Non-invasive assessment of fluid responsiveness to guide fluid therapy in patients with sepsis in the emergency department:a prospective cohort study

BACKGROUND: Little is known about optimal fluid therapy for patients with sepsis without shock who present to the ED. In this study, we aimed to quantify the effect of a fluid challenge on non-invasively measured Cardiac Index (CI) in patients presenting with sepsis without shock. METHODS: In a prospective cohort study, CI, stroke volume (SV) and systemic vascular resistance (SVR) were measured non-invasively in 30 patients presenting with sepsis without shock to the ED of a large teaching hospital in the Netherlands between May 2018 and March 2019 using the ClearSight system. After baseline measurements were performed, a passive leg raise (PLR) was done to simulate a fluid bolus. Measurements were then repeated 30, 60, 90 and 120 s after PLR. Finally, a standardised 500 mL NaCl 0.9% intravenous bolus was administered after which final measurements were done. Fluid responsiveness was defined as >15% increase in CI after a standardised fluid challenge. MEASUREMENTS AND MAIN RESULTS: Seven out of 30 (23%) patients demonstrated a >15% increase in CI after PLR and after a 500 mL fluid bolus. Fluid responders had a higher estimated glomerular filtration rate (eGFR) (64 (44–78) vs 37 (23–47), p=0.009) but otherwise similar patient and treatment characteristics as non-responders. Baseline measurements of cardiac output (CO), CI, SV and SVR were unrelated to PLR fluid responsiveness. The change in CI after PLR was strongly positive correlated to the change in CI after a 500 mL NaCl 0.9% fluid bolus (r=0.88, p<0.001). CONCLUSION: The results of the present study demonstrate that in patients with sepsis in the absence of shock, three out of four patients do not demonstrate a clinically relevant increase in CI after a standardised fluid challenge. Non-invasive CO monitoring in combination with a PLR test has the potential to identify patients who might benefit from fluid resuscitation and may contribute to a better tailored treatment of these patients

Effectiveness and cost-effectiveness of proactive and multidisciplinary integrated care for older people with complex problems in general practice: An individual participant data meta-analysis

Purpose: to support older people with several healthcare needs in sustaining adequate functioning and independence, more proactive approaches are needed. This purpose of this study is to summarise the (cost-) effectiveness of proactive, multidisciplinary, integrated care programmes for older people in Dutch primary care. Methods design: individual patient data (IPD) meta-analysis of eight clinically controlled trials. Setting: primary care sector. Interventions: combination of (i) identification of older people with complex problems by means of screening, followed by (ii) a multidisciplinary integrated care programme for those identified. Main outcome: activities of daily living, i.e. a change on modified Katz-15 scale between baseline and 1-year follow-up. Secondary outcomes: quality of life (visual analogue scale 0-10), psychological (mental well-being scale Short Form Health Survey (SF)-36) and social well-being (single item, SF-36), quality-adjusted life years (Euroqol-5dimensions-3level (EQ-5D-3L)), healthcare utilisation and cost-effectiveness. Analysis: intention-to-treat analysis, two-stage IPD and subgroup analysis based on patient and intervention characteristics. Results: included were 8,678 participants: median age of 80.5 (interquartile range 75.3; 85.7) years; 5,496 (63.3%) women. On the modified Katz-15 scale, the pooled difference in change between the intervention and control group was -0.01 (95% confidence interval -0.10 to 0.08). No significant differences were found in the other patient outcomes or subgroup analyses. Compared to usual care, the probability of the intervention group to be cost-effective was less than 5%. Conclusion: compared to usual care at 1-year follow-up, strategies for identification of frail older people in primary care combined with a proactive integrated care intervention are probably not (cost-) effective

Adjuvanted vaccines in pregnancy:no evidence for effect of the adjuvanted H1N1/09 vaccination on occurrence of preeclampsia or intra-uterine growth restriction

OBJECTIVE: During the H1N1/09 pandemic, pregnant women in the Netherlands were vaccinated with an adjuvanted vaccine. During pregnancy, the maternal immune system changes to enable placental development and growth and acceptance of the semi-allogeneic fetus. As an adjuvant is a pro-inflammatory substance, it may interfere with these immunological changes, resulting in poor placentation or placental growth, which may result in preeclampsia (PE) and fetal intra-uterine growth restriction (IUGR). This study investigated a possible association between adjuvanted H1N1/09 vaccination and the development of PE and/or IUGR. STUDY DESIGN: Case-control study. Cases were Dutch women with PE and/or IUGR occurring during H1N1/09 vaccination program. Controls had uncomplicated pregnancies during the same period. Maternal characteristics, pregnancy and neonatal outcomes were collected from medical files. Participants were contacted by telephone to enquire about vaccination. Data were analyzed using t-tests, Chi-square tests or Fisher's exact tests. Multivariate analysis was conducted to control for confounders. RESULTS: We included 254 cases and 247 controls. Of the cases, 90 (35.4%) were vaccinated, compared to 87 (35.2%) of the controls (OR:1.009, 95% CI:0.70-1.46, p:0.961). The majority (73.5%) had been vaccinated in second and third trimester. In multivariate analysis, there were no confounders influencing these results. Exploratory subgroup analysis did not show an association between vaccination status in subgroups of women with either PE or IUGR. CONCLUSION: Our study showed no association between adjuvanted H1N1/09 vaccination and PE and/or IUGR

Unravelling complex primary-care programs to maintain independent living in older people: a systematic overview

textabstractObjectives: Complex interventions are criticized for being a “black box”, which makes it difficult to determine why they succeed or fail. Recently, nine proactive primary-care programs aiming to prevent functional decline in older adults showed inconclusive effects. The aim of this study was to systematically unravel, compare, and synthesize the development and evaluation of nine primary-care programs within a controlled trial to further improve the development and evaluation of complex interventions. Study Design and Setting: A systematic overview of all written data on the nine proactive primary-care programs was conducted using a validated item list. The nine proactive primary-care programs involved 214 general practices throughout the Netherlands. Results: There was little or no focus on the (1) context surrounding the care program, (2) modeling of processes and outcomes, (3) intervention fidelity and adaptation, and (4) content and evaluation of training for interventionists. Conclusions: An in-depth analysis of the context, modeling of the processes and outcomes, measurement and reporting of intervention fidelity, and implementation of effective training for interventionists is needed to enhance the development and replication of future complex interventions

High treatment uptake in human immunodeficiency virus/ hepatitis C virus-coinfected patients after unrestricted access to direct-acting antivirals in the Netherlands

Background The Netherlands has provided unrestricted access to direct-acting antivirals (DAAs) since November 2015. We analyzed the nationwide hepatitis C virus (HCV) treatment uptake among patients coinfected with human immunodeficiency virus (HIV) and HCV. Methods Data were obtained from the ATHENA HIV observational cohort in which >98% of HIV-infected patients ever registered since 1998 are included. Patients were included if they ever had 1 positive HCV RNA result, did not have spontaneous clearance, and were known to still be in care. Treatment uptake and outcome were assessed. When patients were treated more than once, data were included from only the most recent treatment episode. Data were updated until February 2017. In addition, each treatment center was queried in April 2017 for a data update on DAA treatment and achieved sustained virological response. Results Of 23574 HIV-infected patients ever linked to care, 1471 HCV-coinfected patients (69% men who have sex with men, 15% persons who [formerly] injected drugs, and 15% with another HIV transmission route) fulfilled the inclusion criteria. Of these, 87% (1284 of 1471) had ever initiated HCV treatment between 2000 and 2017, 76% (1124 of 1471) had their HCV infection cured; DAA treatment results were pending in 6% (92 of 1471). Among men who have sex with men, 83% (844 of 1022) had their HCV infection cured, and DAA treatment results were pending in 6% (66 of 1022). Overall, 187 patients had never initiated treatment, DAAs had failed in 14, and a pegylated interferon-alfa–based regimen had failed in 54. Conclusions Fifteen months after unrestricted DAA availability the majority of HIV/HCV-coinfected patients in the Netherlands have their HCV infection cured (76%) or are awaiting DAA treatment results (6%). This rapid treatment scale-up may contribute to future HCV elimination among these patients