An assessment of growth and sex from mandibles of cadaver foetuses and newborns

The quantification of skeletal data is one way in which to demonstrate variation in human growth. In South Africa, few researchers have assessed patterns of growth in immature mandibles. The purpose of this study was to evaluate growth and sexual dimorphism in the mandible from the period of 31 gestational weeks to 36 months. A total of 74 mandibles were used, skeletal tissues were sourced from the Raymond A. Dart Collection (University of Witwatersrand), and cadaveric remains were obtained from the University of Pretoria and the University of Witwatersrand. The sources of cadaver materials (both bequeathment and unclaimed remains) included local provincial hospitals. The sample was divided into four groups, namely 31 to 40 gestational weeks (group1), 0 to 11 months (group 2), 12 to 24 months (group 3), and 25 to 36 months (group 4). Twenty-one osteological landmarks were digitized using a MicroScribe G2. Ten standard measurements were created and included: the longest length of mandible, mandibular body length and width, mandibular notch width and depth, mental foramen to inferior border of mandible, mandibular basilar widths bigonial and biantegonial, bigonial width of mental foramen and mental angle. Data were analyzed using PAST statistical software and Morphologika2 v2.5. For the linear measurements, no statistically significant difference between either the foetal and up to 12 month groups or the 2 to 3 years groups. However, statistically significant increases with age were noted between 12 and 24 months for nine variables. This can be associated with growth of the mandibular arch, development and eruption of the dentition and development of the masticatory structures. No evidence of sexual dimorphism was observed until age 3, where the mental angle and mandibular notch were significantly larger in females than males. In conclusion, the mandible develops and grows so as to accommodate development of the tongue, mastication and dental eruption. Future research that considers the influence of secular trends on mandibular growth is needed. AFRIKAANS : Die kwantifisering van skeletale data is ‘n betroubare metode om variasie in menslike groei aan te toon. Slegs enkele Suid-Afrikaanse navorsers, het groeipatrone in onvolwasse mandibulae nagevors. Die doel van hierdie studie was om groei en geslagsdimorfisme in die mandibula vanaf 31 gestasie weke tot 36 maande na geboorte te evalueer. ‘n Totaal van 74 mandibulae was gebruik. Skeletale weefsel uit die Raymond A. Dart Versameling (Universiteit van die Witwatersrand), en kadaweroorskot van die Universiteite van Pretoria en van die Witwatersrand was verkry. Die oorsprong van kadawermateriale (beide skenkings en onopgeëisde oorskot) het plaaslike provinsiale hospitale ingesluit. Die steekproef was verdeel in vier groepe, naamlik 31 to 40 gestasie weke (groep1), 0 tot 11 maande (groep 2), 12 tot 24 maande (groep 3), en 25 tot 36 maande (groep 4). MicroScribe, G2 is aangewend om 21 standaard antropometriese landmerke te digitiseer. Hieruit is 10 standaard antropometriese afmetings geskep o.a.: langste lengte van mandibula, lengte en breedte van corpus mandibula, afstand tussen foramen mentalis en inferior grens, basale wydte bigoniaal en biantegoniaal, bigoniale wydte van foramen mentalis asook mentale hoek. Inligting is d.m.v. PAST statistiese sagteware en Morphologika2 v2.5 ontleed. Volgens die Kruskal-Wallis-toets was die verskille tussen groepe 1 en 2, asook 3 en 4 statisties onbeduidend. Alle afmetings by groepe 2 en 3 het beduidende toenames getoon, behalwe dié van die afstand tussen foramen mentalis en inferior grens. Die veranderings mag die gevolg wees van die groei van die mandibula en koustrukture. Geslagsdimorfisme was aantoonbaar in groep 4, by die mentale hoeke (p=0.03) asook dimensies van die incisura mandibularis (p=0.0006), waar dié van vroulike individue groter was. Voor geboorte vergroot die arcus mandibularis om die ontwikkelende tong te huisves, terwyl dit na geboorte verander om die koustrukture te huisves. Gevolglik hermodelleer en groei die been as aanpassing vir die kouproses en om strukturele integreteit te behou. Geslagsdimorfisme word ook beïnvloed deur die kouproses. Die meeste veranderinge, veral dié van die koustrukture, was duideliker in vroulike individue. Toekomstige navorsing wat die invloed van sekulêre tendense op die groei van die mandibula oorweeg, is nodig.Dissertation (MSc)--University of Pretoria, 2011.Anatomyunrestricte

An assessment of early mandibular growth

Quantification of skeletal data has been shown to be an effective and reliable method of demonstrating variation in human growth as well as for monitoring and interpreting growth. In South Africa as well as internationally, few researchers have assessed mandibular growth in late fetal period and early childhood and therefore standards for growth and age determination in these groups are limited. The purpose of this study was to evaluate growth in the mandible from the period of 31 gestational weeks to 36 months postnatal. A total of 74 mandibles were used. Dried mandibles were sourced from the Raymond A. Dart Collection (University of Witwatersrand), and cadaveric remains were obtained from the Universities of Pretoria and the Witwatersrand. The sample was divided into four groups; 31–40 gestational weeks (group 1), 0–11 months (group 2), 12–24 months (group 3), and 25–36 months (group 4). Twenty-one osteological landmarks were digitized using a MicroScribe G2. Ten standard measurements were created and included: the maximum length of mandible, mandibular body length and width, mandibular notch width and depth, mental foramen to inferior border of mandible, mandibular basilar widths bigonial and biantegonial, bigonial width of mental foramen and mental angle. Data were analyzed using PAST statistical software and Morphologika2 v2.5. Statistically significant differences were noted in the linear measurements for all group comparisons except between groups 3 and 4. The mandible morphologically changed from a round, smooth contour anteriorly to adopt a more sharp and narrow adult shape. A progressive increase in the depth and definition of the mandibular arch was also noted. In conclusion, the mandible initially grows to accommodate the developing tongue (up to 11 months), progressive dental eruption and mastication from 12 to 36 months. Mastication is associated with muscle mass development; this would necessitate an increase in the dimensions of the mandibular notch and associated muscle attachment sites. These findings might be valuable in the estimation of age in unidentified individuals and to monitor prenatal growth of the mandible for the early diagnosis of conditions associated with stunted mandibular growth.http://www.elsevier.com/locate/forsciin

Effectiveness of a national quality improvement programme to improve survival after emergency abdominal surgery (EPOCH): a stepped-wedge cluster-randomised trial

Background: Emergency abdominal surgery is associated with poor patient outcomes. We studied the effectiveness of a national quality improvement (QI) programme to implement a care pathway to improve survival for these patients. Methods: We did a stepped-wedge cluster-randomised trial of patients aged 40 years or older undergoing emergency open major abdominal surgery. Eligible UK National Health Service (NHS) hospitals (those that had an emergency general surgical service, a substantial volume of emergency abdominal surgery cases, and contributed data to the National Emergency Laparotomy Audit) were organised into 15 geographical clusters and commenced the QI programme in a random order, based on a computer-generated random sequence, over an 85-week period with one geographical cluster commencing the intervention every 5 weeks from the second to the 16th time period. Patients were masked to the study group, but it was not possible to mask hospital staff or investigators. The primary outcome measure was mortality within 90 days of surgery. Analyses were done on an intention-to-treat basis. This study is registered with the ISRCTN registry, number ISRCTN80682973. Findings: Treatment took place between March 3, 2014, and Oct 19, 2015. 22 754 patients were assessed for elegibility. Of 15 873 eligible patients from 93 NHS hospitals, primary outcome data were analysed for 8482 patients in the usual care group and 7374 in the QI group. Eight patients in the usual care group and nine patients in the QI group were not included in the analysis because of missing primary outcome data. The primary outcome of 90-day mortality occurred in 1210 (16%) patients in the QI group compared with 1393 (16%) patients in the usual care group (HR 1·11, 0·96–1·28). Interpretation: No survival benefit was observed from this QI programme to implement a care pathway for patients undergoing emergency abdominal surgery. Future QI programmes should ensure that teams have both the time and resources needed to improve patient care. Funding: National Institute for Health Research Health Services and Delivery Research Programme

Effectiveness of a national quality improvement programme to improve survival after emergency abdominal surgery (EPOCH): a stepped-wedge cluster-randomised trial

BACKGROUND: Emergency abdominal surgery is associated with poor patient outcomes. We studied the effectiveness of a national quality improvement (QI) programme to implement a care pathway to improve survival for these patients. METHODS: We did a stepped-wedge cluster-randomised trial of patients aged 40 years or older undergoing emergency open major abdominal surgery. Eligible UK National Health Service (NHS) hospitals (those that had an emergency general surgical service, a substantial volume of emergency abdominal surgery cases, and contributed data to the National Emergency Laparotomy Audit) were organised into 15 geographical clusters and commenced the QI programme in a random order, based on a computer-generated random sequence, over an 85-week period with one geographical cluster commencing the intervention every 5 weeks from the second to the 16th time period. Patients were masked to the study group, but it was not possible to mask hospital staff or investigators. The primary outcome measure was mortality within 90 days of surgery. Analyses were done on an intention-to-treat basis. This study is registered with the ISRCTN registry, number ISRCTN80682973. FINDINGS: Treatment took place between March 3, 2014, and Oct 19, 2015. 22 754 patients were assessed for elegibility. Of 15 873 eligible patients from 93 NHS hospitals, primary outcome data were analysed for 8482 patients in the usual care group and 7374 in the QI group. Eight patients in the usual care group and nine patients in the QI group were not included in the analysis because of missing primary outcome data. The primary outcome of 90-day mortality occurred in 1210 (16%) patients in the QI group compared with 1393 (16%) patients in the usual care group (HR 1·11, 0·96-1·28). INTERPRETATION: No survival benefit was observed from this QI programme to implement a care pathway for patients undergoing emergency abdominal surgery. Future QI programmes should ensure that teams have both the time and resources needed to improve patient care. FUNDING: National Institute for Health Research Health Services and Delivery Research Programme

Effect of angiotensin-converting enzyme inhibitor and angiotensin receptor blocker initiation on organ support-free days in patients hospitalized with COVID-19

IMPORTANCE Overactivation of the renin-angiotensin system (RAS) may contribute to poor clinical outcomes in patients with COVID-19. Objective To determine whether angiotensin-converting enzyme (ACE) inhibitor or angiotensin receptor blocker (ARB) initiation improves outcomes in patients hospitalized for COVID-19. DESIGN, SETTING, AND PARTICIPANTS In an ongoing, adaptive platform randomized clinical trial, 721 critically ill and 58 non–critically ill hospitalized adults were randomized to receive an RAS inhibitor or control between March 16, 2021, and February 25, 2022, at 69 sites in 7 countries (final follow-up on June 1, 2022). INTERVENTIONS Patients were randomized to receive open-label initiation of an ACE inhibitor (n = 257), ARB (n = 248), ARB in combination with DMX-200 (a chemokine receptor-2 inhibitor; n = 10), or no RAS inhibitor (control; n = 264) for up to 10 days. MAIN OUTCOMES AND MEASURES The primary outcome was organ support–free days, a composite of hospital survival and days alive without cardiovascular or respiratory organ support through 21 days. The primary analysis was a bayesian cumulative logistic model. Odds ratios (ORs) greater than 1 represent improved outcomes. RESULTS On February 25, 2022, enrollment was discontinued due to safety concerns. Among 679 critically ill patients with available primary outcome data, the median age was 56 years and 239 participants (35.2%) were women. Median (IQR) organ support–free days among critically ill patients was 10 (–1 to 16) in the ACE inhibitor group (n = 231), 8 (–1 to 17) in the ARB group (n = 217), and 12 (0 to 17) in the control group (n = 231) (median adjusted odds ratios of 0.77 [95% bayesian credible interval, 0.58-1.06] for improvement for ACE inhibitor and 0.76 [95% credible interval, 0.56-1.05] for ARB compared with control). The posterior probabilities that ACE inhibitors and ARBs worsened organ support–free days compared with control were 94.9% and 95.4%, respectively. Hospital survival occurred in 166 of 231 critically ill participants (71.9%) in the ACE inhibitor group, 152 of 217 (70.0%) in the ARB group, and 182 of 231 (78.8%) in the control group (posterior probabilities that ACE inhibitor and ARB worsened hospital survival compared with control were 95.3% and 98.1%, respectively). CONCLUSIONS AND RELEVANCE In this trial, among critically ill adults with COVID-19, initiation of an ACE inhibitor or ARB did not improve, and likely worsened, clinical outcomes. TRIAL REGISTRATION ClinicalTrials.gov Identifier: NCT0273570

Morphology and function: aspects of mandibular development and growth at different stages across the lifespan

Original published work submitted to the Faculty of Health Sciences, University of the Witwatersrand, Johannesburg, in fulfilment of the requirements for the degree of Doctor of Philosophy Johannesburg, South Africa, 2017.During development and growth, the mandible adapts to accommodate increased biomechanical loading associated with the development and growth of the tongue and the dentition. Biomechanical loads play a vital role in the modelling and remodelling of bone, with site-specific effects on bone density. In the functional transition from the prenatal to the postnatal period, biomechanical loading appears to be intensified and may affect the morphology of the mandible. The aim of this study was to analyze the growth and development of the human mandible during the functionally complex perinatal period of growth in order to investigate biomechanical effects. As edentulism modifies the biomechanical landscape of mastication, the effects of tooth loss on the morphology of the adult mandible were also investigated. Seven hundred and seventeen mandibles were sourced from cadaveric and skeletonized remains forming part of the Paediatric Collection, Raymond A. Dart Collection of Human Skeletons and Johannesburg Forensic Paediatric Collection, University of the Witwatersrand. The morphometric growth relationships between the mandible and tongue were initially investigated. A strong correlation between changes in the dimensions of the mandible and tongue was observed between 20 gestational weeks and 2 years. It was hypothesized, that mandibular growth was directed by the growth of the tongue. This would result in areas of increased bone modelling and remodelling, directly associated with the attachment of the tongue to the mandible and would manifest in areas of lower density bone. Subsequently, variations in bone mineral density of the body of the mandible were assessed. The lingual surface had significantly higher bone density values when compared to the external surface across the period of 30 gestational weeks to 5 years. Variations in the bone density across the external surface of the mandible followed the patterns of postnatal dental development. Thus, the effects of edentulism on the morphology of the adult mandible were also considered. The edentulous mandible had a shorter alveolar height and mandibular body length as well as more obtuse gonial and mental angles, when compared to the dentate mandible. Thus, changes in the morphology of the mandible over time appear to be indicative of an altered mandibular morphology prompted by a changing biomechanical landscape.MT201

Postoperative continuous positive airway pressure to prevent pneumonia, re-intubation, and death after major abdominal surgery (PRISM): a multicentre, open-label, randomised, phase 3 trial

Background: Respiratory complications are an important cause of postoperative morbidity. We aimed to investigate whether continuous positive airway pressure (CPAP) administered immediately after major abdominal surgery could prevent postoperative morbidity. Methods: PRISM was an open-label, randomised, phase 3 trial done at 70 hospitals across six countries. Patients aged 50 years or older who were undergoing elective major open abdominal surgery were randomly assigned (1:1) to receive CPAP within 4 h of the end of surgery or usual postoperative care. Patients were randomly assigned using a computer-generated minimisation algorithm with inbuilt concealment. The primary outcome was a composite of pneumonia, endotracheal re-intubation, or death within 30 days after randomisation, assessed in the intention-to-treat population. Safety was assessed in all patients who received CPAP. The trial is registered with the ISRCTN registry, ISRCTN56012545. Findings: Between Feb 8, 2016, and Nov 11, 2019, 4806 patients were randomly assigned (2405 to the CPAP group and 2401 to the usual care group), of whom 4793 were included in the primary analysis (2396 in the CPAP group and 2397 in the usual care group). 195 (8\ub71%) of 2396 patients in the CPAP group and 197 (8\ub72%) of 2397 patients in the usual care group met the composite primary outcome (adjusted odds ratio 1\ub701 [95% CI 0\ub781-1\ub724]; p=0\ub795). 200 (8\ub79%) of 2241 patients in the CPAP group had adverse events. The most common adverse events were claustrophobia (78 [3\ub75%] of 2241 patients), oronasal dryness (43 [1\ub79%]), excessive air leak (36 [1\ub76%]), vomiting (26 [1\ub72%]), and pain (24 [1\ub71%]). There were two serious adverse events: one patient had significant hearing loss and one patient had obstruction of their venous catheter caused by a CPAP hood, which resulted in transient haemodynamic instability. Interpretation: In this large clinical effectiveness trial, CPAP did not reduce the incidence of pneumonia, endotracheal re-intubation, or death after major abdominal surgery. Although CPAP has an important role in the treatment of respiratory failure after surgery, routine use of prophylactic post-operative CPAP is not recommended

Effect of Antiplatelet Therapy on Survival and Organ Support–Free Days in Critically Ill Patients With COVID-19

International audienc

Empagliflozin in Patients with Chronic Kidney Disease

Background The effects of empagliflozin in patients with chronic kidney disease who are at risk for disease progression are not well understood. The EMPA-KIDNEY trial was designed to assess the effects of treatment with empagliflozin in a broad range of such patients. Methods We enrolled patients with chronic kidney disease who had an estimated glomerular filtration rate (eGFR) of at least 20 but less than 45 ml per minute per 1.73 m(2) of body-surface area, or who had an eGFR of at least 45 but less than 90 ml per minute per 1.73 m(2) with a urinary albumin-to-creatinine ratio (with albumin measured in milligrams and creatinine measured in grams) of at least 200. Patients were randomly assigned to receive empagliflozin (10 mg once daily) or matching placebo. The primary outcome was a composite of progression of kidney disease (defined as end-stage kidney disease, a sustained decrease in eGFR to < 10 ml per minute per 1.73 m(2), a sustained decrease in eGFR of & GE;40% from baseline, or death from renal causes) or death from cardiovascular causes. Results A total of 6609 patients underwent randomization. During a median of 2.0 years of follow-up, progression of kidney disease or death from cardiovascular causes occurred in 432 of 3304 patients (13.1%) in the empagliflozin group and in 558 of 3305 patients (16.9%) in the placebo group (hazard ratio, 0.72; 95% confidence interval [CI], 0.64 to 0.82; P < 0.001). Results were consistent among patients with or without diabetes and across subgroups defined according to eGFR ranges. The rate of hospitalization from any cause was lower in the empagliflozin group than in the placebo group (hazard ratio, 0.86; 95% CI, 0.78 to 0.95; P=0.003), but there were no significant between-group differences with respect to the composite outcome of hospitalization for heart failure or death from cardiovascular causes (which occurred in 4.0% in the empagliflozin group and 4.6% in the placebo group) or death from any cause (in 4.5% and 5.1%, respectively). The rates of serious adverse events were similar in the two groups. Conclusions Among a wide range of patients with chronic kidney disease who were at risk for disease progression, empagliflozin therapy led to a lower risk of progression of kidney disease or death from cardiovascular causes than placebo