A comparison of peak cough flow and peak expiratory flow in children with neuromuscular disorders.

Spirometry and peak cough flow testing (PCF) are commonly used in the respiratory assessment of children with a neuromuscular disorder (NMD). Testing uses two different machines, increases laboratory time, costs and resource utilisation. No studies have assessed the correlation between peak expiratory flow (PEF) obtained from spirometry and PCF in children with NMD using one device. An audit of children with a NMD managed at the Children's Hospital at Westmead in 2022-2024 aged < 20 years who performed spirometry and PCF testing on the same device (Vyaire Body BoxTM, Ultrasonic flow meter-based, or Vyaire PneumotachographTM, Pneumotach flow meter-based; Germany) was conducted to assess the correlation between PCF and PEF. Fifty-one sets of testing were identified, and 40 subjects (9F) had reproducible testing and were included. Median (range) age was 14.95 (7.20-19.00) years. Median PEF (L/min) was 4.05 (1.22-10.26) and median PCF (L/min) was 4.29 (1.69-10.82). PEF and PCF had a strong Pearson's correlation coefficient, (R = 0.97, p = 0.03). The coefficient of determination was 0.93. If laboratory resources permit, spirometry should be the test of choice for children with NMD. On average, spirometry required multiple practices to achieve reproducibility to meet ATS/ERS standards. PCF testing can be utilised for children where performing technically acceptable spirometry is not possible.

Can postural changes in spirometry in children with Duchenne muscular dystrophy predict sleep hypoventilation?

AIM: To explore the relationship between postural changes in lung function and polysomnography (PSG) in children with Duchenne muscular dystrophy (DMD). METHODS: In this prospective cross-sectional study, children with DMD performed spirometry in sitting and supine positions. A control group of age and gender matched healthy children also underwent postural lung function testing. PSG was performed within six months of spirometry. RESULTS: Seventeen children with DMD, aged 12.3 ± 3 years performed sitting spirometry. 14 (84%) performed acceptable spirometry in the supine position. Mean FEV1sit and FVCsit were 77% (SD ± 22) and 74% (SD ± 20.4) respectively, with mean% ΔFVC(sit-sup) 9% (SD ± 11) (range 2% to 20%), and was significantly greater than healthy controls 4% (n = 30, SD ± 3, P < 0.001). PSG data on the 14 DMD children with acceptable supine spirometry showed total AHI 6.9 ± 5.9/hour (0.3 to 29), obstructive AHI 5.2 ± 4.0/hour (0.2 to 10), and REM AHI 14.1 ± -5.3/hour (0.1 to 34.7). ΔFVC(sit-sup) had poor correlation with hypoventilation on polysomnography. CONCLUSION: Children with DMD and mild restrictive lung disease showed greater postural changes in spirometry than healthy controls but lower supine spirometry was not predictive of sleep hypoventilation.

Exercise testing for young athletes.

With increasing competitiveness across the sporting landscape, there is a need for more research into monitoring and managing the young athlete, as the needs of a young athlete are vastly different to those of an older athlete who is already established in their respective sport. As the age of sports specialisation seems to decrease, exercise testing in the younger cohort of athletes is crucial for safety and long-term success. This article provides a comprehensive summary of available testing and monitoring methods that can be used to assist young athletes as they mature and attempt to excel in their chosen sport.

Applying lessons learnt from research of child pneumonia management in Vietnam.

Pneumonia is the leading cause of paediatric hospitalisation in Vietnam, placing a huge burden on the health care system. Pneumonia is also the main reason for antibiotic use in children. Unfortunately many hospital admissions for child pneumonia in Vietnam are unnecessary and inappropriate use of antibiotics is common, as in the rest of Asia, with little awareness of its adverse effects. We explored the value of an alternative approach that, instead of focusing on the identification of children with severe bacterial pneumonia, focuses on the identification of children with 'unlikely bacterial pneumonia' to improve patient care and rational antibiotic use. Implementing improved models of care require pragmatic management algorithms that are well validated, but it is ultimately dependent on financial structures, management support and evidence-based training of healthcare providers at all relevant levels. Apart from better case management, sustained reductions in the pneumonia disease burden also require increased emphasis on primary prevention.

Early Bactericidal Activity Trial of Nitazoxanide for Pulmonary Tuberculosis.

This study was conducted in treatment-naive adults with drug-susceptible pulmonary tuberculosis in Port-au-Prince, Haiti, to assess the safety, bactericidal activity, and pharmacokinetics of nitazoxanide (NTZ). This was a prospective phase II clinical trial in 30 adults with pulmonary tuberculosis. Twenty participants received 1 g of NTZ orally twice daily for 14 days. A control group of 10 participants received standard therapy over 14 days. The primary outcome was the change in time to culture positivity (TTP) in an automated liquid culture system. The most common adverse events seen in the NTZ group were gastrointestinal complaints and headache. The mean change in TTP in sputum over 14 days in the NTZ group was 3.2 h ± 22.6 h and was not statistically significant (P = 0.56). The mean change in TTP in the standard therapy group was significantly increased, at 134 h ± 45.2 h (P < 0.0001). The mean NTZ MIC for Mycobacterium tuberculosis isolates was 12.3 µg/ml; the mean NTZ maximum concentration (Cmax) in plasma was 10.2 µg/ml. Negligible NTZ levels were measured in sputum. At the doses used, NTZ did not show bactericidal activity against M. tuberculosis Plasma concentrations of NTZ were below the MIC, and its negligible accumulation in pulmonary sites may explain the lack of bactericidal activity. (This study has been registered at ClinicalTrials.gov under identifier NCT02684240.).

Pro con debates in clinical medicine infection prevention and control in cystic fibrosis: One size fits all? The argument in favour.

This article advocates for a universal approach to infection control measures in cystic fibrosis. The central tenets of infection control include hand hygiene, contact precautions, regular microbiological surveillance and adopting inpatient, outpatient, domestic and social practices to minimise acquisition of common CF pathogens. Infection control measures should be proactive and prospective, assuming all patients harbour aggressive pathogens, and not relying on past culture results. The challenges of implementing these policies include cost, equipment, education, consistency, meticulousness all whilst balancing additional procedures to a busy clinical workload.

European and United Kingdom COVID-19 pandemic experience: The same but different.

The global healthcare landscape has changed dramatically and rapidly in 2020. This has had an impact upon paediatricians and in particular respiratory paediatricians. The effects in Europe, with its mature healthcare system, have been far faster and greater than most authorities anticipated. Within six weeks of COVID-19 being declared a public health emergency by the World Health Organisation [WHO] in China, Europe had become the new epicentre of disease. A pandemic was finally declared by the WHO on March 11th 2020. Continued international travel combined with the slow response of some political leaders and a variable focus on economic rather than health consequences resulted in varying containment strategies in response to the threat of the initial wave of the pandemic. It is likely that this variation has contributed to widely differing outcomes across Europe. Common to all countries was the stark lack of preparations and initial poor co-ordination of responses between levels of government to this unforeseen but not unheralded global health crisis. In this article we highlight the impact of the first wave of the COVID-19 pandemic in Italy, Austria, Germany, and the United Kingdom.

The efficacy and safety of velagliflozin over 16 weeks as a treatment for insulin dysregulation in ponies.

BACKGROUND: A previous six-week (wk) study demonstrated the potential of the sodium-glucose linked transport inhibitor velagliflozin as a novel treatment for equine insulin dysregulation. The present study examined the safety and efficacy of velagliflozin over 16 wk. of treatment, and over 4 wk. of withdrawal. Twenty-four insulin dysregulated ponies were selected, based on their hyper-responsiveness to a diet challenge meal containing 3.8 g non-structural carbohydrates (NSC)/kg bodyweight (BW). Ponies with serum insulin > 90 µIU/mL either 2 or 4 h after feeding were enrolled, and randomly allocated to receive either velagliflozin (0.3 mg/kg BW orally once daily, n = 12), or a placebo (n = 10-12) for 16 wk. The subjects were fed 7.5 g NSC/kg BW/day to maintain a fat body condition. Safety was assessed through daily monitoring, veterinary examination, and the measurement of fasting blood glucose, biochemistry and haematology. Efficacy at reducing post-prandial hyperinsulinemia was assessed using a diet challenge every 8 wk. during treatment and 4 wk. after withdrawal. RESULTS: Velagliflozin was well accepted by all subjects and caused no adverse effects or hypoglycaemia. Post-prandial serum insulin (insulin Cmax) did not change significantly in the control animals over the entire study period (P = 0.101). In contrast, insulin Cmax (mean ± SE) concentrations fell over time in the velagliflozin-treated group from 205 ± 25 µIU/mL in wk. 0, to 119 ± 19 µIU/mL (P = 0.015) and 117 ± 15 µIU/ml (P = 0.029) after 8 and 16 wk. of treatment, respectively. Although the insulin Cmax in this group was not significantly lower than in controls at wk-8 (P = 0.061), it was lower at wk-16 (P = 0.003), and all 12 treated ponies were below the previously-determined risk threshold for laminitis at this time. After 4 wk. withdrawal, the insulin Cmax returned to 199 ± 36 µIU/mL in the treated group, with no rebound effect. CONCLUSIONS: Velagliflozin appears to be a promising and safe treatment for equine insulin dysregulation, bringing post-prandial insulin concentrations below the laminitis risk threshold, albeit without normalising them.

Can daytime measures of lung function predict respiratory failure in children with neuromuscular disease?

Neuromuscular disorders in children are a heterogeneous group of conditions with a variable age of presentation and overlapping clinical manifestations, many of which have progressive respiratory morbidity. Respiratory insufficiency occurs as a consequence of an imbalance between demands on the respiratory system and respiratory muscle capacity. Daytime measures of pulmonary function are used routinely in these children to assess respiratory status and monitor the consequences of the progression of muscle weakness. This review describes the current evidence for daytime pulmonary function tests and their ability to predict imminent respiratory morbidity.

Blood volumes in cardiac surgery with cardiopulmonary bypass.

PURPOSE: Total blood volume (TBV) estimation potentially impacts various aspects of cardiac surgical care, including pharmacological and transfusion interventions, hemodynamic and volume management and perfusion equipment selection. TBV is commonly computed during cardiopulmonary bypass (CPB), using standardized formulae. We hypothesized that these equations fail to accurately predict individual blood volume variability. The aim of this study was to determine TBV with a dilution technique and compare the results to commonly utilized TBV calculations. METHODS: After institutional review board approval, data was prospectively collected and analyzed for 101 patients undergoing open-heart surgery. Hematocrits (Hct) just prior to and immediately after the initiation of CPB were used to calculate the TBV. Results were compared to (1) the Allen formula and (2) weight-based standards (70 ml/kg for males (SM); 65 ml/kg for females (SF)). RESULTS: The average dilution TBV (male: 4684 ± 1641 ml; female: 3027 ± 1067 ml; total: 4175 ± 1617 ml) was significantly smaller (p<0.05) than TBV estimated by Allen's formula (male: 6328 ± 973 ml; female: 4167 ± 643 ml; total: 5665 ± 1134 ml) and weight-based standards (male: 6278 ± 1256 ml; female: 4924 ± 1064 ml; total: 5862 ± 1350 ml). Allen's formula and the weight-based standards correlated strongly (R(2) = 0.821, p<0.001), suggesting similar estimates of TBV when using these methods. In contrast, hemodilution correlated poorly with the estimates by Allen (R(2) = 0.221, p<0.001) and weight-based formulae (R(2) = 0.122, p<0.001), suggesting different TBV computation. CONCLUSIONS: The dilution method during CPB for TBV estimation is applicable and reproducible in the cardiac surgical arena and can be utilized to calculate TBV. Our results suggest that traditional TBV assessment in cardiac surgical patients by Allen's and weight-based formulae lacks the desired accuracy in estimating true TBV.

Blood volume measurement by hemodilution: association with valve disease and re-evaluation of the Allen Formula.

BACKGROUND: Total blood volume (TBV) assessment is central to the management of cardiac surgical patients with cardiopulmonary bypass (CPB). The widely accepted Allen Formula lacks accuracy in estimating TBV in these patients. Moreover, the impact of commonly encountered cardiac disease states on TBV has not been systematically investigated. The aim of this study was to determine TBV by hemodilution (TBVHD) for patients with valve disease, compare TBVHD to algorithms frequently used during cardiac surgery and to modify the Allen Formula to better fit today's patient population. METHODS: TBVHD was prospectively measured upon initiation of CPB. Ninety-six patients were grouped into 4 cohorts by preoperative diagnosis and compared to Allen and weight-based formulae in a univariate analysis: mitral regurgitation (MR), coronary artery disease requiring bypass surgery (CABG) and aortic stenosis (AS) ± CABG. The independent effects of height and weight on TBV were correlated to the original Allen Formula by multiple linear regression. RESULTS: Patients with MR had significantly larger TBVHD compared to patients with AS, CABG or both. The smallest TBVHD was found in the patients with AS and CABG. The modified Allen Formula had an excellent model fit (R(2) = 0.88 and R(2) = 0.95 for males and females, respectively; p<0.001) while the classic formula overestimated TBV by 30% in males and females. For males, height impacted TBV calculations the most whereas weight was the predominant determinant in females. CONCLUSION: Blood volume assessment via the Allen Formula or bodyweight overestimated TBV in cardiac surgical patients, with potential implications on their management. The assumption that MR frequently presents with increased intravascular volume was confirmed whereas AS patients with coronary disease had a relatively smaller TBV. Lastly, a modified Allen Formula to better reflect today's patient population was derived to reproducibly improve accuracy in mathematical estimates of TBV.

Neural response during attentional control and emotion processing predicts improvement after cognitive behavioral therapy in generalized social anxiety disorder.

BACKGROUND: Individuals with generalized social anxiety disorder (gSAD) exhibit attentional bias to salient stimuli, which is reduced in patients whose symptoms improve after treatment, indicating that mechanisms of bias mediate treatment success. Therefore, pre-treatment activity in regions implicated in attentional control over socio-emotional signals (e.g. anterior cingulate cortex, dorsolateral prefrontal cortex) may predict response to cognitive behavioral therapy (CBT), evidence-based psychotherapy for gSAD. METHOD: During functional magnetic resonance imaging, 21 participants with gSAD viewed images comprising a trio of geometric shapes (circles, rectangles or triangles) alongside a trio of faces (angry, fearful or happy) within the same field of view. Attentional control was evaluated with the instruction to 'match shapes', directing attention away from faces, which was contrasted with 'match faces', whereby attention was directed to emotional faces. RESULTS: Whole-brain voxel-wise analyses showed that symptom improvement was predicted by enhanced pre-treatment activity in the presence of emotional face distractors in the dorsal anterior cingulate cortex and dorsal medial prefrontal cortex. Additionally, CBT success was foretold by less activity in the amygdala and/or increased activity in the medial orbitofrontal gyrus during emotion processing. CONCLUSIONS: CBT response was predicted by pre-treatment activity in prefrontal regions and the amygdala. The direction of activity suggests that individuals with intact attentional control in the presence of emotional distractors, regulatory capacity over emotional faces and/or less reactivity to such faces are more likely to benefit from CBT. Findings indicate that baseline neural activity in the context of attentional control and emotion processing may serve as a step towards delineating mechanisms by which CBT exerts its effects.

'Cough-triggered' tuberculosis screening among adults with diabetes in Tanzania.

AIMS: Diabetes increases the risk of tuberculosis and the prevalence of diabetes is rising in tuberculosis-endemic regions such as sub-Saharan Africa. Resource-appropriate strategies for tuberculosis case finding among African adults with diabetes are needed. The aims of this study were to determine prevalence of tuberculosis and evaluate one screening strategy among adult Tanzanians with diabetes. METHODS: In this prospective cohort study, we evaluated a 'cough-triggered' strategy for tuberculosis case finding among adults with diabetes at our zonal hospital in Tanzania. All adults with diabetes and cough underwent further tuberculosis symptom assessment, and those with productive cough had sputum collected for microscopy and Mycobacterium tuberculosis culture. RESULTS: Between September 2011 and March 2012, 700 adults with diabetes attended our hospital. A total of 693 were enrolled, 121/693 (17.5%) had cough and 32/693 (4.6%) had at least two of the classic symptoms of tuberculosis. Of note, 87/121 (71.9%) of patients with cough could not produce sputum spontaneously. Nine patients were diagnosed with tuberculosis for a prevalence of 1299/100 000 (1.3%), sevenfold greater than the national average. CONCLUSIONS: Tuberculosis is common among Tanzanian adults with diabetes, but tuberculosis case finding is challenging because of the high prevalence of non-productive cough. This low-cost, 'cough-triggered' tuberculosis case-finding strategy may serve as a reasonable first step for improving tuberculosis screening among adults with diabetes in sub-Saharan Africa.

In vitro comparison of two different methods of cell washing.

The storage of red blood cells (RBC) results in increased concentrations of plasma free hemoglobin, potassium, glucose, and lactate, among other undesirable substances. These concentrations continue to increase as RBC products age and can cause deleterious effects to the patient. In the setting of cardiac surgery, the autotransfusion devices are routinely used to wash blood that is shed from the surgical site. These devices could also be used to wash stored RBC units obtained from the blood bank. The objective of this study was to compare the product created by washing a unit of RBCs with the AutoLog autotransfusion device in the operating room to the washed products from a standard cell washer in the blood bank. Eleven outdated RBC units (stored for >42 days at 4 °C) were split in half. One half was washed using the Medtronic AutoLog device; the other half was washed using the blood bank's Cobe 2991 Cell Processor. Analytes were measured on samples from the unwashed parent unit and from the washed daughter units. The parameters measured included hematocrit, free hemoglobin, lactate, lactate dehydrogenase (LDH), potassium, glucose, and pH. When compared to the original untreated RBCs, the glucose, lactate, and potassium levels were decreased when washed in an autotranfusion device. Additionally, the free hemoglobin and LDH levels were significantly lower with the Medtronic Autolog cell saver than in the COBE 2991 Cell Processor. Washing the RBC donor units in an autotransfusion device prior to transfusion can effectively attenuate the increases seen in glucose, potassium, free hemoglobin, and LDH associated with RBC storage lesion.

Examining the impact of premature birth on parental mental health and family functioning in the years following hospital discharge: A review.

BACKGROUND: This review provides an update of the current research related to the impact of extreme and very premature birth on parental mental health and family functioning following discharge from hospital. METHODS: Full-text peer reviewed articles in English, describing parents' and families' health and wellbeing after the discharge from hospital of their baby using validated questionnaires, were evaluated. Results of included studies are presented in a summarized format. Embase, Medline and PsycINFO databases were accessed in January 2021. RESULTS: 38 studies were included. Nine manuscripts reported on parental mental health and 13 on stress, which are a concern after the birth of a premature infant, especially in the first year. Depression, anxiety, and stress are known to measure higher compared to parents of infants born at term. Over several years, these measures of mental health decrease significantly. Four reported on quality of life for parents of premature infants, which is reduced immediately after discharge, but then improves over time. The impact of premature birth on the family functioning was described in ten included studies and was described to have positive and negative consequences. CONCLUSION: The negative impact of the premature birth and hospital journey on parental mental health lessens significantly with time.

Reevaluating the wave power-salt marsh retreat relationship.

Salt marshes are threatened by rising sea levels and human activities, and a major mechanism of marsh loss is edge retreat or erosion. To understand and predict loss in these valuable ecosystems, studies have related erosion to marsh hydrodynamics and wave characteristics such as wave power. Across global studies, erosion is reported to be largely linearly related to wave power, with this relationship having implications for the resilience of marshes to extreme events such as storms. However, there is significant variability in this relationship across marshes because of marsh heterogeneity and the uniqueness of each physical setting. Here, we investigate the results of individual studies throughout the world that report a linear relationship and add a new dataset from the Great Marsh in Massachusetts (USA). We find that most marsh wave power and erosion data are not normally distributed and when these datasets are properly plotted to account for their distributions, the resulting relationships vary from previously published curves. Our Great Marsh data suggest that events from specific wind directions can have an outsized impact on edge erosion due to their larger fetch and wind speeds. We also find that factors other than wave attack such as edge erosion along tidal channels, can have a measurable impact on retreat rates. We show the importance of maintaining statistical assumptions when performing regressions, as well as emphasize the site-specificity of these relationships. Without calibration of a marsh erosion-wave power relationship using robust regressions for each individual marsh, such a relationship is not fully constrained, resulting in unreliable predictions of future marsh resilience and response to climate change.

Is perinatal substance abuse falling through the cracks?

OBJECTIVES: Perinatal substance abuse (PSA) is associated with increased risk of prematurity, low birth weight, neonatal abstinence syndrome, behavioral issues and learning difficulties. It is imperative that robust care pathways are in place for these high-risk pregnancies and that staff and patient education are optimized. The present study explores the knowledge and attitudes of healthcare professionals toward PSA to identify knowledge gaps to enhance care and reduce stigma. METHODS: This is a cross-sectional study using questionnaires to survey healthcare professionals (HCPs) working in a tertiary maternity unit (n = 172). RESULTS: The majority of HCPs were not confident in the antenatal management (75.6%, n = 130) or postnatal management (67.5%, n = 116) of PSA. More than half of HCPs surveyed (53.5%, n = 92) did not know the referral pathway and 32% (n = 55) did not know when to make a TUSLA referral. The vast majority (96.5%, n = 166) felt that they would benefit from further training, and 94.8% (n = 163) agreed or strongly agreed that the unit would benefit from a drug liaison midwife. Among study participants, 54.1% (n = 93) agreed or strongly agreed that PSA should be considered a form of child abuse and 58.7% (n = 101) believe that the mother is responsible for damage done to her child. CONCLUSIONS: Our study highlights the urgent need for increased training on PSA to enhance care and reduce stigma. It is imperative that staff training, drug liaison midwives and dedicated clinics are introduced to hospitals as a matter of high priority.

Respiratory and sleep outcomes in children with SMA treated with nusinersen - real world experience.

It is unclear how improvements in peripheral motor function in children with spinal muscular atrophy (SMA), treated with nusinersen, translate into clinically significant respiratory/sleep outcomes. A retrospective chart review of SMA children at the Sydney Children's Hospital Network was undertaken looking at 2 years before and after receiving their first dose of nusinersen. Polysomnography (PSG), spirometry and clinical data were collected and analysed using paired and unpaired t-tests for PSG parameters and generalised estimating equations for longitudinal lung function data. Forty-eight children (10 Type 1, 23 Type 2, 15 Type 3) at mean age 6.98 yrs (SD 5.25) for nusinersen initiation were included. There was a statistically significant improvement in oxygen nadir during sleep in individuals post nusinersen (mean of 87.9% to 92.3% (95%CI 1.24 - 7.63, p = 0.01)). Based on clinical and PSG findings, 6/21 patients (5 Type 2, 1 Type 3) ceased nocturnal NIV post nusinersen. Non-significant improvements were demonstrated in mean slope for FVC% predicted, FVC Z-score and mean FVC% predicted. Within 2 years of commencing nusinersen, stabilisation of respiratory outcomes occurred. Whilst some of the SMA type 2/3 cohort ceased NIV, there were no statistically significant improvements lung function and most PSG parameters.

Identification of pigment epithelium-derived factor protein forms with distinct activities on tumor cell lines.

PURPOSE: Pigment epithelium-derived factor (PEDF) is a multifunctional serpin. The purpose of this study is to identify PEDF protein forms and investigate their biological activities on tumor cell lines. METHODS: Recombinant human PEDF proteins were purified by cation- and anion-exchange column chromatography. They were subjected to SDS-PAGE, IEF, deglycosylation, heparin affinity chromatography, and limited proteolysis. Cell viability, real-time electrical impedance of cells, and wound healing assays were performed using bladder and breast cancer cell lines, rat retinal R28, and human ARPE-19 cells. RESULTS: Two PEDF protein peaks were identified after anion-exchange column chromatography: PEDF-1 eluting with lower ionic strength than PEDF-2. PEDF-1 had higher pI value and lower apparent molecular weight than PEDF-2. Both PEDF forms were glycosylated, bound to heparin, and had identical patterns by limited proteolysis. However, PEDF-2 emerged as being highly potent in lowering cell viability in all tumor cell lines tested, and in inhibiting tumor and ARPE-19 cell migration. In contrast, PEDF-1 minimally affected tumor cell viability and cell migration but protected R28 cells against death caused by serum starvation. CONCLUSION: Two distinct biochemical forms of PEDF varying in overall charge have distinct biological effects on tumor cell viability and migration. The existence of PEDF forms may explain the multifunctional modality of PEDF.