Establishing an ad hoc COVID-19 mortality surveillance during the first epidemic wave in Belgium, 1 March to 21 June 2020.

BackgroundCOVID-19-related mortality in Belgium has drawn attention for two reasons: its high level, and a good completeness in reporting of deaths. An ad hoc surveillance was established to register COVID-19 death numbers in hospitals, long-term care facilities (LTCF) and the community. Belgium adopted broad inclusion criteria for the COVID-19 death notifications, also including possible cases, resulting in a robust correlation between COVID-19 and all-cause mortality.AimTo document and assess the COVID-19 mortality surveillance in Belgium.MethodsWe described the content and data flows of the registration and we assessed the situation as of 21 June 2020, 103 days after the first death attributable to COVID-19 in Belgium. We calculated the participation rate, the notification delay, the percentage of error detected, and the results of additional investigations.ResultsThe participation rate was 100% for hospitals and 83% for nursing homes. Of all deaths, 85% were recorded within 2 calendar days: 11% within the same day, 41% after 1 day and 33% after 2 days, with a quicker notification in hospitals than in LTCF. Corrections of detected errors reduced the death toll by 5%.ConclusionBelgium implemented a rather complete surveillance of COVID-19 mortality, on account of a rapid investment of the hospitals and LTCF. LTCF could build on past experience of previous surveys and surveillance activities. The adoption of an extended definition of 'COVID-19-related deaths' in a context of limited testing capacity has provided timely information about the severity of the epidemic.

High impact of COVID-19 in long-term care facilities, suggestion for monitoring in the EU/EEA, May 2020.

Residents in long-term care facilities (LTCF) are a vulnerable population group. Coronavirus disease (COVID-19)-related deaths in LTCF residents represent 30-60% of all COVID-19 deaths in many European countries. This situation demands that countries implement local and national testing, infection prevention and control, and monitoring programmes for COVID-19 in LTCF in order to identify clusters early, decrease the spread within and between facilities and reduce the size and severity of outbreaks.

A prolonged QTc-interval at the emergency department: Should we always be prepared for the worst?

INTRODUCTION: QTc-interval prolongation is associated with ventricular arrhythmias and mortality in a general population. Bazett's correction formula (QTcB) is routinely used despite its overcorrection at high heart rates. Recently, we proposed a patient-specific QT correcting algorithm (QTcA) resulting in improved rate correction and predictive value in a general population. We hypothesize risk stratification at the Emergency Department (ED) could be improved using QTcA. METHODS AND RESULTS: A retrospective case-control study including a randomized age- and sex-matched control population was performed at a tertiary care ED. A total of 1930 patients were included in the analysis (63.0% males, age 71.5 ± 15.6 years). Patient characteristics, history, and test results at the time of the electrocardiogram were collected. QTc was dichotomized as prolonged (>450 millisecond for men, >470 millisecond for women) or severely prolonged (>500 millisecond). Implementation of QTcA would reduce the number of patients considered to have a prolonged QTc by 65.2%, for severely prolonged QTc 79.6%. Multivariate regression was performed for in-hospital mortality, cardiovascular endpoints, and hospital admission. Neither a prolonged QTcB (HR 1.04; 95% CI, 0.64-1.69) nor QTcA (HR 0.76; 95% CI, 0.42-1.38) was an independent predictor of in-hospital mortality. A severely prolonged QTcA (OR, 2.54; 95% CI, 1.04-6.23) was an independent predictor of cardiovascular events. Both a prolonged QTcA (OR, 1.52; 95% CI, 1.06-2.18) and a prolonged QTcB (OR, 1.37; 95% CI, 1.05-1.79) were associated with higher hospitalization rates. CONCLUSIONS: QTcA reduced the number of patients considered at risk. Neither QTcB nor QTcA were predictors of in-hospital mortality. A severely prolonged QTcA was associated with cardiovascular events.

Systemic antifungal drug use in Belgium-One of the biggest antifungal consumers in Europe.

BACKGROUND: Reports on the consumption of systemic antifungal drugs on a national level are scarce although of high interest to compare trends and the associated epidemiology in other countries and to assess the need for antifungal stewardship programmes. OBJECTIVES: To estimate patterns of Belgian inpatient and outpatient antifungal use and provide reference data for other countries. METHODS: Consumption records of antifungals were collected in Belgian hospitals between 2003 and 2016. Primary healthcare data were available for the azoles for the period 2010-2016. RESULTS: The majority of the antifungal consumption resulted from prescriptions of fluconazole and itraconazole in the ambulatory care while hospitals were responsible for only 6.4% of the total national consumption and echinocandin use was limited. The annual average antifungal consumption in hospitals decreased significantly by nearly 25% between 2003 and 2016, due to a decrease solely in non-university hospitals. With the exception of specialised burn centres, antifungals are mostly consumed at ICUs and internal medicine wards. A significant decline was also observed in the consumption of azoles in primary health care, attributed to itraconazole. The major part of azoles was prescribed by generalists followed by dermatologists. CONCLUSIONS: In spite of the downward trend in annual use of systemic antifungal drugs, Belgium remains one of the biggest consumers in Europe.

Antibiotic consumption in Belgian acute care hospitals: analysis of the surveillance methodology, consumption evolution 2003 to 2016 and future perspectives.

BackgroundStudies have demonstrated the link between antimicrobial consumption and the development of antimicrobial resistance. Surveillance of antimicrobial consumption is an action point of the European Commission's 'One Health Action Plan Against Antimicrobial Resistance'.AimThis study aims to compare two methodologies for antibiotic consumption surveillance, investigate the 14-year evolution of antibiotic consumption in Belgian acute care hospitals and discuss future perspectives.MethodsWe compared self-reported data (old methodology) and reimbursement data (new methodology) of national antibiotic consumption surveillance in hospitals. Descriptive analyses were performed on the reimbursement data collected per year and per trimester (2003-2016), per hospital and per unit. Antibiotic consumption was compared with European Surveillance of Antimicrobial Consumption Network (ESAC-Net) results.ResultsThe median differences for defined daily doses (DDDs)/1,000 patient days and DDDs/1,000 admissions were 3.09% and 3.94% when comparing the old vs new methodology. Based on reimbursement data, the median antibiotic consumption in 2016 in 102 Belgian acute care hospitals was 577.1 DDDs/1,000 patient days and 3,890.3 DDDs/1,000 admissions with high variation between hospitals (interquartile ranges (IQR): 511.3-655.0 and 3,450.0-4,400.5, respectively), and similar to 2015. Based on DDDs/1,000 patient days, the magnitude of consumption is comparable with the Netherlands, Denmark and Sweden, but is higher when based on DDDs/1,000 admissions.ConclusionAntibiotic consumption in Belgian acute care hospitals has remained overall stable over time. However, the high variation across hospitals should be further investigated. This surveillance data could be used for benchmarking and assessing interventions to improve antibiotic consumption in these hospitals.

A smart algorithm for the prevention and risk management of QTc prolongation based on the optimized RISQ-PATH model.

AIMS: QTc prolongation is a complex problem linked with multiple risk factors. The RISQ-PATH score was previously developed to identify high-risk patients for QTc prolongation. The aim of this study was to optimize and validate this risk score in a large patient cohort, and to propose an algorithm to generate smart QT signals in the electronic medical record. METHODS: A retrospective study was performed in the Nexus hospital network (n = 17) in Belgium. All electrocardiograms performed in 2015 in both ambulatory and hospitalized patients were collected together with risk factors for QTc prolongation (training database). Multiple logistic regression was performed to obtain the optimal prediction (RISQ-PATH) model. The model was tested in a validation database (electrocardiograms between January and April 2016). RESULTS: In total, 60 208 patients (52.8% males, mean age 63 ± 18 years) were included; 3543 patients (5.9%) had a QTc ≥ 450(♂)/470(♀) ms and 453 (0.8%) a QTc ≥ 500 ms. The optimized RISQ-PATH model has an area under the ROC-curve of 0.772 [95% CI 0.763-0.780] to predict QTc ≥ 450(♂)/470(♀)ms. A predicted probability of ≥0.035 was set as cutoff for a high risk of QTc prolongation. This cutoff resulted in a sensitivity of 87.4% [95% CI 86.2-88.5] and a specificity of 46.2% [95% CI 45.8-46.6]. These results could be confirmed for QTc ≥ 500 ms and in the validation database (n = 28 400). CONCLUSIONS: The RISQ-PATH model, with a cutoff probability of 0.035, predicted a prolonged QTc interval ≥ 450/470 ms or ≥500 ms with a sensitivity of ±87% and a specificity of ±45%. This RISQ-PATH model can be used in clinical decision support systems to create smart QT alerts.

QT correction across the heart rate spectrum, in atrial fibrillation and ventricular conduction defects.

BACKGROUND: Incorporation of QTc in clinical decision support systems requires accurate QT-interval correction, also during common electrocardiogram abnormalities as ventricular conduction defects (VCD). We compared the performance and predictive value of QT correction formulas to design a patient-specific QT correction algorithm (QTcA). METHODS: The first ECG in adult patients with sinus rhythm (SR), atrial fibrillation (AF), and ventricular pacing (VP) was collected retrospectively. QT correction was performed with Bazett (QTcB), Fridericia (QTcFri), Framingham, Hodges, and Rautaharju (QTcR) formulas. Correction formulas were compared using QTc/RR linear regression. Adjusted Cox regression was performed to predict 1-year all-cause mortality. RESULTS: A total of 49,737 patients were included (70.0% SR, 24.1% AF, 5.9% VP, 11.1% VCD). Overall 1-year all-cause mortality rate was 11.8%. In patients without VCD or VP, QTcFri showed significantly better heart rate correction, both overall (P < 0.001) and in subgroups by heart rate (bradycardia P ≤ 0.001, normal P ≤ 0.050, tachycardia P ≤ 0.010). Furthermore, QTcFri improved mortality prediction significantly when compared to QTcB (P < 0.001). Patients with VCD or VP QTcR, including correction for QRS duration, had a significant better heart rate correction than QTcB (P ≤ 0.010) and improved mortality prediction significantly compared to all other formulas (P < 0.001). Implementing QTcA, designed based on QTcFri and QTcR depending on the presence of VCD or VP, reduced the patients considered to be at risk by 61.1% when compared to QTcB. CONCLUSIONS: A patient-specific QT correction algorithm would combine accurate heart rate correction, improved predictive value of mortality, and a reduction of patients considered to be at risk.

Risk Management of Hospitalized Psychiatric Patients Taking Multiple QTc-Prolonging Drugs.

PURPOSE/BACKGROUND: Drug-related QTc prolongation has been linked with Torsade de Pointes and sudden cardiac death. The objective of this study was to investigate the impact of starting an additional QTc-prolonging drug on the QTc interval of psychiatric inpatients. METHODS: An observational study was performed between May 2011 and December 2014 in 6 Belgian psychiatric hospitals. Inpatients who were already taking 1 QTc-prolonging drug or more could be included in the study when an additional QTc-prolonging drug was started. Electrocardiograms were performed at baseline and follow-up. Demographic, medical, medication, and laboratory data were collected. A risk score was used to estimate the risk of QTc prolongation based on patient-specific risk factors. A cutoff value of 8 points was set as high risk for QTc prolongation. RESULTS: One hundred fifty-two patients (44.7% women; mean age, 44 [SD, 17] years) were included who received a prescription for an additional QTc-prolonging drug. There was a small but significant difference (P = 0.032) in mean QTc interval between baseline (409.1 [SD, 21.8] milliseconds) and follow-up (411.8 [SD, 21.7] milliseconds). Three patients developed a prolonged QTc interval in the follow-up electrocardiogram (QTc, ≥450 [men]/470 [women] milliseconds); 8 patients had a delta QTc of 30 milliseconds or longer. No cases of torsade de pointes or sudden cardiac death were identified. Fifty-eight patients (38.2%) had a risk score of 8 or higher; these patients had a significantly longer QTc interval at follow-up than did patients with a risk score of lower than 8 (P < 0.001). IMPLICATIONS/CONCLUSIONS: Only a limited number of patients developed a prolonged QTc interval after the start of an additional QTc-prolonging drug. Nevertheless, it is still important to screen for high-risk patients at baseline. A risk score can help to select high-risk patients and to stimulate an appropriate and feasible risk management of QTc prolongation in psychiatry.

COVID-19 Clusters in Belgian Nursing Homes: Impact of Facility Characteristics and Vaccination on Cluster Occurrence, Duration and Severity.

COVID-19 severely affected nursing home residents from March 2020 onwards in Belgium. This study aimed to model the impact of vaccination and facility characteristics on cluster occurrence, duration and severity in this setting. Possible clusters were identified between June 2020 and January 2022, based on the Belgian COVID-19 surveillance in nursing homes. Median attack rates (AR) among residents and staff, case hospitalization rates (CHR) and case fatality rates (CFR) were calculated. A negative binomial model was used to identify the association between nursing home characteristics and the number of cases, hospital admissions and deaths and the duration of the cluster. A total of 2239 clusters were detected in more than 80% of nursing homes. Most of these (62%) occurred before the start of COVID-19 vaccination (end of December 2020). After vaccination, the number of clusters, the AR among residents and staff, the CHR and the CFR dropped. Previous cluster(s) and vaccination decreased the number of cases, hospital admissions and deaths among residents. Previous cluster experience and having started vaccination were protective factors. We recommend continued implementation of targeted interventions such as vaccination, large-scale screening and immediate implementation of additional infection prevention and control measures.

COVID-19 cases, hospitalizations and deaths in Belgian nursing homes: results of a surveillance conducted between April and December 2020.

BACKGROUND: In Belgium, the first COVID-19 death was reported on 10 March 2020. Nursing home (NH) residents are particularly vulnerable for COVID-19, making it essential to follow-up the spread of COVID-19 in this setting. This manuscript describes the methodology of surveillance and epidemiology of COVID-19 cases, hospitalizations and deaths in Belgian NHs. METHODS: A COVID-19 surveillance in all Belgian NHs (n = 1542) was set up by the regional health authorities and Sciensano. Aggregated data on possible/confirmed COVID-19 cases and hospitalizations and case-based data on deaths were reported by NHs at least once a week. The study period covered April-December 2020. Weekly incidence/prevalence data were calculated per 1000 residents or staff members. RESULTS: This surveillance has been launched within 14 days after the first COVID-19 death in Belgium. Automatic data cleaning was installed using different validation rules. More than 99% of NHs participated at least once, with a median weekly participation rate of 95%. The cumulative incidence of possible/confirmed COVID-19 cases among residents was 206/1000 in the first wave and 367/1000 in the second wave. Most NHs (82%) reported cases in both waves and 74% registered ≥10 possible/confirmed cases among residents at one point in time. In 51% of NHs, at least 10% of staff was absent due to COVID-19 at one point. Between 11 March 2020 and 3 January 2021, 11,329 COVID-19 deaths among NH residents were reported, comprising 57% of all COVID-19 deaths in Belgium in that period. CONCLUSIONS: This surveillance was crucial in mapping COVID-19 in this vulnerable setting and guiding public health interventions, despite limitations of aggregated data and necessary changes in protocol over time. Belgian NHs were severely hit by COVID-19 with many fatal cases. The measure of not allowing visitors, implemented in the beginning of the pandemic, could not avoid the spread of SARS-CoV-2 in the NHs during the first wave. The virus was probably often introduced by staff. Once the virus was introduced, it was difficult to prevent healthcare-associated outbreaks. Although, in contrast to the first wave, personal protective equipment was available in the second wave, again a high number of cases were reported.

Point prevalence survey of antimicrobial use and healthcare-associated infections in Belgian acute care hospitals: results of the Global-PPS and ECDC-PPS 2017.

Background: The point prevalence survey of healthcare-associated infections (HAIs) and antimicrobial use organized by the European Centre for Disease Prevention and Control (ECDC-PPS) and the Global Point Prevalence Survey of antimicrobial consumption (Global-PPS) were simultaneously performed in Belgian acute care hospitals in 2017. Methods: Belgian acute care hospitals were invited to participate in either the ECDC or Global-PPS. Hospital/ward/patient-level data were collected between September-December 2017. All patients present in the wards at 8 a.m. on the day of the PPS were included. The data of the ECDC and Global-PPS on antimicrobial consumption were pooled. Detailed data on HAIs were analysed for ECDC-PPS. Results: Overall, 110 Belgian acute care hospital sites participated in the ECDC and Global-PPS (countrywide participation rate: 81.4%, 28,007 patients). Overall, a crude prevalence of patients with at least one antimicrobial of 27.1% (95% confidence interval (CI) 26.5-27.6%) was found. The most frequently reported indications were pneumonia (23.2%), urinary tract infections (15.2%) and skin and soft tissue infections (11.9%). The reason for antimicrobial use was recorded for 81.9% of the prescriptions, a stop/review date for 40.8% and compliance with local antibiotic guidelines for 76.6%. In the ECDC-PPS, the crude prevalence of patients with at least one HAI was 7.3% (95%CI 6.8-7.7%). Most frequently reported HAIs were pneumonia (21.6%) and urinary tract infections (21.3%). Conclusions: HAI and antimicrobial use prevalence remained stable in comparison with the previous PPS (7.1% and 27.4% in 2011 and 2015, respectively). Belgian hospitals should be further stimulated to set local targets to improve antibiotic prescribing and reduce HAI.

Antimicrobial prescribing by Belgian dentists in ambulatory care, from 2010 to 2016.

OBJECTIVES: To describe antimicrobial prescribing by Belgian dentists in ambulatory care, from 2010 until 2016. MATERIALS AND METHODS: Reimbursement data from the Belgian National Institute for Health and Disability Insurance were analysed to evaluate antimicrobial prescribing (WHO ATC-codes J01/P01AB). Utilisation was expressed in defined daily doses (DDDs), and in DDDs and packages per 1000 inhabitants per day (DID and PID, respectively). Additionally, the number of DDD and packages per prescriber was calculated. RESULTS: In 2016, the dentistry-related prescribing rate of 'Antibacterials for systemic use' (J01) and 'Antiprotozoals' (P01AB) was 1.607 and 0.014 DID, respectively. From 2010 to 2016, the DID rate of J01 increased by 6.3%, while the PID rate declined by 6.7%. Amoxicillin and amoxicillin with an enzyme inhibitor were the most often prescribed products, followed by clindamycin, clarithromycin, doxycycline, azithromycin and metronidazole. The proportion of amoxicillin relative to amoxicillin with an enzyme inhibitor was low. The narrow-spectrum antibiotic penicillin V was almost never prescribed. CONCLUSIONS: Antibiotics typically classified as broad- or extended-spectrum were prescribed most often by Belgian dentists during the period 2000-2016. Although the DID rate of all 'Antibacterials for systemic use' (J01) increased over the years, the number of prescriptions per dentist decreased since 2013. The high prescription level of amoxicillin with an enzyme inhibitor is particularly worrying. It indicates that there is a need for comprehensive clinical practice guidelines for Belgian dentists.

Cluster-Controlled Trial of an Intervention to Improve Prescribing in Nursing Homes Study.

OBJECTIVES: To investigate the impact of a complex multifaceted intervention on the appropriateness of prescribing for Belgian nursing home (NH) residents. DESIGN: A multicenter, nonblinded, cluster-randomized controlled trial, with randomization at the NH level, was set up [Cluster-Controlled Trial of an Intervention to Improve Prescribing in Nursing Homes (COME-ON) Study]. The complex intervention consisted of repeated interdisciplinary case conferences (ICCs) involving the general practitioner, pharmacist, and nurse, aimed at performing a medication review for each NH resident included. The ICCs were supported by a blended training program and local interdisciplinary meetings (discussion of the appropriate use of specific medication classes at the NH level). Control NHs delivered usual care. (isrctn.com: ISRCTN66138978). SETTING AND PARTICIPANTS: Belgian NHs with at least 35 NH residents were eligible to participate. Eligible residents were those aged 65 years or over, not receiving palliative care, and being treated by a participating general practitioner. MEASURES: The primary outcome measure related to appropriateness of prescribing at resident level and was considered successful when at least 1 potentially inappropriate medication (PIM) or potential prescribing omission (PPO) present at baseline had been solved at the end of study and when there were no new PIMs or PPOs at the end of study compared with baseline. Secondary outcomes included clinical outcomes, medication use, criterion-specific prevalence of PIMs and PPOs, and ICC outcomes. RESULTS: In total, 54 NHs (24 intervention; 30 control) and 1804 NH residents (847 intervention; 957 control) participated. Using a 3-level mixed-effects model accounting for data clustering, a significant effect in favor of the intervention was observed (odds ratio 1.479 [95% confidence interval 1.062-2.059, P = .021]). There was no significant difference between groups for most clinical outcomes. The median number of medications did not change over time in either group. CONCLUSIONS AND IMPLICATIONS: The complex multifaceted intervention tested in the COME-ON study successfully improved appropriateness of prescribing in NHs.

Incidence of Torsade de Pointes in a tertiary hospital population.

BACKGROUND: Multiple risk factors play a role in the development of QTc-prolongation and Torsade de Pointes (TdP). Cases of TdP are underreported and data on the incidence of TdP is scarce. The aim of this study was to investigate the incidence of TdP in a Belgian university hospital and describe the characteristics of TdP-cases using a risk score. METHODS: All cases from 2011 till 2013 coded with the ICD-9 code 427.1 in the University Hospitals of Leuven were selected. The medical files were reviewed and demographical, medical, medication and electrocardiographic data were collected. We focused on TdP-cases that were probably caused by the acquired long QT-syndrome. The RISQ-PATH score was used to quantify the risk in these cases (≥10 points as high risk for QTc-prolongation/TdP). RESULTS: Over three years, 41 TdP-cases were identified of which 19 cases were secondary to the acquired long QT-syndrome (52.6% females, mean age of 74±12years). This corresponds with an incidence of 0.16‰/year in a hospital population. Most of the patients (N=17) were treated with at least one QTc-prolonging drug (most frequently amiodarone, sotalol and furosemide) of whom 12 patients with ≥1 QTc-prolonging drug of list 1 of CredibleMeds. Fifteen patients had an electrocardiogram in a 24-hours interval before the TdP with a prolonged QTc-interval (≥450/470ms). All the patients had a RISQ-PATH score≥10. CONCLUSIONS: Although the incidence of 0.16‰/year might seem low, this means that approximately 173 possibly lethal TdP-cases can be expected in Belgian hospitals each year. All TdP-cases were associated with a high RISQ-PATH score.

Risk factors for QTc-prolongation: systematic review of the evidence.

Background QTc-interval prolongation has been associated with serious adverse events, such as Torsade de Pointes and sudden cardiac death. In the prevention of QTc-prolongation, special attention should go to high-risk patients. Aim of the review The aim of this review is to summarize and assess the evidence for different risk factors for QTc-prolongation (demographic factors, comorbidities, electrolytes, QTc-prolonging medication). Methods Potential studies were retrieved based on a systematic search of articles published until June 2015 in the databases Medline and Embase. Both terms about QTc-prolongation/Torsade de Pointes and risk factors were added in the search strategy. The following inclusion criteria were applied: randomized controlled trials and observational studies; inclusion of ≥500 patients from a general population (not limited to specific disease states); assessment of association between QTc-interval and risk factors. For the articles that met the inclusion criteria, the following data were extracted: study design, setting and study population, number of patients and cases of QTc-prolongation, method of electrocardiogram-monitoring, QTc-correction formula, definition of QTc-prolongation, statistical methods and results. Quality assessment was performed using the GRADE approach (for randomized controlled trials) and the STROBE-recommendations (for observational studies). Based on the number of significant results and the level of significance, a quotation of the evidence was allocated. Results Ten observational studies could be included, with a total of 89,532 patients [prospective cohort design: N = 6; multiple regression analyses: N = 5; median STROBE score = 17/22 (range 15-18)]. Very strong evidence was found for hypokalemia, use of diuretics, antiarrhythmic drugs and QTc-prolonging drugs of list 1 of CredibleMeds. Little or no evidence was found for hyperlipidemia, the use of digoxin or statins, neurological disorders, diabetes, renal failure, depression, alcohol abuse, heart rate, pulmonary disorders, hormone replacement therapy, hypomagnesemia, history of a prolonged QTc-interval/Torsade de Pointes, familial history of cardiovascular disease, and the use of only QTc-prolonging drugs of list 2 or 3 of CredibleMeds. Conclusion This systematic review gives a clear overview of the available evidence for a broad range of risk factors for QTc-prolongation.

Cases of drug-induced Torsade de Pointes: a review of Belgian cases in the EudraVigilance database.

OBJECTIVES: Post-marketing surveillance is very important, especially for rare adverse drug reactions like QTc-prolongation and Torsade de Pointes (TdP). The objective of this study was to investigate the characteristics of Belgian cases of drug-related TdP reported in the EudraVigilance database. METHODS: The EudraVigilance database was searched for Belgian post-marketing cases of TdP reported between December 2001-April 2015. These cases were identified with MedDRA preferred terms. Duplicate reports were excluded. Each included case report was reviewed to collect data about age, gender, seriousness, suspected drug, concomitant drugs, causality, and other known risk factors for QTc-prolongation. RESULTS: Between 2001 and 2015, only 31 cases coded as TdP were identified; 16 cases were also coded as 'prolonged QT' and 2 patients died. In total, 21 suspected drugs were implicated and most of them (N = 11) were part of list 1 of CredibleMeds. The most common suspected drugs were citalopram (N = 4) and amiodarone (N = 3). In 18 cases, a pharmacodynamic drug-drug interaction with risk of QTc-prolongation was present. Most patients (N = 25) had ≥2 other risk factors for QTc-prolongation. CONCLUSION: Over 15 years, only a low number of Belgian cases of TdP were identified in the EudraVigilance database. In most case reports, multiple risk factors for QTc-prolongation could be detected. This illustrates that there is a clear underreporting of QTc-prolongation and TdP in Belgium. Initiatives are needed to improve the awareness and knowledge of health care professionals regarding the risk of QTc-prolongation and TdP, both to prevent cases of TdP and to stimulate the reporting of these cases.

Development of a risk score for QTc-prolongation: the RISQ-PATH study.

Background More than 170 drugs are linked with QTc-prolongation, which in extreme cases can lead to Torsade de Pointes. Monitoring of this potential side effect is an important challenge in clinical practice. Objective To investigate the risk of QTc-prolongation in hospital patients who started a QTc-prolonging drug, and to develop a risk score to identify patients at high/low risk for QTc-prolongation. Setting University Hospitals Leuven, Belgium. Method All patients starting with haloperidol or a QTc-prolonging antibiotic/antimycotic were eligible for this observational study. Twelve-lead electrocardiograms were recorded at baseline and follow-up (steady state). Demographic, medical and drug data were collected. The obtained data were used to calculate the performance characteristics of a preliminary risk score (RISQ-PATH score), based on a systematic review of risk factors. ROC analysis determined a score of <10 points as a low risk for QTc-prolongation. Main outcome measure QTc-interval in a baseline and follow-up electrocardiogram. Results 178 patients (46.6% female; mean age 69 ± 14 years) were included (levofloxacin: N = 80; haloperidol: N = 41; fluconazole: N = 41). Overall, no significant difference between the mean QTc-values at baseline (425.7 ± 31.7 ms) and follow-up (428.0 ± 30.7 ms) was found (p = 0.328). However, 26 patients (14.6%) did develop a prolonged QTc-interval (≥450(♂)/470(♀) ms) of whom 25 with a RISQ-PATH score ≥10. This score had a sensitivity of 96.2% (95% CI 78.4-99.8%) and a negative predictive value of 98.0% (95% CI 88.2-99.9%). Conclusion This RISQ-PATH score is able to rule out low-risk patients with a negative predictive value of 98.0% and is promising to exclude patients from further follow-up when starting QTc-prolonging drugs. Clinicaltrials.gov Registration Number: NCT02068170.

Risk management of QTc-prolongation in patients receiving haloperidol: an epidemiological study in a University hospital in Belgium.

BACKGROUND: Many drugs, including haloperidol, are linked with a risk of QTc-prolongation, which can lead to Torsade de Pointes and sudden cardiac death. OBJECTIVE: To investigate the prevalence of concomitant risk factors for QTc-prolongation in patients treated with haloperidol, and the use of safety measures to minimize this risk. SETTING: University Hospitals of Leuven, Belgium. Methods A retrospective epidemiological study was performed. On 15 consecutive Mondays, all patients with a prescription for haloperidol were included. A risk score for QTc-prolongation, inspired by the pro-QTc score of Haugaa et al., was calculated based on gender, comorbidities, lab results and concomitant QTc-prolonging drugs (each factor counting for one point). Available electrocardiograms before and during the treatment of haloperidol were registered. MAIN OUTCOME MEASURE: Management of the risk of QTc-prolongation. RESULTS: Two hundred twenty-two patients were included (59.0 % men, median age 77 years) of whom 26.6 % had a risk score of ≥4 (known to significantly increase the mortality). Overall, 24.3 % received haloperidol in combination with other drugs with a known risk of Torsade de Pointes. Half of the patients had an electrocardiogram in the week before the start of haloperidol; only in one-third a follow-up electrocardiogram during haloperidol treatment was performed. Of the patients with a moderately (n = 41) or severely (n = 14) prolonged QTc-interval before haloperidol, 48.8 % and 42.9 % respectively had a follow-up electrocardiogram. In patients with a risk score ≥4, significantly more electrocardiograms were taken before starting haloperidol (p = 0.020). CONCLUSIONS: Although many patients had risk factors for QTc-prolongation (including the use of other QTc-prolonging drugs) or had a prolonged QTc on a baseline electrocardiogram, follow-up safety measures were limited. Persistent efforts should be taken to develop decision support systems to manage this risk.

Which QT Correction Formulae to Use for QT Monitoring?

BACKGROUND: Drug safety precautions recommend monitoring of the corrected QT interval. To determine which QT correction formula to use in an automated QT-monitoring algorithm in our electronic medical record, we studied rate correction performance of different QT correction formulae and their impact on risk assessment for mortality. METHODS AND RESULTS: All electrocardiograms (ECGs) in patients >18 years with sinus rhythm, normal QRS duration and rate <90 beats per minute (bpm) in the University Hospitals of Leuven (Leuven, Belgium) during a 2-month period were included. QT correction was performed with Bazett, Fridericia, Framingham, Hodges, and Rautaharju formulae. In total, 6609 patients were included (age, 59.8±16.2 years; 53.6% male and heart rate 68.8±10.6 bpm). Optimal rate correction was observed using Fridericia and Framingham; Bazett performed worst. A healthy subset showed 99% upper limits of normal for Bazett above current clinical standards: men 472 ms (95% CI, 464-478 ms) and women 482 ms (95% CI 474-490 ms). Multivariate Cox regression, including age, heart rate, and prolonged QTc, identified Framingham (hazard ratio [HR], 7.31; 95% CI, 4.10-13.05) and Fridericia (HR, 5.95; 95% CI, 3.34-10.60) as significantly better predictors of 30-day all-cause mortality than Bazett (HR, 4.49; 95% CI, 2.31-8.74). In a point-prevalence study with haloperidol, the number of patients classified to be at risk for possibly harmful QT prolongation could be reduced by 50% using optimal QT rate correction. CONCLUSIONS: Fridericia and Framingham correction formulae showed the best rate correction and significantly improved prediction of 30-day and 1-year mortality. With current clinical standards, Bazett overestimated the number of patients with potential dangerous QTc prolongation, which could lead to unnecessary safety measurements as withholding the patient of first-choice medication.

Impact of training on pharmacists' counseling of patients starting antidepressant therapy.

OBJECTIVE: To measure the impact of a one-day depression-related training program on pharmacists' counseling of unannounced "mystery shoppers" (MS) starting antidepressant therapy. METHODS: Clustered RCT pharmacies; intervention group pharmacists received communication skills training related to depression (n=21); control pharmacists did not (n=19). Eight months after training, the 40 community pharmacies were visited by MS with a first prescription for antidepressants. The pharmacy interactions were recorded and analyzed using the Roter Interaction Analysis System (RIAS). Mann-Whitney U tests were used to evaluate the impact of training on pharmacy interactions and MS evaluations of the pharmacists' skills and attitudes. RESULTS: Interactions of intervention group pharmacists were significantly longer and consisted of more education and counseling statements about lifestyle and psychosocial concerns. Intervention group pharmacists asked more questions about medical condition and therapeutic regimen, as well as socioemotional concerns. MS gave more socioemotional information to intervention group pharmacists and were more positive in their assessment of these pharmacists' skills and attitudes (p values<0.05). CONCLUSION: Pharmacist training in depression care can positively affect the quality of patient care. PRACTICE IMPLICATIONS: Postgraduate training in depression related services is a worthwhile approach to improve the quality of pharmaceutical care.