Lorie A. Kloda

A systematic literature review of 10 years of research on sex/gender and experimental pain perception – Part 1: Are there really differences between women and men?

Summary Relatively limited support is provided to the hypothesis that healthy women have greater pain sensitivity than men in most experimental pain modalities. Abstract The purpose of this systematic review was to summarize and critically appraise the results of 10 years of human laboratory research on pain and sex/gender. An electronic search strategy was designed by a medical librarian and conducted in multiple databases. A total of 172 articles published between 1998 and 2008 were retrieved, analyzed, and synthesized. The first set of results (122 articles), which is presented in this paper, examined sex difference in the perception of laboratory‐induced thermal, pressure, ischemic, muscle, electrical, chemical, and visceral pain in healthy subjects. This review suggests that females (F) and males (M) have comparable thresholds for cold and ischemic pain, while pressure pain thresholds are lower in F than M. There is strong evidence that F tolerate less thermal (heat, cold) and pressure pain than M but it is not the case for tolerance to ischemic pain, which is comparable in both sexes. The majority of the studies that measured pain intensity and unpleasantness showed no sex difference in many pain modalities. In summary, 10 years of laboratory research have not been successful in producing a clear and consistent pattern of sex differences in human pain sensitivity, even with the use of deep, tonic, long‐lasting stimuli, which are known to better mimic clinical pain. Whether laboratory studies in healthy subjects are the best paradigm to investigate sex differences in pain perception is open to question and should be discussed with a view to enhancing the clinical relevance of these experiments and developing new research avenues.

A systematic literature review of 10 years of research on sex/gender and pain perception - Part 2: Do biopsychosocial factors alter pain sensitivity differently in women and men?

Summary Ecological validity of laboratory findings in healthy humans about the role of certain biopsychological factors on sex differences in pain perception needs to be assessed/improved. Abstract This systematic review summarizes the results of 10 years of laboratory research on pain and sex/gender. An electronic search strategy was designed by a medical librarian to access multiple databases. A total of 172 articles published between 1998 and 2008 were retrieved, analyzed, and synthesized. The second set of results presented in this review (129 articles) examined various biopsychosocial factors that may contribute to differences in pain sensitivity between healthy women and men. The results revealed that the involvement of hormonal and physiological factors is either inconsistent or absent. Some studies suggest that temporal summation, allodynia, and secondary hyperalgesia may be more pronounced in women than in men. The evidence to support less efficient endogenous pain inhibitory systems in women is mixed and does not necessarily apply to all pain modalities. With regard to psychological factors, depression may not mediate sex differences in pain perception, while the role of anxiety is ambiguous. Cognitive and social factors appear to partly explain some sex‐related differences. Finally, past individual history may be influential in female pain responses. However, these conclusions must be treated with much circumspection for various methodological reasons. Furthermore, some factors/mechanisms remain understudied in the field. There is also a need to assess and improve the ecological validity of findings from laboratory studies on healthy subjects, and perhaps a change of paradigm needs to be considered at this point in time to better understand the factors that influence the experience of women and men who suffer from acute or chronic pain.

Oral immunotherapy for milk allergy

BACKGROUNDnThe mainstay of treatment of IgE-mediated cow milk allergy (IMCMA) is an avoidance diet, which is especially difficult with a ubiquitous food like milk. Milk oral immunotherapy (MOIT) may be an alternative treatment, through desensitization or induction of tolerance.nnnOBJECTIVESnWe aim to assess the clinical efficacy and safety of MOIT in children and adults with IMCMA as compared to a placebo treatment or avoidance strategy.nnnSEARCH METHODSnWe searched 13 databases for journal articles, conference proceedings, theses and unpublished trials, without language or date restrictions, using a combination of subject headings and text words. The search is up-to-date as of October 1, 2012.nnnSELECTION CRITERIAnOnly randomised controlled trials (RCT) were considered for inclusion. Blinded and open trial designs were included. Children and adults with IMCMA were included. MOIT administered by any protocol were included.nnnDATA COLLECTION AND ANALYSISnA total of 2111 unique records were identified and screened for potential inclusion. Studies were selected, data extracted and methodological quality assessed independently by two reviewers. We attempted to contact the study investigators to inquire about data not published that was required for the analysis. Statistical heterogeneity was assessed using the I² test. We estimated a pooled risk ratio (RR) for each outcome using a Mantel-Haenzel fixed-effect model if statistical heterogeneity was low as evaluated by an I² value less than 50%.nnnMAIN RESULTSnOf 157 records reviewed, 16 were included, representing five trials. In general, the studies were small and had inconsistent methodological rigor. Overall, the quality of evidence was rated as low. Each study used a different MOIT protocol. A total of 196 patients were studied (106 MOIT, 90 control) and all were children. Three studies were blinded and two used an avoidance diet control.xa0 Sixty-six patients (62%) in the MOIT group were able to tolerate a full serving of milk (about 200 mL) compared to seven (8%) of the control group (RR 6.61, 95% CI 3.51 to 12.44). In addition, 27 (25%) in the MOIT group could ingest a partial serving of milk (10 to 184 mL) while none could in the control group (RR 9.34, 95% CI 2.72 to 32.09). None of the studies assessed the patients following a period off immunotherapy. Adverse reactions were common (97 of 106 MOIT patients had at least one symptom), although most were local and mild. Because of variability in reporting methods, adverse effects could not be combined quantitatively. For every 11 patients receiving MOIT, one required intramuscular epinephrine. One patient required it on two occasions.nnnAUTHORS CONCLUSIONSnStudies to date have involved small numbers of patients and the quality of evidence is generally low. The current evidence shows that MOIT can lead to desensitization in the majority of individuals with IMCMA although the development of long-term tolerance has not been established. A major drawback of MOIT is the frequency of adverse effects, although most are mild and self-limited. The use of parenteral epinephrine is not infrequent. Because there are no standardized protocols, guidelines would be required prior to incorporating desensitization into clinical practice.

There are no randomized controlled trials that support the United States Preventive Services Task Force guideline on screening for depression in primary care: a systematic review

BackgroundThe United States Preventive Services Task Force (USPSTF) recommends screening adults for depression in primary care settings when staff-assisted depression management programs are available. This recommendation, however, is based on evidence from depression management programs conducted with patients already identified as depressed, even though screening is intended to identify depressed patients not already recognized or treated. The objective of this systematic review was to evaluate whether there is evidence from randomized controlled trials (RCTs) that depression screening benefits patients in primary care, using an explicit definition of screening.MethodsWe re-evaluated RCTs included in the 2009 USPSTF evidence review on depression screening, including only trials that compared depression outcomes between screened and non-screened patients and met the following three criteria: determined patient eligibility and randomized prior to screening; excluded patients already diagnosed with a recent episode of depression or already being treated for depression; and provided the same level of depression treatment services to patients identified as depressed in the screening and non-screening trial arms. We also reviewed studies included in a recent Cochrane systematic review, but not the USPSTF review; conducted a focused search to update the USPSTF review; and reviewed trial registries.ResultsOf the nine RCTs included in the USPSTF review, four fulfilled none of three criteria for a test of depression screening, four fulfilled one of three criteria, and one fulfilled two of three criteria. There were two additional RCTs included only in the Cochrane review, and each fulfilled one of three criteria. No eligible RCTs were found via the updated review.ConclusionsThe USPSTF recommendation to screen adults for depression in primary care settings when staff-assisted depression management programs are available is not supported by evidence from any RCTs that are directly relevant to the recommendation. The USPSTF should re-evaluate this recommendation.Please see related article: http://www.biomedcentral.com/1741-7015/12/14RegistrationPROSPERO (#CRD42013004276)

Physicians' assessment of the value of clinical information: Operationalization of a theoretical model

Inspired by the acquisition–cognition–application model (T. Saracevic & K.B. Kantor, 1997), we developed a tool called the Information Assessment Method to more clearly understand how physicians use clinical information. In primary healthcare, we conducted a naturalistic and longitudinal study of searches for clinical information. Forty-one family physicians received a handheld computer with the Information Assessment Method linked to one commercial electronic knowledge resource. Over an average of 320 days, 83% of 2,131 searches for clinical information were rated using the Information Assessment Method. Searches to address a clinical question, as well as the retrieval of relevant clinical information, were positively associated with the use of that information for a specific patient. Searches done out of curiosity were negatively associated with the use of clinical information. We found significant associations between specific types of cognitive impact and information use for a specific patient. For example, when the physician reported “My practice was changed and improved” as a result of this clinical information, the odds that information was used for a specific patient increased threefold. Our findings provide empirical data to support the applicability of the acquisition-cognition-application model, as operationalized through the Information Assessment Method, in primary healthcare. Capturing the use of research-based information in medicine opens the door to further study of the relationships between clinical information and health outcomes.

Clinical information behavior of rehabilitation therapists: a review of the research on occupational therapists, physical therapists, and speech-language pathologists

OBJECTIVESnThe review sought to synthesize existing research relevant to rehabilitation therapists clinical information behavior and to identify gaps in evidence, particularly in comparison to what is already known about the information behavior of other health professionals, such as physicians.nnnMETHODSnA literature review was conducted of both quantitative and qualitative research studies that included information on the clinical information behavior of occupational therapists, physical therapists, and speech-language pathologists. Findings were organized according to a taxonomy of variables derived from the literature.nnnRESULTSnFindings from seventeen studies, mostly surveys, conducted since 1990 demonstrate that very little is known about the clinical information needs of and information use by rehabilitation therapists. The sources most often consulted by rehabilitation therapists are printed materials (books and journals) and colleagues. Databases are consulted less often, and few rehabilitation therapists are aware of databases other than MEDLINE.nnnDISCUSSIONnMethodological flaws limit the generalizability and validity of much of the research conducted on the clinical information behavior of this population. More research is needed to better understand the clinical questions that arise in rehabilitation therapists practice, reasons for consulting certain sources, and ways in which information seeking enhances evidence-based practice.

The Seroprevalence of Hepatitis C Antibodies in Immigrants and Refugees from Intermediate and High Endemic Countries: A Systematic Review and Meta-Analysis

Background & Aims Hepatitis C virus (HCV) infection is a significant global health issue that leads to 350,000 preventable deaths annually due to associated cirrhosis and hepatocellular carcinoma (HCC). Immigrants and refugees (migrants) originating from intermediate/high HCV endemic countries are likely at increased risk for HCV infection due to HCV exposure in their countries of origin. The aim of this study was to estimate the HCV seroprevalence of the migrant population living in low HCV prevalence countries. Methods Four electronic databases were searched from database inception until June 17, 2014 for studies reporting the prevalence of HCV antibodies among migrants. Seroprevalence estimates were pooled with a random-effect model and were stratified by age group, region of origin and migration status and a meta-regression was modeled to explore heterogeneity. Results Data from 50 studies representing 38,635 migrants from all world regions were included. The overall anti-HCV prevalence (representing previous and current infections) was 1.9% (95% CI, 1.4–2.7%, I2 96.1). Older age and region of origin, particularly Sub-Saharan Africa, Asia, and Eastern Europe were the strongest predictors of HCV seroprevalence. The estimated HCV seroprevalence of migrants from these regions was >2% and is higher than that reported for most host populations. Conclusion Adult migrants originating from Asia, Sub-Saharan Africa and Eastern Europe are at increased risk for HCV and may benefit from targeted HCV screening.

The diagnostic accuracy of the patient health questionnaire-2 (PHQ-2), patient health questionnaire-8 (PHQ-8), and patient health questionnaire-9 (PHQ-9) for detecting major depression: Protocol for a systematic review and individual patient data meta-analyses

BackgroundMajor depressive disorder (MDD) may be present in 10%–20% of patients in medical settings. Routine depression screening is sometimes recommended to improve depression management. However, studies of the diagnostic accuracy of depression screening tools have typically used data-driven, exploratory methods to select optimal cutoffs. Often, these studies report results from a small range of cutoff points around whatever cutoff score is most accurate in that given study. When published data are combined in meta-analyses, estimates of accuracy for different cutoff points may be based on data from different studies, rather than data from all studies for each possible cutoff point. As a result, traditional meta-analyses may generate exaggerated estimates of accuracy. Individual patient data (IPD) meta-analyses can address this problem by synthesizing data from all studies for each cutoff score to obtain diagnostic accuracy estimates. The nine-item Patient Health Questionnaire-9 (PHQ-9) and the shorter PHQ-2 and PHQ-8 are commonly recommended for depression screening. Thus, the primary objectives of our IPD meta-analyses are to determine the diagnostic accuracy of the PHQ-9, PHQ-8, and PHQ-2 to detect MDD among adults across all potentially relevant cutoff scores. Secondary analyses involve assessing accuracy accounting for patient factors that may influence accuracy (age, sex, medical comorbidity).Methods/designData sources will include MEDLINE, MEDLINE In-Process & Other Non-Indexed Citations, PsycINFO, and Web of Science. We will include studies that included a Diagnostic and Statistical Manual or International Classification of Diseases diagnosis of MDD based on a validated structured or semi-structured clinical interview administered within 2xa0weeks of the administration of the PHQ. Two reviewers will independently screen titles and abstracts, perform full article review, and extract study data. Disagreements will be resolved by consensus. Risk of bias will be assessed with the Quality Assessment of Diagnostic Accuracy Studies-2 tool. Bivariate random-effects meta-analysis will be conducted for the full range of plausible cutoff values.DiscussionThe proposed IPD meta-analyses will allow us to obtain estimates of the diagnostic accuracy of the PHQ-9, PHQ-8, and PHQ-2.Systematic review registrationPROSPERO CRD42014010673

Selective Cutoff Reporting in Studies of Diagnostic Test Accuracy: A Comparison of Conventional and Individual-Patient-Data Meta-Analyses of the Patient Health Questionnaire-9 Depression Screening Tool

In studies of diagnostic test accuracy, authors sometimes report results only for a range of cutoff points around data-driven optimal cutoffs. We assessed selective cutoff reporting in studies of the diagnostic accuracy of the Patient Health Questionnaire-9 (PHQ-9) depression screening tool. We compared conventional meta-analysis of published results only with individual-patient-data meta-analysis of results derived from all cutoff points, using data from 13 of 16 studies published during 2004-2009 that were included in a published conventional meta-analysis. For the standard PHQ-9 cutoff of 10, accuracy results had been published by 11 of the studies. For all other relevant cutoffs, 3-6 studies published accuracy results. For all cutoffs examined, specificity estimates in conventional and individual-patient-data meta-analyses were within 1% of each other. Sensitivity estimates were similar for the cutoff of 10 but differed by 5%-15% for other cutoffs. In samples where the PHQ-9 was poorly sensitive at the standard cutoff, authors tended to report results for lower cutoffs that yielded optimal results. When the PHQ-9 was highly sensitive, authors more often reported results for higher cutoffs. Consequently, in the conventional meta-analysis, sensitivity increased as cutoff severity increased across part of the cutoff range-an impossibility if all data are analyzed. In sum, selective reporting by primary study authors of only results from cutoffs that perform well in their study can bias accuracy estimates in meta-analyses of published results.

Depression screening and mental health outcomes in children and adolescents: a systematic review protocol

BackgroundDepression is an important cause of disability among children and adolescents. Depression screening is one possible method for managing depression, and screening programs have been initiated in some school and medical settings. However, in 2005, the Canadian Task Force on Preventive Health Care and the United Kingdom National Institute of Clinical Excellence did not recommend depression screening among children and adolescents. By contrast, in 2009, the United States Preventive Services Task Force recommended that all adolescents, but not younger children, be screened for depression in medical settings with integrated depression management services, although no trials of screening were identified. The objectives of this systematic review are to evaluate in children and adolescents the accuracy of depression screening tools; depression treatment efficacy; whether depression screening improves depression outcomes; and potential harms related to depression interventions and screening.Methods/designData sources will include the bibliographic databases MEDLINE, Cochrane CENTRAL, PsycINFO, EMBASE, LILACS and Web of Science, supplemented by reference harvesting of eligible articles, relevant systematic reviews, relevant guidelines and recommendations, and selected journals, and by searches for unpublished studies. Eligible studies will report data for children and adolescents aged 6 to 18 years. Eligible diagnostic accuracy studies must compare a depression screening tool to a validated diagnostic interview for major depressive disorder and report diagnostic accuracy data. Eligible treatment studies must be randomized controlled trials of pharmacological, psychotherapeutic, or other depression treatments commonly available for children and adolescents in pediatric, primary-care, and family medicine settings. Eligible screening studies must be randomized controlled trials that compare depression outcomes between children or adolescents who underwent depression screening versus those who did not. Studies of harms will include randomized controlled trials and observational studies that evaluate harms from depression screening or treatment. Two investigators will independently review titles and abstracts, followed by full article review. Disagreements will be resolved by consensus. Two investigators will independently extract the data, with discrepancies resolved via consensus.DiscussionThe proposed systematic review will determine whether there is sufficient evidence of benefits in excess of harms and costs to support screening for depression in childhood and adolescence.