Bundling Colorectal Cancer Screening Outreach with Screening for Social Risk in Federally Qualified Health Centers: A Stepped-Wedge Implementation-Effectiveness Study.

BACKGROUND: Bundling is combining individual interventions to meet quality metrics. Bundling offers of cancer screening with screening for social determinants of health (SDOH) may enable health centers to assist patients with social risks and yield efficiencies. OBJECTIVE: To measure effects of bundling fecal immunochemical testing (FIT) and SDOH screening in federally qualified health centers (FQHCs). DESIGN: Clustered stepped-wedge trial. PARTICIPANTS: Four Massachusetts FQHCs randomized to implement bundled FIT-SDOH over 8-week "steps." INTERVENTION: Outreach to 50-75-year-olds overdue for CRC screening to offer FIT with SDOH screening. The implementation strategy used facilitation and training for data monitoring and reporting. MAIN MEASURES: Implementation process descriptions, data from facilitation meetings, and CRC and SDOH screening rates. Rates were compared between implementation and control FQHCs in each "step" by fitting generalized linear mixed-effects models with random intercepts for FQHCs, patients, and "step" by FQHC. KEY RESULTS: FQHCs tailored implementation processes to their infrastructure, workflows, and staffing and prioritized different groups for outreach. Two FQHCs used population health outreach, and two integrated FIT-SDOH within established programs, such as pre-visit planning. Of 34,588 patients overdue for CRC screening, 54% were female; 20% Black, 11% Latino, 10% Asian, and 47% white; 32% had Medicaid, 16% Medicare, 32% private insurance, and 11% uninsured. Odds of CRC screening completion in implementation "steps" compared to controls were higher overall and among groups prioritized for outreach (overall: adjusted odds ratio (aOR) 2.41, p = 0.005; prioritized: aOR 2.88, p = 0.002). Odds of SDOH screening did not differ across "steps." CONCLUSIONS: As healthcare systems are required to conduct more screenings, it is notable that outreach for a long-standing cancer screening requirement increased screening, even when bundled with a newer screening requirement. This outreach was feasible in a real-world safety-net clinical population and may conserve resources, especially compared to more complex or intensive outreach strategies. CLINICAL TRIALS REGISTRATION: NCT04585919.

Stressful life events during the perimenopause: longitudinal observations from the seattle midlife women's health study.

BACKGROUND: Midlife is a time of increased responsibilities for women who have multiple roles including taking care of children, caring for elderly parents, managing households, and working outside the home. With little time for themselves, women additionally experience stressful life events (SLEs). The purpose of this study was to describe the longitudinal patterns of SLEs of women during midlife and to identify predictors of the SLE longitudinal patterns using baseline data of socio-economic factors and demographic characteristics. METHODS: Women who were part of the Seattle Midlife Women's Health Study (SMWHS), a longitudinal study spanning more than 23 years, who had SLEs measured at baseline and at years 2, 7, and 10 were included in these analyses (N = 380 women at baseline). The Life Event Scale (LES), a 70-item scale based on a yes/no response and a Likert-based scoring system with 0 (no effect) to 4 (large effect), was used to determine the total and impact scores of midlife women. The LES was adapted to midlife women from the Norbeck Scale for younger, pregnant women. Analytic strategies consisted of a group-based trajectory model (GBTM) to examine subgroups of women with similar exposure to SLEs using socio-economic factors (gross family income, education, race/ethnicity, employment), demographic variables (age, marital status, being a parent), and menopausal transition stage to differentiate trajectories over time. RESULTS: Approximately 86% of women had medium high exposure to undesirable SLEs with a slight decrease (65.5%), or a sharp decrease (20.1%), over 10 years. The majority (approximately 64%) had moderate, sustained impact ratings, while approximately 35% had impact ratings that decreased over time. Most women (approximately 88%) reported desirable life events, which were sustained over the ten years, and which may help to balance or offset the high ratings of undesirable stressful life events. The rated impact of these desirable events decreased slightly over time for 65% of the sample. Socio-economic factors, demographic variables, and menopausal transition stages were not significant predictors of any of the four GBTMs. CONCLUSION: Midlife women experience SLEs throughout the menopausal transition. Most of these midlife women had had a large amount of sustained stress over 10 years although all trajectories decreased to some extent over time. Since the menopausal transition stages were not significant predictors of the ratings of SLEs, a more complex set of factors, including social as well as biological, may explain the ratings of the women over the course of this ten-year observational study.

Quality standards and internal quality control practices in medical laboratories: an IFCC global survey of member societies.

OBJECTIVES: The trueness and precision of clinical laboratory results are ensured through total quality management systems (TQM), which primarily include internal quality control (IQC) practices. However, quality practices vary globally. To understand the current global state of IQC practice and IQC management in relation to TQM the International Federation of Clinical Chemistry and Laboratory Medicine (IFCC) Task Force on Global Laboratory Quality (TF-GLQ) conducted a survey of IFCC member countries on IQC practices and management. METHODS: The survey included 16 questions regarding IQC and laboratory TQM practices and was distributed to IFCC full and affiliate member countries (n=110). A total of 46 (41.8 %) responses were received from all regions except North America. RESULTS: Of the responding countries, 78.3 % (n=36) had legislative regulations or accreditation requirements governing medical laboratory quality standards. However, implementation was not mandatory in 46.7 % (n=21) of responding countries. IQC practices varied considerably with 57.1 % (n=28) of respondents indicating that they run 2 levels of IQC, 66.7 % (n=24) indicating they run IQC every 24 h and 66.7 % (n=28) using assay manufacturer IQC material sources. Only 29.3 % (n=12) of respondents indicated that every medical laboratory in their country has written IQC policies and procedures. By contrast, 97.6 % (n=40) of responding countries indicated they take corrective action and result remediation in the event of IQC failure. CONCLUSIONS: The variability in TQM and IQC practices highlights the need for more formal programs and education to standardize and improve TQM in medical laboratories.

External quality assessment practices in medical laboratories: an IFCC global survey of member societies.

OBJECTIVES: Clinical laboratory results are required for critical medical decisions, underscoring the importance of quality results. As part of total quality management, external quality assessment (EQA) is a vital component to ensure laboratory accuracy. The goal of this survey was to evaluate the current status of global laboratory quality systems and assess the need for implementation, expansion, or harmonization of EQA programs (EQAP) for Clinical Chemistry and Laboratory Medicine. METHODS: The International Federation of Clinical Chemistry and Laboratory Medicine (IFCC) Task Force on Global Laboratory Quality (TF-GLQ) conducted a survey of IFCC full and affiliate members (n=110) on laboratory quality practice. A total of 41 (37.3%) countries representing all IFCC regions except North America provided responses about EQA availability and practices. RESULTS: All 41 countries perform EQA, 38 reported that their laboratories had EQA policies and procedures, and 39 further act/evaluate unacceptable EQA results. 39 countries indicated they have international and/or national EQAP and 30 use alternative performance assessments. EQA frequency varied among countries. Generally, an EQAP provided the EQA materials (40/41) with four countries indicating that they did not have an EQAP in their country. CONCLUSIONS: Globally, most laboratories participate in an EQAP and have defined quality procedures for EQA. There remain gaps in EQA material availability and implementation of EQA as a part of a total laboratory quality system. This survey highlights the need for education, training, and harmonization and will guide efforts of the IFCC TF-GLQ in identifying areas for enhancing global laboratory quality practices.

Stakeholder and Equity Data-Driven Implementation: a Mixed Methods Pilot Feasibility Study.

We conducted a mixed methods pilot feasibility study of a Stakeholder and Equity Data-Driven Implementation (SEDDI) process to facilitate using healthcare data to identify patient groups experiencing gaps in the use of evidence-based interventions (EBIs) and rapidly adapt EBIs to achieve greater access and equitable outcomes. We evaluated the feasibility and acceptability of SEDDI in a pilot hybrid type 2 effectiveness-implementation trial of a paired colorectal cancer (CRC) and social needs screening intervention at four federally qualified community health centers (CHCs). An external facilitator partnered with CHC teams to support initial implementation, followed by the SEDDI phase focused on advancing health equity. Facilitation sessions were delivered over 8 months. Preliminary evaluation of SEDDI involved convergent mixed methods with quantitative survey and focus group data. CHCs used data to identify gaps in outreach and completion of CRC screening with respect to race/ethnicity, gender, age, and language. Adaptations to improve access and use of the intervention included cultural, linguistic, and health literacy tailoring. CHC teams reported that facilitation and systematic review of data were helpful in identifying and prioritizing gaps. None of the four CHCs completed rapid cycle testing of adaptations largely due to competing priorities during the COVID-19 response. SEDDI has the potential for advancing chronic disease prevention and management by providing a stakeholder and data-driven approach to identify and prioritize health equity targets and guide adaptations to improve health equity. ClinicalTrials.gov Identifier: NCT04585919.

A survey of practice in the management of haemolysis, icterus and lipaemia in blood specimens in the United Kingdom and Republic of Ireland.

BACKGROUND: Haemolysis, icterus and lipaemia (HIL) are common interferants in laboratory medicine, potentially impacting patient care. This survey investigates HIL management in medical laboratories across the UK and Republic of Ireland (ROI). METHODS: A survey was sent to members of key professional organisations for laboratory medicine in the UK and ROI. Questions related to the detection, monitoring, quality control, and management of HIL. RESULTS: In total, responses from 124 laboratories were analysed, predominantly from England (52%) and ROI (36%). Most responses were from public hospitals with biochemistry services (90%), serving primary care (91%), inpatients (91%), and outpatients (89%). Most laboratories monitored H (98%), I (88%), and L (96%) using automated indices (93%), alone or in combination with visual inspection.Manufacturer-stated cut-offs were used by 83% and were applied to general chemistries in 79%, and immunoassays in 50%. Where HIL cut-offs are breached, 64% withheld results, while 96% reported interference to users. HIL were defined using numeric scales (70%) and ordinal scales (26%). HIL targets exist in 35% of laboratories, and 54% have attempted to reduce HIL. Internal Quality Control for HIL was lacking in 62% of laboratories, and just 18% of respondents have participated in External Quality Assurance. Laboratories agree manufacturers should: standardise HIL reporting (94%), ensure comparability between platforms (94%), and provide information on HIL cross-reactivity (99%). Respondents (99%) showed interest in evidence-based, standardised HIL cut-offs. CONCLUSIONS: Most respondents monitor HIL, although the wide variation in practice may differentially affect clinical care. Laboratories seem receptive to education and advice on HIL management.

Development of a high-throughput SARS-CoV-2 antibody testing pathway using dried blood spot specimens.

BACKGROUND: Serological assays for Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) have roles in seroepidemiology, convalescent plasma-testing, antibody durability and vaccine studies. Currently, SARS-CoV-2 serology is performed using serum/plasma collected by venepuncture. Dried blood spot (DBS) testing offers significant advantages as it is minimally invasive, avoids venepuncture with specimens being mailed to the laboratory. METHODS: A pathway utilizing a newborn screening laboratory infrastructure was developed using an enzyme-linked immunosorbent assay to detect IgG antibodies against the receptor-binding domain of the SARS-CoV-2 spike protein in DBS specimens. Paired plasma and DBS specimens from SARS-CoV-2 antibody-positive and -negative subjects and polymerase chain reaction positive subjects were tested. DBS specimen stability, effect of blood volume and punch location were also evaluated. RESULTS: DBS specimens from antibody-negative (n = 85) and -positive (n = 35) subjects and polymerase chain reaction positive subjects (n = 11) had a mean (SD; range) optical density (OD) of 0.14 (0.046; 0.03-0.27), 0.98 (0.41; 0.31-1.64) and 1.12 (0.37; 0.49-1.54), respectively. An action value OD >0.28 correctly assigned all cases. The weighted Deming regression for comparison of the DBS and the plasma assay yielded: y = 0.004041 + 1.005x, r = 0.991, Sy/x 0.171, n = 82. Extraction efficiency of antibodies from DBS specimens was >99%. DBS specimens were stable for at least 28 days at ambient room temperature and humidity. CONCLUSIONS: SARS-CoV-2 IgG receptor-binding domain antibodies can be reliably detected in DBS specimens. DBS serological testing offers lower costs than either point of care or serum/plasma assays that require patient travel, phlebotomy and hospital/clinic resources; the development of a DBS assay may be particularly important for resource poor settings.

Undesirable stressful life events, impact, and correlates during midlife: observations from the Seattle midlife women's health study.

PURPOSE: To examine the undesirable stressful life events midlife women experience, including: 1) which life events midlife women reported most frequently; 2) which life events women rated as most undesirable; and 3) whether age, years of education, income, employment, race/ethnicity, marital status, being a parent, and the menopausal transition stage were associated with the impact scores of the life event categories. BACKGROUND: In addition to the menopausal transition, midlife is a time of increased responsibilities for women related to multiple roles such as taking care of children, caring for elderly parents, managing households, and working outside the home. These multiple roles put midlife women at risk for increased stress with little time for themselves in order to relieve stress. METHODS: The sample used in this study is part of a larger longitudinal study, The Seattle Midlife Women's Health Study. Women (N = 380 for Occasion 1) completed the 77-item Life Events Scale on four occasions during the course of the SMWHS: Occasion 1 (1990), Occasion 2 (1992), Occasion 3 (1997), and Occasion 4 (2000). In addition to descriptive analyses of frequency of life events and the undesirable impact of life events, demographic correlates (age, education, income, employment, being a parent as well as marital status, race/ethnicity, and menopausal transition stages) were examined in relation to the stressful life event scores. RESULTS: Highest scores of undesirable life events were for categories of both Financial and Family/Friends over 3 of the 4 occasions. Health and Crime/Legal scores were among the highest for 2 occasions. Impact of the undesirable stressful life events was greatest for categories of Family/Friends; Personal/Social; Work; and, Health. Age, income, marital status, being a parent, and menopausal transition stage were each associated with specific categories of the stressful event impact scores. CONCLUSION: Most commonly reported undesirable life events were not those women described as having the greatest impact. Impact of life event stress reflected women's social roles and connections as seen in the categories with the highest impact scores: Family/Close Friends, Personal/Social, and Work. Menopausal transition stages were related only to undesirable health events.

A survey of clinical laboratory instrument verification in the UK and New Zealand.

BACKGROUND: Clinical laboratory instrument verification testing is often an accreditation requirement. However, it is not known what verification procedures are in routine use or how often the process identifies problems which need addressing prior to testing clinical samples. OBJECTIVE: To investigate which standards are currently being used for laboratory verification in UK and New Zealand (NZ) clinical laboratories and to help establish if the activity justifies the effort required. METHODS: A survey of verification of clinical laboratory instrumentation was distributed to members of the Association for Clinical Biochemistry and Laboratory Medicine and New Zealand Institute of Medical Laboratory Scientists. The survey consisted of questions on the verification elements used and whether acceptance criteria were met. RESULTS: Nineteen of 72 (26%) of responders only used organization-developed protocols for verification, 20/72 (28%) solely used national/international guidelines, while 16/72 (22%) used a combination. Manufacturers' claims were partly or entirely used as acceptance criteria for imprecision (89%), accuracy (64%) and analytical measuring range (94%), with these being met on 61%, 67% and 93% of occasions, respectively. For patient comparison and linearity, acceptance criteria were met by 71% and 91%. Only 27-36% undertook any troubleshooting before accepting a failed component of verification. CONCLUSIONS: Laboratories in the UK and NZ are currently using a variety of verification standards and acceptance criteria for instrument verification. It is common for instruments to fail, especially following the assessment of imprecision and accuracy. While this suggests the process is warranted, only a minority address failed elements before accepting verification.

The challenges of midlife women: themes from the Seattle midlife Women's health study.

BACKGROUND: Midlife, the period of the lifespan between younger and older adulthood, has been described as a period of transition in women's lives. Investigators studying midlife have focused on women 40 to 65 years of age, who typically experience multiple social, psychological and biological challenges, among them the menopausal transition. Investigators have reported a diverse array of stressful events, for example, health concerns, family problems, work-related issues, deaths, frustrated goal attainment, and financial worries; however, none have identified which life events midlife women experience as the most salient. The purpose of this study was to understand the meaning behind the experiences that midlife women identify as the most challenging. METHODS: Participants were enrolled in The Seattle Midlife Women's Health Study, a longitudinal study spanning up to 23 years. Summative content analysis, incorporating manifest and latent analysis approaches, was used to identify life experiences that women described as the most challenging looking back over 15 years of being in the study. Eighty-one women responded to the question, "Since you have been in our study (since 1990 or 1991), what has been the most challenging part of life for you?" RESULTS: Women identified the most challenging aspects of midlife as changing family relationships, re-balancing work/personal life, re-discovering self, securing enough resources, and coping with multiple co-occurring stressors. Within these themes the most frequently reported challenges were: multiple co-occurring stressors, divorce/breaking up with a partner, health problems of self, and death of parents. Few women mentioned menopause as the most challenging aspect of their lives. CONCLUSION: Women found themselves searching for balance in the midst of multiple co-occurring stressors while coping with losses and transitions, for some in a context of limited resources. Menopause was infrequently mentioned. Future research to identify the challenges experienced by more diverse populations of women and further understanding of the dynamics among multiple co-occurring stressors is needed to provide individualized health care appropriately to midlife women.

Analytical performance specifications for external quality assessment - definitions and descriptions.

External Quality Assurance (EQA) is vital to ensure acceptable analytical quality in medical laboratories. A key component of an EQA scheme is an analytical performance specification (APS) for each measurand that a laboratory can use to assess the extent of deviation of the obtained results from the target value. A consensus conference held in Milan in 2014 has proposed three models to set APS and these can be applied to setting APS for EQA. A goal arising from this conference is the harmonisation of EQA APS between different schemes to deliver consistent quality messages to laboratories irrespective of location and the choice of EQA provider. At this time there are wide differences in the APS used in different EQA schemes for the same measurands. Contributing factors to this variation are that the APS in different schemes are established using different criteria, applied to different types of data (e.g. single data points, multiple data points), used for different goals (e.g. improvement of analytical quality; licensing), and with the aim of eliciting different responses from participants. This paper provides recommendations from the European Federation of Laboratory Medicine (EFLM) Task and Finish Group on Performance Specifications for External Quality Assurance Schemes (TFG-APSEQA) and on clear terminology for EQA APS. The recommended terminology covers six elements required to understand APS: 1) a statement on the EQA material matrix and its commutability; 2) the method used to assign the target value; 3) the data set to which APS are applied; 4) the applicable analytical property being assessed (i.e. total error, bias, imprecision, uncertainty); 5) the rationale for the selection of the APS; and 6) the type of the Milan model(s) used to set the APS. The terminology is required for EQA participants and other interested parties to understand the meaning of meeting or not meeting APS.

Analytical performance of 17 general chemistry analytes across countries and across manufacturers in the INPUtS project of EQA organizers in Italy, the Netherlands, Portugal, United Kingdom and Spain.

BACKGROUND: Optimum patient care in relation to laboratory medicine is achieved when results of laboratory tests are equivalent, irrespective of the analytical platform used or the country where the laboratory is located. Standardization and harmonization minimize differences and the success of efforts to achieve this can be monitored with international category 1 external quality assessment (EQA) programs. METHODS: An EQA project with commutable samples, targeted with reference measurement procedures (RMPs) was organized by EQA institutes in Italy, the Netherlands, Portugal, UK, and Spain. Results of 17 general chemistry analytes were evaluated across countries and across manufacturers according to performance specifications derived from biological variation (BV). RESULTS: For K, uric acid, glucose, cholesterol and high-density density (HDL) cholesterol, the minimum performance specification was met in all countries and by all manufacturers. For Na, Cl, and Ca, the minimum performance specifications were met by none of the countries and manufacturers. For enzymes, the situation was complicated, as standardization of results of enzymes toward RMPs was still not achieved in 20% of the laboratories and questionable in the remaining 80%. CONCLUSIONS: The overall performance of the measurement of 17 general chemistry analytes in European medical laboratories met the minimum performance specifications. In this general picture, there were no significant differences per country and no significant differences per manufacturer. There were major differences between the analytes. There were six analytes for which the minimum quality specifications were not met and manufacturers should improve their performance for these analytes. Standardization of results of enzymes requires ongoing efforts.

Post-standardization of routine creatinine assays: are they suitable for clinical applications.

Introduction Reliable serum creatinine measurements are of vital importance for the correct classification of chronic kidney disease and early identification of kidney injury. The National Kidney Disease Education Programme working group and other groups have defined clinically acceptable analytical limits for creatinine methods. The aim of this study was to re-evaluate the performance of routine creatinine methods in the light of these defined limits so as to assess their suitability for clinical practice. Method In collaboration with the Dutch External Quality Assurance scheme, six frozen commutable samples, with a creatinine concentration ranging from 80 to 239 µmol/L and traceable to isotope dilution mass spectrometry, were circulated to 91 laboratories in four European countries for creatinine measurement and estimated glomerular filtration rate calculation. Two out of the six samples were spiked with glucose to give high and low final concentrations of glucose. Results Results from 89 laboratories were analysed for bias, imprecision (%CV) for each creatinine assay and total error for estimated glomerular filtration rate. The participating laboratories used analytical instruments from four manufacturers; Abbott, Beckman, Roche and Siemens. All enzymatic methods in this study complied with the National Kidney Disease Education Programme working group recommended limits of bias of 5% above a creatinine concentration of 100 µmol/L. They also did not show any evidence of interference from glucose. In addition, they also showed compliance with the clinically recommended %CV of ≤4% across the analytical range. In contrast, the Jaffe methods showed variable performance with regard to the interference of glucose and unsatisfactory bias and precision. Conclusion Jaffe-based creatinine methods still exhibit considerable analytical variability in terms of bias, imprecision and lack of specificity, and this variability brings into question their clinical utility. We believe that clinical laboratories and manufacturers should work together to phase out the use of relatively non-specific Jaffe methods and replace them with more specific methods that are enzyme based.

Assessment of a semi-quantitative screening method for diagnosis of ethylene glycol poisoning.

Background Ethylene glycol poisoning remains a rare but important presentation to acute toxicology units. Guidelines recommended that ethylene glycol should be available as an 'urgent' test within 4 h, but these are difficult to deliver in practice. This study assessed a semi-quantitative enzymatic spectrophotometric assay for ethylene glycol compatible with automated platforms. Methods The ethylene glycol method was assessed in 21 samples from patients with an increased anion gap and metabolic acidosis not due to ethylene glycol ingestion, and seven samples known to contain ethylene glycol. All samples were analysed in random order in a blinded manner to their origin on a laboratory spectrophotometer. Results In this study, seven samples were known to contain ethylene glycol at concentrations >100 mg/L. The method correctly identified all seven samples as containing ethylene glycol. No false-positives were observed. Thirteen samples gave clear negative results. Ethylene glycol was present at <20 mg/L in one sample, but this sample remained within the limits of the negative control. Passing-Bablock correlation of estimates of ethylene glycol concentration against results obtained when the samples had been analysed using the quantitative method on an automated analyser showed a good correlation (R = 0.84) but with an apparent under-recovery. Conclusions A semi-quantitative assay for ethylene glycol was able to discriminate well between samples containing ethylene glycol and those with other causes of acidosis. It is a practical small-scale assay for rapid identification of cases of ethylene glycol poisoning.

Effects of isoflavones and amino acid therapies for hot flashes and co-occurring symptoms during the menopausal transition and early postmenopause: a systematic review.

AIMS: Review controlled clinical trials of isoflavones and amino acid preparation effects on hot flashes and at least one other symptom including mood, sleep, pain, and cognitive function that women report during the menopausal transition and early postmenopause. METHODS: An experienced reference librarian searched PubMed/Medline, CINAHL Plus, PsycInfo, Cochrane Database of Systematic Reviews, Cochrane Central Register of Controlled Trials, Web of Science, EMBASE, AMED, and Alt-Health Watch for English-language randomized controlled trials between 2004 and July 2011. Seventeen trials of isoflavones and amino acid effects on hot flashes and one additional symptom were identified. RESULTS: In five trials of soy isoflavone preparations, two (6g soy germ extract and 25 g soy protein in soy nuts) significantly decreased hot flashes, but no other symptoms. In the seven trials of other isoflavones, six significantly reduced hot flashes; in addition, red clover (80 mg) significantly reduced mood symptoms; Rexflavone (350 mg) for women with Kupperman Index>20 significantly reduced sleep symptoms; two trials had significant reductions for pain: isoflavone powder (90 mg) and red clover (80 mg). The only trial in this systematic review that significantly reduced cognitive symptoms was red clover (80 mg). In one trial, red clover isoflavone (80 mg/day) significantly relieved hot flashes, mood, pain, and cognitive symptoms. Amino acids yielded no significant results. Equol supplements of 30 mg/day for non-Equol producing women significantly reduced mood symptoms in one trial. The magnolia bark extract combination significantly reduced hot flashes, mood, and sleep symptoms. CONCLUSIONS: Isoflavone trials yielded significant reductions on hot flashes and co-occurring symptoms during the menopausal transition and postmenopause, but studies require replication with larger sample sizes and attention to measurement of outcomes.

A category 1 EQA scheme for comparison of laboratory performance and method performance: An international pilot study in the framework of the Calibration 2000 project.

INTRODUCTION: In the modern healthcare service, patients receive care in multiple hospitals and healthcare settings. Therefore, harmonization of results from different methods and instruments, both between and within laboratories, is of the utmost importance. The present pilot study aims to test the use of a Category 1 EQA scheme across four European countries by assessing the current level of equivalence of test results. METHOD: This work was led by the Dutch External Quality Assurance Scheme SKML and involved 28 laboratories from three regions in the UK, Spain and Portugal, and 120 laboratories from The Netherlands. A set of six commutable samples, targeted with reference methods, were circulated and 18 biochemistry analytes were tested. RESULTS AND CONCLUSIONS: The Total Error (TE) score, defined as the probability (%) that results are within the Total Error Acceptable (TEA) limits, for the eighteen analytes was calculated. Our data show that there is a need for further harmonization of laboratory data, in particular for electrolytes (calcium, chloride, magnesium, sodium), enzymes (ALT, amylase, AST, LDH), lipids (HDL-cholesterol), and for substrates (creatinine, total protein). Lack of performance consistency between instruments was seen for most analytes. The lack of harmonization is still present despite manufacturer claims of established traceability.

Can current analytical quality performance of UK clinical laboratories support evidence-based guidelines for diabetes and ischaemic heart disease?--A pilot study and a proposal.

BACKGROUND: The implementation of national and international guidelines is beginning to standardise clinical practice. However, since many guidelines have decision limits based on laboratory tests, there is an urgent need to ensure that different laboratories obtain the same analytical result on any sample. A scientifically-based quality control process will be a pre-requisite to provide this level of analytical performance which will support evidence-based guidelines and movement of patients across boundaries while maintaining standardised outcomes. We discuss the finding of a pilot study performed to assess UK clinical laboratories readiness to work to a higher grade quality specifications such as biological variation-based quality specifications. METHODS: Internal quality control (IQC) data for HbA1c, glucose, creatinine, cholesterol and high density lipoprotein (HDL)-cholesterol were collected from UK laboratories participating in the Bio-Rad Unity QC programme. The median of the coefficient of variation (CV%) of the participating laboratories was evaluated against the CV% based on biological variation. RESULTS: Except creatinine, the other four analytes had a variable degree of compliance with the biological variation-based quality specifications. More than 75% of the laboratories met the biological variation-based quality specifications for glucose, cholesterol and HDL-cholesterol. Slightly over 50% of the laboratories met the analytical goal for HBA1c. Only one analyte (cholesterol) had a performance achieving the higher quality specifications consistent with 5σ. CONCLUSIONS: Our data from IQC do not consistently demonstrate that the results from clinical laboratories meet evidence-based quality specifications. Therefore, we propose that a graded scale of quality specifications may be needed at this stage.

Screening bacterial metabolites for inhibitory effects against Batrachochytrium dendrobatidis using a spectrophotometric assay.

Certain bacteria present on frog skin can prevent infection by the pathogenic fungus Batrachochytrium dendrobatidis (Bd), conferring disease resistance. Previous studies have used agar-based in vitro challenge assays to screen bacteria for Bd-inhibitory activity and to identify candidates for bacterial supplementation trials. However, agar-based assays can be difficult to set up and to replicate reliably. To overcome these difficulties, we developed a semi-quantitative spectrophotometric challenge assay technique. Cell-free supernatants were prepared from filtered bacterial cultures and added to 96-well plates in replicated wells containing Bd zoospores suspended in tryptone-gelatin hydrolysate-lactose (TGhL) broth medium. Plates were then read daily on a spectrophotometer until positive controls reached maximum growth in order to determine growth curves for Bd. We tested the technique by screening skin bacteria from the Australian green-eyed tree frog Litoria serrata. Of bacteria tested, 31% showed some degree of Bd inhibition, while some may have promoted Bd growth, a previously unknown effect. Our cell-free supernatant challenge assay technique is an effective in vitro method for screening bacterial isolates for strong Bd-inhibitory activity. It contributes to the expanding field of bioaugmentation research, which could play a significant role in mitigating the effects of chytridiomycosis on amphibians around the world.