Contemporary modern total ankle arthroplasty (TAA): A systematic review and meta-analysis of indications, survivorship and complication rates.

BACKGROUND: This study evaluates the clinical outcomes of contemporary total ankle arthroplasty (TAAs) to primarily establish the current benefits and risks to facilitate informed decision making to secondarily establish if improvements are seen between subsequent generations of implants, bearing philosophy, and associated surgical technique. METHODS: A systematic review and meta-analysis of published data from January 2000 to January 2020 was conducted following PRISMA guidelines. INCLUSION CRITERIA: English language papers, adult population, ≥20 ankles with a minimum follow up ≥24 months, pre- and post-operative functional scores available. Ankle implants were characterised by generations, which were determined from the original studies and confirmed based on literature set definitions. RESULTS: A total of 4642 TAAs in 4487 patients from 51 studies were included. The mean age was 61.9-years and follow up 57.8-months. Overall, 10-year survivorship rates were 77.63 %, with mobile bearing designs showing a small but significant advantage. Improved survivorship favoured the most modern implants at both two (p < 0.05), and 10-years (p < 0.01). The relative risk of a complication occurring improved with the evolution of implants e.g., nerve injury, and post-operative complications such as fracture, wound complications (e.g., dehiscence or heamatoma) and radiological abnormalities (e.g., radiolucencies, heterotopic bone formation and aseptic loosening). However, surgical site infection, and intra-operative fracture rates remain implant independent. CONCLUSIONS: Modern TAA offers improved survivorship, even with a trend to lower mean implantation age, similar complexity and ever changing indications. It would appear that implant evolution has reduced risks, especially those associated with revision, without affecting functional outcomes.

Monitoring persistent pulmonary hypertension of the newborn using the arterial to end tidal carbon dioxide gradient.

Persistent pulmonary hypertension of the newborn (PPHN) can be monitored theoretically by the difference of the partial pressure of arterial (PaCO2) to end-tidal CO2 (EtCO2). We aimed to test the hypothesis that the PaCO2-EtCO2 gradient in infants with PPHN would be higher compared to infants without PPHN. Prospective, observational study of term-born ventilated infants with echocardiographically-confirmed PPHN with right-to-left shunting and term-born control infants without respiratory disease. The PaCO2-EtCO2 gradient was calculated as the difference between the PaCO2 measured from indwelling arterial sample lines and EtCO2 measured by continuous Microstream sidestream capnography. Twenty infants (9 with PPHN and 11 controls) were studied with a median (IQR) gestational age of 39.5 (38.7-40.4) weeks, a birthweight of 3.56 (3.15-3.93) kg and a birthweight z-score of 0.03 (- 0.91 to 1.08). The PaCO2-EtCO2 gradient was larger in the infants with PPHN compared to those without PPHN after adjusting for differences in the mean airway pressure and fraction of inspired oxygen (adjusted p = 0.037). In the infants with PPHN the median PaCO2-EtCO2 gradient decreased from 10.7 mmHg during the acute illness to 3.3 mmHg pre-extubation. The median difference in the gradient was significantly higher in infants with PPHN (6.2 mmHg) compared to infants without PPHN (-3.2 mmHg, p = 0.022). The PaCO2-EtCO2 gradient was higher in infants with PPHN compared to term born infants without PPHN and decreased over the first week of life in infants with PPHN. The gradient might be utilised to monitor the evolution and resolution of PPHN.

Ventilatory response to added dead space in infants exposed to second-hand smoke in pregnancy.

Maternal cigarette smoking in pregnancy can adversely affect infant respiratory control. In utero nicotine exposure has been shown to blunt the infant ventilatory response to hypercapnia, which could increase the risk of sudden infant death syndrome. The potential impact of maternal second-hand smoke exposure, however, has not yet been determined. The aim of this study was to assess ventilatory response to added dead-space (inducing hypercapnia) in infants with second-hand smoke exposure during pregnancy, in infants whose mothers smoked and in controls (non-smoke exposed). Infants breathed through a face mask and specialised "tube-breathing" circuit, incorporating a dead space of 4.4 ml/kg body weight. The maximum minute ventilation (MMV) during added dead space breathing was determined and the time taken to achieve 63% of the MMV calculated (the time constant (TC) of the response). Infants were studied on the postnatal ward prior to discharge home. Thirty infants (ten in each group) were studied with a median gestational age of 39 [range 37-41] weeks, birthweight of 3.1 [2.2-4.0] kg, and postnatal age of 33 (21-62) h. The infants whose mothers had second-hand smoke exposure (median TC 42 s, p = 0.001), and the infants of cigarette smoking mothers (median TC 37 s, p = 0.002) had longer time constants than the controls (median TC 29 s). There was no significant difference between the TC of the infants whose mothers had second-hand smoke exposure and those whose mothers smoked (p = 0.112).    Conclusion: Second-hand smoke exposure during pregnancy was associated with a delayed newborn ventilatory response. What is Known: • Maternal cigarette smoking in pregnancy can adversely affect infant respiratory control. • The potential impact of maternal second-hand smoke exposure, however, has not yet been determined. What is New: • We have assessed the ventilatory response to added dead-space (inducing hypercapnia) in newborns with second-hand smoke exposure during pregnancy, in infants whose mothers smoked, and in controls (non-smoke exposed). • Maternal second-hand smoke exposure, as well as maternal smoking, during pregnancy was associated with a delayed newborn ventilatory response.

The impact of COVID-19 on smoking cessation in pregnancy.

OBJECTIVES: A greater proportion of non-pregnant smokers attempted to stop smoking during compared to before the COVID-19 pandemic. The objective of this study was to determine if a greater proportion of pregnant women also attempted to stop smoking during the pandemic rather than before. METHODS: The use of antenatal smoking cessation services and nicotine replacement therapies (NRT) in pregnant women was audited before (2019-2020) and during the COVID pandemic (2020-2021). Anonymised data from January 2019 to March 2021 were analysed from the Lambeth and Southwark smoking cessation service. RESULTS: A total of 252 pregnant women who smoked were referred to their local antenatal smoking cessation service, of which 90 (35.7%) (median age: 31 years [19-52 years]) chose to attend smoking cessation clinics. The COVID-19 pandemic was not associated with an increase in the number of women attending smoking cessation clinics, (2020-2021 n=46 [40.8%] of 110); compared to (2019-2020 n=44 [30.9%] of 142 referred pregnant women pre-pandemic) p=0.061. Eighty-two women utilised NRT to help them stop smoking and the frequency of NRT use did not change during the pandemic (2019-2020 n=39, 2020-2021 n=43; p=0.420). No significant difference in smoking cessation rates between the two periods was observed at either the four-week (p=0.285) or twelve-week follow-up (p=0.829). CONCLUSIONS: Smoking cessation rates in pregnant women and the demand for antenatal smoking cessation services was unchanged during compared to before the COVID-19 pandemic.

A randomised crossover trial of closed loop automated oxygen control in preterm, ventilated infants.

AIM: To determine whether closed loop automated oxygen control resulted in a reduction in the duration and severity of desaturation episodes and the number of blood gases and chest radiographs in preterm, ventilated infants. METHODS: Infants were studied on two consecutive days for 12 hours on each day. They were randomised to receive standard care (standard period) or standard care with a closed loop automated oxygen control system (automated oxygen control period) first. RESULTS: Twenty-four infants with a median gestational age of 25.7 (range 23.1-32.6) weeks were studied at a median postconceptional age of 27.4 (range 24.3-34.9) weeks. During the automated oxygen control period, there were fewer desaturations that lasted >30 seconds (P = .032) or >60 seconds (P = .002), infants spent a higher proportion of the time within their target SpO2 range during the automated oxygen control period (P < .001), and fewer manual adjustments were made to the inspired oxygen concentration (mean 0.58 vs mean 11.29) (P < .001). There were no significant differences in the number of blood gases (P = .872) or chest radiographs (P = .366) between the two periods. CONCLUSION: Closed loop automated oxygen delivery resulted in fewer prolonged desaturations with more time spent in the targeted oxygen range.

Pathophysiological dissociation of the interaction between time pressure and trait anxiety during spatial orientation judgments.

Spatial orientation is achieved by integrating visual, vestibular and proprioceptive cues. Individuals that rely strongly upon visual cues to facilitate spatial orientation are termed visually dependent. Heightened visual reliance commonly occurs in patients following vestibular dysfunction and can influence clinical outcome. Additionally, psychological factors, including anxiety, are associated with poorer clinical outcome following vestibular dysfunction. Given that visual dependency measures are affected by psychological and contextual influences, such as time pressure, we investigated the interaction between time pressure and anxiety upon visual dependency in healthy controls and vestibular migraine patients. Visual dependency was assessed using a "Rod and Disk" task at baseline and under time pressure (3 s to complete the task). Non-situational (trait) and situational (state) anxiety levels were quantified using the Spielberg State-Trait Anxiety Inventory. We calculated the change in visual dependency (VD) [∆VD = VDtime pressure  - VDbaseline ] and correlated it with participants' trait anxiety scores. We observed a significant negative correlation between trait anxiety and the change in VD (R2  = .393, p < .001) in healthy controls and a positive correlation in dizzy patients (R2  = .317, p < .001). That is, healthy individuals that were more anxious became less visually dependent under time pressure (i.e., more accurate), whereas less anxious individuals became more visually dependent. The reverse was observed in vestibular migraine patients. Our results illustrate that anxiety can differentially modulate task performance during spatial orientation judgements under time pressure in healthy individuals and dizzy patients. These findings have potential implications for individualised patient rehabilitation therapies.

Abnormal visuo-vestibular interactions in vestibular migraine: a cross sectional study.

Vestibular migraine is among the commonest causes of episodic vertigo. Chronically, patients with vestibular migraine develop abnormal responsiveness to both vestibular and visual stimuli characterized by heightened self-motion sensitivity and visually-induced dizziness. Yet, the neural mechanisms mediating such symptoms remain unknown. We postulate that such symptoms are attributable to impaired visuo-vestibular cortical interactions, which in turn disrupts normal vestibular function. To assess this, we investigated whether prolonged, full-field visual motion exposure, which has been previously shown to modulate visual cortical excitability in both healthy individuals and avestibular patients, could disrupt vestibular ocular reflex and vestibular-perceptual thresholds of self-motion during rotations. Our findings reveal that vestibular migraine patients exhibited abnormally elevated reflexive and perceptual vestibular thresholds at baseline. Following visual motion exposure, both reflex and perceptual thresholds were significantly further increased in vestibular migraine patients relative to healthy controls, migraineurs without vestibular symptoms and patients with episodic vertigo due to a peripheral inner-ear disorder. Our results provide support for the notion of altered visuo-vestibular cortical interactions in vestibular migraine, as evidenced by vestibular threshold elevation following visual motion exposure.

Vestibulo-cortical hemispheric dominance: The link between anxiety and the vestibular system?

Vestibular processing and anxiety networks are functionally intertwined, as demonstrated by reports of reciprocal influences upon each other. Yet whether there is an underlying link between these two systems remains unknown. Previous findings have highlighted the involvement of hemispheric lateralisation in processing of both anxiety and vestibular signals. Accordingly, we explored the interaction between vestibular cortical processing and anxiety by assessing the relationship between anxiety levels and the degree of hemispheric lateralisation of vestibulo-cortical processing in 64 right-handed, healthy individuals. Vestibulo-cortical hemispheric lateralisation was determined by gaging the degree of caloric-induced nystagmus suppression following modulation of cortical excitability using trans-cranial direct current stimulation targeted over the posterior parietal cortex, an area implicated in the processing of vestibular signals. The degree of nystagmus suppression yields an objective biomarker, allowing the quantification of the degree of right vestibulo-cortical hemisphere dominance. Anxiety levels were quantified using the Trait component of the Spielberger State-Trait Anxiety Questionnaire. Our findings demonstrate that the degree of an individual's vestibulo-cortical hemispheric dominance correlates with their anxiety levels. That is, those individuals with greater right hemispheric vestibulo-cortical dominance exhibited lower levels of anxiety. By extension, our results support the notion that hemispheric lateralisation determines an individual's emotional processing, thereby linking cortical circuits involved in processing anxiety and vestibular signals, respectively.

Factors affecting the arterial to end-tidal carbon dioxide gradient in ventilated neonates.

Objective. To determine factors which influenced the relationship between blood carbon dioxide (pCO2) and end-tidal carbon dioxide (EtCO2) values in ventilated, newborn infants. Furthermore, to assess whether pCO2levels could be predicted from continuous EtCO2monitoring.Approach. An observational study of routinely monitored newborn infants requiring mechanical ventilation in the first 28 d after birth was undertaken. Infants received standard clinical care. Daily pCO2and EtCO2levels were recorded and the difference (gradient: ∆P-EtCO2) between the pairs were calculated. Ventilatory settings corresponding to the time of each blood gas assessment were noted. End-tidal capnography monitoring was performed using the Microstream sidestream Filterline H set capnograph.Main results. A total of 4697 blood gas results from one hundred and fifty infants were analysed. The infants had a median gestational age of 33.3 (range 22.3-42.0) weeks and birth weight of 1880 (395-5520) grams. Overall, there was moderate correlation between pCO2and EtCO2levels (r= 0.65,p< 0.001). The ∆P-EtCO2for infants born less than 32 weeks of gestation was significantly higher (1.4 kPa) compared to infants born at greater than 32 weeks of gestation (0.8 kPa) (p< 0.001). In infants born at less than 32 completed weeks of gestation, pCO2levels were independently associated with EtCO2, day after birth, birthweight and fraction of inspired oxygen (FiO2) (modelr2 = 0.52,p< 0.001).Significance. The results of end-tidal capnography monitoring have the potential to predict blood carbon dioxide values within the neonatal population.

Nicotine replacement therapy and e-cigarettes in pregnancy and infant respiratory outcomes.

BACKGROUND: Nicotine replacement therapy (NRT) and e-cigarettes are recommended to pregnant women who wish to stop smoking. Albeit eliminating other harmful components of cigarettes, those alternatives still expose the developing fetus to nicotine. The lungs may be particularly vulnerable to damage by nicotine as there is widespread nicotinic-acetylcholine receptor expression in the lungs. There is, however, a paucity of information about the effect of NRT and e-cigarette use in pregnancy on infant respiratory outcomes. AIMS: To explore the effect of NRT and e-cigarettes on the developing lung. STUDY DESIGN: A literature search was undertaken to examine the use and safety of nicotine-replacement strategies in pregnancy, with a focus on infant respiratory outcomes. This included experimental studies investigating the effect of isolated "gestational" nicotine on the developing lung. OUTCOME MEASURES: Respiratory outcomes in animal studies and infants. RESULTS: Animal studies investigating the effect of gestational nicotine exposure on fetal lung development demonstrated abnormal lung growth; including abnormal airway branching and alveolar development. Consequently, offspring display altered pulmonary mechanics, including both increased respiratory rate and airway resistance. These findings mirror respiratory pathology observed in infants born to smoking mothers. Human trials of NRT and e-cigarette use in pregnancy have not identified adverse perinatal outcomes regarding reduced birthweight or prematurity, but have not considered infant and childhood respiratory outcomes. CONCLUSIONS: Nicotine can impair fetal lung development, leading to concerns regarding the safety of NRT and e-cigarettes in pregnancy. Studies have yet to explore the impact of these nicotine-containing products on infant respiratory outcomes.

Carboxyhaemoglobin levels and free-radical-related diseases in prematurely born infants.

BACKGROUND: Carboxyhaemoglobin (COHb) levels may reflect the level of early oxidative stress which plays a role in mediating free-radical-related diseases in prematurely born infants. AIM: To assess the relationship of COHb levels in the first seven days of after birth to the development of bronchopulmonary dysplasia (BPD) and other free-radical-related diseases. STUDY DESIGN: Retrospective analysis of routinely performed COHb via blood gas samples of infants born at less than 30 weeks of gestation admitted to a tertiary neonatal intensive care unit was undertaken. SUBJECTS: One hundred and four infants were included with a median (range) gestational age of 27.4 (22.4-29.9) weeks and a birthweight of 865 (395-1710) grams. OUTCOMES: The maximum COHb per infant per day was recorded for the first 28 days and BPD and other free-radical-related diseases including intraventricular haemorrhage (IVH) were noted. The severity of BPD, requirement for home oxygen on discharge and survival to discharge were also recorded. RESULTS: Infants who developed BPD (n = 76) had significantly higher COHb levels in the first seven days [1.7% (0.3-6.8)] compared to those that did not develop BPD [1.6% (0.9-3.8); p = 0.001]. Higher COHb levels in the first seven days after birth were also observed in infants with grade three/four IVH [n = 20; 1.9% (1.0-6.8)] compared to those without [1.6% (0.3-5.6); p < 0.001]. COHb levels, however, were not associated with the duration of ventilation, BPD severity or survival to discharge. CONCLUSION: Higher COHb levels in prematurely born infants were associated with the development of BPD and IVH.

Universal newborn hearing screening in South Africa: a single-centre study.

Hearing screening for newborn babies is an established protocol in many high-income countries. Implementing such screening has yielded significant socioeconomic advantages at both an individual and societal level. This has yet to permeate low/middle-income countries (LMIC). Here, we illustrate how newborn hearing screening needs to be contextually adapted for effective utilisation and implementation in an LMIC. Specifically, this advocates the use of auditory brainstem testing as the first-line approach. We propose that such adaptation serves to maximise clinical efficacy and community participation at a reduced cost.

The Role of Maternal Smoking in Sudden Fetal and Infant Death Pathogenesis.

Maternal smoking is a risk factor for both sudden infant death syndrome (SIDS) and sudden intrauterine unexplained death syndrome (SIUDS). Both SIDS and SIUDS are more frequently observed in infants of smoking mothers. The global prevalence of smoking during pregnancy is 1.7% and up to 8.1% of women in Europe smoke during pregnancy and worldwide 250 million women smoke during pregnancy. Infants born to mothers who smoke have an abnormal response to hypoxia and hypercarbia and they also have reduced arousal responses. The harmful effects of tobacco smoke are mainly mediated by release of carbon monoxide and nicotine. Nicotine can enter the fetal circulation and affect multiple developing organs including the lungs, adrenal glands and the brain. Abnormalities in brainstem nuclei crucial to respiratory control, the cerebral cortex and the autonomic nervous system have been demonstrated. In addition, hypodevelopment of the intermediolateral nucleus in the spinal cord has been reported. It initiates episodic respiratory movements that facilitate lung development. Furthermore, abnormal maturation and transmitter levels in the carotid bodies have been described which would make infants more vulnerable to hypoxic challenges. Unfortunately, smoking cessation programs do not appear to have significantly reduced the number of pregnant women who smoke.

Prospective assessment of a critical appraisal teaching programme on medical students' confidence and performance in appraising medical literature.

BACKGROUND: Previous research has demonstrated that medical students have insufficient knowledge of critical appraisal, a fundamental aspect of evidence-based medicine. We aimed to enhance medical students' critical appraisal skills using an innovative mixed-methods programme. METHODS: We designed a 2-day, mixed-methods, national teaching programme, including an interactive lecture and workshop, quiz and viva-style examination. Course efficacy was assessed using pre- and post-course confidence questionnaires and a quiz adapted from the validated Berlin Questionnaire. Data were analysed primarily using Wilcoxon Signed Ranks test. RESULTS: Fifty-nine participants from 17 medical schools completed the programme. Pre- and post-course scores demonstrated significant improvement in confidence (median score 5 vs 8; p < 0.001) and quiz performance (median score 9 vs 13; p < 0.001). CONCLUSION: Our study demonstrates the efficacy of a novel mixed-methods programme in teaching medical students about critical appraisal. Implementation of our approach within the undergraduate curriculum should enhance the uptake of these fundamental skills.

Interhemispheric control of sensory cue integration and self-motion perception.

Spatial orientation necessitates the integration of visual and vestibular sensory cues, in-turn facilitating self-motion perception. However, the neural mechanisms underpinning sensory integration remain unknown. Recently we have illustrated that spatial orientation and vestibular thresholds are influenced by interhemispheric asymmetries associated with the posterior parietal cortices (PPC) that predominantly house the vestibulo-cortical network. Given that sensory integration is a prerequisite to both spatial orientation and motion perception, we hypothesized that sensory integration is similarly subject to interhemispheric influences. Accordingly, we explored the relationship between vestibulo-cortical dominance - assessed using a biomarker, the degree of vestibular-nystagmus suppression following transcranial direct current stimulation over the PPC - with visual dependence measures obtained during performance of a sensory integration task (the rod-and-disk task). We observed that the degree of visual dependence was correlated with vestibulo-cortical dominance. Specifically, individuals with greater right hemispheric vestibulo-cortical dominance had reduced visual dependence. We proceeded to assess the significance of such dominance on behavior by correlating measures of visual dependence with self-motion perception in healthy subjects. We observed that right-handed individuals experienced illusionary self-motion (vection) quicker than left-handers and that the degree of vestibular cortical dominance was correlated with the time taken to experience vection, only during conditions that induced interhemispheric conflict. To conclude, we demonstrate that interhemispheric asymmetries associated with vestibulo-cortical processing in the PPC functionally and mechanistically link sensory integration and self-motion perception, facilitating spatial orientation. Our findings highlight the importance of dynamic interhemispheric competition upon control of vestibular behavior in humans.