Increase in Incidence Rates and Risk Factors for Multidrug Resistant Bacteria in Septic Children: A Nationwide Spanish Cohort Study (2013-2019).

The emergence of multidrug-resistant (MDR) bacteria in children is a growing concern, particularly among septic patients, given the need for first-right dosing. Our aim was to determine the incidence rates and factors associated with MDR-sepsis in the pediatric intensive care unit (PICU), using data from the Spanish ENVIN-HELICS PICU registry between 2013 and 2019. The rate of MDR bacteria among septic children ranged between 5.8 and 16.2% throughout this study period, with a significant increase since 2015 (p = 0.013). MDR-gram-negative bacteria (92%), particularly EBL-Enterobacterales (63.7%), were the most frequent causative microorganisms of MDR-sepsis. During this study period, sixteen MDR-sepsis (32.6%) corresponded to intrahospital infections, and 33 (67.4%) had community-onset sepsis, accounting for 10.5% of the overall community-onset sepsis. Independent risk factors associated with MDR-sepsis were antibiotics 48 h prior to PICU admission (OR 2.38) and PICU onset of sepsis (OR 2.58) in >1 year-old children, and previous malnourishment (OR 4.99) in <1 year-old children. Conclusions: There was an alarming increase in MDR among septic children in Spain, mainly by gram-negative (ESBL-Enterobacterales), mostly coming from the community setting. Malnourished infants and children on antibiotics 48 h prior to PICU are at increased risk and therefore require closer surveillance.

Device Exposure and Patient Risk Factors' Impact on the Healthcare-Associated Infection Rates in PICUs.

Healthcare-associated infections related to device use (DA-HAIs) are a serious public health problem since they increase mortality, length of hospital stay and healthcare costs. We performed a multicenter, prospective study analyzing critically ill pediatric patients admitted to 26 Spanish pediatric intensive care units (PICUs) over a 3-month period each year from 2014 to 2019. To make comparisons and evaluate the influence of HAI Zero Bundles (care bundles that intend to reduce the DA-HAI rates to zero) on PICU HAI rates, the analysis was divided into two periods: 2014-2016 and 2017-2019 (once most of the units had incorporated all the Zero Bundles). A total of 11,260 pediatric patients were included. There were 390 episodes of HAIs in 317 patients and the overall rate of HAIs was 6.3 per 1000 patient days. The DA-HAI distribution was: 2.46/1000 CVC days for central-line-associated bloodstream infections (CLABSIs), 5.75/1000 MV days for ventilator-associated pneumonia (VAP) and 3.6/1000 UC days for catheter-associated urinary tract infections (CAUTIs). Comparing the two periods, the HAI rate decreased (p = 0.061) as well as HAI episodes (p = 0.011). The results demonstrate that exposure to devices constitutes an extrinsic risk factor for acquiring HAIs. The multivariate analysis highlights previous bacterial colonization by multidrug-resistant (MDR) bacteria as the most important extrinsic risk factor for HAIs (OR 20.4; 95%CI 14.3-29.1). In conclusion, HAI Zero Bundles have been shown to decrease HAI rates, and the focus should be on the prompt removal of devices, especially in children with important intrinsic risk factors.

Antimicrobial Stewardship Improvement in Pediatric Intensive Care Units in Spain-What Have We Learned?

Antibiotic misuse in pediatric intensive care units (PICUs) can lead to increased antimicrobial resistance, antibiotic-triggered side effects, hospital costs, and mortality. We performed a multicenter, prospective study, analyzing critically ill pediatric patients (≥1 month to ≤18 years) admitted to 26 Spanish PICUs over a 3-month period each year (1 April−30 June) from 2014−2019. To make comparisons and evaluate the influence of AMS programs on antibiotic use in PICUs, the analysis was divided into two periods: 2014−2016 and 2017−2019 (once 84% of the units had incorporated an AMS program). A total of 11,260 pediatric patients were included. Total antibiotic prescriptions numbered 15,448 and, overall, 8354 patients (74.2%) received at least one antibiotic. Comparing the two periods, an increase was detected in the number of days without antibiotics in patients who received them divided by the number of days in PICUs, for community-acquired infections (p < 0.001) and healthcare-associated infections (HAIs) acquired in PICUs (p < 0.001). Antibiotics were empirical in 7720 infections (85.6%), with an increase in appropriate antibiotic indications during the second period (p < 0.001). The main indication for antibiotic adjustment was de-escalation, increasing in the second period (p = 0.045). Despite the high rate of antibiotic use in PICUs, our results showed a significant increase in appropriate antibiotic use and adjustment following the implementation of AMS programs.

Phlebotonics for venous insufficiency.

BACKGROUND: Chronic venous insufficiency (CVI) is a condition in which veins are unable to transport blood unidirectionally towards the heart. CVI usually occurs in the lower limbs. It might result in considerable discomfort, with symptoms such as pain, itchiness and tiredness in the legs. Patients with CVI may also experience swelling and ulcers. Phlebotonics are a class of drugs often used to treat CVI. This is the second update of a review first published in 2005. OBJECTIVES: To assess the efficacy and safety of phlebotonics administered orally or topically for treatment of signs and symptoms of lower extremity CVI. SEARCH METHODS: The Cochrane Vascular Information Specialist searched the Cochrane Vascular Specialised Register, CENTRAL, MEDLINE, Embase, and CINAHL databases and the World Health Organization International Clinical Trials Registry Platform and Clinicaltrials.gov trials register up to 12 November 2019. We searched the reference lists of the articles retrieved by electronic searches for additional citations. We also contacted authors of unpublished studies. SELECTION CRITERIA: We included randomised, double-blind, placebo-controlled trials (RCTs) assessing the efficacy of phlebotonics (rutosides, hidrosmine, diosmine, calcium dobesilate, chromocarbe, Centella asiatica, disodium flavodate, French maritime pine bark extract, grape seed extract and aminaftone) in patients with CVI at any stage of the disease. DATA COLLECTION AND ANALYSIS: Two review authors independently extracted data and assessed the quality of included RCTs. We estimated the effects of treatment by using risk ratios (RRs), mean differences (MDs) and standardized mean differences (SMDs), according to the outcome assessed. We calculated 95% confidence intervals (CIs) and percentage of heterogeneity (I2). Outcomes of interest were oedema, quality of life (QoL), assessment of CVI and adverse events. We used GRADE criteria to assess the certainty of the evidence. MAIN RESULTS: We identified three new studies for this update. In total, 69 RCTs of oral phlebotonics were included, but only 56 studies (7690 participants, mean age 50 years) provided quantifiable data for the efficacy analysis. These studies used different phlebotonics (28 on rutosides, 11 on hidrosmine and diosmine, 10 on calcium dobesilate, two on Centella asiatica, two on aminaftone, two on French maritime pine bark extract and one on grape seed extract). No studies evaluating topical phlebotonics, chromocarbe, naftazone or disodium flavodate fulfilled the inclusion criteria. Moderate-certainty evidence suggests that phlebotonics probably reduce oedema slightly in the lower legs, compared with placebo (RR 0.70, 95% CI 0.63 to 0.78; 13 studies; 1245 participants); and probably reduce ankle circumference (MD -4.27 mm, 95% CI -5.61 to -2.93 mm; 15 studies; 2010 participants). Moderate-certainty evidence shows that phlebotonics probably make little or no difference in QoL compared with placebo (SMD -0.06, 95% CI -0.22 to 0.10; five studies; 1639 participants); and similarly, may have little or no effect on ulcer healing (RR 0.94, 95% CI 0.79 to 1.13; six studies; 461 participants; low-certainty evidence). Thirty-seven studies reported on adverse events. Pooled data suggest that phlebotonics probably increase adverse events slightly, compared to placebo (RR 1.14, 95% CI 1.02 to 1.27; 37 studies; 5789 participants; moderate-certainty evidence). Gastrointestinal disorders were the most frequently reported adverse events. We downgraded our certainty in the evidence from 'high' to 'moderate' because of risk of bias concerns, and further to 'low' because of imprecision. AUTHORS' CONCLUSIONS: There is moderate-certainty evidence that phlebotonics probably reduce oedema slightly, compared to placebo; moderate-certainty evidence of little or no difference in QoL; and low-certainty evidence that these drugs do not influence ulcer healing. Moderate-certainty evidence suggests that phlebotonics are probably associated with a higher risk of adverse events than placebo. Studies included in this systematic review provided only short-term safety data; therefore, the medium- and long-term safety of phlebotonics could not be estimated. Findings for specific groups of phlebotonics are limited due to small study numbers and heterogeneous results. Additional high-quality RCTs focusing on clinically important outcomes are needed to improve the evidence base.

Phlebotonics for venous insufficiency.

BACKGROUND: Chronic venous insufficiency (CVI) is a common condition caused by valvular dysfunction with or without associated obstruction, usually in the lower limbs. It might result in considerable discomfort with symptoms such as pain, itchiness and tiredness in the legs. Patients with CVI may also experience swelling and ulcers. Phlebotonics are a class of drugs often used to treat CVI. This is an update of a review first published in 2005. OBJECTIVES: To assess the efficacy and safety of phlebotonics administered both orally and topically for treatment of signs and symptoms of lower extremity CVI. SEARCH METHODS: For this update, the Cochrane Vascular Trials Search Co-ordinator (TSC) searched the Specialised Register (August 2015), as well as the Cochrane Central Register of Controlled Trials (CENTRAL; 2015, Issue 7). The reference lists of the articles retrieved by electronic searches were searched for additional citations. We also contacted pharmaceutical companies and searched the World Health Organization (WHO) International Clinical Trials Registry Platform Search Portal for ongoing studies (last searched in August 2015). SELECTION CRITERIA: Randomised, double-blind, placebo-controlled trials (RCTs) assessing the efficacy of rutosides, hidrosmine, diosmine, calcium dobesilate, chromocarbe, Centella asiatica, disodium flavodate, french maritime pine bark extract, grape seed extract and aminaftone in patients with CVI at any stage of the disease. DATA COLLECTION AND ANALYSIS: Two review authors independently extracted data and assessed the quality of included RCTs. We estimated the effects of treatment by using risk ratios (RRs), mean differences (MDs) and standardised mean differences (SMDs), according to the outcome assessed. We calculated 95% confidence interval (CIs) and percentage of heterogeneity (I(2)). Additionally, we performed sensitivity analyses. MAIN RESULTS: We included 66 RCTs of oral phlebotonics, but only 53 trials provided quantifiable data (involving 6013 participants; mean age 50 years) for the efficacy analysis: 28 for rutosides, 10 hidrosmine and diosmine, nine calcium dobesilate, two Centella asiatica, two aminaftone, two french maritime pine bark extract and one grape seed extract. No studies evaluating topical phlebotonics, chromocarbe, naftazone or disodium flavodate fulfilled the inclusion criteria.Moderate-quality evidence suggests that phlebotonics reduced oedema in the lower legs compared with placebo. Phlebotonics showed beneficial effects among participants including reduced oedema (RR 0.70, 95% CI 0.63 to 0.78; I(2) = 20%; 1245 participants) and ankle circumference (MD -4.27 mm, 95% CI -5.61 to -2.93 mm; I(2) = 47%; 2010 participants). Low-quality evidence reveals no difference in the proportion of ulcers cured with phlebotonics compared with placebo (RR 0.94, 95% CI 0.79 to 1.13; I(2) = 5%; 461 participants). In addition, phlebotonics showed greater efficacy for trophic disorders, cramps, restless legs, swelling and paraesthesia, when compared with placebo. We identified heterogeneity for the variables of pain, itching, heaviness, quality of life and global assessment by participants. For quality of life, it was not possible to pool the studies because heterogeneity was high. However, high-quality evidence suggests no differences in quality of life for calcium dobesilate compared with placebo (MD -0.60, 95% CI -2.15 to 0.95; I(2) = 40%; 617 participants), and low-quality evidence indicates that in the aminaftone group, quality of life was improved over that reported in the placebo group (MD -10.00, 95% CI -17.01 to - 2.99; 79 participants). Moderate-quality evidence shows that the phlebotonics group had greater risk of non-severe adverse events than the placebo group (RR 1.21, 95% CI 1.05 to 1.41; I(2) = 0; 3975 participants). Gastrointestinal disorders were the most frequently reported adverse events. AUTHORS' CONCLUSIONS: Moderate-quality evidence shows that phlebotonics may have beneficial effects on oedema and on some signs and symptoms related to CVI such as trophic disorders, cramps, restless legs, swelling and paraesthesia when compared with placebo but can produce more adverse effects. Phlebotonics showed no differences compared with placebo in ulcer healing. Additional high-quality RCTs focused on clinically important outcomes are needed to improve the evidence base.

Estudio de contactos de casos pediátricos de tos ferina en un hospital de tercer nivel de Barcelona / Contact tracing of paediatric pertussis cases at a tertiary hospital in Barcelona, Spain

Fundamento y objetivo: La tos ferina sigue siendo una importante causa de morbimortalidad a pesar de las actuales estrategias vacunales. Se diseñó este estudio para describir los resultados y las características de los contactos estrechos de casos de tos ferina diagnosticados en menores de 16 años en un hospital de tercer nivel de Barcelona. Pacientes y método: Estudio transversal. Los datos se recogieron a partir de las historias clínicas de los contactos de los casos pediátricos diagnosticados de tos ferina en el Hospital Universitario Vall d’Hebron de 2005 a 2009. Se incluyeron solo pacientes con estudio microbiológico realizado. Se calculó la odds ratio (OR) con su intervalo de confianza del 95% (IC 95%) como medida de asociación. Resultados: Fueron estudiados 91 casos índice y 404 contactos. La prevalencia de casos positivos entre los contactos fue del 33,2%. Los contactos de los casos índice menores de 6 meses presentaron más riesgo de ser positivos que los contactos de los niños mayores (OR 3,38; IC 95% 1,88-6,10). Se identificaron como casos primarios el 16,7% de los contactos estudiados. Estos representaron la fuente de contagio para el 67,7% de los casos índice menores de 6 meses y para el 26,9% de los niños mayores. Conclusiones: El estudio de contactos de casos pediátricos de tos ferina es una actividad clínica necesaria. Es más probable hallar casos primarios en el estudio de contactos de niños menores de 6 meses. Las estrategias preventivas deben ir dirigidas fundamentalmente a los contactos frecuentes de este grupo (AU)

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Drug therapy for preventing post-dural puncture headache.

BACKGROUND: Post-dural (post-lumbar or post-spinal) puncture headache (PDPH) is one of the most common complications of diagnostic, therapeutic or inadvertent lumbar punctures. Many drug options have been used to prevent headache in clinical practice and have also been tested in some clinical studies, but there are still some uncertainties about their clinical effectiveness. OBJECTIVES: To assess the effectiveness and safety of drugs for preventing PDPH in adults and children. SEARCH METHODS: The search strategy included the Cochrane Central Register of Controlled Trials (CENTRAL, The Cochrane Library 2012, Issue 5), MEDLINE (from 1950 to May 2012), EMBASE (from 1980 to May 2012) and CINAHL (from 1982 to June 2012). There was no language restriction. SELECTION CRITERIA: We considered randomised controlled trials (RCTs) that assessed the effectiveness of any drug used for preventing PDPH. DATA COLLECTION AND ANALYSIS: Review authors independently selected studies, assessed risks of bias and extracted data. We estimated risk ratios (RR) for dichotomous data and mean differences (MD) for continuous outcomes. We calculated a 95% confidence interval (CI) for each RR and MD. We did not undertake meta-analysis because participants' characteristics or assessed doses of drugs were too different in the included studies. We performed an intention-to-treat (ITT) analysis. MAIN RESULTS: We included 10 RCTs (1611 participants) in this review with a majority of women (72%), mostly parturients (women in labour) (913), after a lumbar puncture for regional anaesthesia. Drugs assessed were epidural and spinal morphine, spinal fentanyl, oral caffeine, rectal indomethacin, intravenous cosyntropin, intravenous aminophylline and intravenous dexamethasone.All the included RCTs reported data on the primary outcome, i.e. the number of participants affected by PDPH of any severity after a lumbar puncture. Epidural morphine and intravenous cosyntropin reduced the number of participants affected by PDPH of any severity after a lumbar puncture when compared to placebo. Also, intravenous aminophylline reduced the number of participants affected by PDPH of any severity after a lumbar puncture when compared to no intervention, while intravenous dexamethasone increased it. Spinal morphine increased the number of participants affected by pruritus when compared to placebo, and epidural morphine increased the number of participants affected by nausea and vomiting when compared to placebo. Oral caffeine increased the number of participants affected by insomnia when compared to placebo.The remainder of the interventions analysed did not show any relevant effect for any of the outcomes.None of the included RCTs reported the number of days that patients stayed in hospital. AUTHORS' CONCLUSIONS: Morphine and cosyntropin have shown effectiveness for reducing the number of participants affected by PDPH of any severity after a lumbar puncture, when compared to placebo, especially in patients with high risk of PDPH, such as obstetric patients who have had an inadvertent dural puncture. Aminophylline also reduced the number of participants affected by PDPH of any severity after a lumbar puncture when compared to no intervention in patients undergoing elective caesarean section. Dexamethasone increased the risk of PDPH, after spinal anaesthesia for caesarean section, when compared to placebo. Morphine also increased the number of participants affected by adverse events (pruritus and nausea and vomiting)There is a lack of conclusive evidence for the other drugs assessed (fentanyl, caffeine, indomethacin and dexamethasone).These conclusions should be interpreted with caution, owing to the lack of information, to allow correct appraisal of risk of bias and the small sample sizes of studies.

Efficacy and Safety of Needle Acupuncture for Treating Gynecologic and Obstetric Disorders: An Overview.

Background: Acupuncture is being used increasingly to treat gynecologic and obstetric disorders. Objective: The aim of this review was to determine the efficacy and safety of acupuncture for treating pelvic and low-back pain during pregnancy, pain during labor, primary dysmenorrhea, and menopausal symptoms. Design: This is an overview of systematic reviews (SRs) and randomized controlled trials (RCTs). Search strategy: A literature search was conducted, in July 2010, in MEDLINE,® the Cochrane Database of Systematic Reviews, CENTRAL, the Database of Abstracts of Reviews of Effects, and Tripdatabase. Selection criteria: Published SRs and RCTs found during the literature search were included as well as RCTs that were published after completion of the literature search. Analysis: Data from SRs and RCTs that provided quantitative information were pooled. Results: Eight SRs and nine RCTs were included. One SR and 4 RCTs showed that acupuncture reduced pelvic and low-back pain, compared to physiotherapy or usual prenatal care. Results were contradictory when interventions were compared with sham acupuncture. With respect to reduction of pain during labor, two SRs showed no differences between acupuncture and sham acupuncture. None of the three SRs included on primary dysmenorrhea produced conclusive results. Two SRs of studies on menopausal symptoms showed no differences between acupuncture and sham acupuncture. A meta-analysis of three additional RCTs identified a favorable effect of acupuncture for reducing frequency and intensity of hot flashes. Adverse effects were mild and infrequent. Conclusions: Evidence for the efficacy of needle acupuncture for treating the disorders evaluated remains inconclusive. The intervention showed promising results for reducing pelvic and back pain during pregnancy and climacteric vasomotor symptoms, although well-designed studies are needed to make the results more precise and reliable.

[Contact tracing of paediatric pertussis cases at a tertiary hospital in Barcelona, Spain]. / Estudio de contactos de casos pediátricos de tos ferina en un hospital de tercer nivel de Barcelona.

BACKGROUND AND OBJECTIVES: Pertussis remains an important cause of morbimortality despite current vaccination strategies. This study was designed to describe the results and characteristics of close contacts of pertussis cases diagnosed in children less than 16 years in a tertiary hospital in Barcelona. PATIENTS AND METHODS: Cross-sectional study. Data were collected from chart review of contacts of paediatric cases of pertussis in Vall d'Hebron University Hospital from 2005 to 2009. Only patients with microbiological study done were included. The odds ratio (OR) and 95% confidence interval (95% CI) were calculated as association measure. RESULTS: Ninety-one index cases and 404 contacts were studied. The prevalence of positive cases among contacts was 33.2%. Contacts of index cases younger than 6 months had a higher risk of being positive for pertussis than contacts of older children (OR: 3.38; 95% CI: 1.88-6.10). Primary cases were identified as 16.7% of the contacts studied, who were the source of infection for 67.7% of index cases younger than 6 months and for 26.9% of older index cases. CONCLUSIONS: Contact tracing of paediatric pertussis cases is a necessary clinical activity. It is more likely to find primary cases in the contact investigation of children less than 6 months. Preventive strategies should be targeted primarily to frequent contacts of this age group.