Mastering Linked Datasets: The Future of Emergency Health Care Research.

Objectives: The aim of this work is to describe routine integration of prehospital emergency health records into a health master linkage file, delivering ongoing access to integrated patient treatment and outcome information for ambulance-attended patients in Queensland.Methods: The Queensland Ambulance Service (QAS) data are integrated monthly into the Queensland Health Master Linkage File (MLF) using a linkage algorithm that relies on probabilistic matches in combination with deterministic rules based on patient demographic details, date, time and facility identifiers. Each ambulance record is assigned an enduring linkage key (unique patient identifier) and further processing determines whether each record matches with a corresponding hospital emergency department, admission or death registry record. In this study, all QAS electronic ambulance report form (eARF) records from October 2016 to December 2018 where at least 1 key linkage variable was present (n = 1,771,734) were integrated into the MLF.Results: The majority of records (n = 1,456,502; 82.2%) were for transported patients, and 90.1% (n = 1,312,176) of these transports were to public hospital facilities. Of these transport records, 93.9% (n = 1,231,951) matched to emergency department (ED) records and 59.3% (n = 864,394) also linked to admitted patient records. Of ambulance non-transport records integrated into the MLF, 23.6% (n = 74,311) matched with ED records.Conclusion: This study demonstrates robust linkage methods, quality assurance processes and high linkage rates of data across the continuum of care (prehospital/emergency department/admitted patient/death) in Queensland. The resulting infrastructure provides a high-quality linked dataset that facilitates complex research and analysis to inform critical functions such as quality improvement, system evaluation and design.

A systematic review and meta-analysis of efficacy, cost-effectiveness, and safety of selected complementary and alternative medicine for neck and low-back pain.

Background. Back pain is a common problem and a major cause of disability and health care utilization. Purpose. To evaluate the efficacy, harms, and costs of the most common CAM treatments (acupuncture, massage, spinal manipulation, and mobilization) for neck/low-back pain. Data Sources. Records without language restriction from various databases up to February 2010. Data Extraction. The efficacy outcomes of interest were pain intensity and disability. Data Synthesis. Reports of 147 randomized trials and 5 nonrandomized studies were included. CAM treatments were more effective in reducing pain and disability compared to no treatment, physical therapy (exercise and/or electrotherapy) or usual care immediately or at short-term follow-up. Trials that applied sham-acupuncture tended towards statistically nonsignificant results. In several studies, acupuncture caused bleeding on the site of application, and manipulation and massage caused pain episodes of mild and transient nature. Conclusions. CAM treatments were significantly more efficacious than no treatment, placebo, physical therapy, or usual care in reducing pain immediately or at short-term after treatment. CAM therapies did not significantly reduce disability compared to sham. None of the CAM treatments was shown systematically as superior to one another. More efforts are needed to improve the conduct and reporting of studies of CAM treatments.

Diagnosis and management of febrile infants (0-3 months).

OBJECTIVES: To review the evidence for diagnostic accuracy of screening for serious bacterial illness (SBI) and invasive herpes simplex virus (HSV) infection in febrile infants 3 months or younger; ascertain harms and benefits of various management strategies; compare prevalence of SBI and HSV between different clinical settings; determine how well the presence of viral infection predicts against SBI; and review evidence on parental compliance to return for followup assessments (infants less than 6 months). DATA SOURCES: MEDLINE, CINAHL, Embase, Cochrane Central Register of Controlled Trials, the Cochrane Database of Systematic Reviews, abstracts, and unpublished materials. REVIEW METHODS: Two independent reviewers screened the literature and extracted data on population characteristics, index/diagnostic test characteristics. Diagnostic test accuracy studies were assessed using Quality Assessment of Diagnostic Accuracy Studies. RESULTS: Eighty-four original studies were included. The combined clinical and laboratory criteria (Rochester, Philadelphia, Boston, and Milwaukee) demonstrated similar overall accuracy (sensitivity: 84.4 percent to 100.0 percent; specificity: 26.6 percent to 69.0 percent; negative predictive value: 93.7 percent to 100.0 percent; and positive predictive value: 3.3 percent to 48.6 percent) for identifying infants with SBI. The criteria based on history of recent immunization or rapid influenza test demonstrated higher sensitivity but lower specificity compared with criteria based on age, gender, and the degree of fever. The overall accuracy of C-reactive protein was greater than that for absolute neutrophil count and absolute band counts , white blood cell, and procalcitonin. For correctly identifying infants with and without SBI (or bacteremia), the Boston, Philadelphia, and Milwaukee criteria/protocol showed better overall accuracy when applied to older infants versus neonates. The Rochester criteria were more accurate in neonates than in older infants. Evidence on HSV was scarce. Most of the criteria/protocols demonstrated high negative predictive values and low positive predictive values for correctly predicting the absence or presence of SBI. In studies reporting outcomes of delayed treatment for infants with SBI initially classified as low risk, all infants recovered uneventfully. The reported adverse events following immediate antibiotic therapy were limited to drug related rash and infiltration of intravenous line. There was a higher prevalence of SBI in infants without viral infection or clinical bronchiolitis compared to infants with viral infection or bronchiolitis. The prevalence of SBI tended to be higher in the emergency departments versus primary care setting offices. The parental compliance to followup for return visits/reassessment of infants after initial examination across four studies ranged from 77.4 percent to 99.8 percent. There was no evidence to determine the influence of parental factors and clinical settings on the degree of parental compliance. CONCLUSIONS: Overall, the focus of the literature has been on ruling out SBI. Harms associated with testing or management strategies have been less well studied. Combined criteria showed fairly high sensitivity and (therefore) reliability in not missing possible cases of SBI. Attempts to identify high-risk groups specifically, described in a minority of reports, were not as successful. There is very little literature on factors associated with compliance to followup care, although that information could be crucial to improving management strategies in the low-risk group. Future studies should focus on identifying the risks associated with testing and management strategies and factors that predict compliance.

Searching for controlled trials of complementary and alternative medicine: a comparison of 15 databases.

This project aims to assess the utility of bibliographic databases beyond the three major ones (MEDLINE, EMBASE and Cochrane CENTRAL) for finding controlled trials of complementary and alternative medicine (CAM). Fifteen databases were searched to identify controlled clinical trials (CCTs) of CAM not also indexed in MEDLINE. Searches were conducted in May 2006 using the revised Cochrane highly sensitive search strategy (HSSS) and the PubMed CAM Subset. Yield of CAM trials per 100 records was determined, and databases were compared over a standardized period (2005). The Acudoc2 RCT, Acubriefs, Index to Chiropractic Literature (ICL) and Hom-Inform databases had the highest concentrations of non-MEDLINE records, with more than 100 non-MEDLINE records per 500. Other productive databases had ratios between 500 and 1500 records to 100 non-MEDLINE records-these were AMED, MANTIS, PsycINFO, CINAHL, Global Health and Alt HealthWatch. Five databases were found to be unproductive: AGRICOLA, CAIRSS, Datadiwan, Herb Research Foundation and IBIDS. Acudoc2 RCT yielded 100 CAM trials in the most recent 100 records screened. Acubriefs, AMED, Hom-Inform, MANTIS, PsycINFO and CINAHL had more than 25 CAM trials per 100 records screened. Global Health, ICL and Alt HealthWatch were below 25 in yield. There were 255 non-MEDLINE trials from eight databases in 2005, with only 10% indexed in more than one database. Yield varied greatly between databases; the most productive databases from both sampling methods were Acubriefs, Acudoc2 RCT, AMED and CINAHL. Low overlap between databases indicates comprehensive CAM literature searches will require multiple databases.

Complementary and alternative therapies for back pain II.

BACKGROUND: Back and neck pain are important health problems with serious societal and economic implications. Conventional treatments have been shown to have limited benefit in improving patient outcomes. Complementary and Alternative Medicine (CAM) therapies offer additional options in the management of low back and neck pain. Many trials evaluating CAM therapies have poor quality and inconsistent results. OBJECTIVES: To systematically review the efficacy, effectiveness, cost-effectiveness, and harms of acupuncture, spinal manipulation, mobilization, and massage techniques in management of back, neck, and/or thoracic pain. DATA SOURCES: MEDLINE, Cochrane Central, Cochrane Database of Systematic Reviews, CINAHL, and EMBASE were searched up to 2010; unpublished literature and reference lists of relevant articles were also searched. study selection: All records were screened by two independent reviewers. Primary reports of comparative efficacy, effectiveness, harms, and/or economic evaluations from randomized controlled trials (RCTs) of the CAM therapies in adults (age ≥ 18 years) with back, neck, or thoracic pain were eligible. Non-randomized controlled trials and observational studies (case-control, cohort, cross-sectional) comparing harms were also included. Reviews, case reports, editorials, commentaries or letters were excluded. DATA EXTRACTION: Two independent reviewers using a predefined form extracted data on study, participants, treatments, and outcome characteristics. RESULTS: 265 RCTs and 5 non-RCTs were included. Acupuncture for chronic nonspecific low back pain was associated with significantly lower pain intensity than placebo but only immediately post-treatment (VAS: -0.59, 95 percent CI: -0.93, -0.25). However, acupuncture was not different from placebo in post-treatment disability, pain medication intake, or global improvement in chronic nonspecific low back pain. Acupuncture did not differ from sham-acupuncture in reducing chronic non-specific neck pain immediately after treatment (VAS: 0.24, 95 percent CI: -1.20, 0.73). Acupuncture was superior to no treatment in improving pain intensity (VAS: -1.19, 95 percent CI: 95 percent CI: -2.17, -0.21), disability (PDI), functioning (HFAQ), well-being (SF-36), and range of mobility (extension, flexion), immediately after the treatment. In general, trials that applied sham-acupuncture tended to produce negative results (i.e., statistically non-significant) compared to trials that applied other types of placebo (e.g., TENS, medication, laser). Results regarding comparisons with other active treatments (pain medication, mobilization, laser therapy) were less consistent Acupuncture was more cost-effective compared to usual care or no treatment for patients with chronic back pain. For both low back and neck pain, manipulation was significantly better than placebo or no treatment in reducing pain immediately or short-term after the end of treatment. Manipulation was also better than acupuncture in improving pain and function in chronic nonspecific low back pain. Results from studies comparing manipulation to massage, medication, or physiotherapy were inconsistent, either in favor of manipulation or indicating no significant difference between the two treatments. Findings of studies regarding costs of manipulation relative to other therapies were inconsistent. Mobilization was superior to no treatment but not different from placebo in reducing low back pain or spinal flexibility after the treatment. Mobilization was better than physiotherapy in reducing low back pain (VAS: -0.50, 95 percent CI: -0.70, -0.30) and disability (Oswestry: -4.93, 95 percent CI: -5.91, -3.96). In subjects with acute or subacute neck pain, mobilization compared to placebo significantly reduced neck pain. Mobilization and placebo did not differ in subjects with chronic neck pain. Massage was superior to placebo or no treatment in reducing pain and disability only amongst subjects with acute/sub-acute low back pain. Massage was also significantly better than physical therapy in improving back pain (VAS: -2.11, 95 percent CI: -3.15, -1.07) or disability. For subjects with neck pain, massage was better than no treatment, placebo, or exercise in improving pain or disability, but not neck flexibility. Some evidence indicated higher costs for massage use compared to general practitioner care for low back pain. Reporting of harms in RCTs was poor and inconsistent. Subjects receiving CAM therapies reported soreness or bleeding on the site of application after acupuncture and worsening of pain after manipulation or massage. In two case-control studies cervical manipulation was shown to be significantly associated with vertebral artery dissection or vertebrobasilar vascular accident. CONCLUSIONS: Evidence was of poor to moderate grade and most of it pertained to chronic nonspecific pain, making it difficult to draw more definitive conclusions regarding benefits and harms of CAM therapies in subjects with acute/subacute, mixed, or unknown duration of pain. The benefit of CAM treatments was mostly evident immediately or shortly after the end of the treatment and then faded with time. Very few studies reported long-term outcomes. There was insufficient data to explore subgroup effects. The trial results were inconsistent due probably to methodological and clinical diversity, thereby limiting the extent of quantitative synthesis and complicating interpretation of trial results. Strong efforts are warranted to improve the conduct methodology and reporting quality of primary studies of CAM therapies. Future well powered head to head comparisons of CAM treatments and trials comparing CAM to widely used active treatments that report on all clinically relevant outcomes are needed to draw better conclusions.

Assessment of thiopurine methyltransferase activity in patients prescribed azathioprine or other thiopurine-based drugs.

OBJECTIVES: To examine whether pretreatment determination of thiopurine methyltransferase (TPMT) enzymatic activity (phenotyping) or TPMT genotype, to guide thiopurine therapy in chronic autoimmune disease patients, reduces treatment harms. Other objectives included assessing: preanalytic, analytic, and postanalytic requirements for TPMT testing; diagnostic accuracy of TPMT genotyping versus phenotyping; association of thiopurine toxicity with TPMT genotypic or phenotypic status; and costs of testing, care, and treating drug-associated complications. DATA SOURCES: MEDLINE®, EMBASE®, and Healthstar were searched from inception to May 2010; the Cochrane Library® to October 2009; and BIOSIS®, Genetics Abstracts, and EconLit™ to May 2009, for English language records. REVIEW METHODS: A reviewer screened records, and a second reviewer verified exclusions and subsequent selection of relevant studies. Studies in patients with leukemia and organ transplant were excluded. Additionally, laboratories that provide TPMT analytical services were surveyed to assess means of TPMT testing in practice. Where possible, risk of bias was assessed using standard criteria. Meta-analyses estimated diagnostic sensitivity, and specificity; and odds ratios of associations. RESULTS: 1790 titles or abstracts, and 538 full text records were screened. 114 observational studies and one RCT were included. Majority of studies were rated fair quality, except for diagnostic studies with 37 percent of studies rated poor. In general, there were few patients who were homozygous (or compound heterozygous) for TPMT variant alleles in the included studies limiting applicability. There is insufficient evidence examining effectiveness of pretesting in terms of reduction in clinical adverse events. Sufficient preanalytical data were available regarding preferred specimen collection, stability and storage conditions for TPMT testing. There was no clinically significant effect of age, gender, various coadministered drugs, or most morbidities (with the exception of renal failure and dialysis). TPMT phenotyping methods had coefficients of variation generally below 10 percent. TPMT genotyping reproducibility is generally between 95-100 percent. The sensitivity of genotyping to identify patients with low or intermediate TPMT enzymatic activity is imprecise, ranging from 70.70 to 82.10 percent (95 percent CI, lower bound range 37.90 to 54.00 percent; upper bound range 84.60 to 96.90 percent). Sensitivity of homozygous TPMT genotype to correctly identify patients with low to absent enzymatic activity was 87.10 percent (95 percent CI 44.30 to 98.30 percent). Genotyping specificity approached 100 percent. Leukopenia was significantly associated with low and intermediate enzymatic activity (low activity OR 80.00, 95 percent CI 11.5 to 559; and intermediate activity OR 2.96, 95 percent CI 1.18 to 7.42), and homozygous and heterozygous TPMT variant allele genotype (OR 18.60, 95 percent CI 4.12 to 83.60; and 4.62, 95 percent CI 2.34 to 9.16, respectively). In general, TPMT phenotyping costs less than genotyping, although estimates across studies are quite heterogeneous. CONCLUSIONS: There is insufficient direct evidence regarding the effectiveness of pretesting of TPMT status in patients with chronic autoimmune diseases. Indirect evidence confirms strong association of leukopenia with lower levels of TPMT activity and carrier genotype already established in the literature.

Oral phosphodiesterase-5 inhibitors and hormonal treatments for erectile dysfunction: a systematic review and meta-analysis.

BACKGROUND: Erectile dysfunction (ED) is a common male sexual disorder. The relative benefits and harms of pharmacologic therapies for ED, as well as the value of hormonal testing in men with ED, are uncertain. PURPOSE: To evaluate the efficacy and harms of oral phosphodiesterase-5 (PDE-5) inhibitors and hormonal treatments for ED and assess the effect of measuring serum hormone levels on treatment outcomes for ED. DATA SOURCES: English-language studies from MEDLINE, EMBASE, Cochrane Central Register of Controlled Trials, PsycINFO, AMED, and SCOPUS through April 2009. Trial reference lists also were scanned. STUDY SELECTION: Randomized, controlled trials (RCTs) of oral PDE-5 inhibitors and hormonal treatment for ED, and observational studies reporting measurement of serum hormone levels, prevalence of hormonal abnormalities, or both in men with ED. DATA EXTRACTION: Two independent reviewers abstracted data on study, participant, and treatment characteristics; efficacy and harms outcomes; and prevalence of hormonal abnormalities. DATA SYNTHESIS: Data, primarily from short-term trials (

Oral sildenafil citrate (viagra) for erectile dysfunction: a systematic review and meta-analysis of harms.

OBJECTIVES: To summarize and compare evidence on harms in sildenafil- and placebo-treated men with erectile dysfunction (ED) in a systematic review and meta-analysis. METHODS: Randomized placebo-controlled trials (RCTs) were identified using an electronic search in MEDLINE, EMBASE, PsycINFO, SCOPUS, and Cochrane CENTRAL. The rates of any adverse events (AEs), most commonly reported AEs, withdrawals because of adverse events, and serious adverse events were ascertained and compared between sildenafil and placebo groups. The results of men with ED were stratified by clinical condition(s). Statistical heterogeneity was explored. Meta-analyses based on random-effects model were also performed. RESULTS: A total of 49 RCTs were included. Sildenafil-treated men had a higher risk for all-cause AEs (RR = 1.56, 95% CI: 1.38, 1.76), headache, flushing, dyspepsia, and visual disturbances compared with placebo-treated men. The magnitude of excess risk was greater in fixed- than in flexible-dose trials. The rates of serious adverse events and withdrawals because of adverse events did not differ in sildenafil vs placebo groups. A higher dose of sildenafil corresponded to a greater risk of AEs. The increased risk of harms was observed within and across clinically defined specific groups of patients. CONCLUSIONS: There was a lack of RCTs reporting long-term (>6 months) harms data. In short-term trials, men with ED randomized to sildenafil had an increased risk of all-cause any AEs, headache, flushing, dyspepsia, and visual disturbances. The exploration of different modes of dose optimization of sildenafil may be warranted.

Factors predicting completion and time to publication of Cochrane reviews.

BACKGROUND: Cochrane reviews are regarded as scientifically rigorous, yet a review's time to publication can be affected by factors such as the statistical significance of the findings. When this happens, misrepresentation of the literature and subsequent inappropriate decisions may result. We aimed to examine the factors associated with the time to publication of Cochrane reviews. METHODS: Review protocols published in issue 2, 2000, of the Cochrane Database of Systematic Reviews were included in this analysis if the corresponding review was published by issue 1, 2008. We used univariable and multivariate analyses to examine the time from publication of the protocol to publication of the first review and review-related factors predicting the time to publication. RESULTS: Of 118 eligible protocols published in issue 2, 2000, we identified 93 Cochrane reviews that had been published by January 2008. Of these, 36 (39%) were updates. The median time to publication was 1.63 years (range 0.15-7.31 years). A change in authors between publication of the protocol and publication of the final review was associated with longer time to publication (p = 0.002), whereas updated reviews were associated with shorter time to publication (p = 0.030). INTERPRETATION: In our study, 79% of the Cochrane protocols were published as a final review, and some Cochrane reviews took over 7 years from publication of the protocol to publication of the final review. Strategies to increase the number of published Cochrane reviews and decrease the time to publication should be considered, such as providing support to reviewers when a change in authorship occurs.

Surveillance search techniques identified the need to update systematic reviews.

OBJECTIVE: This article reports on literature surveillance methods to identify new evidence eligible for updating systematic reviews. STUDY DESIGN AND SETTING: Five surveillance search approaches are tested in the context of identifying studies that would signal major or invalidating new evidence for existing systematic reviews of health care interventions. Recall for each search approach was assessed as proportion of a composite yield of relevant studies across all search approaches that were identified by that approach. Screening burden was the number of studies that would need to be reviewed to identify the evidence that would necessitate updating. RESULTS: Searches were tested in a cohort of 77 systematic reviews. No one method yielded consistently high recall of relevant new evidence, so combinations of the strategies were examined. A search algorithm based on PubMed's related article search in combination with a subject searching using clinical queries was the most effective combination, retrieving all relevant new records in 68 cases. Screening burden was a median of 71 new records per review (inter-quartile range: 42-161). CONCLUSION: Surveillance for emerging evidence that signals the need to update systematic reviews is feasible using a combination of subject searching and searching based on the PubMed's related article function.

The absence of HIV seropositivity contrasts with a high prevalence of markers of sexually transmitted infections among registered female sex workers in Toliary, Madagascar.

In a cross-sectional study in 1998 we assessed human immunodeficiency virus (HIV) and syphilis infections and their risk factors among the 316 registered female sex workers (FSWs) of Toliary, south-west Madagascar. No case of HIV infection was detected, but 18.4% of registered FSWs had syphilis. Only half of these women regularly used condoms. In a multiple logistic regression analysis, risk factors for syphilis infection were multiple clients per week and, paradoxically, regular use of condoms. The variables associated with irregular use of condoms were younger ages of registered FSWs, multiple clients per week and Malagasy clients. The high prevalence of syphilis infection associated with irregular use of condoms might facilitate a very fast spread of HIV infection among these FSWs. Promotion of condom use and surveillance of sexually transmitted infections and HIV infection incidence are needed in the south of Madagascar.