The log transformation is often used to reduce skewness of a measurement variable. If, after transformation, the distribution is symmetric, then the Welch t-test might be used to compare groups. If, also, the distribution becomes close to normal, then a reference interval might be determined.

Clinical biochemists often wish to compare two groups of measurements. In order to do so, they must be familiar with Student's t-test. This article provides guidance for the use of the Welch t-test, with subtle but important differences and validity in a broader range of settings: advises the use of the Welch t-test rather than Student's t-test.

Increased physical activity levels benefit both an individuals' health and productivity at work. The purpose of the current study was to explore the impact and cost-effectiveness of a workplace physical activity intervention designed to increase physical activity levels.

What effects did treatment using hyaluronic acid (HA) binding/selection prior to ICSI have on clinical outcomes in the Hyaluronic Acid Binding sperm Selection (HABSelect) clinical trial? Older women randomized to the trial’s experimental arm (selection of sperm bound to immobilized (solid-state) HA) had the same live birth rates as younger women, most likely a result of better avoidance of sperm with damaged DNA. Recent randomized controlled trials (RCTs) investigating the efficacy of HA-based sperm selection prior to ICSI, including HABSelect, have consistently reported reductions in the numbers of miscarriages among couples randomized to the intervention, suggesting a pathological sperm-mediated factor mitigated by prior HA-binding/selection. The mechanism of that protection is unknown. The original HABSelect Phase 3 RCT ran from 2014 to 2017 and included 2752 couples from whom sperm samples used in control (ICSI) and intervention (Physiological IntraCytoplasmic Sperm Injection; PICSI) arms of the trial were stored frozen for later assessment of DNA quality (DNAq). The trial overlapped with its mechanistic arm, running from 2016 to 2018. As miscarriage reduction was a significant secondary outcome of the trial, samples (n = 1247) selected for the mechanistic analysis were deliberately enriched for miscarriage outcomes (n = 92 or 7.4%) from a total of 154 miscarriages (5.6%) among all (n = 2752) couples randomized by stratified random sampling. Values from fresh semen samples for sperm concentration (mml), percentage forward progressive motility and percentage HA-binding score (HBS) were obtained before being processed by differential density gradient centrifugation or (rarely) by swim-up on the day of treatment. Surplus sperm pellets were recovered, aliquoted and cryopreserved for later analysis of DNAq using slide-based Comet, TUNEL, acridine orange (AO) and the sperm chromatin dispersion (SCD) assays. Following their classification into normal and abnormal sample subcategories based on reference values for sperm concentration and motility, relationships with HBS and DNAq were examined by Spearman correlation, Student’s t-tests, Mann Whitney U tests, and logistic regression (univariable and multivariable). Parsimonious selection enabled the development of models for exploring and explaining data trends. Potential differences in future cumulative pregnancy rates relating to embryo quality were also explored. Results from the 1247 sperm samples assayed for HBS and/or DNAq, generated data that were considered in relation to standard physiological measures of (sperm) vitality and to treatment outcomes. All measures of HBS and DNAq discriminated normal from abnormal sperm samples (P < 0.001). SCD correlated negatively with the Comet (r = −0.165; P < 0.001) and TUNEL assays (r = −0.200; P < 0.001). HBS correlated negatively with AO (r = −0.211; P < 0.001), Comet (r = −0.127; P < 0.001) and TUNEL (r = −0.214; P < 0.001) and positively with SCD (r = 0.255; P < 0.001). A model for predicting live birth (and miscarriage) rates included treatment allocation (odds ratio: OR 2.167, 95% CI 1.084–4.464, P = 0.031), female age (OR 0.301, 95% CI 0.133–0.761, P = 0.013, per decade) and the AO assay (OR 0.79, 95% CI 0.60–1. 02.761, P = 0.073, per 10 points rise). A model predicting the expected rate of biochemical pregnancy included male age (OR 0.464, 95% CI 0.314–0.674, P < 0.001, per decade) and the SCD assay (OR 1.04, 95% CI 1.007–1.075, P = 0.018, per 10 point rise). A model for conversion from biochemical to clinical pregnancy did not retain any significant patient or assay variables. A model for post-injection fertilization rates included treatment allocation (OR 0.83, 95% CI 0.75–0.91, P < 0.001) and the Comet assay (OR 0.950, 95% CI 0.91–1.00, P = 0.041). HABSelect was a prospective RCT and the mechanistic study group was drawn from its recruitment cohort for retrospective analysis, without the full benefit of randomization. The clinical and mechanistic aspects of the study were mutually exclusive in that measures of DNAq were obtained from residual samples and not from HA-selected versus unselected sperm. Models for fitting mechanistic with baseline and other clinical data were developed to compensate for variable DNAq data quality. HABSelect used a solid-state version of PICSI and we did not assess the efficacy of any liquid-state alternatives. PICSI reduced fertilization rates and did not improve the outlook for cumulative pregnancy rates. Notwithstanding the interventional effect on fertilization rates and possibly blastocyst formation (neither of which influenced pregnancy rates), poor sperm DNAq, reflected by lower HBS, probably contributed to the depression of all gestational outcomes including live births, in the HABSelect trial. The interventional avoidance of defective sperm is the best explanation for the equalization in live birth rates among older couples randomized to the trial’s PICSI arm. As patients going forward for assisted conception cycles globally in future are likely to be dominated by an older demographic, HA-based selection of sperm for ICSI could be considered as part of their treatment plan. The study was supported by the National Institute for Health Research (NIHR) EME (Efficacy and Mechanism Evaluation)-11-14-34. National Research Ethics Service approval 11/06/2013: 13/YH/0162. S.L. is CEO of ExamenLab Ltd (company number NI605309). ISRCTN99214271.

Aims: The aim of this study was to compare open reduction and internal fixation (ORIF) with revision surgery for the surgical management of Unified Classification System (UCS) type B periprosthetic femoral fractures around cemented polished taper-slip femoral components following primary total hip arthroplasty (THA). Methods: Data were collected for patients admitted to five UK centres. The primary outcome measure was the two-year reoperation rate. Secondary outcomes were time to surgery, transfusion requirements, critical care requirements, length of stay, two-year local complication rates, six-month systemic complication rates, and mortality rates. Comparisons were made by the form of treatment (ORIF vs revision) and UCS type (B1 vs B2/B3). Kaplan-Meier survival analysis was performed with two-year reoperation for any reason as the endpoint. Results: A total of 317 periprosthetic fractures (in 317 patients) with a median follow-up of 3.6 years (interquartile range (IQR) 2.0 to 5.4) were included. The fractures were type B1 in 133 (42.0%), B2 in 170 (53.6%), and B3 in 14 patients (4.4%). ORIF was performed in 167 (52.7%) and revision in 150 patients (47.3%). The two-year reoperation rate (15.3% vs 7.2%; p = 0.021), time to surgery (4.0 days (IQR 2.0 to 7.0) vs 2.0 days (IQR 1.0 to 4.0); p < 0.001), transfusion requirements (55 patients (36.7%) vs 42 patients (25.1%); p = 0.026), critical care requirements (36 patients (24.0%) vs seven patients (4.2%); p < 0.001) and two-year local complication rates (26.7% vs 9.0%; p < 0.001) were significantly higher in the revision group. The two-year rate of survival was significantly higher for ORIF (91.9% (standard error (SE) 0.023%) vs 83.9% (SE 0.031%); p = 0.032) compared with revision. For B1 fractures, the two-year reoperation rate was significantly higher for revision compared with ORIF (29.4% vs 6.0%; p = 0.002) but this was similar for B2 and B3 fractures (9.8% vs 13.5%; p = 0.341). The most common indication for reoperation after revision was dislocation (12 patients; 8.0%). Conclusion: Revision surgery has higher reoperation rates, longer surgical waiting times, higher transfusion requirements, and higher critical care requirements than ORIF in the management of periprosthetic fractures around polished taper-slip femoral components after THA. ORIF is a safe option providing anatomical reconstruction is achievable. Cite this article: Bone Joint J 2023;105-B(2):124–134.

Background: Despite the known multi-factorial nature of atrophic fracture non-unions, a possible genetic predisposition for the development of this complication after long bone fractures remains unknown. This pilot study aimed to address this issue by performing a preliminary SNP analysis of specific genes known to regulate fracture healing. Methods: A total of fifteen SNPs within four genes of the Bone Morphogenetic Protein (BMP) pathway (BMP-2, BMP-7, NOGGIN and SMAD6) were examined, in 109 randomly selected patients with long bone fractures as a result of motor vehicle accident, fall or direct blow. There were sixty-two patients with atrophic non-union and forty-seven patients (54 fractures) with uneventful fracture union. Overall SNPs frequencies were computed with respect to patient's age, gender, smoking habits, fracture-associated parameters and the use of nonsteroidal anti-inflammatory drugs (NSAIDs), and tested for their association to the impaired bone healing process, using binary logistic regression (STATA 11.1; StataCorp, Texas USA). Results: Statistical analysis revealed age to be an important covariate in the development of atrophic non-union (p = 0.01, OR 1.05 [per year]), and two specific genotypes (G/G genotype of the rs1372857 SNP, located on NOGGIN and T/T genotype of the rs2053423 SNP, located on SMAD6) to be associated with a greater risk of fracture non-union (p = 0.02, OR 4.56 and p = 0.04, OR 10.27, respectively, after adjustment for age). Conclusions: This is the first clinical study to investigate the potential existence of genetic susceptibility to fracture non-union. Even though no concrete conclusions can be obtained from this pilot study, our results indicate the existence of a potential genetically predetermined impairment within the BMP signalling cascade, initiated after a fracture and when combined with other risk factors could synergistically increase the susceptibility of a patient to develop non-union. Further research is desirable in order to clarify the genetic component and its role and interaction with other risk factors in the development of atrophic long bone non-union, as simple genetic testing may contribute to the early identification of patients at risk in the future and the on-time intervention at the biologic aspects of bone healing.