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Nutrients Jul 2021Experimental studies suggest that sodium induced inflammation might be another missing link leading to atherosclerosis. To test the hypothesis that high daily sodium... (Meta-Analysis)
Meta-Analysis
Experimental studies suggest that sodium induced inflammation might be another missing link leading to atherosclerosis. To test the hypothesis that high daily sodium intake induces systemic inflammatory response in humans, we performed a systematic review according to PRISMA guidelines of randomized controlled trials (RCTs) that examined the effect of high versus low sodium dose (HSD vs. LSD), as defined per study, on plasma circulating inflammatory biomarkers. Eight RCTs that examined CRP, TNF-a and IL-6 were found. Meta-analysis testing the change of each biomarker in HSD versus LSD was possible for CRP ( = 5 studies), TNF-a ( = 4 studies) and IL-6 ( = 4 studies). The pooled difference (95% confidence intervals) per biomarker was for: CRP values of 0.1(-0.3, 0.4) mg/L; TNF-a -0.7(-5.0, 3.6) pg/mL; IL-6 -1.1(-3.3 to 1.1) pg/mL. Importantly, there was inconsistency between RCTs regarding major population characteristics and the applied methodology, including a very wide range of LSD (460 to 6740 mg/day) and HSD (2800 to 7452 mg/day). Although our results suggest that the different levels of daily sodium intake are not associated with significant changes in the level of systemic inflammation in humans, this outcome may result from methodological issues. Based on these identified methodological issues we propose that future RCTs should focus on young healthy participants to avoid confounding effects of comorbidities, should have three instead of two arms (very low, "normal" and high) of daily sodium intake with more than 100 participants per arm, whereas an intervention duration of 14 days is adequate.
Topics: Biomarkers; Blood Pressure; Databases, Factual; Humans; Inflammation; Interleukin-6; Randomized Controlled Trials as Topic; Sodium, Dietary; Systemic Inflammatory Response Syndrome; Tumor Necrosis Factor-alpha
PubMed: 34444792
DOI: 10.3390/nu13082632 -
Clinical Toxicology (Philadelphia, Pa.) Dec 2021The use of activated charcoal in poisoning remains both a pillar of modern toxicology and a source of debate. Following the publication of the joint position statements...
INTRODUCTION
The use of activated charcoal in poisoning remains both a pillar of modern toxicology and a source of debate. Following the publication of the joint position statements on the use of single-dose and multiple-dose activated charcoal by the American Academy of Clinical Toxicology and the European Association of Poison Centres and Clinical Toxicologists, the routine use of activated charcoal declined. Over subsequent years, many new pharmaceuticals became available in modified or alternative-release formulations and additional data on gastric emptying time in poisoning was published, challenging previous assumptions about absorption kinetics. The American Academy of Clinical Toxicology, the European Association of Poison Centres and Clinical Toxicologists and the Asia Pacific Association of Medical Toxicology founded the Clinical Toxicology Recommendations Collaborative to create a framework for evidence-based recommendations for the management of poisoned patients. The activated charcoal workgroup of the Clinical Toxicology Recommendations Collaborative was tasked with reviewing systematically the evidence pertaining to the use of activated charcoal in poisoning in order to update the previous recommendations.
OBJECTIVES
The main objective was: Does oral activated charcoal given to adults or children prevent toxicity or improve clinical outcome and survival of poisoned patients compared to those who do not receive charcoal? Secondary objectives were to evaluate pharmacokinetic outcomes, the role of cathartics, and adverse events to charcoal administration. This systematic review summarizes the available evidence on the efficacy of activated charcoal.
METHODS
A medical librarian created a systematic search strategy for Medline (Ovid), subsequently translated for Embase ( Ovid), CINAHL ( EBSCO), BIOSIS Previews ( Ovid), Web of Science, Scopus, and the Cochrane Library/DARE. All databases were searched from inception to December 31, 2019. There were no language limitations. One author screened all citations identified in the search based on predefined inclusion/exclusion criteria. Excluded citations were confirmed by an additional author and remaining articles were obtained in full text and evaluated by at least two authors for inclusion. All authors cross-referenced full-text articles to identify articles missed in the searches. Data from included articles were extracted by the authors on a standardized spreadsheet and two authors used the GRADE methodology to independently assess the quality and risk of bias of each included study.
RESULTS
From 22,950 titles originally identified, the final data set consisted of 296 human studies, 118 animal studies, and 145 studies. Also included were 71 human and two animal studies that reported adverse events. The quality was judged to have a Low or Very Low GRADE in 469 (83%) of the studies. Ninety studies were judged to be of Moderate or High GRADE. The higher GRADE studies reported on the following drugs: paracetamol (acetaminophen), phenobarbital, carbamazepine, cardiac glycosides (digoxin and oleander), ethanol, iron, salicylates, theophylline, tricyclic antidepressants, and valproate. Data on newer pharmaceuticals not reviewed in the previous American Academy of Clinical Toxicology/European Association of Poison Centres and Clinical Toxicologists statements such as quetiapine, olanzapine, citalopram, and Factor Xa inhibitors were included. No studies on the optimal dosing for either single-dose or multiple-dose activated charcoal were found. In the reviewed clinical data, the time of administration of the first dose of charcoal was beyond one hour in 97% ( = 1006 individuals), beyond two hours in 36% ( = 491 individuals), and beyond 12 h in 4% ( = 43 individuals) whereas the timing of the first dose in controlled studies was within one hour of ingestion in 48% ( = 2359 individuals) and beyond two hours in 36% ( = 484) of individuals.
CONCLUSIONS
This systematic review found heterogenous data. The higher GRADE data was focused on a few select poisonings, while studies that addressed patients with unknown and or mixed ingestions were hampered by low rates of clinically meaningful toxicity or death. Despite these limitations, they reported a benefit of activated charcoal beyond one hour in many clinical scenarios.
Topics: Acetaminophen; Animals; Carbamazepine; Charcoal; Decontamination; Drug Overdose; Humans
PubMed: 34424785
DOI: 10.1080/15563650.2021.1961144 -
Nutrients Jul 2021Epidemiological studies suggest that high intake of soy isoflavones may protect against breast cancer, but causal relationships can only be established by experimental...
Epidemiological studies suggest that high intake of soy isoflavones may protect against breast cancer, but causal relationships can only be established by experimental trials. Thus, we aimed to provide a systematic review of randomized controlled trials (RCTs) on the effect of an isoflavone intake on risk factors of breast cancer in healthy subjects. After a systematic literature search in PubMed, 18 different RCTs with pre- and/or postmenopausal women were included and investigated for details according to the PRISMA guideline. In these studies, isoflavones were provided by soy food or supplements in amounts between 36.5-235 mg/d for a period of 1-36 months. Breast density, estrogens including precursors, metabolites, estrogen response such as length of menstrual cycle, and markers of proliferation and inflammation were considered. However, in most studies, differences were not detectable between isoflavone and control/placebo treatment despite a good adherence to isoflavone treatment, irrespective of the kind of intervention, the dose of isoflavones used, and the duration of isoflavone treatment. However, the lack of significant changes in most studies does not prove the lack of effects as a sample size calculation was often missing. Taking into account the risk of bias and methodological limitations, there is little evidence that isoflavone treatment modulates risk factors of breast cancer in pre- and postmenopausal women. Future studies should calculate the sample size to detect possible effects and consider methodological details to improve the study quality.
Topics: Adult; Aged; Bias; Breast Neoplasms; Diet; Dietary Supplements; Eating; Female; Humans; Isoflavones; Middle Aged; Postmenopause; Premenopause; Randomized Controlled Trials as Topic; Risk Factors; Soy Foods
PubMed: 34371819
DOI: 10.3390/nu13072309 -
Drugs Jul 2021Adequate dosing of antimicrobials is critical to properly treat infections and limit development of resistance and adverse effects. Limited guidance exists for...
PURPOSE
Adequate dosing of antimicrobials is critical to properly treat infections and limit development of resistance and adverse effects. Limited guidance exists for antimicrobial dosing adjustments in patients requiring extracorporporeal membrane oxygenation (ECMO) therapy. A systematic review was conducted to delineate the pharmacokinetics (PK) and pharmacodynamics (PD) of antimicrobials in critically ill adult patients requiring ECMO.
METHODS
Medline, EMBASE, Global Health, and All EBM Reviews databases were searched. Grey literature was examined. All studies reporting PK/PD parameters of antimicrobials in critically ill adults treated with ECMO were included, except for case reports and congress abstracts. Ex vivo studies were included. Two independent reviewers applied the inclusion and exclusion criteria. Reviewers were then paired to independently abstract data and evaluate methodological quality of studies using the ROBINS-I tool and the compliance with ClinPK guidelines. Patients' and studies' characteristics, key PK/PD findings, details of ECMO circuits and co-treatments were summarized qualitatively. Dosing recommendations were formulated based on data from controlled studies.
RESULTS
Thirty-two clinical studies were included; most were observational and uncontrolled. Fourteen ex vivo studies were analysed. Information on patient characteristics and co-treatments was often missing. The effect of ECMO on PK/PD parameters of antimicrobials varied depending on the studied drugs. Few dosing recommendations could be formulated given the lack of good quality data.
CONCLUSION
Limited data exist on the PK/PD of antimicrobials during ECMO therapy. Rigorously designed and well powered populational PK studies are required to establish empiric dosing guidelines for antimicrobials in patients requiring ECMO support.
PROSPERO REGISTRATION NUMBER
CRD42018099992 (Registered: July 24th 2018).
Topics: Adolescent; Adult; Aged; Aged, 80 and over; Anti-Infective Agents; Comorbidity; Critical Illness; Dose-Response Relationship, Drug; Drug Monitoring; Extracorporeal Membrane Oxygenation; Female; Humans; Male; Middle Aged; Organ Dysfunction Scores; Patient Acuity; Renal Replacement Therapy; Young Adult
PubMed: 34224115
DOI: 10.1007/s40265-021-01557-3 -
International Journal of Implant... May 2021Dental implants are a common restorative method used to replace missing teeth. Implant placement techniques guided by three-dimensional imaging and navigation are... (Review)
Review
BACKGROUND
Dental implants are a common restorative method used to replace missing teeth. Implant placement techniques guided by three-dimensional imaging and navigation are becoming more widely available.
OBJECTIVE
The present review focused on the following questions: 1. What are the advantages and disadvantages of 2-D versus 3-D imaging in dental implantology? 2. What are the advantages and disadvantages of freehand implant placement in comparison with navigation-guided implant placement?
METHODS
A systematic review was performed, based on the Preferred Reporting Items for Systematic Reviews and Meta-analysis (PRISMA) statement. The following libraries were searched for relevant literature: PubMed, Embase, Arbeitsgemeinschaft der Wissenschaftlichen Medizinischen Fachgesellschaften (AWMF) Online, and the Cochrane Library. The risk of bias was assessed using the Scottish Intercollegiate Guidelines Network (SiGN) checklist. A total of 70 studies were included after screening, and the evidence from these was gathered for review.
RESULTS
Three-dimensional imaging is advantageous in terms of image quality, and it provides a distortion-free evaluation of the implant site. However, it is also associated with higher costs and increased radiation exposure. Dynamic and static navigation are equal in accuracy and are both more accurate compared with the freehand method. No benefit in terms of implant survival could be demonstrated within the first 5 years for any specific method.
DISCUSSION
A panoramic X-ray with a reference body often provides sufficient imaging and is the primary method for two-dimensional imaging. Cone beam computed tomography with low-dose protocol settings should be used if three-dimensional imaging is needed. Navigational support should be considered in the event of especially complex cases.
CONCLUSION
The guidance technique used for implant placement should be decided on an individual basis. With the increasing availability of three-dimensional imaging, there should also be an increase in awareness of radiation exposure.
Topics: Cone-Beam Computed Tomography; Costs and Cost Analysis; Imaging, Three-Dimensional; Radiography, Panoramic
PubMed: 34041613
DOI: 10.1186/s40729-021-00328-9 -
The Lancet. Psychiatry Jun 2021Dose reduction of antipsychotic maintenance treatment in individuals with schizophrenia could be desirable to minimise adverse effects, but evidence for this strategy is... (Comparative Study)
Comparative Study Meta-Analysis
Standard versus reduced dose of antipsychotics for relapse prevention in multi-episode schizophrenia: a systematic review and meta-analysis of randomised controlled trials.
BACKGROUND
Dose reduction of antipsychotic maintenance treatment in individuals with schizophrenia could be desirable to minimise adverse effects, but evidence for this strategy is unclear. We aimed to compare risks and benefits of reduced versus standard doses of antipsychotics.
METHODS
We searched Embase, Medline, PsycINFO, and the Cochrane Library from database inception until June 17, 2020, for randomised trials in adults with schizophrenia or schizoaffective disorder lasting at least 24 weeks, including individuals clinically stable at baseline, and comparing at least two doses of the same antipsychotic, excluding trials in first-episode psychosis or treatment-resistant schizophrenia. We compared low-dose (within 50-99% of the lower limit of the standard dose) and very-low dose (less than 50% of the lower limit) with standard dose, defined as doses higher than the lower limit of the treatment dose recommended by the International Consensus Study. Data from published reports on number of participants, treatment, sex, age, number of events, and changes in psychopathology scores were extracted independently by at least two authors. Investigators or sponsors were contacted by email to obtain missing information regarding outcomes. Co-primary outcomes were relapse and all-cause discontinuation. Study-level data were meta-analysed using random-effects models, calculating risk ratios (RRs) for dichotomous data, and Hedges' g for continuous data. The protocol was registered with OSF registries.
FINDINGS
7853 references were identified in the database search and one additional reference from a manual review of relevant studies. 5744 abstracts were assessed for eligibility, and 101 references were assessed for full-text review. Of these, 79 were excluded for a variety of reasons, resulting in 22 studies being included in the meta-analysis, reporting on 24 trials and 3282 individuals. Study participants had a median age of 38 years (IQR 36-40) with 2166 (65·9%) males and 1116 (34·0%) females. Compared with standard dose, low dose increased the risk of relapse by 44% (16 trials, 1920 participants; RR 1·44, 95% CI 1·10-1·87; p=0·0076; I=46%) and the risk of all-cause discontinuation by 12% (16 trials, 1932 participants; RR 1·12, 1·03-1·22; p=0·0085; I=0%). Very low dose increased the risk of relapse by 72% (13 trials, 2058 participants; RR 1·72, 95% CI 1·29-2·29; p=0·0002; I=70%) and all-cause discontinuation by 31% (11 trials, 1866 participants; RR 1·31, 1·11-1·54; p=0·0011; I=63%). Compared with low dose, very low dose did not significantly increase the risk of relapse (five trials, 686 participants; RR 1·31, 95% CI 0·96-1·79; p=0·092; I=51%) or all-cause discontinuation (five trials 686 participants; RR 1·11, 95% CI 0·95-1·30; p=0·18; I=43%). Subgroup analyses comparing double-blind versus open-label studies, first-generation versus second-generation antipsychotics, and oral versus long-acting injectable antipsychotics were consistent with the overall results. Most studies were classified as having some concerns in the risk of bias assessment, which was mainly caused by absence of publicly available study registrations.
INTERPRETATION
During maintenance treatment in multi-episode schizophrenia, antipsychotic doses should probably not be reduced below the standard dose range recommended for acute stabilisation, because reducing the dose further is associated with an increased risk of both relapse and all-cause discontinuation.
FUNDING
None.
Topics: Adult; Antipsychotic Agents; Dose-Response Relationship, Drug; Humans; Randomized Controlled Trials as Topic; Recurrence; Schizophrenia; Secondary Prevention; Treatment Outcome
PubMed: 34023019
DOI: 10.1016/S2215-0366(21)00078-X -
Infectious Diseases and Therapy Jun 2021Despite modern diphtheria-tetanus-pertussis (DTP) vaccines and high vaccine coverage, a resurgence of pertussis (whooping cough) has been observed globally. In North... (Review)
Review
Despite modern diphtheria-tetanus-pertussis (DTP) vaccines and high vaccine coverage, a resurgence of pertussis (whooping cough) has been observed globally. In North America and Europe, high vaccine coverage in children has led to a shift in the age-specific peak incidence of infection away from infants and towards older children and adolescents. However, much less is known about the prevalence of pertussis in older children and adults in the Middle East. A systematic search of MEDLINE, EMBASE, and BIOSIS was undertaken to identify studies published between 1 January 1990 and 17 June 2019, with information on pertussis epidemiology, burden of illness, and mortality in school-aged children, adolescents, and adults in the Middle East. Studies identified for inclusion were reviewed narratively because a statistical comparison was not possible because of the mix of methodologies used. The results showed that surveillance data are weak or missing in most Middle Eastern countries, and among 24 epidemiological studies identified, most were from Iran (14), Israel (4), and Turkey (3), with single studies from the United Arab Emirates and Iraq. Despite various surveillance periods, clinical definitions, and antibody cut-off values used across the studies, the reported seroprevalence of pertussis antibodies suggested that adolescents and adults are commonly exposed to pertussis in the community and that vaccine-acquired immunity from childhood wanes. Few countries in the Middle East include a diphtheria-tetanus-acellular pertussis (Tdap) booster for adolescents on the national schedule. Israel was the only country with epidemiological data in a population that received Tdap, and the study showed that after the introduction of the adolescent booster dose, there was decrease in pertussis among children aged 5-14 years. To conclude, results from the Middle East suggest that in common with other regions, pertussis is widely circulating and that it might be shifting towards older age groups.
PubMed: 33905101
DOI: 10.1007/s40121-021-00440-8 -
European Journal of Nuclear Medicine... Nov 2021To systematically review all current evidence into the dose-response relation of yttrium-90 and holmium-166 selective internal radiation therapy (SIRT) in primary and... (Review)
Review
PURPOSE
To systematically review all current evidence into the dose-response relation of yttrium-90 and holmium-166 selective internal radiation therapy (SIRT) in primary and secondary liver cancer.
METHODS
A standardized search was performed in PubMed (MEDLINE), Embase, and the Cochrane Library in order to identify all published articles on dose-response evaluation in SIRT. In order to limit the results, all articles that investigated SIRT in combination with other therapy modalities (such as chemotherapy) were excluded.
RESULTS
A total of 3038 records were identified of which 487 were screened based on the full text. Ultimately, 37 studies were included for narrative analysis. Meta-analysis could not be performed due to the large heterogeneity in study and reporting designs. Out of 37 studies, 30 reported a 'mean dose threshold' that needs to be achieved in order to expect a response. This threshold appears to be higher for hepatocellular carcinoma (HCC, 100-250 Gy) than for colorectal cancer metastases (CRC, 40-60 Gy). Reported thresholds tend to be lower for resin microspheres than when glass microspheres are used.
CONCLUSION
Although the existing evidence demonstrates a dose-response relationship in SIRT for both primary liver tumours and liver metastases, many pieces of the puzzle are still missing, hampering the definition of standardized dose thresholds. Nonetheless, most current evidence points towards a target mean dose of 100-250 Gy for HCC and 40-60 Gy for CRC. The field would greatly benefit from a reporting standard and prospective studies designed to elucidate the dose-response relation in different tumour types.
Topics: Brachytherapy; Carcinoma, Hepatocellular; Humans; Liver Neoplasms; Microspheres; Prospective Studies; Yttrium Radioisotopes
PubMed: 33839892
DOI: 10.1007/s00259-021-05340-0 -
British Journal of Clinical Pharmacology Nov 2021To identify and critically appraise studies of prediction models, developed using machine learning (ML) methods, for determining the optimal dosing of unfractionated... (Review)
Review
AIM
To identify and critically appraise studies of prediction models, developed using machine learning (ML) methods, for determining the optimal dosing of unfractionated heparin (UFH).
METHODS
Embase, PubMed, CINAHL, Web of Science, International Pharmaceutical Abstracts and IEEE Xplore databases were searched from inception to 31 January 2020 to identify relevant studies using key search terms synonymous with artificial intelligence or ML, 'prediction', 'dose', 'activated partial thromboplastin time (aPTT)' and 'UFH.' Studies had to have used ML methods for developing models that predicted optimal dose of UFH or target therapeutic aPTT levels in the hospital setting. The CHARMS Checklist was used to assess quality and risk of bias of included studies.
RESULTS
Of 8393 retrieved abstracts, 61 underwent full text review and eight studies met inclusion criteria. Four studies described models for predicting aPTT, three studies described models predicting optimal dose of heparin during dialysis and one study described a model that used surrogate outcomes of clotting and bleeding to predict a therapeutic aPTT. Studies varied widely in reporting of study participants, feature characterisation and selection, handling of missing data, sample size calculations and the intended clinical application of the model. Only one study conducted an external validation and no studies evaluated model impacts in clinical practice.
CONCLUSION
Studies of ML models for UFH dosing are few and none report a model ready for routine clinical use. Existing studies are limited by low methodological quality, inadequate reporting of study factors and absence of external validation and impact analysis.
Topics: Anticoagulants; Artificial Intelligence; Heparin; Humans; Machine Learning; Partial Thromboplastin Time
PubMed: 33835524
DOI: 10.1111/bcp.14852 -
Research in Social & Administrative... Nov 2021Medicine self-administration errors (MSEs) are a longstanding issue in patient safety. Although many studies have examined MSEs in the general adult population, the MSEs... (Review)
Review
BACKGROUND
Medicine self-administration errors (MSEs) are a longstanding issue in patient safety. Although many studies have examined MSEs in the general adult population, the MSEs that occur specifically in the older adult population and their contributing factors are not well understood.
OBJECTIVE
To identify the types of MSEs and their contributing factors among community-dwelling older adults.
METHODS
PubMed, Medline, Embase, CINAHL and Scopus were searched for primary studies published between January 1, 2014 and June 12, 2020. Studies which reported MSEs among community-dwelling older adults (≥50 years of age) and written in English were included in the review.
RESULTS
Eleven studies met the inclusion criteria. The most commonly reported MSE was a dosing error, followed by missed dose, wrong medicine, incorrect administration methods, wrong administration time and wrong frequency. Seven of the included studies also described factors which contributed to the occurrence of MSEs. The most commonly reported factor contributing to MSEs was complex treatment regimens due to use of multiple medicines. Other factors identified included cognitive decline, decline in physical abilities, lack of social support, lack of knowledge about treatment regimens and negative attitudes and beliefs towards medicines. In most cases, MSEs occurred when multiple contributing factors were present.
CONCLUSION
The literature highlights a number of types of MSEs and their contributing factors which occur in the older adult population. Given that many MSEs are preventable, future research is needed into how pharmacists can support the identification and mitigation of factors contributing to MSEs in the older adult population.
Topics: Aged; Humans; Medication Errors; Patient Safety; Pharmaceutical Preparations; Pharmacists; Self Administration
PubMed: 33811011
DOI: 10.1016/j.sapharm.2021.03.008