Self-monitoring of blood glucose in patients with diabetes who do not use insulin--are guidelines evidence-based?

AIMS: To evaluate if clinical practice guideline recommendations regarding self-monitoring of blood glucose in patients with diabetes not using insulin follow the principles of evidence-based medicine. METHODS: After a search from 1999 to 2011, 18 clinical practice guidelines were included. Recommendations regarding self-monitoring of blood glucose were graded on a scale from one (strongly against self-monitoring) to four (strongly in favour of self-monitoring) and compared with the similarly graded conclusions of systematic reviews that were cited by the clinical practice guidelines. We also investigated how clinical practice guideline characteristics, for example funding sources, and quality of references cited could be related to the guideline recommendations. RESULTS: The clinical practice guidelines cited in total 15 systematic reviews, 14 randomized controlled trials, 33 non-randomized controlled trials papers and 18 clinical practice guidelines or position statements. The clinical practice guideline recommendations had an average grade of 3.4 (range 2.0-4.0). Higher grades were seen for clinical practice guidelines that acknowledged industry funding (mean value 4.0) or were issued by organizations depending on private funding (mean value 3.6 vs. 3.0 for governmental funding). The conclusions of the 15 systematic reviews had a mean grade of 2.2 (range 1.0-3.8). Systematic reviews with low grades were less cited. In total, 21 randomized controlled trials were included in the systematic reviews. Approximately half of these evaluated an educational intervention where the effect of self-monitoring of blood glucose could not be clearly isolated. CONCLUSIONS: Clinical practice guidelines were more in favour of self-monitoring use than the systematic reviews that were cited. The citation practice was non-systematic and industry funding seemingly led to a more positive attitude towards use of self-monitoring of blood glucose.

Grading quality of evidence and strength of recommendations in clinical practice guidelines part 3 of 3. The GRADE approach to developing recommendations.

This is the third and last article in the series about the Grading of Recommendations Assessment, Development and Evaluation (GRADE) approach to grading the quality of evidence and the strength of recommendations in clinical practice guidelines and its application in the field of allergy. We describe the factors that influence the strength of recommendations about the use of diagnostic, preventive and therapeutic interventions: the balance of desirable and undesirable consequences, the quality of a body of evidence related to a decision, patients' values and preferences, and considerations of resource use. We provide examples from two recently developed guidelines in the field of allergy that applied the GRADE approach. The main advantages of this approach are the focus on patient important outcomes, explicit consideration of patients' values and preferences, the systematic approach to collecting the evidence, the clear separation of the concepts of quality of evidence and strength of recommendations, and transparent reporting of the decision process. The focus on transparency facilitates understanding and implementation and should empower patients, clinicians and other health care professionals to make informed choices.

[Peritonitis due to glycopeptides-resistant Staphylococcus epidermidis]. / Péritonite à Staphylococcus epidermidis résistant aux glycopeptides.

A 71 years old male patient with a history of hypertension for more than 20 years, with chronic kidney failure under intra-peritoneal (IP) dialysis since June 2004, presents in March 2008 with glycopeptides-resistant Staphylococcus epidermidis peritonitis. Under vancomycin IP (alone or in association), clinical symptoms do not entirely subside and bacteria as well as white blood cells do persist in the peritoneal dialysis fluid. Under rifampicin IP, all clinical and laboratory abnormalities disappear. All 4 isolates of S. epidermidis obtained in the laboratory during this infectious episode appear to be susceptible to glycopeptides by the disk diffusion method, but MICs measurements confirm resistance. The only (blood) concentration of vancomycin measured during this episode does neither allow us to affirm, nor to exclude, that sub-inhibitory concentrations of vancomycin facilitated resistance to glycopeptides. This case-report raises the question of the optimal follow-up of those patients with residual kidney function: when, how often, and how do we need to measure blood vancomycin?

[Screening and diagnosis of gestational diabetes. Evaluation of the methodological quality of the guidelines of the Haute Autorité de Santé, of the American Diabetes Association, and of the World Health Organisation]. / Dépistage et diagnostic du diabète gestationnel: évaluation de la qualité méthodologique des avis de la Haute autorité de santé, de l'American diabetes association et de l'Organisation mondiale de la santé

We critically appraised the methodological quality of the clinical practice guideline (CPG) published by the Haute autorité de santé (HAS) about screening and diagnosis of gestational diabetes, and we compared its quality with that of two other CPGs, i.e. that of the American diabetes association (ADA) and that of the World health organisation (WHO). According to the AGREE criteria, HAS and ADA have produced CPGs that have approximately got the same levels of quality. Both these CPGs obtain AGREE scores that are better than those of WHO. Although the CPG of the HAS suffers from a few methodological drawbacks, regarding more particularly stakeholder involvement (AGREE domain n degrees 2), applicability (AGREE domain n degrees 5) and editorial independence (AGREE domain n degrees 6), this CPG summarises, and allows to compare most, if not all, other CPGs available with each other, with their possible benefits or harms, which may be useful for professionals involved in the care of the patient.

[Practice guidelines: let us sort them]. / Guides de pratique clinique: trions-les.

A growing number of clinical practice guidelines (CPG) is published. This is understandable because CPG are the corner stone in the evaluation of professional practices (EPP). One cannot deny that EPP is necessary. However, in order for the EPP to reach their objectives, which are to use our resources better and to improve health-care, CPG at our disposal should be of good quality, both in their form and in their content. This is not always the case. What is more, health-care professionals are often not properly trained to distinguish "good" from "not so good" CPG. In this context, the Société française de biologie clinique has created a working group on "CPG and Evidence-Based Laboratory Medicine (EBLM)". One of the main objectives of our group is to publish critical appraisals of CPG on a regular basis in the Annales de Biologie Clinique (ABC). Thus, the ABC will follow the example set by other medical journals, for example in France: Prescrire. We will more particularly appraise CPGs in relation with laboratory medicine. In this first article, we describe the methods that we will use in order to distinguish "good" from "not so good" CPG. Just like Prescrire as well as like many others, our first tool will be the AGREE instrument, which is quite consensual at an international level. The AGREE tool makes it possible to appraise quite easily, and in a reproducible way, the methodological quality of CPG. We also briefly discuss the more complicated methods that can be used to make judgments about the content of CPG, bearing in mind that equity, patients' autonomy, balancing risks and benefits, are the four universal principles of medical ethics, that is of good medicine, that is of EB(L)M.

[Propositions of interpretative comments for thyroid function tests]. / Propositions de commentaires interprétatifs pour les bilans biologiques thyroïdiens.

In the field of thyroid disease, a number of governmental organisms or professional associations have published practice guidelines containing laboratory-related recommendations, eg the Haute autorité de la santé (HAS), or the American Thyroid Association (ATA). Among the physicians who prescribe thyroid function tests, all have not read and memorized all these recommendations. In order to help them to better integrate these recommendations in their practice, we have composed a thesaurus of ready-made interpretative comments, trying to adapt our proposed comments to each possible combination of results of TSH and/or free T4 and/or free T3. The laboratorians who would prefer to use only the comments based strictly on the recommendations of HAS and/or ATA, will be able to select among our comments what is really validated by these two organizations. In addition, our work aims at enabling the patients who want it, to benefit from written information, which may be complementary to the more often spoken information provided by the clinicians.

[Chromobacterium violaceum peritonitis: case report and literature review]. / Péritonite à Chromobacterium violaceum: observation et revue de la littérature.

We report a case of Chromobacterium violaceum infection and we review the literature for all published cases. C. violaceum grew from a peritoneal fluid of a 47-year-old woman operated on for peritonitis following perforative gastroduodenal ulcer. She was just coming back from a 1-month-holyday in French Guyana, where she might have been in contact with this micro-organism. The patient fully recovered after surgical management associated with antibiotic therapy consisting of ofloxacin plus piperacillin-tazobactam. Among the more than a hundred of published cases of human infections with C. violaceum that we retrieved, there was not any other case of peritonitis.

How Useful are Laboratory Practice Guidelines?

Clinical practice guidelines (CPGs) relating to laboratory diagnostic testing are increasingly produced with the aim of standardizing practice and improving patient care based on the best available evidence. However, the production of a CPG is merely the first step in the process of getting evidence into practice, to be undertaken by laboratories and other stakeholders. This process should evaluate the information provided in the guidelines on laboratory tests, devise a strategy for implementing the CPG or the laboratory aspects of the CPG and finally, once implemented, assess the impact of the CPG on clinical practice, patient outcomes and costs of care. The purpose of CPG evaluation by the laboratory is to determine whether sufficient information is provided on the particular test recommended. CPGs may not always be written with the involvement of a laboratory specialist and this underlies the paucity of relevant information in some national guidelines. When laboratory specialists are involved, CPGs can provide practical information which supports local laboratories as well as clinicians in the implementation and appropriate use of recommendations. Implementation of CPGs is an often neglected area that needs attention and thought. There are many barriers to successful implementation, which may vary at local level. These need to be identified early if CPGs are to be successfully adhered to. The effectiveness of CPGs also needs to be audited using process and health outcome indicators. Clinical audit is an effective tool for assessing adherence to recommendations and for measuring the impact and success of the CPG.

Epidemiologically related and unrelated strains of Pseudomonas aeruginosa serotype O12 cannot be distinguished by phenotypic and genotypic typing.

A clonal origin for European isolates of antibiotic multi-resistant Pseudomonas aeruginosa serotype O12 has been suggested. This study was designed to assess the value and limitations of several typing methods for the investigation of outbreaks due to this serotype. In Hôpital de Rodez, France, this organism is endemic, and a prospective clinical epidemiological study was undertaken over a 15 month period, encompassing all patients at the hospital from whom P. aeruginosa O12 was isolated. All isolates were examined by auxanogram, antibiogram, phage-typing, electrophoresis of esterases and pulsed-field gel electrophoresis of DNA. The results suggest that (1) the methods used did not clearly differentiate between clinically-related and epidemiologically-unrelated European isolates, (2) in Hôpital de Rodez, while some isolates were likely to have been transmitted from patient-to-patient, most infections or colonizations with this organism were sporadic and their origin is unknown. The limits of typing methods for the investigation of outbreaks of nosocomial infection with multi-resistant P. aeruginosa O12 are emphasized.

In vivo pefloxacin-resistant Campylobacter fetus responsible for gastro-intestinal infection and bacteremia associated with arthritis of the hip.

The authors report a case of Campylobacter fetus subsp. fetus gastro-intestinal infection and bacteremia with poly-arthritis, mainly of the hip, in a French patient simultaneously suffering from cirrhosis of the liver. The outcome was eventually favorable, however only after a trial of ineffective pefloxacin-gentamicin therapy. The authors suggest: (i) gentamicin should not be given alone in C. fetus subsp. fetus infections, and (ii) pefloxacin should not be given if antibiotic sensitivities data are not available. The inconclusive reliability of disk diffusion tests for C. fetus subsp. fetus should be recognized.

[Biological variables and stratification of patients with inoperable non-small-cell bronchial cancer: recommendations for future trials]. / Variables biologiques et stratification des patients atteints de cancer bronchique non à petites cellules non opérés: recommandations pour de futurs essais.

OBJECTIVE: To identify, through a review of the literature, the laboratory variables that would allow a more accurate stratification of unresected non small-cell lung cancer patients who participate in clinical trials. METHOD: Systematic review, without meta-analysis, following the recommendations of the International Federation of Clinical Chemistry and Laboratory Medicine, and taking into account the Consolidated Standards of Reporting Trials statement. RESULTS: Of 1106 publications retrieved, we were able to include only fourteen studies in our review. Available evidence would support the use of several laboratory variables as prognostic covariables to stratify non resected non small-cell lung cancer patients in clinical trials, but blood haemoglobin would be the only one that could be recommended on a routine basis, and only in patients treated with radiotherapy (three studies out of three). The possible consequences in terms of therapeutic decision of haemoglobin measurements remain however to be clarified. CONCLUSION: Until better designed studies are published, a number of arguments would support the pre-treatment measurements of the following variables in patients participating in clinical trials: blood haemoglobin, white blood cell count with differential, serum LDH, albumin, calcium, and NSE. Further studies would also be necessary to support the addition to this list, of other tumour markers (including Cyfra 21-1), and/or measurements during or after treatment.

[Unresected colorectal liver metastases: prognostic value of laboratory variables]. / Métastases hépatiques non opérées des cancers colorectaux: valeur pronostique des variables biologiques.

OBJECTIVE: To search for laboratory variables having independent prognostic signification in patients with unresected colorectal liver metastases. METHODS: We have systematically reviewed the biomedical literature using the methodology recommended by the Committee on Evidence-Based Laboratory Medicine of the International Federation of Clinical Chemistry and Laboratory Medicine, and taking into account the Consolidated Standards of Reporting Trials Statement. RESULTS: Of 644 publications retrieved, the application of strict exclusion and inclusion criteria allowed us to include only eight studies in our systematic review. The main laboratory variables evaluated in these eight studies were serum carcino-embryonic antigen, alkaline phosphatase, albumin, bilirubin, and plasma prothrombin time. None of these variables were unanimously found to have an independent prognostic significance. A meta-analysis was not possible, mainly because of heterogeneity within the primary studies and these contradictory results. CONCLUSIONS: Current evidence would not support the routine use of laboratory variables as independent prognostic variables in patients with unresected colorectal liver metastases. Taking into account the inadequate quality of the published studies, this negative conclusion might be provisory only. Until better designed studies are published, a number of arguments would support to recommend pre-treatment measurement of serum carcino-embryonic antigen and alkaline phosphatase in patients participating in clinical trials.

[Systematic reviews and meta-analysis in laboratory medicine: principles and methods]. / Revues systématiques et méta-analyses en biologie clinique: principes et méthodes.

BACKGROUND: Systematic reviews and meta-analyses can help health-care professionals to base their decisions on the highest levels of evidence, and are therefore the cornerstone in practicing evidence-based medicine. In the field of diagnosis in general, and in laboratory medicine in particular, systematic reviews are scarcer, and often of lower quality than in other areas of medicine. AIM: To summarize the principles and methods that can be advised to perform systematic reviews of good quality in laboratory medicine. METHODS: A narrative review of the literature and discussions with members of the Committee on Evidence-Based Laboratory Medicine of the International Federation of Clinical Chemistry and Laboratory Medicine, in particular during our last three meetings, enabled us to adapt to laboratory medicine the methods which are currently being advocated to perform systematic reviews of good quality in other medical areas. RESULTS: The process of systematic reviewing consists of six key steps: 1) preparation: formulation of question(s); 2) systematic search of the literature; 3) selection of primary studies; 4) critical appraisal of the quality of the selected literature; 5) extraction and synthesis of data; 6) interpretation. The main differences between systematic reviews of diagnostic interventions and those of therapeutic interventions bear on question formulation, the choice of study designs to be included or excluded, the assessment of study quality and the statistical methods used to combine their results. The quoted references will help interested readers to deepen by themselves the most technical or controversial points. CONCLUSION: In order to improve quality of care as well as the balance between benefits, harms and costs of practice, each recommendation in guidelines should be based on a systematic review. In addition, such reviews can help to better identify gaps in biomedical knowledge, and improve critical skills, education, and training of professionals. One can therefore reasonably expect that the current multiplication of systematic reviews in laboratory medicine will favor the diffusion of diagnostic technologies with the highest levels of proven efficacy and effectiveness, at the detriment of the others.

[Laboratory variables and stratification of small-cell lung cancer patients: recommendations for therapeutic trials and for clinical practice guidelines]. / Variables biologiques et stratification des patients porteurs de cancer bronchopulmonaire à petites cellules: recommandations pour les essais cliniques et les guides de bonne pratique.

OBJECTIVE: To identify, through a systematic review of the literature, the laboratory variables that, in addition to performance status and to extent of the disease, would allow a more accurate stratification of small-cell lung cancer patients who participate in chemotherapy trials, with or without radiotherapy. Secondary aim: to compare the results of our systematic review with the recommendations made in current clinical practice guidelines. METHODS: Update of two recently published systematic reviews, without meta-analysis, following the recommendations of the International Federation of Clinical Chemistry and Laboratory Medicine, and taking into account the Consolidated Standards of Reporting Trials statement. RESULTS: Of 1143 publications retrieved, exclusion and inclusion criteria allow us to include 13 studies in our review. The three variables which were the most often found significant in multivariate statistical analysis, were: pre-therapeutic levels of laboratory variables (13/13), performance status (12/13), and degree of tumour invasion (10/10). Among the laboratory variables, serum lactate dehydrogenase (LDH) is the only one that was quite consistently found to be of independent prognostic significance, with p values or hazard ratios quite close to those obtained with performance status, or with extent of the disease. The recommendations made in the four clinical practice guidelines that we retrieved, are often vague regarding laboratory variables, and sometimes they even contradict each others. CONCLUSIONS: Available evidence would support the recommendation that pretreatment LDH should be systematically measured in order to stratify patients in therapeutic trials. If other laboratory variables were to be measured in addition to LDH for this purpose, it seems that alkaline phosphatase (ALP), and to a lesser extent, sodium and white blood cell counts, might be the best suited ones. Nevertheless, further studies are necessary to more clearly support this latter recommendation. Available evidence would not support the measurement of any other laboratory variable in this context, before, during, or after treatment. Our recommendations are more in agreement with the recommendations made in the clinical practice guidelines that use evidence-based methods than with the guidelines that do not.

[Bibliographic analysis of the use of laboratory blood parameters for the prognosis of primary lung cancer]. / Analyse critique de la bibliographie sur l'utilisation de paramètres biologiques sanguins pour l'evaluation pronostique de cancer bronchopulmonaire primitif.

In the daily clinical practice, serum calcium, albumin, and cyfra 21-1, are the only laboratory parameters officially recommended for the prognostic evaluation of primary lung cancer patients by the American, European or French respiratory/thoracic societies (and only in non-small cell lung cancer). The present review of the biomedical literature suggests that serum calcium for non operable non-small cell lung cancer, serum orosomucoid (alpha1-acid-glycoprotein) and serum cyfra 21-1 for non-small cell lung cancer, and perhaps plasma prothrombin time, might be the best laboratory parameters for the pre-therapeutic prognostic evaluation of the lung cancer patients, independently from the usual radio-clinical and histological parameters. Further prognostic evaluation studies are necessary in order notably to compare the prognostic values of the aforementioned parameters, not only aimed at evaluating the value of their pre-therapeutic levels, but also aimed at evaluating the value of their post-therapeutic changes. A higher pluridisciplinarity for such future publications also seem necessary.

[Orosomucoid prealbumin ratio in bronchopulmonary cancers]. / Rapport orosomucoïde sur préalbumine dans les cancers broncho-pulmonaires.

Lung cancer is a common pathology with high mortality due to late diagnosis. The 1987 TNM classification clearly defines the different steps and their prognosis. Although the prognostic value of some biological parameters (mainly serum LDH, sodium and/or albumin) has been established, these are not much used. We have prospectively studied the serum levels of seven proteins (RBP, prealbumin, albumin, transferrin, haptoglobin, orosomucoid, CRP) and we demonstrate the predominant value of prealbumin for the establishment of the prognosis of lung cancer; determination of orosomucoid increases the prognostic value of prealbumin. We confirm, for lung cancer, the prognostic value of the orosomucoid-prealbumin ratio, already known for other cancers.

[Are the ATS (American Thoracic Society) and the ERS (European Respiratory Society) correct in not recommending routine tumor marker assays foeening, staging, or evaluation of non-small cell lung cancer?]. / Faut-il suivre les sociétés savantes de pneumologie dans leurs recommandations concernant l'utilisation des marqueurs tumoraux sériques pour l'évaluation pronostique des cancers bronchiques primitifs non à petites cellules?

The American Thoracic Society (ATS) and the European Respiratory Society (ERS) do not recommend routine tumor marker assay for screening, staging or evaluation of non-small-cell lung cancer (NSCLC). In contrast to this position, the statement of the French society of pneumology (Société de Pneumologie de Langue Française, SPLF) suggests such assays may be useful for prognostic evaluation of NSCLC (and certainly so before treatment) and that the usefulness of serum CEA (carcino-embryonic antigen) measurements before and after treatment is not clearly excluded. Our own review of the literature indicates that other routine tests less expensive than tumor markers such as LDH, prothrombin time, calcium, blood cell counts and even serum proteins might, alone or in combination, have a prognostic significance similar to, or even higher than, tumor markers. Since routine clinical laboratories have to set priorities for useful analyses, a clear reading of the biomedical literature suggests that it is not currently necessary to routinely measure serum tumor markers (including Cyfra 21-1) for the prognostic evaluation of NSCLC patients.

[Primary small-cell bronchial cancer: value of serum tumor markers in the prognostic evaluation]. / Cancer bronchique primitif à petites cellules: intérêt du dosage des marqueurs tumoraux sériques pour l'évaluation pronostique.

TUMOR MARKERS: We reviewed the biomedical literature searching for the most well-documented serum markers with prognostic value independent of the usual radioclinical and histological parameters of small cell lung cancer. RELATIVE PROGNOSTIC VALUES: Neuron specific enolase (NSE) would have a pretherapeutic prognostic value better than LDH (lacto-dehydrogenase) and perhaps better than serum sodium, biocarbonates, and uric acid. The superiority of NSE over serum albumin remains to be proven. Although there are only a few reports, TK (thymine kinase), TPA (tissue polypeptide antigen), Cyfra 21-1 and/or IL-2 (interleukin-2) secretion might have better pretherapeutic prognostic value than NSE. We also found that iterative blood assays to follow therapeutic effects in patients with small-cell lung cancer have not been proven to provide independent prognostic information. CONCLUSION: As medical laboratory resources must be concentrated on priority exploitable assays, the currently available data would suggest that it is not necessary to routinely measure serum tumor markers, and in particular NSE, for the prognostic evaluation of small-cell lung cancer patients.

Evaluation of ICSH schistocyte measurement guidelines in France.

INTRODUCTION: The schistocytes are fragmented red blood cells mainly observed in the setting of hemolytic anemias where they remain an important criterion for the diagnosis. As the identification of these cells is still problematic, the International Council for Standardization in Hematology (ICSH) set up a consensus report in November, 2011. The French Group of Cellular Hematology (GFHC) aimed to collect the opinion of French biologists directly confronted to schistocytes measurements, about these guidelines. METHODS: Among the 578 professionals, 169 (29%) answered to the 10 questions dealing with the identification and measurements of schistocytes as proposed by the ICSH. RESULTS: A consensus was reached for the urgent need of such guidelines documents, especially in the current background of the European accreditation EN ISO 15189 rules. A traduction in native (French) language was warmly wished in order to facilitate the diffusion of the information. The pathologic threshold for the diagnosis of thrombotic microangiopathic anemia (TMA) (>1%) remained questionable. For half of the biologists, the new fragmented red blood cell (FRC) parameter recently provided by two manufacturers of automated blood cell counters was still doubtful for routine use. CONCLUSION: This survey assessed the impact of international 'guidelines' on the French biological community. The will to implement validated recommendations was strong, reflecting the awareness of the biologists to standardize the laboratory investigations.