Intra- and interobserver variability of novel magnetic resonance imaging parameters for hip screening and treatment outcomes at age 5 years.

BACKGROUND: The outcome measure of neonatal hip screening is usually the radiographic acetabular index. OBJECTIVE: To assess the feasibility of magnetic resonance imaging (MRI) without sedation and compare the utility of outcome parameters measured from MRI images. MATERIALS AND METHODS: The invitation for MRI scanning at 5 years of age was incorporated into follow-up for babies who had more than one ultrasound examination during treatment or surveillance. RESULTS: Diagnostic images were obtained in 132 of 134 children. The mean osseous acetabular index (standard deviation [SD]) was 16.6 (3.3) degrees for the right hip and 17.8 (3.2) for the left; the values for the cartilaginous acetabular index were 3.1 (3) and 3.4 (3.2). The mean downslope of a tangent to the lateral bony acetabular roof was 10.4 (4.5) and 9.0 (4.3) with respect to Hilgenreiner's line and that of a line drawn through the apex to the margin of the acetabulum was 3.7 (4.6) and 3.9 (4.7). Intra- and interobserver variation was greater for measures specific to the lateral acetabular roof than for ossific and cartilaginous indices. There was significant negative correlation between the downslope of the tangent to the lateral roof index and the age at onset of treatment on both sides, but no significant correlation for ossific or cartilaginous acetabular indices or apex-marginal index. CONCLUSION: MRI without sedation at 5 years of age is feasible as an outcome measure for hip screening programmes. Parameters specific to the lateral acetabulum may better reflect acetabular sufficiency, despite having greater observer variation than cartilaginous and ossific acetabular indices.

Does sexuality matter? A cross-sectional study of drug use, social injecting, and access to injection-specific care among men who inject drugs in Melbourne, Australia.

BACKGROUND: Gay, bisexual and other men who have sex with men (GBMSM) are overrepresented in cohorts of people who inject drugs. GBMSM's substance use is usually explored in the context of its contribution to sexual risk. We examined drug use practices, connectedness to other people who inject drugs, peer-to-peer injecting, and access to care among men who inject drugs in Melbourne, Australia. We aim to describe similarities and differences in these parameters for GBMSM and other men. METHODS: Data were drawn from a prospective cohort study of people who inject drugs conducted in Melbourne, Australia, since 2009. This cross-sectional study used data collected between 2016 and 2021. Descriptive statistics were used to assess differences between GBMSM and other men. RESULTS: Of 525 men who injected drugs over the study period, 48 (9%) identified as gay or bisexual, or reported sex with other men in the past 12 months. GBMSM and other men reported similar socio-demographics, drug practices (age of injecting initiation, most injected drug, peer-to-peer injecting, receptive syringe sharing) and access to injecting-specific care (drug treatment, source of needle-syringes). A significantly greater percentage of GBMSM reported past 12-month hepatitis C testing (69% vs. 52%, p = 0.028) and preferring methamphetamine (31% vs. 16%, p = 0.022). A higher percentage of GBMSM reported knowing > 50 other people who inject drugs (46% vs. 37%), but this difference was not statistically significant. Both groups primarily obtained injecting equipment from needle-syringe programs; a minority had accessed injecting-specific primary care. CONCLUSION: Men who injected drugs in this cohort and those who identified as GBMSM reported similar drug and health-seeking practices. The higher prevalence of methamphetamine injecting among GBMSM may warrant different harm reduction support for this group. Health promotion should utilise opportunities to connect men who inject drugs in Melbourne to injecting-specific primary health care.

Where in the world is Florence Nightingale's medicine chest?

BACKGROUND: In the 121st anniversary year of the birth of Florence Nightingale, and during the COVID-19 pandemic, it is both interesting and salient to be reminded of the foundational work of this famous woman who began modern nursing. Her work in nursing care and nursing, health and public policy has been a continuing strong foundation to practices in societies around the world. METHODS: In this short communication about historical research, various aspects of Florence's life and work are described, as well as the locations, memorials and museum significant to our remembrance of her. RESULTS: A particular focus of this paper is the description of a larger but little-known medicine chest located at the College of Nursing, University of Saskatchewan, in Saskatoon, SK, Canada, and attributed as belonging to Florence. CONCLUSION: Best known to this point in time is a smaller medicine chest at the Florence Nightingale Museum in London.

Using the EM algorithm for Bayesian variable selection in logistic regression models with related covariates.

We develop a Bayesian variable selection method for logistic regression models that can simultaneously accommodate qualitative covariates and interaction terms under various heredity constraints. We use expectation-maximization variable selection (EMVS) with a deterministic annealing variant as the platform for our method, due to its proven flexibility and efficiency. We propose a variance adjustment of the priors for the coefficients of qualitative covariates, which controls false-positive rates, and a flexible parameterization for interaction terms, which accommodates user-specified heredity constraints. This method can handle all pairwise interaction terms as well as a subset of specific interactions. Using simulation, we show that this method selects associated covariates better than the grouped LASSO and the LASSO with heredity constraints in various exploratory research scenarios encountered in epidemiological studies. We apply our method to identify genetic and non-genetic risk factors associated with smoking experimentation in a cohort of Mexican-heritage adolescents.

Maternal systemic or cord blood inflammation is associated with birth anthropometry in a Tanzanian prospective cohort.

OBJECTIVES: HIV infection is associated with chronic systemic inflammation, with or without antiretroviral therapy. Consequences for foetal growth are not understood, particularly in settings where multiple maternal infections and malnutrition are common. The study was designed to examine maternal systemic circulating and umbilical cord blood cytokine concentrations in relation to birth anthropometry in a Tanzanian prospective cohort. METHODS: A 9-plex panel of maternal plasma cytokines in HIV-positive (n = 44) and HIV-negative (n = 70) mothers and the same cytokines in umbilical cord blood collected at delivery was assayed. Linear regression modelled associations between maternal or cord blood cytokines and birth anthropometry. RESULTS: Health indicators (haemoglobin, mid-upper-arm circumference, body mass index) in HIV-positive mothers without considerable immunosuppression did not differ from HIV-negative women. Despite this, HIV-exposed infants had lower birthweight and length. Subgroup analyses indicated that HIV management using HAART was associated with lower plasma TNF-α, as were longer durations of any antiretroviral therapy (≥2 months). Greater maternal plasma TNF-α was associated with earlier delivery (-1.7 weeks, P = 0.039) and lower birthweights (-287 g; P = 0.020), while greater umbilical cord TNF-α (-1.43 cm; P = 0.036) and IL-12p70 (-2.4 cm; P = 0.008) were associated with shorter birth length. Birthweight was inversely associated with cord IL-12p70 (-723 g; P = 0.001) and IFN-γ (-482 g, P = 0.007). Maternal cytokines during pregnancy did not correlate with umbilical cord cytokines at delivery. CONCLUSIONS: Systemic inflammation identified in maternal plasma or umbilical cord blood was associated with poorer birth anthropometrics in HIV-exposed and HIV-unexposed infants. Controlling maternal and/or foetal systemic inflammation may improve birth anthropometry.

Diffraction effects and inelastic electron transport in angle-resolved microscopic imaging applications.

We analyse the signal formation process for scanning electron microscopic imaging applications on crystalline specimens. In accordance with previous investigations, we find nontrivial effects of incident beam diffraction on the backscattered electron distribution in energy and momentum. Specifically, incident beam diffraction causes angular changes of the backscattered electron distribution which we identify as the dominant mechanism underlying pseudocolour orientation imaging using multiple, angle-resolving detectors. Consequently, diffraction effects of the incident beam and their impact on the subsequent coherent and incoherent electron transport need to be taken into account for an in-depth theoretical modelling of the energy- and momentum distribution of electrons backscattered from crystalline sample regions. Our findings have implications for the level of theoretical detail that can be necessary for the interpretation of complex imaging modalities such as electron channelling contrast imaging (ECCI) of defects in crystals. If the solid angle of detection is limited to specific regions of the backscattered electron momentum distribution, the image contrast that is observed in ECCI and similar applications can be strongly affected by incident beam diffraction and topographic effects from the sample surface. As an application, we demonstrate characteristic changes in the resulting images if different properties of the backscattered electron distribution are used for the analysis of a GaN thin film sample containing dislocations.

Low birth weight and intelligence in adolescence and early adulthood: a meta-analysis.

BACKGROUND: Research has demonstrated an association between low birth weight (LBW; <2500 g) and adverse intelligence quotient (IQ) outcomes in childhood and early adolescence. We systematically evaluated whether this association persists into late adolescence and early adulthood and also assessed the influence of age of IQ assessment on effect size. METHODS: During Stage 1 (meta-analysis of data on adolescents/adults), we searched for relevant articles in PsychINFO, PubMed, Ovid, CINAHL, ProQuest and ERIC until February 2011 (no lower limit). Studies which assessed full-scale IQ among LBW individuals (<2500 g), aged 13 years and older, with a normal birth weight (NBW; ≥2500 g) comparison group were eligible. A random-effects meta-analysis provided a pooled estimate of the difference in IQ scores between LBW and NBW individuals. Publication bias was assessed using Rosenthal's classic fail-safe N and Duval and Tweedie's Trim and Fill. During Stage 2, we added data from the Kerr-Wilson et al. meta-analysis (which included data from children; in Meta-analysis of the association between preterm delivery and intelligence. Journal Public Health 2011;33:1-8) to our sample from Stage 1 and conducted a meta-regression to evaluate the effect of age of IQ assessment. RESULTS: Using a total of 15 studies in Stage 1, it was demonstrated that NBW individuals scored an average of 7.63 IQ points higher than LBW individuals, CI = 5.95-9.31. After adjusting for publication bias, NBW samples demonstrated an IQ of 4.98 points higher than LBW samples, CI = 3.20-6.77. Furthermore, age at IQ assessment was a significant moderator of the association between birth weight and IQ, in that the effect size decreased from childhood into young adulthood. CONCLUSIONS: Cognitive impairments associated with LBW persist into adolescence and early adulthood; however, the influence of LBW on IQ decreases from childhood to young adulthood. These conclusions must be interpreted with caution due to unmeasured variables and possible influence from publication bias.

Health service accreditation reinforces a mindset of high-performance human resource management: lessons from an Australian study.

OBJECTIVE: To investigate whether an accreditation program facilitates healthcare organizations (HCOs) to evolve and maintain high-performance human resource management (HRM) systems. DESIGN: Cross-sectional multimethod study. SETTING AND PARTICIPANTS: Healthcare organizations participating in the Australian Council on Healthcare Standards Evaluation and Quality Improvement Program (EQuIP 4) between 2007 and 2011. MAIN OUTCOME MEASURES: Ratings across the EQuIP 4 HRM criteria, a clinical performance measure, surveyor reports (HRM information) and interview data (opinions and experiences regarding HRM and accreditation). RESULTS: Healthcare organizations identified as high performing on accreditation HRM criteria seek excellence primarily because of internal motivations linked to best practice. Participation in an accreditation program is a secondary and less significant influence. Notwithstanding, the accreditation program provides the HCO opportunity for internal and external review and assessment of their performance; the accreditation activities are reflective learning and feedback events. CONCLUSIONS: This study reveals that HCOs that pursue highly performing HRM systems use participation in an accreditation program as an opportunity. Their organizational mindset is to use the program as a tool by which to reflect and obtain feedback on their performance so to maintain or improve their management of staff and delivery of care.

A method for the automated long-term monitoring of three-spined stickleback Gasterosteus aculeatus shoal dynamics.

This paper describes and evaluates a flexible, non-invasive tagging system for the automated identification and long-term monitoring of individual three-spined sticklebacks Gasterosteus aculeatus. The system is based on barcoded tags, which can be reliably and robustly detected and decoded to provide information on an individual's identity and location. Because large numbers of fish can be individually tagged, it can be used to monitor individual- and group-level dynamics within fish shoals.

Ukaipo niho: the place of nurturing for oral health.

OBJECTIVES: To report on oral-health-related characteristics, beliefs, and behaviours among participants in a randomised control trial of an intervention to prevent early childhood caries (ECC) among Maori children, and to determine whether there were any systematic differences between the intervention and control groups at baseline. DESIGN: Baseline measurements from a randomised control trial (involving 222 pregnant Maori women allocated randomly to either Intervention or Delayed groups) which is currently underway. SETTING: The rohe (tribal area) of Waikato-Tainui. METHODS: Self-report information collected on sociodemographic characteristics, pregnancy details, self-reported general and oral health and health-related behaviours, and oral health beliefs. RESULTS: Other than those in the Delayed group being slightly older, on average, there were no significant differences between the two groups. Some 37.0% were expecting their first child. Most reported good health; 43.6% were current smokers, and 26.4% had never smoked. Only 8.2% were current users of alcohol. Almost all were dentate, and 57.7% described their oral health as fair or poor. One in six had had toothache in the previous year; 33.8% reported being uncomfortable about the appearance of their teeth, and 27.7% reported difficulty in eating. Dental service-use was relatively low and symptom-related; 78.9% needed to see a dentist. Overall, most of the sample believed that it was important to avoid sweet foods, visit dentists and to brush the teeth, while about half thought that using fluoride toothpaste and using floss were important. Some 38.2% felt that drinking fluoridated water was important. Oral-health-related fatalism was apparent, with 74.2% believing that most people usually get dental problems, 58.6% believing that most people will need extractions at some stage, and that most children eventually get dental caries. CONCLUSIONS: Mothers' important role in nurturing the well-being of the young child includes the protection and maintenance of the growing child's oral health (or ukaipo niho). The findings provide important insights into Maori mothers' oral health knowledge, beliefs and practices.

Dichloroacetate inhibits aerobic glycolysis in multiple myeloma cells and increases sensitivity to bortezomib.

BACKGROUND: Dichloroacetate (DCA), through the inhibition of aerobic glycolysis (the 'Warburg effect') and promotion of pyruvate oxidation, induces growth reduction in many tumours and is now undergoing several clinical trials. If aerobic glycolysis is active in multiple myeloma (MM) cells, it can be potentially targeted by DCA to induce myeloma growth inhibition. METHODS: Representative multiple myeloma cell lines and a myeloma-bearing mice were treated with DCA, alone and in combination with bortezomib. RESULTS: We found that aerobic glycolysis occurs in approximately half of MM cell lines examined, producing on average 1.86-fold more lactate than phorbol myristate acetate stimulated-peripheral blood mononuclear cells and is associated with low-oxidative capacity. Lower doses of DCA (5-10 mM) suppressed aerobic glycolysis and improved cellular respiration that was associated with activation of the pyruvate dehydrogenase complex. Higher doses of DCA (10-25 mM) induced superoxide production, apoptosis, suppressed proliferation with a G0/1 and G2M phase arrest in MM cell lines. In addition, DCA increased MM cell line sensitivity to bortezomib, and combinatorial treatment of both agents improved the survival of myeloma-bearing mice. CONCLUSION: Myeloma cells display aerobic glycolysis and DCA may complement clinically used MM therapies to inhibit disease progression.

Rapid nondestructive analysis of threading dislocations in wurtzite materials using the scanning electron microscope.

We describe the use of electron channeling contrast imaging in the scanning electron microscope to rapidly and reliably image and identify threading dislocations (TDs) in materials with the wurtzite crystal structure. In electron channeling contrast imaging, vertical TDs are revealed as spots with black-white contrast. We have developed a simple geometric procedure which exploits the differences observed in the direction of this black-white contrast for screw, edge, and mixed dislocations for two electron channeling contrast images acquired from two symmetrically equivalent crystal planes whose g vectors are at 120° to each other. Our approach allows unambiguous identification of all TDs without the need to compare results with dynamical simulations of channeling contrast.

Anaerobic digestion of corn ethanol thin stillage in batch and by high-rate down-flow fixed film reactors.

Thin stillage (CTS) from a dry-grind corn ethanol plant was evaluated as a carbon source for anaerobic digestion (AD) by batch and high rate semi-continuous down-flow stationary fixed film (DSFF) reactors. Biochemical methane potential (BMP) assays were carried out with CTS concentrations ranging from approximately 2,460-27,172 mg total chemical oxygen demand (TCOD) per litre, achieved by diluting CTS with clean water or a combination of clean water and treated effluent. High TCOD, SCOD and volatile solids (VS) removal efficiencies of 85 ± 2, 94 ± 0 and 82 ± 1% were achieved for CTS diluted with only clean water at an organic concentration of 21,177 mg TCOD per litre, with a methane yield of 0.30 L methane per gram TCOD(removed) at standard temperature and pressure (STP, 0 °C and 1 atmosphere). Batch studies investigating the use of treated effluent for dilution showed promising results. Continuous studies employed two mesophilic DSFF anaerobic digesters treating thin stillage, operated at hydraulic retention times (HRT) of 20, 14.3, 8.7, 6.3, 5 and 4.2 d. Successful digestion was achieved up to an organic loading rate (OLR) of approximately 7.4 g TCOD L(-1)d(-1) at a 5 d HRT with a yield of 2.05 LCH(4) L(-1)d(-1) (at STP) and TCOD and VS removal efficiencies of 89 ± 3 and 85 ± 3%, respectively.

Emotional self-regulation, impulsivity, 5-HTTLPR and tobacco use behavior among psychiatric inpatients.

BACKGROUND: While the serotonin transporter (SLC6A4) gene, 5-HTTLPR, interacts with the social environment to influence both emotional self-regulation and smoking behavior, less is known about interactions between emotional self-regulation and 5-HTTLPR or their joint influence on tobacco use. Here, we examined such interactions among psychiatric inpatients, the population with the highest rates of smoking. METHODS: Participants (506 adults) were psychiatric inpatients at The Menninger Clinic in Houston TX between 2012 and 16. Most were white (89%), male (55%), with a mean age of 32.3 years. Participants completed the Difficulties in Emotional Regulation Scale (DERS) at admission. We examined interactions with smoking among three DERS subscales and 5-HTTLPR, controlling for sex, race and age. RESULTS: Smoking rates were higher among those with the 5-HTTPLR L'L' genotype compared to peers carrying an S' allele (47.9% vs. 37.4%, respectively). Among S' allele carrying participants, impulse control difficulties (OR = 1.09; 95%CI: 1.03-1.14) and lack of emotion clarity (OR = 1.06; 95%CI: 1.00-1.11) increased risk for ever using tobacco, while accessing more ways to regulate emotion (OR = 0.95; 95%CI: 0.92-0.99) offered a protective effect against ever using tobacco. Neither demographic nor DERS covariates were associated with using tobacco among the L'L' group. LIMITATIONS: This ethnically homogenous sample limits generalizability and using a binary outcome can over-estimate a gene environment interaction effect. CONCLUSIONS: Emotional self-regulation exerts a stronger influence on using tobacco among carriers of an S' allele of 5-HTTLPR than peers with the L'L' genotype. Promoting emotional self-regulatory skills may have benefits for preventing tobacco use.

Platelet function in dogs with chronic liver disease.

OBJECTIVES: To assess platelet function, buccal mucosal bleeding time and plasma von Willebrand factor concentration in dogs with chronic inflammatory and/or fibrotic liver disease and to compare results with those obtained in healthy dogs. MATERIALS AND METHODS: Preliminary study including 18 dogs with chronic inflammatory and/or fibrotic liver disease undergoing liver biopsy and 18 healthy age-matched control dogs. Platelet function was assessed by measuring closure time with the PFA-100® analyser using adenosine diphosphate (ADP) as an agonist. Buccal mucosal bleeding time, closure time and plasma von Willebrand factor antigen were measured in dogs in both groups. After undergoing ultrasound-guided needle biopsy, dogs were monitored for haemorrhage to determine if there was an association of any measurement with post-biopsy bleeding. RESULTS: The closure time was not different between the liver disease group (median 76.3; range 53 to 118.5 seconds) and control group (72.8; 57 to 89.5 seconds). The buccal mucosal bleeding time was longer in the liver disease group (median 138; range 95 to 229 seconds) than the control group (103; 63 to 200 seconds). The plasma von Willebrand factor antigen concentration was not different between the liver disease group (median 203; range 109 to 351%) and control group (165.5; 63 to 246%). CLINICAL SIGNIFICANCE: In this study, dogs with chronic necroinflammatory and/or fibrotic liver disease did not have overt, clinically relevant derangements in platelet function as assessed by buccal mucosal bleeding time, closure time and von Willebrand factor analysis. In addition, none of the dogs undergoing percutaneous ultrasound-guided biopsy in the study exhibited bleeding complications post-biopsy procedure.

A mixed-methods evaluation of the impact of a pharmacist-led feedback pilot intervention on insulin prescribing in a hospital setting.

AIMS: To explore the impact of a prescribing feedback intervention on insulin prescribing. METHODS: This was a mixed-methods study in a hospital setting. An insulin prescribing feedback intervention was delivered verbally and in writing to twelve doctors. Insulin prescribing error frequency was compared to ten doctors who had not received the feedback intervention. Insulin prescribing was audited over four weeks at the start and end of the intervention period. Semi-structured interviews were conducted with participating doctors who had received feedback, and qualitative data analysed thematically to explore the impact of the intervention on their prescribing practice. RESULTS: Prescribing data were collected on 370 insulin prescriptions with 241 errors identified. A significant reduction (χ2 = 22.6, p=<0.05) in insulin prescribing error frequency was observed in the intervention group, with a non-significant increase reported in the control group. Feedback was received positively and considered valuable by doctors, supporting development of their knowledge and skills and encouraging reflection on their prescribing performance. Doctors described enhanced confidence in insulin prescribing and a desire to improve as a prescriber and avoid harm, with feedback raising awareness of their development needs. Prescribers also described enhanced team work, with greater information and feedback seeking behavior to inform future prescribing decisions. CONCLUSIONS: Feedback has potential to improve insulin prescribing and is a valued and acceptable process intervention for doctors. The impact on insulin prescribing practice is varied and complex influencing the capability, opportunity and motivation of prescribers to adapt and evolve their behavior in response to ongoing feedback.

Neonatal hip ultrasound: tangent to lateral roof angle correlates better with stability than alpha angle according to Graf or percentage femoral head coverage.

The aim of this study was to determine the relationship of tangent to the lateral roof angle (TLRA), Graf's alpha angle and percentage femoral head cover (PHC) and to observed stability, and to establish intraobserver and interobserver errors for measurement of alpha angle and TLRA. In total, 2235 babies referred to the hip review clinic over a period of 8 years. Intraobserver and interobserver errors were calculated from readings of 383 hip images by an experienced paediatric radiologist and a trainee. Taking TLRA <70° as abnormal resulted in sensitivity for unstable right hips of 88% compared with 77% for alpha angle <60° (P = 0.002) and 81% for PHC <60% (P = 0.028) and specificity of TLRA 89%, alpha angle 90% (P = 0.07) and PHC 83% (P < 0.001). Corresponding figures for left hips are sensitivity of TLRA 99%, alpha angle 91% (P < 0.001) and PHC 96% (P = 0.013), and specificity TLRA 86%, alpha angle 83% (P = 0.001) and PHC 67% (P < 0.001). Mean intraobserver errors for alpha angle were 1.85° and 1.81° for consultant and trainee compared to 2.54 and 2.55 for TLRA. Mean interobserver errors were 2.22 for alpha angle and 3.42 for TLRA. TLRA, a new parameter, correlated better with observed stability with significant improvement in sensitivity in both hips and specificity in left hips compared with Graf's alpha angle, and significantly improved sensitivity and specificity in both hips compared with percentage femoral head cover.

Asynchronous, out-of-sequence, transcontinental chain kidney transplantation: a novel concept.

The organ donor shortage has been the most important hindrance in getting listed patients transplanted. Living kidney donors who are incompatible with their intended recipients are an untapped resource for expanding the donor pool through participation in transplant exchanges. Chain transplantation takes this concept further, with the potential to benefit even more recipients. We describe the first asynchronous, out of sequence transplant chain that was initiated by transcontinental shipment of an altruistic donor kidney 1 week after that recipient's incompatible donor had already donated his kidney to the next recipient in the chain. The altruistic donor kidney was transported from New York to Los Angeles and functioned immediately after transplantation. Our modified-sequence asynchronous transplant chain (MATCH) enabled eight recipients, at four different institutions, to benefit from the generosity of one altruistic donor and warrants further exploration as a promising step toward addressing the organ donor shortage.

Ezetimibe monotherapy for cholesterol lowering in 2,722 people: systematic review and meta-analysis of randomized controlled trials.

OBJECTIVES: To study the evidence on the efficacy and safety of ezetimibe monotherapy for the treatment of primary (heterozygous familial and non-familial) hypercholesterolaemia. DESIGN: Systematic review and meta-analysis of randomized controlled trials (RCTs). METHODS: Eleven electronic bibliographic databases covering the biomedical, scientific and grey literature were searched from inception and supplemented by contact with experts in the field. Two reviewers independently determined the eligibility of RCTs, with a minimum treatment duration of 12 weeks, which compared ezetimibe monotherapy (10 mg per day) with placebo. RESULTS: In the absence of data from clinical outcome trials, surrogate endpoints such as changes in lipid concentrations were used as indicators of clinical outcomes. A meta-analysis of eight randomized, double-blind, placebo-controlled trials (all 12 weeks) showed that ezetimibe monotherapy was associated with a statistically significant mean reduction in LDL cholesterol (from baseline to endpoint) of -18.58%, (95% CI: -19.67 to -17.48, P < 0.00001) compared with placebo. Significant (P < 0.00001) changes were also found in total cholesterol (-13.46%, 95% CI: -14.22 to -12.70), HDL cholesterol (3.00%, 95% CI: 2.06-3.94) and triglyceride levels (-8.06%, 95% CI: -10.92 to -5.20). Ezetimibe monotherapy appeared to be well tolerated with a safety profile similar to placebo. CONCLUSIONS: In a meta-analysis restricted to short-term trials in hypercholesterolaemia, significant potentially favourable changes in lipid and lipoprotein levels relative to baseline occurred with ezetimibe monotherapy. Further long-term studies with cardiovascular and other clinical outcome data are needed to assess the efficacy and safety of ezetimibe more fully.