Clinical characteristics and favorable treatment responses of recurrent focal segmental glomerulosclerosis or steroid-resistant nephrotic syndrome in children after kidney transplantation.

BACKGROUND: Recurrence of focal segmental glomerulosclerosis (FSGS) or steroid-resistant nephrotic syndrome (SRNS) after kidney transplant leads to significant morbidity and potentially earlier allograft loss. To date however, reported rates, risk factors and treatment outcomes have varied widely. METHODS: We applied computational phenotypes to a multicenter aggregation of electronic health records data from 7 large pediatric health systems in the USA, to identify recurrence rates, risk factors, and treatment outcomes. We refined the data collection by chart review. RESULTS: From > 7 million patients, we compared children with primary FSGS/SRNS who received a kidney transplant between 2009 and 2020 and who either developed recurrence (n = 67/165; 40.6%) or did not (n = 98/165). Serum albumin level at time of transplant was significantly lower and recipient HLA DR7 presence was significantly higher in the recurrence group. By 36 months post-transplant, complete remission occurred in 58.2% and partial remission in 17.9%. Through 6 years post-transplant, no remission after recurrence was associated with an increased risk of allograft loss over time (p < 0.0001), but any remission showed similar allograft survival and function decline to those with no recurrence. Since treatments were used in non-random fashion, using spline curves and multivariable non-linear analyses, complete + partial remission chance was significantly higher with greater plasmapheresis sessions, CTLA4-Ig doses or LDL-apheresis sessions. Only treatment with anti-CD20, CTLA4-Ig agents, or LDL-apheresis sessions were associated with complete remission. Excluding 25 patients with mutations did not significantly change our results. CONCLUSIONS: Our contemporary high-risk cohort had higher favorable response rates than most prior reports, from combinations of agents.

Should left- and right-sided unilateral cleft lip and palate patients be grouped together when reporting the outcomes?

OBJECTIVES: Investigate associations between cleft laterality in patients with non-syndromic unilateral cleft lip and palate (UCLP) and oral-health, dental-arch, speech, audiological, psychological and nasolabial-aesthetic outcomes. METHODS: Secondary data analysis of the outcomes of 5-year-old children with non-syndromic complete UCLP identified from three studies: Cleft Collective (n = 155), Cleft Care UK (CCUK) (n = 266) and Clinical Standards Advisory Group (CSAG) study (n = 238). Outcome measures included occlusal assessment using the 5-year-old's index score, speech intelligibility rating using the CAPS-A Audit tool, audiological assessment using pure tone audiometry, nasolabial aesthetic assessment using the Asher-McDade tool, oral-health assessment using decayed, missing, filled teeth scores and parent-reported outcomes. Logistic regression with adjustment for age, sex and index-of-multiple-deprivation scores were performed. RESULTS: No differences were found in patient-reported outcomes between the left and right clefts in the Cleft Collective study. From the CCUK study, right clefts had poorer speech (n = 236; 95% CI 1.09, 3.42; and P = .03) and hearing outcomes (n = 211; 95% CI 1.03, 3.43; P = .04). In the CSAG study, patients with left clefts were more likely to be teased (n = 213; 95% CI 0.26, 0.85; and P = .01). CONCLUSION: Weak associations between cleft laterality, speech, hearing and psychological outcomes were found, however the findings were inconsistent across the studies. This study contributes to evidence of associations between laterality and outcomes in children born with UCLP.

Prevalence and Factors Associated with Behavioral Problems in 5-Year-Old Children Born with Cleft Lip and/or Palate from the Cleft Collective.

OBJECTIVES: To determine the UK prevalence of behavioral problems in 5-year-old children born with isolated or syndromic cleft lip and/or palate (CL/P) compared to the general population and identify potentially associated factors. DESIGN: Observational study using questionnaire data from the Cleft Collective 5-Year-Old Cohort study and three general population samples. MAIN OUTCOME MEASURE: The Strengths and Difficulties Questionnaire (SDQ). PARTICIPANTS: Mothers of children (age: 4.9-6.8 years) born with CL/P (n = 325). UK general population cohorts for SDQ scores were: Millennium Cohort Study (MCS) (n = 12 511), Office of National Statistics (ONS) normative school-age SDQ data (n = 5855), and Avon Longitudinal Study of Parents and Children (ALSPAC) (n = 9386). RESULTS: By maternal report, 14.2% of children born with CL/P were above clinical cut-off for behavioral problems, which was more likely than in general population samples: 7.5% of MCS (OR = 2.05 [1.49-2.82], P < 0.001), 9.8% of ONS (OR = 1.52 [1.10-2.09], P = 0.008), and 6.6% of ALSPAC (OR = 2.34 [1.70-3.24], P < 0.001). Children in the Cleft Collective had higher odds for hyperactivity, emotional and peer problems, and less prosocial behaviors. Maternal stress, lower maternal health-related quality of life and family functioning, receiving government income support, and maternal smoking showed evidence of association (OR range: 4.41-10.13) with behavioral problems, along with maternal relationship status, younger age, and lower education (OR range: 2.34-3.73). CONCLUSIONS: Findings suggest elevated levels of behavioral problems in children born with CL/P compared to the general population with several associated maternal factors similar to the general population.

Acceptability of prehabilitation for cancer surgery: a multi-perspective qualitative investigation of patient and 'clinician' experiences.

BACKGROUND: 'Prehabilitation' interventions aim to enhance individuals' physical fitness prior to cancer treatment, typically involve exercise training as a key component, and may continue to support physical activity, strength, and fitness during or after treatment. However, uptake of prehabilitation is variable. This study investigated how patients from diverse socio-economic status groups perceived an exemplar prehabilitation and recovery programme, aiming to understand factors impacting acceptability, engagement and referral. METHODS: This research was conducted in the context of the Prehab4Cancer and Recovery Programme, a prehabilitation and recovery programme available across Greater Manchester, UK. Qualitative, semi-structured phone/video-call interviews were conducted with 18 adult patient participants referred to the programme (16 'engagers', 2 'non-engagers'; half the sample lived in localities with low socio-economic status scores). An online questionnaire with free-response and categorical-response questions was completed by 24 'clinician' participants involved in referral (nurses, doctors and other staff roles). An inductive, multi-perspective, thematic analysis was performed, structured using the Framework approach. RESULTS: Discussing and referring patients to prehabilitation can be challenging due to large quantities of information for staff to cover, and for patients to absorb, around the time of diagnosis. The programme was highly valued by both participant groups; the belief that participation would improve recovery seemed a major motivator for engagement, and some 'clinicians' felt that prehabilitation should be treated as a routine part of treatment, or extended to support other patient groups. Engagers seemed to appreciate a supportive approach where they did not feel forced to do any activity and tailoring of the programme to meet individual needs and abilities was appreciated. Initial engagement could be daunting, but gaining experience with the programme seemed to increase confidence. CONCLUSIONS: The prehabilitation programme was highly valued by engagers. Introducing prehabilitation at a challenging time means that personalised approaches might be needed to support engagement, or participation could be encouraged at a later time. Strategies to support individuals lacking in confidence, such as buddying, may be valuable. STUDY REGISTRATION: The study protocol was uploaded onto the Open Science Framework 24 September 2020 ( https://osf.io/347qj/ ).

Impact of a prehabilitation and recovery programme on emotional well-being in individuals undergoing cancer surgery: a multi-perspective qualitative study.

BACKGROUND: Prehabilitation and recovery programmes aim to optimise patients' physical fitness and mental well-being before, during and after cancer treatment. This paper aimed to understand the impact of such a programme on emotional well-being in individuals undergoing cancer surgery. The programme was multi-modal, containing physical activity, well-being and nutritional support. METHODS: Qualitative interviews were conducted with 16 individuals who participated in a prehabilitation and recovery programme. Twenty-four health care staff involved in referral completed an online survey. An inductive, thematic analysis was conducted, integrating perspectives of patients and staff, structured with the Framework approach. RESULTS: Patients seemed to experience emotional benefits from the programme, appearing less anxious and more confident in their ability to cope with treatment. They seemed to value having something positive to focus on and control over an aspect of treatment. Ongoing, implicit psychological support provided by Exercise Specialists, who were perceived as expert, available and caring, seemed valued. Some patients appeared to appreciate opportunities to talk about cancer with peers and professionals. Discomfort with talking about cancer with other people, outside of the programme, was expressed. CONCLUSIONS: Participation in a prehabilitation and recovery programme appeared to yield valuable emotional well-being benefits, even without referral to specialist psychological support. STUDY REGISTRATION: The study protocol was uploaded onto the Open Science Framework 24 September 2020 ( https://osf.io/347qj/ ).

Skeletal Outcomes in Children and Young Adults with Glomerular Disease.

BACKGROUND: Children with glomerular disease have unique risk factors for compromised bone health. Studies addressing skeletal complications in this population are lacking. METHODS: This retrospective cohort study utilized data from PEDSnet, a national network of pediatric health systems with standardized electronic health record data for more than 6.5 million patients from 2009 to 2021. Incidence rates (per 10,000 person-years) of fracture, slipped capital femoral epiphysis (SCFE), and avascular necrosis/osteonecrosis (AVN) in 4598 children and young adults with glomerular disease were compared with those among 553,624 general pediatric patients using Poisson regression analysis. The glomerular disease cohort was identified using a published computable phenotype. Inclusion criteria for the general pediatric cohort were two or more primary care visits 1 year or more apart between 1 and 21 years of age, one visit or more every 18 months if followed >3 years, and no chronic progressive conditions defined by the Pediatric Medical Complexity Algorithm. Fracture, SCFE, and AVN were identified using SNOMED-CT diagnosis codes; fracture required an associated x-ray or splinting/casting procedure within 48 hours. RESULTS: We found a higher risk of fracture for the glomerular disease cohort compared with the general pediatric cohort in girls only (incidence rate ratio [IRR], 1.6; 95% CI, 1.3 to 1.9). Hip/femur and vertebral fracture risk were increased in the glomerular disease cohort: adjusted IRR was 2.2 (95% CI, 1.3 to 3.7) and 5 (95% CI, 3.2 to 7.6), respectively. For SCFE, the adjusted IRR was 3.4 (95% CI, 1.9 to 5.9). For AVN, the adjusted IRR was 56.2 (95% CI, 40.7 to 77.5). CONCLUSIONS: Children and young adults with glomerular disease have significantly higher burden of skeletal complications than the general pediatric population.

Current Surgical Practice for Children Born with a Cleft lip and/or Palate in the United Kingdom.

OBJECTIVE: This study describes primary surgical reconstructions performed for children born with a cleft lip and/or palate (CL ± P) in the United Kingdom (UK). DESIGN: Data forms completed at the time of surgery included details on timing, technique, and adjuncts used during the operative period. Demographic data on participants were validated via parental questionnaires. SETTING: Data were obtained from the Cleft Collective, a national longitudinal cohort study. PATIENTS: Between 2015 and 2021, 1782 Cleft Collective surgical forms were included, relating to the primary reconstructions of 1514 individual children. RESULTS: The median age at primary cheiloplasty was 4.3 months. Unilateral cleft lips (UCL) were reconstructed with an anatomical subunit approximation technique in 53%, whereas bilateral cleft lips (BCL) were reconstructed with a broader range of eponymous techniques. Clefts of the soft palate were reconstructed at a median age of 10.3 months with an intravelar veloplasty in 94% cases. Clefts of the hard palate were reconstructed with a vomer flap in 84% cases in a bimodal age distribution, relating to reconstruction carried out simultaneously with either lip or soft palate reconstruction. Antibiotics were used in 96% of cases, with an at-induction-only regimen used more commonly for cheiloplasties (P < .001) and a 5 to 7-day postoperative regime used more commonly for soft palatoplasties (P < .001). Perioperative steroids were used more commonly in palatoplasties than cheiloplasties (P < .001) but tranexamic acid use was equivalent (P = .73). CONCLUSIONS: This study contributes to our understanding of current cleft surgical pathways in the UK and will provide a baseline for analysis of the effectiveness of utilized protocols.

Sidedness in Unilateral Orofacial Clefts: A Systematic Scoping Review.

OBJECTIVE: An overview of the literature relating to the sidedness of unilateral cleft lip with or without cleft palate to map current knowledge on the cause and impact of directional asymmetry. DESIGN: Scoping review with a systematic search of Medline and Embase from inception to May 2023. PATIENTS, PARTICIPANTS: Humans born with a left or right unilateral cleft lip with or without a cleft palate. MAIN OUTCOME MEASURES: Cleft sidedness as a co-occurrence, an outcome or an exposure. RESULTS: Forty studies were eligible for inclusion and confirmed the predilection for the occurrence of left sided cleft lips; 12 studies reported cleft sidedness co-occurring with another phenotype, 11 studies report sidedness as an outcome and 17 studies as an exposure. Phenotypes which were reported to co-occur with either left or right sided clefts included congenital dental anomalies, handedness and additional congenital anomalies. Variables investigated as a potential cause of left or right sided clefts as an outcome included chromosomal anomalies, genetic variants and environmental factors. Outcomes investigated in relation to cleft sidedness as an exposure included facial anatomical features, facial growth, educational attainment, functional and psychological characteristics. More studies showed worse outcomes in right sided clefts versus left sided clefts than vice versa, although studies were inconsistent, and a quality assessment was not performed. CONCLUSIONS: The field of cleft sidedness research is expanding and there are promising early findings to differentiate cause and outcome by sidedness of the cleft.

Stroke in patients with cancer in the era of hyperacute stroke intervention.

BACKGROUND: The natural history of patients with stroke and cancer remains poorly understood in the modern era of hyperacute stroke therapies (recombinant tissue plasminogen activator and endovascular clot retrieval (ECR)). Prior to these advances in stroke treatment, a highly cited study reported median overall survival (mOS) 4.5 months after stroke in a cohort of patients with cancer (2004, n = 96). AIMS: Our hypothesis is that patients with stroke and cancer have better outcome than in earlier studies. METHODS: Retrospective analysis of admission to a tertiary Stroke Unit between January 2015 and September 2017 (n = 1910), evaluation of hospital records and cancer treatment records. Cancer was categorised as early stage (Stages I and II) and advanced stage (Stage III or IV) using the RD-Staging system. Survival analysis was performed in R. RESULTS: There were 143 stroke patients with cancer (62% male) with mean age 73.2 ± 12.5 years. Ischaemic stroke occurred in 74.1% and 45 of 106 (42.5%) patients received intravenous thrombolysis (34/45) and/or ECR (11/45). One patient who received ECR died within 30 days of stroke. Those with early stage disease had mOS of 19.6 months (interquartile range (IQR) 3.1-31.5 months) and in advanced stage cancer mOS was 2.5 months (IQR 0.4-6.3 months; P < 0.01). CONCLUSION: In the modern era of stroke therapy, our cohort of patients with advanced cancer has lower survival post-stroke compared to those with early stage cancer.

Adolescents encouraging healthy lifestyles through a peer-led social marketing intervention: Training and key competencies learned by peer leaders.

BACKGROUND: Adolescents who participate as peer leaders can benefit and acquire competencies from their peer leadership experience. OBJECTIVES: To identify the competencies gained by adolescents who participated as peer leaders in a healthy lifestyle study and to determine whether the training characteristics were related to improvement in competencies. DESIGN: The present study was part of the European Youth Tackling Obesity (EYTO) project, a multicentre social marketing intervention involving four European countries. SETTING AND PARTICIPANTS: Eighteen peer leaders (aged 13-15 years, three or five leaders per country) from disadvantaged neighbourhoods received training in designing and implementing activities for their peers. MEASURES: The peer leaders' confidence, experience and interest in 11 tasks related to lifelong learning competencies were assessed with questions rated on a colour scale at baseline and at the end of the study. RESULTS: The peer leaders demonstrated improvements in experience, confidence and interest in different tasks, such as research, website or logo design, oral presentations, social media use and collaboration with people from other countries. They increased their confidence in management tasks (p = 0.03) and their confidence and experience in communication tasks (p = 0.01). The peer leaders from Spain and Portugal had greater improvements than those from the other countries. CONCLUSION: The peer leaders improved their confidence in management tasks and their confidence and experience in communication tasks. Slight differences were detected in improvement in competencies by country, likely due to the differences in the peer training applied. Recommendations for peer leader training are proposed, although these results should be verified with larger sample size. PATIENT OR PUBLIC CONTRIBUTION: The peer leaders contributed to the design and implementation of the training and intervention.

Exploring the Relationship Between Palatal Cleft Type and Width With the Use of Relieving Incisions in Primary Repair.

OBJECTIVE: The mainstay of palatal repair in the United Kingdom is the intravelar veloplasty (IVVP). It is not always possible to align the oral mucosa in the midline to achieve tension-free repair. The addition of lateral relieving incisions may aid transposition of the oral mucosa to allow closure. The aim of this study was to explore cleft features that may predispose to a requirement for relieving incisions in order to allow palate closure. DESIGN: We performed a national multiinstitutional retrospective study using data from the UK Cleft Collective cohort study. PATIENTS: The study sample consisted of 474 patients who had undergone IVVP at the time of palatal closure across all 16 of the UK cleft units. RESULTS: We found strong evidence for the requirement for relieving incisions in patients with an increased degree of clefting per the Veau classification (P < .001), increasing palatal soft-edge width (P < .001) and moderate evidence of an associated use in patients with Pierre Robin sequence (P = .015). Insufficient data were available to explore the relationship between intertuberosity distance and the presence of fistula formation with the use of relieving incisions. CONCLUSIONS: The results of this study identify cleft features that increase the likelihood for requiring lateral relieving incisions to allow palatal closure. The degree to which the addition of relieving incisions to IVVP affects maxillary growth and speech outcomes is unknown. Further study is required to answer this important question.

A Longitudinal Comparison of Alternatives to Body Mass Index Z-Scores for Children with Very High Body Mass Indexes.

OBJECTIVE: The current Centers for Disease Control and Prevention (CDC) body mass index (BMI) z-scores are inaccurate for BMIs of ≥97th percentile. We, therefore, considered 5 alternatives that can be used across the entire BMI distribution: modified BMI-for-age z-score (BMIz), BMI expressed as a percentage of the 95th percentile (%CDC95th percentile), extended BMIz, BMI expressed as a percentage of the median (%median), and %median adjusted for the dispersion of BMIs. STUDY DESIGN: We illustrate the behavior of the metrics among children of different ages and BMIs. We then compared the longitudinal tracking of the BMI metrics in electronic health record data from 1.17 million children in PEDSnet using the intraclass correlation coefficient to determine if 1 metric was superior. RESULTS: Our examples show that using CDC BMIz for high BMIs can result in nonsensical results. All alternative metrics showed higher tracking than CDC BMIz among children with obesity. Of the alternatives, modified BMIz performed poorly among children with severe obesity, and %median performed poorly among children who did not have obesity at their first visit. The highest intraclass correlation coefficients were generally seen for extended BMIz, adjusted %median, and %CDC95th percentile. CONCLUSIONS: Based on the examples of differences in the BMI metrics, the longitudinal tracking results and current familiarity BMI z-scores and percentiles. Both extended BMIz and extended BMI percentiles may be suitable replacements for the current z-scores and percentiles. These metrics are identical to those in the CDC growth charts for BMIs of <95th percentile and are superior for very high BMIs. Researchers' familiarity with the current CDC z-scores and clinicians with the CDC percentiles may ease the transition to the extended BMI scale.

Recent advances in the use of stimulated Raman scattering in histopathology.

Stimulated Raman histopathology (SRH) utilises the intrinsic vibrational properties of lipids, proteins and nucleic acids to generate contrast providing rapid image acquisition that allows visualisation of histopathological features. It is currently being trialled in the intraoperative setting, where the ability to image unprocessed samples rapidly and with high resolution offers several potential advantages over the use of conventional haematoxylin and eosin stained images. Here we review recent advances in the field including new updates in instrumentation and computer aided diagnosis. We also discuss how other non-linear modalities can be used to provide additional diagnostic contrast which together pave the way for enhanced histopathology and open up possibilities for in vivo pathology.

Anti-cancer therapy made easier: a 25-year update.

In 1993, the Internal Medicine Journal published 'Chemotherapy made easier', outlining developments in supportive care of patients undergoing chemotherapy. This described the contemporary state of anti-emetics, colony stimulating factors, cardiac toxicity, neurotoxicity, development of drug analogues and venous access devices. Twenty-five years later, we update the measures that improve the tolerability of the plethora of new anti-cancer therapies, which have extended well beyond traditional chemotherapy agents to include immunotherapy and targeted therapies. Optimisation of supportive care is paramount to allow safe delivery with the least possible impact on quality of life of these new treatments, many of which have resulted dramatically improved outcomes across multiple cancer types. This state of the art update summarises advances in supportive care therapies relating to improving the patient experience during and after anti-cancer treatment, including new anti-emetics, hair preservation techniques, bone marrow support and improved venous access devices; the ongoing challenge of neurotoxicity; and the advent of multidisciplinary sub-specialised fields such as cardio-oncology and oncofertility. Supportive care medications for immuno-oncology therapies is a new section; these highly effective (although not universally so) agents were a mere illusion in 1993.

Parent-reported socioemotional and cognitive development in children with a cleft lip and/or palate at 18 months: Findings from a UK birth cohort.

BACKGROUND: One of the most common congenital conditions in the world, cleft lip and/or palate (CL/P) has been shown to potentially impact long-term physical and developmental outcomes in affected children. However, little is known about the factors that contribute to such outcomes, and there is a lack of consensus about which screening tools may be most effective. The aims of the current study were (a) to assess parent-reported socioemotional and cognitive development in children born with CL/P at 18 months of age; (b) to identify factors associated with the incidence of developmental concerns; and (c) to assess the utility of the widely recommended Ages and Stages Questionnaires (ASQs) in identifying developmental concerns from an early age in the CL/P population. METHODS: Parent-reported questionnaire data were extracted from The Cleft Collective Cohort Study for 322 mothers of children with CL/P aged 18 months. RESULTS: Mean scores across both ASQ measures indicated typical development in the study sample overall. However, 31.1% of children met a referral criterion on at least one domain. Child-related risk factors included problems with physical development and feeding method. Parent-related risk factors included the mother's levels of anxiety and depression and mother's marital status. Additional developmental concerns extracted from mothers' qualitative data included feeding difficulties, speech development, sleep patterns, aggressive behaviours, vision, oral health, hearing, breathing and motor skills. CONCLUSIONS: The majority of children in this study were developing as expected at 18 months of age. However, parent-reported developmental concerns were identified in a minority of children, suggesting a need to screen for potential risk factors in routine practice. Further, the ASQ appears to offer a viable option in the early identification of developmental concerns in children with CL/P. A combined medical and systemic approach to healthcare is recommended to support the prevention of long-term developmental concerns in the child and poor psychological adjustment in parents.

Intelligibility in 3-Year-Olds With Cleft Lip and/or Palate Using the Intelligibility in Context Scale: Findings from the Cleft Collective Cohort Study.

OBJECTIVE: To provide comparison data on the Intelligibility in Context Scale (ICS) for a sample of 3-year-old English-speaking children born with any cleft type. DESIGN: Questionnaire data from the Cleft Collective Cohort Study were used. Descriptive and inferential statistics were carried out to determine difference according to children's cleft type and syndromic status. PARTICIPANTS: A total of 412 children born with cleft lip and/or palate whose mothers had completed the ICS when their child was 3 years old. MAIN OUTCOME MEASURE(S): Mothers' rating of their children's intelligibility using the ICS. RESULTS: The average ICS score for the total sample was 3.75 (sometimes-usually intelligible; standard deviation [SD] = 0.76, 95% CIs = 3.68-3.83) of a possible score of 5 (always intelligible). Children's speech was reported to be most intelligible to their mothers (mean = 4.33, SD = 0.61, 95% CIs = 4.27-4.39) and least intelligible to strangers (mean = 3.36, SD = 1.00, 95% CIs = 3.26-3.45). There was strong evidence (P < .001) for a difference in intelligibility between children with cleft lip only (n = 104, mean = 4.13, SD = 0.62, 95% CIs = 4.01-4.25) and children with any form of cleft palate (n = 308, mean = 3.63, SD = 0.76, 95% CIs = 3.52-3.71). Children born with cleft palate with or without cleft lip and an identified syndrome were rated as less intelligible (n = 63, mean = 3.28, SD = 0.85, 95% CIs = 3.06-3.49) compared to children who did not have a syndrome (n = 245, mean = 3.72, SD = 0.71, 95% CIs = 3.63-3.81). CONCLUSIONS: These results provide preliminary comparative data for clinical services using the outcome measures recommended by the International Consortium for Health Outcomes Measurement.

The Cleft Multidisciplinary Collaborative: Establishing a Network to Support Cleft Lip and Palate Research in the United Kingdom.

BACKGROUND: As a growing paradigm of health research, trainee collaboratives can influence clinical practice through the generation of cost-effective multicenter audit and research projects. The aims of the present article are to outline and discuss the establishment of a multidisciplinary collaborative in the context of cleft lip and/or palate (CL/P). METHODS: The Cleft Multidisciplinary Collaborative (CMC) was formed in April 2016 under the overarching supervision of the National Institute for Health Research. Membership of the CMC is open to all members of the CL/P multidisciplinary team, who are encouraged to submit ideas for new research projects that will benefit clinical practice. RESULTS: To date, 48 clinical participants are involved in the CMC. These participants represent all 17 cleft teams from the United Kingdom and encompass a wide range of disciplines. The CMC has undertaken 2 major projects so far. The first involved collection of phenotype data to support a national cohort study. The second, still in progress, is a systematic review investigating factors associated with outcomes for velopharyngeal competence following cleft palate repair. CONCLUSIONS: The concept of a multidisciplinary collaborative in CL/P has been demonstrated through the generation of a United Kingdom-wide network of committed clinicians and researchers and the effective undertaking of 2 large research projects. As the CMC gathers momentum, it hopes to attract funding to support its activities, to promote more involvement from the allied health and nursing professions, to encourage a more ingrained research culture within the CL/P community, and to promote the wider ambition of a global collaborative.

Squamous cell carcinoma of the nasal cavity: A descriptive analysis of cases from the head and neck 5000 study.

OBJECTIVES: This paper aims to provide contemporary epidemiological data on squamous cell carcinoma (SCC) of the nasal cavity, which represents a rare type of head and neck cancer. DESIGN, SETTING & PARTICIPANTS: A descriptive analysis of people with nasal cavity SCC treated with curative intent from the Head and Neck 5000 study; a multicentre clinical cohort study of people from the UK with head and neck cancer. People with tumours of the nasopharynx, paranasal sinuses and other sub-sites of the head and neck were excluded. MAIN OUTCOME MEASURES: Demographic data and treatment details are presented for all participants. The main outcomes were overall survival and survival according to categories of characteristics (eg, smoker vs non-smoker); these were explored using Kaplan-Meier plots. RESULTS: Thirty people with nasal cavity SCC were included in the study, of which most were male (67%) and current or ex-smokers (70%). The majority (70%) presented with early-stage (T1/2, N0) tumours. Cervical lymph node metastases at presentation were rare, occurring in only one person. Nine people died during the follow-up period (30%). Worse survival outcomes were seen in people with moderate or severe co-morbidities. CONCLUSIONS: This paper provides epidemiological data on nasal cavity SCC in the UK. Patterns of disease and survival outcomes are described, identifying high-risk groups. Further studies should explore whether primary treatment modality alters survival.

Cylindrical microlensing for enhanced collection efficiency of small pixel SPAD arrays in single-molecule localisation microscopy.

Single-photon avalanche photodiode (SPAD) image sensors offer time-gated photon counting, at high binary frame rates of >100 kFPS and with no readout noise. This makes them well-suited to a range of scientific applications, including microscopy, sensing and quantum optics. However, due to the complex electronics required, the fill factor tends to be significantly lower (< 10%) than that of EMCCD and sCMOS cameras (>90%), whilst the pixel size is typically larger, impacting the sensitivity and practicalities of the SPAD devices. This paper presents the first characterisation of a cylindrical-shaped microlens array applied to a small, 8 micron, pixel SPAD imager. The enhanced fill factor, ≈50% for collimated light, is the highest reported value amongst SPAD sensors with comparable resolution and pixel pitch. We demonstrate the impact of the increased sensitivity in single-molecule localisation microscopy, obtaining a resolution of below 40nm, the best reported figure for a SPAD sensor.

Setting up a cohort study in speech and language therapy: lessons from The UK Cleft Collective Speech and Language (CC-SL) study.

BACKGROUND: Efforts to increase the evidence base in speech and language therapy are often limited by methodological factors that have restricted the strength of the evidence to the lower levels of the evidence hierarchy. Where higher graded studies, such as randomized controlled trials, have been carried out, it has sometimes been difficult to obtain sufficient power to detect a potential effect of intervention owing to small sample sizes or heterogeneity in the participants. With certain clinical groups such as cleft lip and palate, systematic reviews of intervention studies have shown that there is no robust evidence to support the efficacy of any one intervention protocol over another. AIMS: To describe the setting up of an observational clinical cohort study and to present this as an alternative design for answering research questions relating to prevalence, risk factors and outcomes from intervention. METHODS: The Cleft Collective Speech and Language (CC-SL) study is a national cohort study of children born with cleft palate. Working in partnership with regional clinical cleft centres, a sample size of over 600 children and 600 parents is being recruited and followed up from birth to age 5 years. Variables being collected include demographic, psychological, surgical, hearing, and speech and language data. MAIN CONTRIBUTION: The process of setting up the study has led to the creation of a unique, large-scale data set which is available for researchers to access now and in future. As well as exploring predictive factors, the data can be used to explore the impact of interventions in relation to individual differences. Findings from these investigations can be used to provide information on sample criteria and definitions of intervention and dosage which can be used in future trials. CONCLUSIONS: The observational cohort study is a useful alternative design to explore questions around prevalence, risk factors and intervention for clinical groups where robust research data are not yet available. Findings from such a study can be used to guide service-delivery decisions and to determine power for future clinical trials.