, major bleeding and ischemic stroke) were compared for the year before and year after introduction of POC monitoring. Cox proportional hazard models were used to estimate hazard ratios and 95% confidence intervals for major clinical events between exposure groups. RESULTS: In total, 1973 patients during the 1-year laboratory-monitoring observation period and 1959 patients during the 1-year POC-monitoring observation period were included. Median TTR was significantly lower during POC monitoring (77.9%; 95% CI, 67.2-87.4) than during laboratory INR monitoring (81.0%; 95% CI, 71.1-90.5). Adjusted hazard ratios for major clinical events were all around unity. CONCLUSIONS: Although associated with lower TTR, POC INR monitoring is a safe and effective alternative to laboratory INR monitoring in NSM patients on VKA.

Vitamin K1 in oral solution or tablets: a crossover trial and two randomized controlled trials to compare effects.

BACKGROUND: Vitamin K1 (VK1) reverses the effects of vitamin K antagonists (VKAs). The literature shows that the bioavailability from solutions might be higher than that from tablets, possibly resulting in different effects. OBJECTIVES: To compare the bioavailability and effect on the International Normalized Ratio (INR) of 5-mg VK1 tablets and solution in three randomized clinical trials. METHODS AND RESULTS: The bioavailability was determined in a crossover trial with 25 healthy volunteers. VK1 plasma concentrations were assessed at 0, 2, 4, 5, 6, 8, 10 and 24 h, and the area under the curve was higher in the solution group than in the tablet group (mean difference 365 µg L(-1) h, 95% confidence interval [CI] 230-501, P < 0.0001). In the other two trials, the effects of both formulations on the INR were measured at 0, 24 and 48 h. In the second trial, on 72 patients on phenprocoumon with planned invasive procedures, both formulations were similarly effective, because all patients reached an INR of < 2.0, which was the primary endpoint. In the last trial, on 72 patients on phenprocoumon with an INR of 7.0-11.0, the INR decreased slightly more in the solution group (4.7, 95% CI 4.3-5.1) than in the tablet group (4.2, 95% CI 3.8-4.6). The solution group had a 3.3-fold increased likelihood (95% CI 0.7-15.1) of reaching an INR of < 2.0 at 48 h. Additionally, the increases in VK1 concentrations were similar (tablets, 3.2 µg L(-1) ; solution, 3.4 µg L(-1) ; P = 0.99) after 24 h. CONCLUSIONS: VK1 tablets are at least as clinically effective as the solution in countering VKAs.

Suspected tuberculosis case detection and referral in private pharmacies in Viet Nam.

SETTINGS: Private pharmacies in Hanoi, Viet Nam. OBJECTIVES: To explore the response of health care providers (HCPs) in private pharmacies to suspected tuberculosis (TB) patients. METHODS: A simulated patient method combined with an interview in 128 randomly selected private pharmacies and 10 private pharmacies near TB hospitals. RESULTS: In the simulated patient method and interview, respectively 59 (46%) and 70 (55%) of HCPs referred the TB suspect to general health care. Only 11 (9%) referred the simulated patient to a TB care facility. Fifty-two (42%) of the HCPs identified suspected TB from a fictitious case described on paper; 34 (27%) were aware that free treatment was provided under the National Tuberculosis Programme (NTP). Knowledge about free NTP treatment predicted a higher rate of direct referrals to TB facilities (OR 5.80, 95%CI 1.88-19.62) and greater ability to identify suspected TB from a fictitious case on paper (OR 5.14, 95%CI 2.36-11.73). Pharmacies with Good Pharmacy Practice (GPP) certification were less likely to refer simulated patients to TB facilities than non-GPP pharmacies (OR 0.10, 95%CI ≤0.01-0.79). CONCLUSIONS: Nearly half of HCPs in private pharmacies do not refer TB suspects, possibly contributing to delays in diagnosis and treatment. Knowledge about free NTP treatment predicted better performance of HCPs.