Minimal change in structural, functional and inflammatory markers of lung disease in newborn screened infants with cystic fibrosis at one year

BACKGROUND: With the widespread introduction of newborn screening for cystic fibrosis (CF), there has been considerable emphasis on the need to develop objective markers of lung health that can be used during infancy. We hypothesised that in a newborn screened (NBS) UK cohort, evidence of airway inflammation and infection at one year would be associated with adverse structural and functional outcomes at the same age. METHODS: Infants underwent lung function testing, chest CT scan and bronchoscopy with bronchoalveolar lavage (BAL) at 1 year of age when clinically well. Microbiology cultures were also available from routine cough swabs. RESULTS: 65 infants had lung function, CT and BAL. Mean (SD) lung clearance index and forced expiratory volume in 0.5 s z-scores were 0.9(1.2) and -0.6(1.1) respectively; median Brody II CF-CT air trapping score on chest CT =0 (interquartile range 0-1, maximum possible score 27). Infants isolating any significant pathogen by 1 yr of age had higher LCI z-score (mean difference 0.9; 95%CI:0.4-1.4; p = 0.001) and a trend towards higher air trapping scores on CT (p = 0.06). BAL neutrophil elastase was detectable in 23% (10/43) infants in whom BAL supernatant was available. This did not relate to air trapping score on CT. CONCLUSIONS: In this UK NBS cohort at one year of age, lung and airway damage is much milder and associations between inflammation, abnormal physiology and structural changes were at best weak, contrary to our hypothesis and previously published reports. Continued follow-up will clarify longer term implications of these very mild structural, functional and inflammatory changes

Nutrient recovery and microalgae biomass production from urine by membrane photobioreactor at low biomass retention times

Urine has been considered as an ideal nutrient source for microalgae cultivation thanks to its composition containing the high concentrations of nitrogen and phosphorus. Herein, the microalgae growth in urine was evaluated in a lab-scale membrane photobioreactor (MPBR) system. This work aimed to validate the influence of low biomass retention times (BRT) (10, 7, 5, 3, 2 d) on nutrient remediation and biomass productivity. It revealed that BRT of 7 d resulted in synergistically high biomass production (biomass productivity of 313 mg/L.d) and removal rates (TN of 90.5 mg/L.d and TP of 4.7 mg/L.d). Notably, the short BRT of 2–5 d was not sufficient to trigger actively growing microalgae and thus reduced biomass production rate. In addition, as operated at a low flux of 2 L/m2.h, MPBR system required no physical cleaning for 100 days of operation. The BRT-dependent biomass concentration played a pivotal role in changing the fouling rate of MPBR; however, the fouling is reversible in the MPBR system under the low flux condition

Cross-sectional and prospective relationships of passive and mentally active sedentary behaviours and physical activity with depression

Background Sedentary behaviour can be associated with poor mental health, but it remains unclear whether all types of sedentary behaviour have equivalent detrimental effects. Aims To model the potential impact on depression of replacing passive with mentally active sedentary behaviours and with light and moderate-to-vigorous physical activity. An additional aim was to explore these relationships by self-report data and clinician diagnoses of depression. Method In 1997, 43 863 Swedish adults were initially surveyed and their responses linked to patient registers until 2010. The isotemporal substitution method was used to model the potential impact on depression of replacing 30 min of passive sedentary behaviour with equivalent durations of mentally active sedentary behaviour, light physical activity or moderate-to-vigorous physical activity. Outcomes were self-reported depression symptoms (cross-sectional analyses) and clinician-diagnosed incident major depressive disorder (MDD) (prospective analyses). Results Of 24 060 participants with complete data (mean age 49.2 years, s.d. 15.8, 66% female), 1526 (6.3%) reported depression symptoms at baseline. There were 416 (1.7%) incident cases of MDD during the 13-year follow-up. Modelled cross-sectionally, replacing 30 min/day of passive sedentary behaviour with 30 min/day of mentally active sedentary behaviour, light physical activity and moderate-to-vigorous activity reduced the odds of depression symptoms by 5% (odds ratio 0.95, 95% CI 0.94–0.97), 13% (odds ratio 0.87, 95% CI 0.76–1.00) and 19% (odds ratio 0.81, 95% CI 0.93–0.90), respectively. Modelled prospectively, substituting 30 min/day of passive with 30 min/day of mentally active sedentary behaviour reduced MDD risk by 5% (hazard ratio 0.95, 95% CI 0.91–0.99); no other prospective associations were statistically significant. Conclusions Substituting passive with mentally active sedentary behaviours, light activity or moderate-to-vigorous activity may reduce depression risk in adults

Feasibility of establishing a rehabilitation programme in a Vietnamese intensive care unit

Increasing numbers of people are surviving critical illness throughout the world, but survivorship is associated with long-term disability. In high-income settings physical rehabilitation is commonly employed to counter this and improve outcomes. These utilize highly-trained multidisciplinary teams and are unavailable and unaffordable in most low and middle income countries (LMICs). We aimed to design a sustainable intensive care unit (ICU) rehabilitation program and to evaluate its feasibility in a LMIC setting. In this project patients, care-givers and experts co-designed an innovative rehabilitation programme that can be delivered by non-expert ICU staff and family care-givers in a LMIC. We implemented this programme in adult patient with patients with tetanus at the Hospital for Tropical Diseases, Ho Chi Minh City over a 5-month period, evaluating the programme's acceptability, enablers and barriers. A 6-phase programme was designed, supported by written and video material. The programme was piloted in total of 30 patients. Rehabilitation was commenced a median 14 (inter quartile range (IQR) 10-18) days after admission. Each patient received a median of 25.5 (IQR 22.8-34.8) rehabilitation sessions out of a median 27 (22.8-35) intended (prescribed) sessions. There were no associated adverse events. Patients and staff found rehabilitation to be beneficial, enhanced relationships between carers, patients and staff and was deemed to be a positive step towards recovery and return to work. The main barrier was staff time. The programme was feasible for patients with tetanus and viewed positively by staff and participants. Staff time was identified as the major barrier to ongoing implementation

The role of the gastrointestinal tract in toxigenic Clostridium tetani infection: a case-control study

Tetanus arises from wound contamination with Clostridium tetani, but approximately one fifth of patients have no discernable entry wound. Clostridium tetani is culturable from animal feces, suggesting the gastrointestinal tract could be an endogenous reservoir or direct-entry portal, but human data are lacking. In this study of 101 Vietnamese adults with tetanus and 29 hospitalized control subjects, admission stool samples were cultured for C. tetani. Anti-tetanus toxin antibodies were measured by ELISA. Clostridium tetani toxigenicity was evaluated using polymerase chain reaction and sequencing. Toxigenic C. tetani was cultured from stool samples in 50 of 100 (50%) tetanus cases and 12 of 28 (42.9%) control subjects (P = 0.50), and stool samples of 44 of 85 (52.4%) tetanus cases with clinically identified wounds compared with 6 of 15 (47.6%) patients without clinically identified wounds (P = 0.28). Nine of 12 (75%) control subjects with toxigenic C. tetani in their stool samples lacked protective antibody concentrations. These findings fail to show evidence of an association between gastrointestinal C. tetani and tetanus infection, but emphasize the importance of increasing vaccination coverage

Human versus equine intramuscular antitoxin, with or without human intrathecal antitoxin, for the treatment of adults with tetanus: a 2 × 2 factorial randomised controlled trial

Background Intramuscular antitoxin is recommended in tetanus treatment, but there are few data comparing human and equine preparations. Tetanus toxin acts within the CNS, where there is limited penetration of peripherally administered antitoxin; thus, intrathecal antitoxin administration might improve clinical outcomes compared with intramuscular injection. Methods In a 2  × 2 factorial trial, all patients aged 16 years or older with a clinical diagnosis of generalised tetanus admitted to the intensive care unit of the Hospital for Tropical Diseases, Ho Chi Minh City, Vietnam, were eligible for study entry. Participants were randomly assigned first to 3000 IU human or 21 000 U equine intramuscular antitoxin, then to either 500 IU intrathecal human antitoxin or sham procedure. Interventions were delivered by independent clinicians, with attending clinicians and study staff masked to treatment allocations. The primary outcome was requirement for mechanical ventilation. The analysis was done in the intention-to-treat population. The study is registered at ClinicalTrials.gov, NCT02999815; recruitment is completed. Findings 272 adults were randomly assigned to interventions between Jan 8, 2017, and Sept 29, 2019, and followed up until May, 2020. In the intrathecal allocation, 136 individuals were randomly assigned to sham procedure and 136 to antitoxin; in the intramuscular allocation, 109 individuals were randomly assigned to equine antitoxin and 109 to human antitoxin. 54 patients received antitoxin at a previous hospital, excluding them from the intramuscular antitoxin groups. Mechanical ventilation was given to 56 (43%) of 130 patients allocated to intrathecal antitoxin and 65 (50%) of 131 allocated to sham procedure (relative risk [RR] 0·87, 95% CI 0·66–1·13; p=0·29). For the intramuscular allocation, 48 (45%) of 107 patients allocated to human antitoxin received mechanical ventilation compared with 48 (44%) of 108 patients allocated to equine antitoxin (RR 1·01, 95% CI 0·75–1·36, p=0·95). No clinically relevant difference in adverse events was reported. 22 (16%) of 136 individuals allocated to the intrathecal group and 22 (11%) of 136 allocated to the sham procedure experienced adverse events related or possibly related to the intervention. 16 (15%) of 108 individuals allocated to equine intramuscular antitoxin and 17 (16%) of 109 allocated to human antitoxin experienced adverse events related or possibly related to the intervention. There were no intervention-related deaths. Interpretation We found no advantage of intramuscular human antitoxin over intramuscular equine antitoxin in tetanus treatment. Intrathecal antitoxin administration was safe, but did not provide overall benefit in addition to intramuscular antitoxin administration