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1.

Objectives

With increasing global interest in hospital antimicrobial stewardship (AMS) programmes, there is a strong demand for core elements of AMS to be clearly defined on the basis of principles of effectiveness and affordability. To date, efforts to identify such core elements have been limited to Europe, Australia, and North America. The aim of this study was to develop a set of core elements and their related checklist items for AMS programmes that should be present in all hospitals worldwide, regardless of resource availability.

Methods

A literature review was performed by searching Medline and relevant websites to retrieve a list of core elements and items that could have global relevance. These core elements and items were evaluated by an international group of AMS experts using a structured modified Delphi consensus procedure, using two-phased online in-depth questionnaires.

Results

The literature review identified seven core elements and their related 29 checklist items from 48 references. Fifteen experts from 13 countries in six continents participated in the consensus procedure. Ultimately, all seven core elements were retained, as well as 28 of the initial checklist items plus one that was newly suggested, all with ≥80% agreement; 20 elements and items were rephrased.

Conclusions

This consensus on core elements for hospital AMS programmes is relevant to both high- and low-to-middle-income countries and could facilitate the development of national AMS stewardship guidelines and adoption by healthcare settings worldwide.  相似文献   

2.

Background

Dyslipidemia is among the most significant risk factors of cardiovascular disease. Many patients with dyslipidemia fail to meet certain therapeutic targets as a result of clinical inertia.

Aims

To explore the views and opinions of physicians who often see and provide healthcare to patients with dyslipidemia on clinical inertia and to achieve consensus on the factors they believed promote clinical inertia in the Palestinian clinical practice.

Methods

This study was conducted in an observational design using the Delphi technique as a formal consensus method. A panel of fifty physicians participated this study. A two Delphi rounds were followed to achieve consensus on a list of factors they believed promoted clinical inertia.

Results

The majority (86%) of the panelists believed that clinical inertia was prevalent in caring for patients with dyslipidemia. Of the 40 factors initially included in the questionnaire, consensus was achieved on 21 (52.5%) factors related to the physician, 10 (25.0%) factors related to the patient, and 5 (12.5%) factors related to the office and healthcare system as promoters of clinical inertia in the first and second Delphi rounds.

Discussion

This study highlights factors promoting clinical inertia in managing dyslipidemia from the views of physicians who often provide healthcare to patients with dyslipidemia.

Conclusion

Consensus was achieved on factors related to the physician, patient, and healthcare system that promote clinical inertia in caring for patients with dyslipidemia in the Palestinian clinical practice by a panel of physicians who often provide healthcare to those patients. Further studies are still needed to design strategies to eliminate or reduce the phenomenon of clinical inertia in caring for patients with dyslipidemia and improve patient outcomes.  相似文献   

3.

Background

Penicillin allergy is the most commonly reported drug allergy in hospitalized patients, resulting in increased second-line antibiotic use, nosocomial infections, and health care use. Given that most patients are not truly allergic, a safe strategy that empowers the admitting physician is needed.

Objective

To assess the effect on antibiotic prescribing practices for hospitalized patients with penicillin allergy using a validated intervention.

Methods

An intervention was implemented to educate health care professionals on management of patients with penicillin allergy using a validated risk stratification algorithm to guide testing and antibiotic use. Thirty days of control data using current standard of care was compared with 60 days of postintervention data measuring documentation of penicillin allergy history and antibiotic selection.

Results

The relative use of cephalosporin and penicillin antibiotics increased by 121.2% (P = .03) and 256% (P = .04), respectively, without an increase in adverse drug reactions. There was a decrease in the use of broad-spectrum antibiotics: vancomycin, 67.2% (P = .04); quinolones, 33.3% (P = .31); carbapenems, 81.9% (P = .08); and aztreonam, 73.8% (P = .18).

Conclusion

The antibiotic choice in patients admitted to the hospital with a reported penicillin allergy can be improved by better evaluation of the allergy history and the use of a risk stratification guideline.  相似文献   

4.

Objective

To review the published medical literature on the clinical presentation, risk factors, and natural history of hypersensitivity reactions to progestogens.

Data Sources

Through the use of PubMed, we conducted a review of allergy, dermatology, and obstetric literature for cases and case series of patients with hypersensitivity reactions to exogenous or endogenous progestogens. There are no longitudinal, prospective studies related to progestogen hypersensitivity.

Study Selections

Publications were selected that described cases that were clinically consistent with progesterone hypersensitivity and positive test results or clear symptoms with exposure to progestogens to confirm the diagnosis.

Results

Progestogen hypersensitivity symptoms can be triggered by endogenous progesterone or exogenous progestins used for contraception or fertility treatments. Symptoms are varied and include dermatitis, urticaria, asthma, and anaphylaxis.

Conclusion

Although the medical literature on progestogen hypersensitivity is limited to case reports and small case series, significant heterogeneity exists in clinical presentation among patients.  相似文献   

5.

Background

Leptospirosis is under-diagnosed by clinicians in many high-incidence countries, because reference diagnostic tests are largely unavailable. Lateral flow assays (LFA) that use antigen derived from heat-treated whole cell Leptospira biflexa serovar Patoc have the potential to improve leptospirosis diagnosis in resource-limited settings.

Objectives

We sought to summarize estimates of sensitivity and specificity of LFA by conducting a systematic review and meta-analysis of evaluations of the accuracy of LFA to diagnose human leptospirosis.

Data sources

On 4 July 2017 we searched three medical databases.Study eligibility criteriaArticles were included if they were a study of LFA sensitivity and specificity.

Participants

Patients with suspected leptospirosis.

Interventions

Nil.

Methods

For included articles, we assessed study quality, characteristics of participants and diagnostic testing methods. We estimated sensitivity and specificity for each study against the study-defined case definition as the reference standard, and performed a meta-analysis using a random-effects bivariate model.

Results

Our search identified 225 unique reports, of which we included nine (4%) published reports containing 11 studies. We classified one (9%) study as high quality. Nine (82%) studies used reference tests with considerable risk of misclassification. Our pooled estimates of sensitivity and specificity were 79% (95% CI 70%–86%) and 92% (95% CI 85%–96%), respectively.

Conclusions

As the evidence base for determining the accuracy of LFA is small and at risk of bias, pooled estimates of sensitivity and specificity should be interpreted with caution. Further studies should use either reference tests with high sensitivity and specificity or statistical techniques that account for an imperfect reference standard.  相似文献   

6.

Objective

This article reviews the latest science and epidemiologic studies related to drug allergy in children and adults to explore possible mechanisms related to female propensity for drug allergy.

Data Sources

PubMed literature review, focusing primarily on the last 5 years.

Study Selections

Articles reviewing the science behind female predisposition to atopic and asthmatic conditions and epidemiologic studies reviewing drug allergy and drug-induced anaphylaxis.

Results

Despite adult female predilection for atopic conditions, few laboratory studies explore sex-specific mechanisms in atopic/allergic diseases, and most are focused on autoimmunity and asthma. Drug allergy is more frequently reported in adult females compared with adult males. Adult females are also more likely to have drug-induced anaphylaxis (DIA), although no clear sex predominance has been reported in fatal or severe DIA. Studies in children suggest the reverse picture, with prepubertal males more likely to have drug allergy and DIA than prepubertal girls.

Conclusion

Possible explanations for female predisposition for drug allergy are multifactorial and include disproportionate utilization of health care with more exposure to antibiotics or medications, genetic factors related to the X chromosome, epigenetic changes, and discrepant hormonal interactions with immune cells.  相似文献   

7.

Background

The development of an in vitro diagnostic test from a good idea to a clinically relevant tool takes several steps, with more stringent requirements at every step.

Objectives

This article aims to summarize the necessary questions to be asked about a test and to illustrate study designs answering these questions. We also aim to relate Regulation (EU) 2017/746 to the needs of evidence-based diagnostic testing, where applicable.

Sources

We used literature on evidence-based diagnostics, a text book on clinical trials in the development and marketing of medical devices and the English version of Regulation 2017/746 of the European Parliament and of the Council on in vitro diagnostic medical devices.

Content

The combination of different test uses and different stages of development determine the required test characteristics and suitability of study designs. In an earlier stage of test development it may be crucial to know whether a test can differentiate diseased persons from healthy controls, although this tells us little about how a test will perform in practice. Later stages focus on the diagnostic accuracy of a test in a clinically relevant situation. However, a test that perfectly distinguishes between patients with and without a certain condition may still have little effect on patient outcomes. Therefore, randomized controlled trials of testing may be needed, as well as post-marketing monitoring.

Implications

Both researchers and users of tests need to be aware of the limitations of diagnostic test accuracy and realize that accuracy is only indirectly linked to people's health status.  相似文献   

8.

Background

Congenital disorders of glycosylation (CDG) are a group of rare metabolic diseases due to impaired lipid and protein glycosylation. It comprises a characteristic high frequency of intellectual disability (ID) and a wide range of clinical phenotypes.

Objective

To identify the underlying diagnosis in two families each with two siblings with variable level of ID through trio whole exome sequencing.

Methods

Both the families were recruited to the Deciphering Developmental Disorders (DDD) study to identify the aetiology for their ID. Further work-up included isoelectric focusing (IEF) of serum transferrin done to add evidence to the molecular diagnosis.

Results

These patients were found to have three novel variants in MAN1B1 inherited from their healthy parents. Serum transferrin IEF showed a type 2 pattern.

Discussion

MAN1B1 variants were initially described in association with non-syndromic ID; subsequent literature suggested that variants in MAN1B1 resulted in a CDG-type II syndrome. However, there remains a paucity of literature on detailed clinical phenotyping and it still remains a rare form of CDG. The present patients showed the phenotype previously reported in MAN1B1-CDG: a characteristic facial dysmorphism, hypotonia, truncal obesity and in some, behavioural problems.

Conclusions

In unexplained ID, serum transferrin should be included in the first-line screening. With advances in genomic medicine, it is important to diagnose CDG as this has implications for management and recurrence risk counselling.  相似文献   

9.

Background

Encephalitis and meningoencephalitis are severe, sometime life-threatening infections of the central nervous system. Travellers may be exposed to a variety of neurotropic pathogens.

Aims

We propose to review known infectious causes of encephalitis in adults acquired outside Europe, and how to identify them.

Sources

We used Pubmed and Embase, to search the most relevant publications over the last years.

Content

Microbiologic tests and radiological tools to best identify the causative pathogen in travellers presenting with encephalitis and ME are presented in this narrative review, as well as a diagnostic approach tailored to the visited area and types of exposures.

Implications

This review highlights the diagnostic difficulties inherent to exotic causes of central nervous system infections, and attempts to guide clinicians with respect to which microbiological tests to consider, in addition to brain MRI, when approaching a returning traveller presenting with encephalitis.  相似文献   

10.

Background

Systemic antibiotics are commonly used in hospitalized patients with severe atopic dermatitis (AD) exacerbation. However, the antibiotic prescribing patterns are unclear.

Objective

To compare the prescribing patterns of antibiotics for children who were hospitalized for AD exacerbation and infectious complications.

Methods

Electronic medical records were reviewed for patients younger than 18 years who were hospitalized for AD exacerbation or infectious complications based on International Classification of Diseases, Ninth Revision, Clinical Modification and International Classification of Diseases, Tenth Revision, Clinical Modification codes from 2003 to 2018. The following information was obtained: history, physical examination findings, physician discharge summary, antibiotic treatments, serum tests, and wound cultures. The t test was used to compare clinical and laboratory features.

Results

A total of 174 patients with AD were included. Seventy patients had AD exacerbation and 104 had infectious complications, including cellulitis, abscesses, invasive infections, and eczema herpeticum. The differences between these 2 groups of patients were further verified by length of stay, serum total IgE level, and inflammatory markers (C-reactive protein and erythrocyte sedimentation rate). A total of 56 of 70 patients (80%) with AD exacerbation were treated with a systemic antibiotic. Clindamycin and vancomycin together accounted for 88% of antibiotics on admission for both groups, whereas clindamycin and sulfamethoxazole-trimethoprim were prescribed at similar rates for both groups at discharge. Wound culture results showed that the methicillin-resistant Staphylococcus aureus (MRSA) rate was significantly lower in children with AD exacerbation (22%) vs infectious complications (39%).

Conclusion

Children were treated with a high frequency of anti-MRSA antibiotics for inpatient AD exacerbation and infectious complications. However, the rate of MRSA was significantly lower in children with AD exacerbation. Thus, empiric antibiotic choice for infectious complications may not be appropriate for AD exacerbation.  相似文献   

11.

Objectives

Early empiric antibiotic therapy in patients can improve clinical outcomes in Gram-negative bacteraemia. However, the widespread prevalence of antibiotic-resistant pathogens compromises our ability to provide adequate therapy while minimizing use of broad antibiotics. We sought to determine whether readily available electronic medical record data could be used to develop predictive models for decision support in Gram-negative bacteraemia.

Methods

We performed a multi-centre cohort study, in Canada and the USA, of hospitalized patients with Gram-negative bloodstream infection from April 2010 to March 2015. We analysed multivariable models for prediction of antibiotic susceptibility at two empiric windows: Gram-stain-guided and pathogen-guided treatment. Decision-support models for empiric antibiotic selection were developed based on three clinical decision thresholds of acceptable adequate coverage (80%, 90% and 95%).

Results

A total of 1832 patients with Gram-negative bacteraemia were evaluated. Multivariable models showed good discrimination across countries and at both Gram-stain-guided (12 models, areas under the curve (AUCs) 0.68–0.89, optimism-corrected AUCs 0.63–0.85) and pathogen-guided (12 models, AUCs 0.75–0.98, optimism-corrected AUCs 0.64–0.95) windows. Compared to antibiogram-guided therapy, decision-support models of antibiotic selection incorporating individual patient characteristics and prior culture results have the potential to increase use of narrower-spectrum antibiotics (in up to 78% of patients) while reducing inadequate therapy.

Conclusions

Multivariable models using readily available epidemiologic factors can be used to predict antimicrobial susceptibility in infecting pathogens with reasonable discriminatory ability. Implementation of sequential predictive models for real-time individualized empiric antibiotic decision-making has the potential to both optimize adequate coverage for patients while minimizing overuse of broad-spectrum antibiotics, and therefore requires further prospective evaluation.

Summary

Readily available epidemiologic risk factors can be used to predict susceptibility of Gram-negative organisms among patients with bacteraemia, using automated decision-making models.  相似文献   

12.

Objectives

The aim was to investigate an outbreak of invasive meningococcal disease (IMD) in Southern Sardinia.

Methods

Epidemiological and microbiological investigations were performed. The latter included antimicrobial susceptibility testing and whole-genome sequencing (WGS).

Results

Seven individuals with severe IMD were found to be infected with serogroup B (MenB) Neisseria meningitidis in the first quarter of 2018. Five of the seven cases (five males; mean age 19 years; range 18–21 years; CFR 40%) were due to a unique strain B:P1.5-1,10-8:F3-6:ST-11(cc11), probably switched from the hypervirulent C-cc11, as confirmed by WGS. All five patients had attended the same nightclub in the 2 weeks prior to symptom onset. Public health measures, including chemoprophylaxis of contacts and active immunization against MenB, were implemented.

Conclusions

We observed five IMD cases due to the same switched MenB strain. The hypervirulent B:P1.5-1,10-8:F3-6:ST-11(cc11) strain, probably switched from C-cc11, is of concern due to the observed high virulence and case fatality rates. All the patients shared the same place of probable exposure. The molecular characterization of the invasive strain allowed the outbreak to be confirmed, which was then controlled through timely public health action.  相似文献   

13.

Objective

To evaluate relevant studies and documents that address the cost-effectiveness and comparative effectiveness of biologics current approved by the US Food and Drug Administration for the treatment of asthma.

Data Sources

Publications currently available on biologics, the Global Initiative for Asthma pocket book on difficult-to-treat asthma in adolescents and adults, and the recent Institute for Clinical and Economic Review on biologic therapies for the treatment of asthma.

Study Selections

Priority was placed on studies that speak to the cost-effectiveness and comparative effectiveness of biologic therapies published from 2016 to 2019.

Results

Current pricing for all biologics exceeds measures of cost-effectiveness. To meet available measures indicating cost-effectiveness, prices would have to be reduced by a minimum of approximately 60%. The effect of biologics on exacerbations is similar but should be interpreted in the context of comparable patient phenotypes. The effect on quality of life is deemed modest based on the available study designs.

Conclusion

To maximize cost-effectiveness of the biologics, emphasis should be placed on identifying predictors of response, focusing on those patients receiving oral corticosteroid therapy, and assessing the effect of treatment for decisions that relate to continuation. Multidisciplinary stakeholder efforts are needed to ensure responsible application of biologic therapy.  相似文献   

14.
15.

Objectives

A comprehensive overview of the ways control measures directed at carriers of multidrug-resistant organisms (MDRO) affect daily life of carriers is lacking. In this systematic literature review, we sought to explore how carriers experience being a carrier and how they experience being subjected to control measures by looking at the impact on basic capabilities.

Methods

We searched Medline, Embase and PsychINFO until 26 May 2016 for studies addressing experiences of MDRO carriers. Twenty-seven studies were included, addressing experiences with methicillin-resistant Staphylococcus aureus (n = 21), ESBL (n = 1), multiple MDRO (n = 4) and other (n = 1, not specified). We categorized reported experiences according to Nussbaum's capability approach.

Results

Carriage and control measures were found to interfere with quality of care, cause negative emotions, limit interactions with loved ones, cause stigmatization, limit recreational activities and create financial and professional insecurity. Further, carriers have difficulties with full comprehension of the problem of antimicrobial resistance, thus affecting six out of ten basic capabilities.

Conclusions

Applying Nussbaum's capability approach visualizes an array of unintended consequences of control measures. Carriers experience stigmatization, especially in healthcare settings, and have limited understanding of their situation and the complexities of antimicrobial resistance.  相似文献   

16.

Background

The paucity of licensed monoclonal antibodies (mAbs) in the infectious diseases arena strongly contrasts with the ready availability of these therapeutics for use in other conditions.

Aims

This narrative review aims to assess the potential of monoclonal antibody-based interventions for infectious diseases.

Sources

A review of the literature via the Medline database was performed and complemented by published official documents on licensed anti-infective mAbs. In addition, ongoing trials were identified through a search of the clinical trial registration platform ClinicalTrials.gov.

Content

We identified the few infections for which mAbs have been added to the therapeutic armamentarium and stressed their potential in representing a readily available protection tool against biothreats and newly emerging and reemerging infectious agents. In reviewing the historical context and main features of mAbs, we assert a potentially wider applicability and cite relevant examples of ongoing therapeutic developments. Factors hindering successful introduction of mAbs on a larger scale are outlined and thoughts are offered on how to possibly address some of these limitations.

Implications

mAbs may represent important tools in treating or preventing infections occurring with reasonably sufficient prevalence to justify demand and for which existing alternatives are not deemed fully adequate. Future initiatives need to address the prohibitive costs encountered in the development process. The feasibility of more large-scale administration of alternative modalities merits further exploration. In order to ensure optimal prospect of regulatory success, an early dialogue with competent authorities is encouraged.  相似文献   

17.

Background

The vaginal microbiota may modulate susceptibility to human papillomavirus (HPV), Chlamydia trachomatis, Neisseria gonorrhoeae and Mycoplasma genitalium infections. Persistent infection with a carcinogenic HPV is a prerequisite for cervical cancer, and C. trachomatis, N. gonorrheae and M. genitalium genital infections are all associated with pelvic inflammatory disease and subsequent infertility issues.

Objectives

To evaluate the association between these infections and the vaginal microbiota.

Data sources

The search was conducted on Medline and the Web of Science for articles published between 2000 and 2016.

Study eligibility criteria

Inclusion criteria included a measure of association for vaginal microbiota and one of the considered STIs, female population, cohort, cross-sectional and interventional designs, and the use of PCR methods for pathogen detection.

Methods

The vaginal microbiota was dichotomized into high-Lactobacillus vaginal microbiota (HL-VMB) and low-Lactobacillus vaginal microbiota (LL-VMB), using either Nugent score, Amsel's criteria, presence of clue cells or gene sequencing. A random effects model assuming heterogeneity among the studies was used for each STI considered.

Results

The search yielded 1054 articles, of which 39 met the inclusion criteria. Measures of association with LL-VMB ranged from 0.6 (95% CI 0.3–1.2) to 2.8 (95% CI 0.3–28.0), 0.7 (95% CI 0.4–1.2) to 5.2 (95% CI 1.9–14.8), 0.8 (95% CI 0.5–1.4) to 3.8 (95% CI 0.4–36.2) and 0.4 (95% CI 0.1–1.5) to 6.1 (95% CI 2.0–18.5) for HPV, C. trachomatis, N. gonorrhoeae and M. genitalium infections, respectively.

Conclusions

Although no clear trend for N. gonorrhoeae and M. genitalium infections could be detected, our results support a protective role of HL-VMB for HPV and C. trachomatis. Overall, these findings advocate for the use of high-resolution characterization methods for the vaginal microbiota and the need for longitudinal studies to lay the foundation for its integration in prevention and treatment strategies.  相似文献   

18.

Background

Since its sudden appearance and link to microcephaly in 2015, the number of PubMed references for Zika virus (ZIKV) has risen from 181 to 5163, at time of writing, with a vast proportion focused on the consequences of ZIKV infection during pregnancy. This level of attention underlies increased demand for sensitive and specific diagnostic tools able to assess risk to an unborn child, as well as to understand the dynamics and consequences of viral persistence.

Aim

Review the expanding knowledge on ZIKV persistence and diagnostic challenges and summarize current advancements in detection.

Sources

Peer-reviewed articles based on the search terms ‘Zika’ and ‘ZIKV’ combined with the terms ‘diagnostics’ ‘point-of-care diagnostics’ ‘viral load’ ‘persistence’ ‘detection’ ‘treatment’ ‘nucleic acid amplification testing’ ‘microsphere’ ‘PVRT’ ‘RVNT’ ‘RT-LAMP’ ‘NASBA’ SIBA’ ‘RPA’ ‘SHERLOCK’ ‘ELISA’, and ‘TMA’ as well as laboratory experience of the authors.

Content

Topics covered include the emergence of the ZIKV epidemic, pathogenesis of ZIKV infection, the nature of ZIKV persistence, complications in serological diagnosis, tried and novel diagnostic laboratory techniques, and a recent accounting of point-of-care testing (POCT) methods.

Implications

Surveillance and research in the case of ZIKV has shifted into a more rapid and coordinated worldwide directive than has occurred with most viral epidemics to date. The particular concentration of outbreaks in resource-limited settings increases the need for simple assays capable of reliable, inexpensive, high-throughput ZIKV diagnosis. This review serves to both catalogue current diagnostic options and consider their suitability at point-of-care.  相似文献   

19.

Objectives

We carried out a randomized multicentre study in China to investigate whether the clofazimine would improve the efficacy of the standardized regimen in patients with multidrug-resistant tuberculosis (MDR-TB).

Methods

Patients with MDR-TB managed in 17 TB specialist hospitals in China between September 2009 and September 2011 were randomly assigned to the treatment groups at enrolment. In the intervention group, 100 mg clofazimine per day was added to the standardized regimen. The primary outcome was the proportion of patients with successful outcomes.

Results

From the 156 patients that were screened, 74 were assigned to the control group and 66 to the clofazimine group. Of the 66 cases analysed for clinical outcome in the clofazimine group, 36 patients were cured, and seven completed treatment, yielding a favourable outcome rate of 65.1%. The proportion of patients with favourable outcomes receiving the control regimen was 47.3% (35/74), which was significantly lower than that in the clofazimine group (p 0.034, relative risk 0.661, 95% CI 0.243–0.949).

Conclusions

The addition of clofazimine to the standard regimen improved the treatment of MDR-TB.  相似文献   

20.

Introduction

The World Health Organization (WHO) has been asserting the importance of health care in today’s world. The objective of this research is to find out the type of medication that needs to be provided to the people at early stages to prevent behavioural risk factors. The health department of United States has a great vision to improve the immune system of the people and has taken measures to do the same through a Behavioural Risk Factor Surveillance System (BRFSS). This research aims to prevent behavioural risk factors by predictive analysis using the above mentioned dataset from the Centres for Disease Control and Prevention (CDC).

Methodology

The methods of ensemble classification and clustering is applied on the dataset, pre and post weighted classification, thereby classifying and prescribing the type of healthcare required for people exhibiting behaviours such as obesity, nutrition and physical activity.

Results and Discussion

This analyses help improve the quality of health of the citizens. In an extensive study, it was observed that the result obtained was 92.87% accurate.  相似文献   

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