Comparability between wearable inertial sensors and an electronic walkway for spatiotemporal and relative phase data in young children aged 6-11 years.

BACKGROUND: Approaches to gait analysis are evolving rapidly and now include a wide range of options: from e-patches to video platforms to wearable inertial measurement unit systems. Newer options for gait analysis are generally more inclusive for the assessment of children, more cost effective and easier to administer. However, there is limited data on the comparability of newer systems with more established traditional approaches in young children. RESEARCH QUESTION: To determine comparability between the Physilog®5 wearable inertial sensor and GAITRite® electronic walkway for spatiotemporal (stride length, time and velocity, cadence) and relative phase (double support time, stance, swing, loading, foot flat and push off) data in young children. METHODS: A total 34 typically developing participants (41% female) aged 6-11 years old median age 8.99 years old (interquartile range 2.83) were assessed walking at self-selected speed over the GAITRite® electronic walkway while concurrently wearing shoe-attached Physilog®5 IMU sensors. Level of agreement was analysed by Lin's concordance correlation coefficient (CCC), Bland-Altman plots and 95% limit of agreement. Systematic bias was assessed using 95% confidence interval of the mean difference. RESULTS: Excellent to almost perfect agreement was observed between systems for spatiotemporal metrics: cadence (CCC=0.996), stride length (CCC=0.993), stride time (CCC=0.996), stride velocity (CCC=0.988). The relative phase metrics adjusted for stride velocity showed improved comparability when compared to the unadjusted metrics: swing adjusted (adj) (CCC=0.635); stance adj (CCC: 0.879); loading adj: (CCC=0.626). SIGNIFICANCE: Spatiotemporal metrics are highly compatible across GAITRite® electronic walkway and Physilog®5 IMU systems in young children. Relative phase metrics were somewhat compatible between systems when adjusted for stride velocity.

A US-based national surveillance study for the susceptibility and epidemiology of Clostridioides difficile isolates with special reference to ridinilazole: 2020-2021.

We have previously reported on the susceptibility and epidemiology of Clostridioides difficile isolates from six geographically dispersed medical centers in the United States. This current survey was conducted with isolates collected in 2020-2021 from six geographically dispersed medical centers in the United States, with specific attention to susceptibility to ridinilazole as well as nine comparators. C. difficile isolates or stools from patients with C. difficile antibiotic-associated diarrhea were collected and referred to a central laboratory. After species confirmation of 300 isolates at the central laboratory, antibiotic susceptibilities were determined by the agar dilution method [M11-A9, Clinical and Laboratory Standards Institute (CLSI)] against the 10 agents. Ribotyping was performed by PCR capillary gel electrophoresis on all isolates. Ridinilazole had a minimum inhibitory concentration (MIC) 90 of 0.25 mcg/mL, and no isolate had an MIC greater than 0.5 mcg/mL. In comparison, fidaxomicin had an MIC 90 of 0.5 mcg/mL. The vancomycin MIC 90 was 2 mcg/mL with a 0.7% resistance rate [both CLSI and European Committee on Antimicrobial Susceptibility Testing (EUCAST) criteria]. The metronidazole MIC 90 was 1 mcg/mL, with none resistant by CLSI criteria, and a 0.3% resistance rate by EUCAST criteria. Among the 50 different ribotypes isolated in the survey, the most common ribotype was 014-020 (14.0%) followed by 106 (10.3%), 027 (10%), 002 (8%), and 078-126 (4.3%). Ridinilazole maintained activity against all ribotypes and all strains resistant to any other agent tested. Ridinilazole showed excellent in vitro activity against C. difficile isolates collected between 2020 and 2021 in the United States, independent of ribotype.

Validation of shoe-worn Gait Up Physilog®5 wearable inertial sensors in adolescents.

BACKGROUND: Gait Up Physilog® wearable inertial sensors are a powerful alternative to traditional laboratory-based gait assessment for children with gait impairment. To build clinician trust in these devices and ultimately facilitate their use outside confined spaces, studies have examined performance of previous versions of Physilog® wearable inertial sensors but predominant focus has been on older adults. Despite their different gait patterns and behavioural/cognitive profiles, there are limited studies in children. RESEARCH QUESTION: To determine whether key spatiotemporal gait parameters (stride length, time and velocity) collected by shoe-worn Physilog®5 sensors in a hallway assessment protocol are a valid method of gait assessment in typically developing adolescents aged 12-15 years. METHODS: A total 30 typically developing participants (50 % female) median age 13.7 (interquartile range 2.34) were assessed in an exploratory study whilst walking at self-selected speed over the GAITRite® electronic walkway, concurrently wearing Physilog®5 sensors. Concurrent validity was analysed by Lin's concordance correlation coefficient (CCC), Bland-Altman plots and 95 % limit of agreement. Systematic bias was assessed using 95 % confidence interval of the mean difference. RESULTS: Mean stride data demonstrated substantial agreement for stride length (CCC = 0.975) and stride velocity (CCC = 0.979) to almost perfect agreement for stride time (CCC > 0.996). Agreement between the technologies for individual stride-to-stride data remained high for stride time (CCC = 0.952); yet reduced for stride length (CCC = 0.868) and stride velocity (CCC = 0.877). Male/female differences in performance of the technology were observed for stride velocity, favouring females. SIGNIFICANCE: Physilog®5 inertial sensors accurately measure walking in adolescents, with stride time the most accurately detected parameter. This demonstrates that wearables can be used by researchers and clinicians working with adolescent groups as an alternative to fixed systems. These findings will ultimately pave the way to using wearables for assessments with children outside of the laboratory environment.

The development of a consensus statement for the prescription of powered wheelchair standing devices in Duchenne muscular dystrophy.

PURPOSE: To develop a consensus statement for the prescription of a Powered Wheelchair Standing Device (PWSD) in young people with Duchenne muscular dystrophy (DMD). MATERIALS AND METHODS: An international multidisciplinary panel comprising clinicians and users (young people with DMD) along with their parents was consulted. A literature review was undertaken and a Delphi method was utilised to generate consensus statements. To supplement limited literature, round one of the Delphi process comprised questions consistent with the International Classification of Functioning, Disability and Health model of disability to generate items based on expert opinion and was completed by 38 clinicians and nine users. Thirty-seven participants completed two further rounds rating the importance of each item with a five-point scale. Agreement of 70% or more participants for items indicated consensus. RESULTS: Consensus was reached for 47 of 80 items. Tolerance and comfort in supported standing for at least 10 min, ankle contracture less than 10 degrees and user goals reflecting motivation to use the standing function were agreed as necessary in guiding the decision to trial a PWSD. Evidence of family, therapist and servicing support were also considered critical in enabling continuity of PWSD use. CONCLUSIONS: PWSD is a mobility option that offers choice, control and opportunity for independence. This consensus statement can assist clinicians with decision-making around factors influencing successful implementation and optimisation of PWSD for young people with DMD.Implications for RehabilitationTolerance and comfort in supported standing for at least 10 minutes, ankle contracture limited to less than 10 degrees and the child's goals reflecting motivation to use the standing position were agreed to be necessary considerations in guiding the decision to trial a PWSD.Trialling a PWSD when the child is predicted to lose the ability to walk within a one to two year period was recommended although a PWSD could be suitable for a child who was unable to walk.Evidence of family, therapist and servicing support was considered critical in enabling continuity of PWSD use.

Reliability and validity of the FSHD-composite outcome measure in childhood facioscapulohumeral dystrophy.

This study aims to investigate intra-rater reliability and construct validity of the Facioscapulohumeral Dystrophy Composite Outcome Measure (FSHD-COM), in childhood FSHD. Participants included eighteen children with FSHD, and matched healthy controls. Reliability data were collected from 15 participants with FSHD over two testing sessions. Validity data were collected from all participants. Participants with FSHD completed; the FSHD-COM (and modified pediatric version), Motor Function Measure-32 (MFM-32), FSHD Severity Scales, Performance of the Upper Limb 2.0, Pediatric Quality of Life™ Neuromuscular Module and pediatric FSHD Health-Index Questionnaire. Both versions of the FSHD-COM showed excellent intra-rater reliability (ICC1,2 > 0.99, lower 95%CI > 0.98) with a Minimal Detectable Change (MDC95%) of ≤14.5%. The FSHD-COM had robust and widespread correlations with other related outcome measures. The FSHD-COM versions and 6 min walk test effectively discriminated between children with and without FSHD; the MFM-32 and 10 m walk/run test did not. Ceiling effects were not observed on either version of the FSHD-COM. Reliability and validity findings in this childhood FSHD study concord with estimates in adults. Both versions of the FSHD-COM were effective in discriminating disease in children with mild FSHD symptoms. The FSHD-COM has the potential to be a useful measure of function across the life span.

Epidemiological investigation of recurrent outbreaks of haemolytic uraemic syndrome caused by Shiga toxin-producing Escherichia coli serotype O55:H7 in England, 2014-2018.

Recurrent outbreaks of haemolytic uraemic syndrome (HUS) caused by Shiga toxin-producing Escherichia coli (STEC) serotype O55:H7 occurred in England between 2014 and 2018. We reviewed the epidemiological evidence to identify potential source(s) and transmission routes of the pathogen, and to assess the on-going risk to public health. Over the 5-year period, there were 43 confirmed and three probable cases of STEC O55:H7. The median age of cases was 4 years old (range 6 months to 69 years old) and over half of all cases were female (28/46, 61%). There were 36/46 (78.3%) symptomatic cases, and over half of all cases developed HUS (25/46, 54%), including two fatal cases. No common food or environmental exposures were identified, although the majority of cases lived in rural or semi-rural environments and reported contact with both wild and domestic animals. This investigation informed policy on the clinical and public health management of HUS caused by STEC other than serotype O157:H7 (non-O157 STEC) in England, including comprehensive testing of all household contacts and household pets and more widespread use of polymerase chain reaction assays for the rapid diagnosis of STEC-HUS.

Shiga toxin-producing Escherichia coli diagnosed by Stx PCR: assessing the public health risk of non-O157 strains.

BACKGROUND: The implementation by diagnostic laboratories in England of polymerase chain reaction (PCR) to screen faecal specimens for Shiga toxin-producing Escherichia coli (STEC) has resulted in a significant increase in notifications mainly due to non-O157 strains. The purpose of this study was to develop an approach to public health risk assessment that prioritizes follow-up to cases caused by haemolytic uraemic syndrome (HUS) associated E. coli (HUSEC) strains and minimizes unnecessary actions. METHODS: Epidemiological and microbiological data were prospectively collected from 1 November 2013 to 31 March 2017 and used to compare three risk assessment approaches. RESULTS: A history of HUS/bloody diarrhoea/age under 6 years and faecal specimens positive for stx-predicted HUSEC with a diagnostic accuracy of 84% (95% CI; 81-88%). STEC isolated by Gastrointestinal Bacteria Reference Unit (GBRU) and stx2 and eae positive predicted HUSEC with a diagnostic accuracy of 99% (95% CI; 98-100%). Risk assessment combining these two tests predicts the most efficient use of resources, predicting that 18% (97/552) of cases would be eligible for follow-up at some stage, 16% (86/552) following local stx PCR results, 1% (7/552) following GBRU results of stx2 and eae status and 0.7% (4/552) following whole-genome sequencing. Follow-up could be stopped in 78% (76/97) of these cases, 97% (74/76) following second stage risk assessment. CONCLUSIONS: This three-stage risk assessment approach prioritizes follow-up to HUSEC and minimizes unnecessary public health actions. We developed it into the algorithm for public health actions included in the updated PHE Guidance for management of STEC published in August 2018.

Targeted rapid testing for SARS-CoV-2 in the emergency department is associated with large reductions in uninfected patient exposure time.

Opportunity exists to decrease healthcare-related exposure to severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2), preserve infection control resources, and increase care capacity by reducing the time to diagnosis of coronavirus disease 2019 (COVID-19). A retrospective cohort analysis was undertaken to measure the effect of targeted rapid molecular testing for SARS-CoV-2 on these outcomes. In comparison with standard platform testing, rapid testing was associated with a 65.6% reduction (12.6 h) in the median time to removal from the isolation cohort for patients with negative diagnostic results. This translated to an increase in COVID-19 treatment capacity of 3028 bed-hours and 7500 fewer patient interactions that required the use of personal protective equipment per week.

Marijuana use and its influence on sperm morphology and motility: identified risk for fertility among Jamaican men.

BACKGROUND: The growing international movement legislating medical marijuana has brought renewed interest to the role of marijuana smoking on fertility potential. Although studies have identified that sperm quality can be compromised by marijuana use, little focus has been placed specifically on those trying to conceive. In this study, we aimed to clarify the impact of marijuana use in semen quality in men being investigated for assisted reproduction. MATERIALS AND METHODS: We conducted a cross-sectional study at a university-based facility in Jamaica. Routine semen analyses were performed on 229 men ages 23-72 years who were new clients. Logistic regression analyses were performed in order to independently predict quantifiable measures of the impact of marijuana use. The main outcome measures were sperm motility, total motile spermatozoa and morphology. RESULTS: Overall, 47% of the participants reported marijuana use with 21% of these men reporting recent use. Regression analyses showed that recent use and users of large quantities of marijuana were 2.6 times (aOR = 2.6; 95% CI, 1.0-6.8, p = 0.044) and 4.3 times (aOR = 4.3; 95% CI, 1.1-15.9, p = 0.030) at greater risk of being diagnosed with abnormal motility (asthenozoospermia). Additionally, moderate quantity users were 3.4 times (aOR = 3.4; 95% CI, 1.5-7.9, p = 0.004) more likely to be diagnosed with abnormal morphology (teratozoospermia). DISCUSSION AND CONCLUSION: Recent use of marijuana as well as moderate to large quantities had an impact on sperm motility and morphology in men being investigated for infertility. We recommend therefore that men undergoing fertility investigations be routinely asked about their recreational use of marijuana and in particular recent and heavy users counselled to stop.

Pyloric outflow obstruction secondary to sclerosing encapsulating peritonitis in a dog.

A 6-year-old, male neutered mixed breed dog was presented emergently with a three-week history of hyporexia, vomiting, diarrhoea and weight loss. Upon examination, the patient was dull, had generalised muscle atrophy, moderate abdominal pain and a mild amount of peritoneal effusion. A fluid-filled, distended, corrugated small bowel with marked gastroparesis and moderate peritoneal effusion was noted on abdominal ultrasonography. Endoscopy revealed hyperaemic and friable mucosa and a subjectively narrowed pylorus. Emergency exploratory celiotomy was performed due to worsening patient condition and revealed thick, diffuse, fibrous adhesions of the abdominal cavity. Based on these findings, sclerosing encapsulating peritonitis (SEP) was suspected. A large mass of omentum adjacent to the greater curvature of the stomach had caused a pyloric outflow obstruction. Adhesiolysis was attempted but was unsuccessful due to the friability of the small intestines. The dog was humanely euthanased under anaesthesia. A diagnosis of SEP was confirmed via necropsy. No underlying cause was identified. This is the first known case of a pyloric outflow obstruction secondary to SEP in a dog. Although rare, this condition should be considered as a differential for dogs with signs of a pyloric outflow obstruction with concurrent ascites and abdominal pain, hyporexia, vomiting and diarrhoea.

Intraoperative placement of total hip arthroplasty components with robotic-arm assisted technology correlates with postoperative implant position: a CT-based study.

AIMS: The aim of this study was to evaluate the accuracy of implant placement when using robotic assistance during total hip arthroplasty (THA). PATIENTS AND METHODS: A total of 20 patients underwent a planned THA using preoperative CT scans and robotic-assisted software. There were nine men and 11 women (n = 20 hips) with a mean age of 60.8 years (sd 6.0). Pelvic and femoral bone models were constructed by segmenting both preoperative and postoperative CT scan images. The preoperative anatomical landmarks using the robotic-assisted system were matched to the postoperative 3D reconstructions of the pelvis. Acetabular and femoral component positions as measured intraoperatively and postoperatively were evaluated and compared. RESULTS: The system reported accurate values for reconstruction of the hip when compared to those measured postoperatively using CT. The mean deviation from the executed overall hip length and offset were 1.6 mm (sd 2.9) and 0.5 mm (sd 3.0), respectively. Mean combined anteversion was similar and correlated between intraoperative measurements and postoperative CT measurements (32.5°, sd 5.9° versus 32.2°, sd 6.4°; respectively; R2 = 0.65; p < 0.001). There was a significant correlation between mean intraoperative (40.4°, sd 2.1°) acetabular component inclination and mean measured postoperative inclination (40.12°, sd 3.0°, R2 = 0.62; p < 0.001). There was a significant correlation between mean intraoperative version (23.2°, sd 2.3°), and postoperatively measured version (23.0°, sd 2.4°; R2 = 0.76; p < 0.001). Preoperative and postoperative femoral component anteversion were significantly correlated with one another (R2 = 0.64; p < 0.001). Three patients had CT scan measurements that differed substantially from the intraoperative robotic measurements when evaluating stem anteversion. CONCLUSION: This is the first study to evaluate the success of hip reconstruction overall using robotic-assisted THA. The overall hip reconstruction obtained in the operating theatre using robotic assistance accurately correlated with the postoperative component position assessed independently using CT based 3D modelling. Clinical correlation during surgery should continue to be practiced and compared with observed intraoperative robotic values. Cite this article: Bone Joint J 2018;100-B:1303-9.

Association of prenatal folate status with early childhood wheeze and atopic dermatitis.

BACKGROUND: Prenatal folic acid supplementation is recommended to prevent birth defects. Some foods are fortified in the USA to ensure sufficient intake among reproductive-aged women. However, high prenatal folate exposure may be a risk factor for childhood atopic diseases. We investigated associations between prenatal folate and early childhood wheeze and atopic dermatitis in a US cohort. METHODS: We studied 858 mother-child dyads, enrolled prenatally. Folate was measured in 2nd and 3rd trimester maternal plasma. Parents reported current wheeze (previous 12 months) and healthcare provider diagnosis of atopic dermatitis at 3 years. We examined associations using logistic regression, modeling folate continuously and dichotomously (< or ≥20 ng/mL), a level often considered supraphysiologic. RESULTS: Over half of women were African American and on Medicaid. Median (interquartile range) folate levels were 22.6 (15.9-30.0) and 23.1 (16.1-30.0) ng/mL for 2nd and 3rd trimesters, respectively. Current wheeze and atopic dermatitis were reported for 20.4% and 26.8% of children, respectively. Second trimester folate as a continuous exposure was not significantly associated with outcomes. Decreased odds of current wheeze were observed in children born to mothers who had 2nd trimester folate ≥20 ng/mL (adjusted odds ratios = 0.67, 95% confidence interval = 0.46, 0.97) compared to children with maternal levels <20 ng/mL. Third trimester folate was not associated with outcomes. CONCLUSIONS: High plasma folate in mid-pregnancy was associated with decreased odds of current wheeze at age 3. Our findings do not support harmful effects of high prenatal folate levels on childhood atopic diseases in this setting.

Between-Batch Pharmacokinetic Variability Inflates Type I Error Rate in Conventional Bioequivalence Trials: A Randomized Advair Diskus Clinical Trial.

We previously demonstrated pharmacokinetic differences among manufacturing batches of a US Food and Drug Administration (FDA)-approved dry powder inhalation product (Advair Diskus 100/50) large enough to establish between-batch bio-inequivalence. Here, we provide independent confirmation of pharmacokinetic bio-inequivalence among Advair Diskus 100/50 batches, and quantify residual and between-batch variance component magnitudes. These variance estimates are used to consider the type I error rate of the FDA's current two-way crossover design recommendation. When between-batch pharmacokinetic variability is substantial, the conventional two-way crossover design cannot accomplish the objectives of FDA's statistical bioequivalence test (i.e., cannot accurately estimate the test/reference ratio and associated confidence interval). The two-way crossover, which ignores between-batch pharmacokinetic variability, yields an artificially narrow confidence interval on the product comparison. The unavoidable consequence is type I error rate inflation, to ∼25%, when between-batch pharmacokinetic variability is nonzero. This risk of a false bioequivalence conclusion is substantially higher than asserted by regulators as acceptable consumer risk (5%).

Geographic Differences in Endovascular Treatment and Retreatment of Cerebral Aneurysms.

BACKGROUND AND PURPOSE: Comparing outcomes between endovascular aneurysm coiling trials can be difficult because of heterogeneity in patients and end points. We sought to understand the impact of geography on aneurysm retreatment in patients enrolled in the Matrix and Platinum Science Trial. MATERIALS AND METHODS: Post hoc analysis was performed on data from the Matrix and Platinum Science trial. Patients were stratified as either North American or international. Baseline patient demographics, comorbidities, aneurysm characteristics, procedural complications, and clinical and angiographic outcomes were compared. RESULTS: We evaluated 407 patients from 28 North American sites and 219 patients from 15 international sites. Patient demographics differed significantly between North American and international sites. Aneurysms were well occluded postprocedure more often at international than North American sites (P < .001). Stents were used significantly more often at North American sites (32.7% [133 of 407]) compared with international sites (10.0% [22 of 219]; P < .001). At 455 days, there was no difference in the proportion of patients alive and free of disability (P = .56) or with residual aneurysm filling (P = .10). Ruptured aneurysms were significantly more likely to have been retreated at North American sites within the first year (P < .001) and at 2 years (P < .001). Among all patients for whom the treating physician believed there to be Raymond 3 aneurysm filling at follow-up, absolute rates of retreatment at international and North American sites were similar by 2-year follow-up. CONCLUSIONS: Data from the Matrix and Platinum Science Trial demonstrate that aneurysm retreatment occurs with different frequency and at different times in different regions of the world. This trend has critical value when interpreting trials reporting short-term outcomes, especially when judgment-based metrics such as retreatment are primary end points that may or may not take place within the defined study follow-up period. Though these variations can be controlled for and balanced within a given randomized trial, such differences in practice patterns must be accounted for in any attempt to compare outcomes between different trials. Despite these differences, endovascular-treated intracranial aneurysms around the world have similar clinical outcomes.

Thermochemical scanning probe lithography of protein gradients at the nanoscale.

Patterning nanoscale protein gradients is crucial for studying a variety of cellular processes in vitro. Despite the recent development in nano-fabrication technology, combining nanometric resolution and fine control of protein concentrations is still an open challenge. Here, we demonstrate the use of thermochemical scanning probe lithography (tc-SPL) for defining micro- and nano-sized patterns with precisely controlled protein concentration. First, tc-SPL is performed by scanning a heatable atomic force microscopy tip on a polymeric substrate, for locally exposing reactive amino groups on the surface, then the substrate is functionalized with streptavidin and laminin proteins. We show, by fluorescence microscopy on the patterned gradients, that it is possible to precisely tune the concentration of the immobilized proteins by varying the patterning parameters during tc-SPL. This paves the way to the use of tc-SPL for defining protein gradients at the nanoscale, to be used as chemical cues e.g. for studying and regulating cellular processes in vitro.

Batch-to-batch pharmacokinetic variability confounds current bioequivalence regulations: A dry powder inhaler randomized clinical trial.

Current pharmacokinetic (PK) bioequivalence guidelines do not account for batch-to-batch variability in study design or analysis. Here we evaluate the magnitude of batch-to-batch PK variability for Advair Diskus 100/50. Single doses of fluticasone propionate and salmeterol combinations were administered by oral inhalation to healthy subjects in a randomized clinical crossover study comparing three different batches purchased from the market, with one batch replicated across two treatment periods. All pairwise comparisons between different batches failed the PK bioequivalence statistical test, demonstrating substantial PK differences between batches that were large enough to demonstrate bio-inequivalence in some cases. In contrast, between-replicate PK bioequivalence was demonstrated for the replicated batch. Between-batch variance was ∼40-70% of the estimated residual error. This large additional source of variability necessitates re-evaluation of bioequivalence assessment criteria to yield a result that is both generalizable and consistent with the principles of type I and type II error rate control.

Male attitude towards masturbating: an impediment to infertility evaluation and sperm parameters.

Male attitude about masturbation may influence early diagnosis and treatment of infertility and may be of particular burden in developing countries. We sought to explore attitude about masturbating and examine comfort/discomfort with masturbating and sexual history, pregnancy history and sperm quality in men investigating fertility potential. The study consisted of 83 male volunteers, 23-61 years, attending a fertility management unit in Kingston, Jamaica. Comfort with masturbation was assessed by a self-administered questionnaire. Participants also completed the unit's standard intake form for infertility investigations and produced a semen sample. T-tests, Mann-Whitney U-test and chi-square were used to compare differences in comfort level with outcome variables. We found 59% were comfortable masturbating although requiring external stimulation to produce a sample (48%); 6% (n = 5) failed to produce a sample after repeated attempts. A higher percentage of men uncomfortable with masturbating reported sexual problems (P < 0.05) and spending a longer time trying to have a baby (P < 0.05). Semen quality was not associated with masturbating comfort. Producing a sample by masturbation is standard for many assisted conception treatments. As comfort with masturbating may influence delay in infertility investigations and fertility outcome, efforts to improve men's comfort level with semen production should be considered in pre-treatment fertility counselling.

Subphenotyping and Classification of Orofacial Clefts: Need for Orofacial Cleft Subphenotyping Calls for Revised Classification.

Nonsyndromic orofacial clefting (OFC) describes a range of phenotypes that represent the most common craniofacial birth defects in humans, with an overall birth prevalence of 1:700 live births. Because of the lifelong negative implications on health and well-being associated with OFC and the numbers of people affected, quality research into its etiology, diagnosis, treatment outcomes, and preventative strategies is essential. A range of different methods is used for recording and classifying OFC subphenotypes, one of which is the International Classification of Diseases (ICD) system. However, there is a general perception that research is being hampered by a lack of sensitivity and specificity in grouping those with OFC into subphenotypes, with potential heterogeneity and confounding in epidemiologic, genetic, and genotype-phenotype correlation studies. This article provides a background to the necessity of OFC research, discusses current controversies within cleft subphenotyping, and provides a brief overview of current OFC classifications as well as their limitations. The LAHSHAL classification is described in the context of a potentially useful tool for OFC that could complement the ICD-10/ICD-11 Beta coding systems to become a simply understood, universally accepted, clinically friendly, and research-sensitive instrument. Empowering registries, clinicians, and researchers to use a common classification system would have significant implications for OFC research across the world at a time when accurate subphenotyping is crucial and health care research is becoming increasingly tailored toward the individual.