Background and objectives
The modified Rankin Scale (mRS) is one of the most frequently used outcome measures in trials in patients with an aneurysmal subarachnoid hemorrhage (aSAH). The assessment ...method of the mRS is often not clearly described in trials, while the method used might influence the mRS score. The aim of this study is to evaluate the inter-method reliability of different assessment methods of the mRS.
Methods
This is a prospective, randomized, multicenter study with follow-up at 6 weeks and 6 months. Patients aged ≥ 18 years with aSAH were randomized to either a structured interview or a self-assessment of the mRS. Patients were seen by a physician who assigned an mRS score, followed by either the structured interview or the self-assessment. Inter-method reliability was assessed with the quadratic weighted kappa score and percentage of agreement. Assessment of feasibility of the self-assessment was done by a feasibility questionnaire.
Results
The quadratic weighted kappa was 0.60 between the assessment of the physician and structured interview and 0.56 between assessment of the physician and self-assessment. Percentage agreement was, respectively, 50.8 and 19.6%. The assessment of the mRS through a structured interview and by self-assessment resulted in systematically higher mRS scores than the mRS scored by the physician. Self-assessment of the mRS was proven feasible.
Discussion
The mRS scores obtained with different assessment methods differ significantly. The agreement between the scores is low, although the reliability between the assessment methods is good. This should be considered when using the mRS in clinical trials.
Trial registration
www.trialregister.nl
; Unique identifier: NL7859.
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EMUNI, FIS, FZAB, GEOZS, GIS, IJS, IMTLJ, KILJ, KISLJ, MFDPS, NLZOH, NUK, OILJ, PNG, SAZU, SBCE, SBJE, SBMB, SBNM, UKNU, UL, UM, UPUK, VKSCE, ZAGLJ
•Following a global push for the use of hydroxychloroquine and chloroquine, there is ongoing discussion about the effectivity of these drugs.•The findings of this observational study provide crucial ...data on a potential protective effect of hydroxychloroquine in non-ICU, hospitalized, COVID-19 patients.•Early treatment with HCQ on the first day of admission is associated with a 53% reduction in risk of transfer to the ICU for mechanical ventilation.•This protective effect was not observed for chloroquine; therefore, these drugs cannot be regarded as interchangeable.
The global push for the use of hydroxychloroquine (HCQ) and chloroquine (CQ) against COVID-19 has resulted in an ongoing discussion about the effectivity and toxicity of these drugs. Recent studies report no effect of (H)CQ on 28-day mortality. We investigated the effect of HCQ and CQ in hospitalized patients on the non-ICU COVID-ward.
A nationwide, observational cohort study was performed in The Netherlands. Hospitals were given the opportunity to decide independently on the use of three different COVID-19 treatment strategies: HCQ, CQ, or no treatment. We compared the outcomes between these groups. The primary outcomes were 1) death on the COVID-19 ward, and 2) transfer to the intensive care unit (ICU).
The analysis included 1064 patients from 14 hospitals: 566 patients received treatment with either HCQ (n = 189) or CQ (n = 377), and 498 patients received no treatment. In a multivariate propensity-matched weighted competing regression analysis, there was no significant effect of (H)CQ on mortality on the COVID ward. However, HCQ was associated with a significantly decreased risk of transfer to the ICU (hazard ratio (HR) = 0.47, 95% CI = 0.27–0.82, p = 0.008) when compared with controls. This effect was not found in the CQ group (HR = 0.80, 95% CI = 0.55–1.15, p = 0.207), and remained significant after competing risk analysis.
The results of this observational study demonstrate a lack of effect of (H)CQ on non-ICU mortality. However, we show that the use of HCQ — but not CQ — is associated with a 53% reduction in risk of transfer of COVID-19 patients from the regular ward to the ICU. Recent prospective studies have reported on 28-day, all-cause mortality only; therefore, additional prospective data on the early effects of HCQ in preventing transfer to the ICU are still needed.
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GEOZS, IJS, IMTLJ, KILJ, KISLJ, NLZOH, NUK, OILJ, PNG, SAZU, SBCE, SBJE, UILJ, UL, UM, UPCLJ, UPUK, ZAGLJ, ZRSKP
We aimed to determine the prevalence and phenotypic spectrum of NOTCH1 mutations in left-sided congenital heart disease (LS-CHD). LS-CHD includes aortic valve stenosis, a bicuspid aortic valve, ...coarctation of the aorta, and hypoplastic left heart syndrome.
NOTCH1 was screened for mutations in 428 nonsyndromic probands with LS-CHD, and family histories were obtained for all. When a mutation was detected, relatives were also tested.
In 148/428 patients (35%), LS-CHD was familial. Fourteen mutations (3%; 5 RNA splicing mutations, 8 truncating mutations, 1 whole-gene deletion) were detected, 11 in familial disease (11/148 (7%)) and 3 in sporadic disease (3/280 (1%)). Forty-nine additional mutation carriers were identified among the 14 families, of whom 12 (25%) were asymptomatic. Most of these mutation carriers had LS-CHD, but 9 (18%) had right-sided congenital heart disease (RS-CHD) or conotruncal heart disease (CTD). Thoracic aortic aneurysms (TAAs) occurred in 6 mutation carriers (probands included 6/63 (10%)).
Pathogenic mutations in NOTCH1 were identified in 7% of familial LS-CHD and in 1% of sporadic LS-CHD. The penetrance is high; a cardiovascular malformation was found in 75% of NOTCH1 mutation carriers. The phenotypic spectrum includes LS-CHD, RS-CHD, CTD, and TAA. Testing NOTCH1 for an early diagnosis in LS-CHD/RS-CHD/CTD/TAA is warranted.Genet Med 18 9, 914-923.
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GEOZS, IJS, IMTLJ, KILJ, KISLJ, NLZOH, NUK, OILJ, PNG, SAZU, SBCE, SBJE, UILJ, UL, UM, UPCLJ, UPUK, ZAGLJ, ZRSKP
Background Direct-acting antivirals (DAAa) cure hepatitis C virus (HCV) infections in 95% of infected patients. Modeling studies predict that universal HCV treatment will lead to a decrease in the ...incidence of new infections but real-life data are lacking. The incidence of HCV among Dutch human immunodeficiency virus (HIV)–positive men who have sex with men (MSM) has been high for >10 years. In 2015 DAAs became available to all Dutch HCV patients and resulted in a rapid treatment uptake in HIV-positive MSM. We assessed whether this uptake was followed by a decrease in the incidence of HCV infections. Methods Two prospective studies of treatment for acute HCV infection enrolled patients in 17 Dutch HIV centers, having 76% of the total HIV-positive MSM population in care in the Netherlands. Patients were recruited in 2014 and 2016, the years before and after unrestricted DAA availability. We compared the HCV incidence in both years. Results The incidence of acute HCV infection decreased from 93 infections during 8290 person-years of follow-up (PYFU) in 2014 (11.2/1000 PYFU; 95% confidence interval CI, 9.1–13.7) to 49 during 8961 PYFU in 2016 (5.5/1000 PYFU; 4.1–7.2). The incidence rate ratio of 2016 compared with 2014 was 0.49 (95% CI, .35–.69). Simultaneously, a significant increase in the percentage positive syphilis (+2.2%) and gonorrhea (+2.8%) tests in HIV-positive MSM was observed at sexual health clinics across the Netherlands and contradicts a decrease in risk behavior as an alternative explanation. Conclusions Unrestricted DAA availability in the Netherlands was followed by a 51% decrease in acute HCV infections among HIV-positive MSM.
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BFBNIB, NUK, PNG, UL, UM, UPUK
In patients with mild disabilities after aneurysmal subarachnoid hemorrhage (aSAH), invisible symptoms might be easily overlooked during consultations in the outpatient clinic. We hypothesize that ...the Questionnaire for the Screening of Symptoms in aneurysmal Subarachnoid Hemorrhage (SOS-SAH), a disease-specific patient-reported outcome measure, might aid in screening for symptoms after aSAH. The objective of this explorative study is to evaluate the perceived impact of using the SOS-SAH in daily clinical practice for patients after aSAH, as well as to explore potential barriers to further implementation.
This multi-method study consists of a quantitative and a qualitative component. To evaluate differences in quality of care, a patient experience survey was sent to patients receiving usual care and to patients who received the SOS-SAH. A multiple linear regression model was applied, with the intervention group and case mix adjusters as independent variables. We described differences in the number of symptoms discussed between patients receiving usual care and those receiving care post-implementation. Following implementation, 16 patients and 6 healthcare professionals were interviewed about their perceptions concerning the impact of and barriers to using the SOS-SAH. A thematic analysis was performed to identify the main themes.
The survey did not reveal any differences between the usual-care group and the post-implementation group on the scales of the patient experience survey. After implementation of the SOS-SAH, the number of symptoms discussed during consultation did not increase. The interviews suggest that the SOS-SAH may improve the preparation of patients by providing them with greater insight into their complaints and by raising issues for the consultation. It could also enhance the structure and efficiency of consultation, in addition to improving communication about issues that matter to patients. All patients and healthcare professionals recommended continuing the use of the SOS-SAH in daily practice.
Although no quantitative improvements were found in patient experience and symptoms discussed during consultation, implementation of the SOS-SAH could aid in screening for symptoms in patients after aSAH, and it might have a positive influence on patient preparation, while helping to structure consultations between patients and healthcare professionals.
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DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
The modified Rankin Scale (mRS), a clinician-reported outcome measure of global disability, has never been validated in patients with aneurysmal subarachnoid hemorrhage (aSAH). The aims of this study ...are to assess: (1) convergent validity of the mRS; (2) responsiveness of the mRS; and (3) the distribution of mRS scores across patient-reported outcome measures (PROMs).
This is a prospective randomized multicenter study. The mRS was scored by a physician for all patients, and subsequently by structured interview for half of the patients and by self-assessment for the other half. All patients completed EuroQoL 5D-5L, RAND-36, Stroke Specific Quality of Life scale (SS-QoL) and Global Perceived Effect (GPE) questionnaires. Convergent validity and responsiveness were assessed by testing hypotheses.
In total, 149 patients with aSAH were included for analysis. The correlation of the mRS with EQ-5D-5L was r = - 0.546, while with RAND-36 physical and mental component scores the correlation was r = - 0.439and r = - 0.574 respectively, and with SS-QoL it was r = - 0.671. Three out of four hypotheses for convergent validity were met. The mRS assessed through structured interviews was more highly correlated with the mental component score than with the physical component score of RAND-36. Improvement in terms of GPE was indicated by 83% of patients; the mean change score of these patients on the mRS was - 0.08 (SD 0.915). None of the hypotheses for responsiveness were met.
The results show that the mRS generally correlates with other instruments, as expected, but it lacks responsiveness. A structured interview of the mRS is best for detecting disabling neuropsychological complaints.
URL: https://trialsearch.who.int ; Unique identifier: NL7859, Date of first administration: 08-07-2019.
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DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
Abstract Background Cardiomyopathies are usually inherited and predominantly affect adults, but they can also present in childhood. Although our understanding of the molecular basis of pediatric ...cardiomyopathy has improved, the underlying mechanism remains elusive in a substantial proportion of cases. Objectives This study aimed to identify new genes involved in pediatric cardiomyopathy. Methods The authors performed homozygosity mapping and whole-exome sequencing in 2 consanguineous families with idiopathic pediatric cardiomyopathy. Sixty unrelated patients with pediatric cardiomyopathy were subsequently screened for mutations in a candidate gene. First-degree relatives were submitted to cardiac screening and cascade genetic testing. Myocardial samples from 2 patients were processed for histological and immunohistochemical studies. Results We identified 5 patients from 3 unrelated families with pediatric cardiomyopathy caused by homozygous truncating mutations in ALPK3 , a gene encoding a nuclear kinase that plays an essential role in early differentiation of cardiomyocytes. All patients with biallelic mutations presented with severe hypertrophic and/or dilated cardiomyopathy in utero, at birth, or in early childhood. Three patients died from heart failure within the first week of life. Moreover, 2 of 10 (20%) heterozygous family members showed hypertrophic cardiomyopathy with an atypical distribution of hypertrophy. Deficiency of alpha-kinase 3 has previously been associated with features of both hypertrophic and dilated cardiomyopathy in mice. Consistent with studies in knockout mice, we provide microscopic evidence for intercalated disc remodeling. Conclusions Biallelic truncating mutations in the newly identified gene ALPK3 give rise to severe, early-onset cardiomyopathy in humans. Our findings highlight the importance of transcription factor pathways in the molecular mechanisms underlying human cardiomyopathies.
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GEOZS, IJS, IMTLJ, KILJ, KISLJ, NLZOH, NUK, OILJ, PNG, SAZU, SBCE, SBJE, UILJ, UL, UM, UPCLJ, UPUK, ZAGLJ, ZRSKP
Anal and penile high-risk human papillomavirus (HPV) infection is associated with anogenital cancer, which is especially common in HIV-infected MSM. We assessed HPV prevalence and determinants in ...MSM.
Analysis of baseline data from a prospective cohort study.
MSM aged 18 years or older were recruited in Amsterdam, the Netherlands. Participants completed risk-factor questionnaires. HPV DNA was analyzed in anal and penile shaft self-swabs and genotyped using a sensitive PCR and reverse line blot assay (SPF10-PCR-DEIA-LiPA25-system). Multivariable logistic regression analyses were performed to assess determinants of high-risk HPV infection.
MSM (n = 778) were recruited in 2010-2011, of whom 317 (41%) were HIV-infected. Prevalence of anal high-risk HPV infection was 45% in HIV-negative versus 65% in HIV-infected MSM (P <0.001). HPV-16 was the most frequently detected type and was more common in HIV-infected MSM (13% in HIV-negative and 22% in HIV-infected MSM; P = 0.001). Prevalence of penile high-risk HPV infection was 16% in HIV-negative and 32% in HIV-infected MSM (P <0.001). In multivariable analyses, HIV infection remained associated with anal adjusted odds ratio (aOR) 2.2; 1.8-2.7 and penile (aOR 2.0; 1.4-2.9) high-risk HPV infection. Higher number of lifetime male sex partners was significantly associated with anal and penile high-risk HPV in HIV-negative, but not HIV-infected MSM. Receptive anal intercourse was associated with anal high-risk HPV in HIV-infected MSM.
Anal and penile high-risk HPV infections are very common in MSM. HIV infection is a strong and independent determinant for anal and penile high-risk HPV infection. Determinants for HPV infection appear to differ between HIV-negative and HIV-infected MSM.
Oral infection with human papillomavirus (HPV) is associated with a subset of head and neck cancers. We compared prevalence of, and risk factors for, oral HPV infection among HIV-negative and ...HIV-infected MSM.
Analysis of baseline data from a prospective cohort study.
MSM aged 18 years or older were recruited from three study sites in Amsterdam, the Netherlands. Participants completed a self-administered risk-factor questionnaire. Oral-rinse and gargle specimens were analyzed for HPV DNA and genotyped using a highly sensitive PCR and reverse line blot assay short PCR fragment (SPF)10-PCR-DNA Enzyme Immuno Assay (DEIA)/LiPA25 system.
In 2010-2011, 794 MSM were included, of whom 767 participants had sufficient data for analysis. Median age was 40.1 years interquartile range (IQR) 34.8-47.5 and 314 men were HIV-infected (40.9%). Any of 25 typable HPV types was present in 24.4% of all oral samples. Oncogenic HPV types were detected in 24.8 and 8.8% of oral samples from HIV-infected and HIV-negative MSM, respectively (P < 0.001). Of these high-risk types, HPV-16 was the most common (overall 3.4%). Oral infection with high-risk HPV was associated with HIV infection in multivariable analysis (P < 0.001). Increasing age was significantly associated with oral HPV infection in HIV-negative, but not in HIV-infected MSM.
Oral HPV infection is very common among MSM. HIV infection was independently associated with high-risk oral HPV infection, suggesting an important role of HIV in oral HPV infection.
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