Cross-sectional study of the prevalence, causes and management of hospital-onset diarrhoea.

BACKGROUND: The National Health Service in England advises hospitals collect data on hospital-onset diarrhoea (HOD). Contemporaneous data on HOD are lacking. AIM: To investigate prevalence, aetiology and management of HOD on medical, surgical and elderly-care wards. METHODS: A cross-sectional study in a volunteer sample of UK hospitals, which collected data on one winter and one summer day in 2016. Patients admitted ≥72 h were screened for HOD (definition: ≥2 episodes of Bristol Stool Type 5-7 the day before the study, with diarrhoea onset >48 h after admission). Data on HOD aetiology and management were collected prospectively. FINDINGS: Data were collected on 141 wards in 32 hospitals (16 acute, 16 teaching). Point-prevalence of HOD was 4.5% (230/5142 patients; 95% confidence interval (CI) 3.9-5.0%). Teaching hospital HOD prevalence (5.9%, 95% CI 5.1-6.9%) was twice that of acute hospitals (2.8%, 95% CI 2.1-3.5%; odds ratio 2.2, 95% CI 1.7-3.0). At least one potential cause was identified in 222/230 patients (97%): 107 (47%) had a relevant underlying condition, 125 (54%) were taking antimicrobials, and 195 (85%) other medication known to cause diarrhoea. Nine of 75 tested patients were Clostridium difficile toxin positive (4%). Eighty (35%) patients had a documented medical assessment of diarrhoea. Documentation of HOD in medical notes correlated with testing for C. difficile (78% of those tested vs 38% not tested, P<0.001). One-hundred and forty-four (63%) patients were not isolated following diarrhoea onset. CONCLUSION: HOD is a prevalent symptom affecting thousands of patients across the UK health system each day. Most patients had multiple potential causes of HOD, mainly iatrogenic, but only a third had medical assessment. Most were not tested for C. difficile and were not isolated.

The benefits to communities and individuals of screening for active tuberculosis disease: a systematic review.

BACKGROUND: Screening for tuberculosis (TB) disease aims to improve early TB case detection. The ultimate goal is to improve outcomes for people with TB and to reduce Mycobacterium tuberculosis transmission in the community through improved case detection, reduction in diagnostic delays and early treatment. Before screening programmes are recommended, evidence is needed of individual and/or community-level benefits. METHODS: We conducted a systematic review of the literature to assess the evidence that screening for TB disease 1) initially increases the number of TB cases initiated on anti-tuberculosis treatment, 2) identifies cases earlier in the course of disease, 3) reduces mortality and morbidity, and 4) impacts on TB epidemiology. RESULTS: A total of 28 798 publications were identified by the search strategy: 27 087 were excluded on initial screening and 1749 on full text review, leaving 62 publications that addressed at least one of the study questions. Screening increases the number of cases found in the short term. In many settings, more than half of the prevalent TB cases in the community remain undiagnosed. Screening tends to find cases earlier and with less severe disease, but this may be attributed to case-finding studies using more sensitive diagnostic methods than routine programmes. Treatment outcomes among people identified through screening are similar to outcomes among those identified through passive case finding. Current studies provide insufficient evidence to show that active screening for TB disease impacts on TB epidemiology. CONCLUSION: Individual and community-level benefits from active screening for TB disease remain uncertain. So far, the benefits of earlier diagnosis on patient outcomes and transmission have not been established.

Verteporfin photodynamic therapy for neovascular age-related macular degeneration: cohort study for the UK.

OBJECTIVES: The verteporfin photodynamic therapy (VPDT) cohort study aimed to answer five questions: (a) is VPDT in the NHS provided as in randomised trials?; (b) is 'outcome' the same in the nhs as in randomised trials?; (c) is 'outcome' the same for patients ineligible for randomised trials?; (d) is VPDT safe when provided in the NHS?; and (e) how effective and cost-effective is VPDT? DESIGN: Treatment register. SETTING: All hospitals providing VPDT in the NHS. PARTICIPANTS: All patients attending VPDT clinics. INTERVENTIONS: Infusion of verteporfin followed by infrared laser exposure is called VPDT, and is used to treat neovascular age-related macular degeneration (nAMD). The VPDT cohort study advised clinicians to follow patients every 3 months during treatment or active observation, retreating based on criteria used in the previous commercial 'TAP' (Treatment of Age-related macular degeneration with Photodynamic therapy) trials of VPDT. MAIN OUTCOME MEASURES: The primary outcome was logarithm of the minimum angle of resolution monocular best-corrected distance visual acuity (BCVA). Secondary outcomes were adverse reactions and events; morphological changes in treated nAMD (wet) lesions; and for a subset of patients, 6-monthly contrast sensitivity, generic and visual health-related quality of life (HRQoL) and resource use. Treated eyes were classified as eligible for the TAP trials (EFT), ineligible (IFT) or unclassifiable (UNC). RESULTS: Forty-seven hospitals submitted data for 8323 treated eyes in 7748 patients; 4919 eyes in 4566 patients were treated more than 1 year before the last data submission or had completed treatment. Of 4043 eyes with nAMD in 4043 patients, 1227 were classified as EFT, 1187 as IFT and 1629 as UNC. HRQoL and resource use data were available for about 2000 patients. The mean number of treatments in years 1 and 2 was 2.3 and 0.4 respectively. About 50% of eyes completed treatment within 1 year. BCVA deterioration in year 1 did not differ between eligibility groups. EFT eyes lost 11.6 letters (95% confidence interval 10.1 to 13.0 letters) compared with 9.9 letters in VPDT-treated eyes in the TAP trials. EFT eyes had poorer BCVA at baseline than IFT and UNC eyes. Adverse reactions and events were reported for 1.4% of first visits - less frequently than those reported in the TAP trials. Associations between BCVA in the best-seeing eye with HRQoL and community health and social care resource use showed that the 11-letter difference in BCVA between VPDT and sham treatment in the TAP trials corresponded to differences in utility of 0.012 and health and social service costs of £60 and £92 in years 1 and 2, respectively. VPDT provided an incremental cost per quality-adjusted life-year (QALY) of £170,000 over 2 years. CONCLUSIONS: VPDT was administered less frequently than in the TAP trials, with less than half of those treated followed up for > 1 year in routine clinical practice. Deterioration in BCVA over time in EFT eyes was similar to that in the TAP trials. The similar falls in BCVA after VPDT across the pre-defined TAP eligibility groups do not mean that the treatment is equally effective in these groups because deterioration in BCVA can be influenced by the parameters that determined group membership. Safety was no worse than in the TAP trials. The estimated cost per QALY was similar to the highest previous estimate. Although VPDT is no longer in use as monotherapy for neovascular AMD, its role as adjunctive treatment has not been fully explored. VPDT also has potential as monotherapy in the management of vascular malformations of the retina and choroid and with trials underway in neovascularisation due to myopia and polypoidal choroidopathy. FUNDING: The National Institute for Health Research Health Technology Assessment programme.

Neonatal ventilation with inhaled nitric oxide vs. ventilatory support without inhaled nitric oxide for infants with severe respiratory failure born at or near term: the INNOVO multicentre randomised controlled trial.

BACKGROUND: Evidence from European centres to support the use of nitric oxide (NO) in mature newborns with evidence of severe respiratory failure is sparse. METHODS: Infants of >33 weeks' gestation, <28 days old, and with severe respiratory failure requiring ventilatory support were randomised to receive or not to receive inhaled NO (iNO). The study was not blinded. RESULTS: Sixty infants were recruited (29 allocated iNO, 31 no iNO) from 15 neonatal units in the UK, Finland, Belgium and the Republic of Ireland. 15/60 recruited babies died, and 8.1% of the survivors (4/45) were classified as severely disabled at 1 year. There was no statistically significant difference between the randomised groups in terms of the primary outcome of death or severe disability by the corrected age of 1 year (relative risk = 0.96 (95% confidence interval = 0.46-2.03); p = 0.86) (Fisher's exact p = 1.00). The costs of NO were outweighed by reduced extra corporeal membrane oxygenation costs in the iNO group. The mean total hospitalisation costs were lower in the iNO group, although the mean difference (1,697 pounds) was not statistically significant (95% confidence interval = -14,472 to 11,478). CONCLUSIONS: The results complement those of previous studies that suggest NO is cost-effective and reduces the need for extra corporeal membrane oxygenation in this group of babies. Overall survival rates compare unfavourably with results of US trials.

Invasive pneumococcal disease and the potential for prevention by vaccination in the United Kingdom.

OBJECTIVES: Invasive pneumococcal disease (IPD) is associated with a high mortality despite antimicrobial therapy, but may be preventable by pneumococcal vaccination. The extent of previous exposure to pneumococcal capsular polysaccharide vaccination prior to an episode of IPD in hospitalised adults in the United Kingdom is unclear. METHODS: We conducted a retrospective cohort study in adults with IPD admitted to either of two teaching hospitals in Sheffield, United Kingdom during 1992-2000. Receipt of pneumococcal vaccination, risk factors for IPD, death and disability were determined. RESULTS: The number of cases of IPD was 552 and 187/230 patient records from one site were reviewed. According to UK pneumococcal vaccination guidelines 59% of patients should have received the vaccine and 76% of patients if updated guidelines, which include age>65 years as an indication, are applied. In patients with known risk factors, excluding age, only 8% had been vaccinated. The mortality from IPD was 21% and an additional 6% suffered major complications. CONCLUSIONS: In patients hospitalised with IPD there is a high rate of pre-existing risk factors and a low rate of administration of pneumococcal vaccination. IPD incurs significant mortality, morbidity and economic cost and there is potential for reducing this by improved uptake of pneumococcal vaccination.

A dose response study of inhaled nitric oxide in hypoxic respiratory failure in preterm infants.

BACKGROUND: Inhaled nitric oxide (iNO) is used widely in newborn infants with hypoxic respiratory failure, despite the known and theoretical toxicity of iNO, and a relative lack of information about appropriate doses. AIM: To determine whether a dose-response relationship existed for iNO in preterm infants. DESIGN: A four-period, four-dose, cross-over design was used with iNO given for 15 min in a randomised sequence in concentrations of 5, 10, 20 and 40 parts per million (ppm), with a minimum 5 min wash-out period. Data on ventilatory, blood gas and other physiological measurements were recorded before and at the end of each period. The relationship of clinical response with iNO dose and period was analysed using multivariate regression. SUBJECTS: Infants with gestational age < 34 weeks and < 28 days postnatal age with hypoxic respiratory failure were recruited. OUTCOME MEASURE: A clinically significant dose-response was defined as a rise in the post-ductal arterial oxygen tension (PaO(2)) of at least 3 kPa. RESULTS: Thirteen infants were recruited. At trial entry, ten were < 3 days of age; 11 were being treated with high frequency oscillatory ventilation; median (inter-quartile range) gestational age 27 (25-29) weeks; birthweight 983 (765-1120) g; oxygenation index 27.1 (21.8-28.8). Six infants (46%) showed a clinically significant response. After adjusting for period and patient effect, no evidence for an overall dose effect was identified (likelihood ratio test, p=0.34). CONCLUSION: No evidence of a dose-response relationship with iNO was found in this study of very preterm infants with respiratory failure.

Neonatal Ventilation With Inhaled Nitric Oxide Versus Ventilatory Support Without Inhaled Nitric Oxide for Preterm Infants With Severe Respiratory Failure: the INNOVO multicentre randomised controlled trial (ISRCTN 17821339).

BACKGROUND: Although inhaled nitric oxide (iNO) may be a promising treatment for newborn infants with severe respiratory failure, the results from 3 previous small trials were inconclusive. METHODS: Infants of <34 weeks' gestation, <28 days old, and with severe respiratory failure requiring ventilatory support were randomized to receive or not receive iNO. The study was not blinded. FINDINGS: Recruited were 108 infants (55 allocated to receive iNO and 53 not allocated to receive iNO) from 15 neonatal units in the United Kingdom and Republic of Ireland. Fifty-nine percent (64 of 108) died, and 84% of the survivors (37 of 44) had signs of some impairment or disability, 9 (20%) of them classified as severely disabled. There was no evidence of an effect of iNO on the primary outcomes: death or severe disability at 1 year corrected age (relative risk [RR]: 0.99; 95% confidence interval [CI]: 0.76 to 1.29); death or supplemental oxygen on expected date of delivery (RR: 0.84; 95% CI: 0.68 to 1.02); or death or supplemental oxygen at 36 weeks' postmenstrual age (RR: 0.98; 95% CI: 0.87 to 1.12). There was a trend for infants allocated to the iNO group to spend more time on the ventilator (log rank: 3.6), on supplemental oxygen (log rank: 1.4), and in hospital (log rank: 3.5) than those allocated to receive no iNO. This pattern predominantly reflected the infants who died. Mean total costs at 1 year corrected age were significantly higher in the iNO group, partly because of the costs of the gas but mainly because of the difference in initial hospitalization costs. INTERPRETATION: Evidence of prolongation of intensive care and increased costs of such care, without clear beneficial effects, implies that iNO cannot be recommended for preterm infants with severe hypoxic respiratory failure.

Interspecies biofilms of Pseudomonas aeruginosa and Burkholderia cepacia.

The leading cause of morbidity and mortality in cystic fibrosis (CF) continues to be lung infections with Pseudomonas aeruginosa biofilms. Co-colonization of the lungs with P aeruginosa and Burkholderia cepacia can result in more severe pulmonary disease than P. aeruginosa alone. The interactions between P. aeruginosa biofilms and B. cepacia are not yet understood; one possible association being that mixed species biofilm formation may be part of the interspecies relationship. Using the Calgary Biofilm Device (CBD), members of all genomovars of the B. cepacia complex were shown to form biofilms, including those isolated from CF lungs. Mixed species biofilm formation between CF isolates of P. aeruginosa and B. cepacia was readily achieved using the CBD. Oxidation-fermentation lactose agar was adapted as a differential agar to monitor mixed biofilm composition. Scanning electron micrographs of the biofilms demonstrated that both species readily integrated in close association in the biofilm structure. Pseudomonas aeruginosa laboratory strain PAO1, however, inhibited mixed biofilm formation of both CF isolates and environmental strains of the B. cepacia complex. Characterization of the soluble inhibitor suggested pyocyanin as the active compound.

Oral nicotine solution for smoking cessation: a pilot tolerability study.

This study was conducted to determine the preliminary tolerability of an oral nicotine solution with minimal behavioral intervention for smoking cessation. Twenty-five healthy volunteers who smoked at least 10 cigarettes per day and were motivated to quit smoking were enrolled in an open-labeled trial with a 12-week treatment and a 6-month follow-up period. After reviewing self-help materials and setting a quit-smoking day, subjects were provided nicotine solution to mix with their beverages to control smoking urges, and returned for refills eight times over 12 weeks. Abstinence (point prevalence) was defined as self-report of 0 cigarettes smoked for the previous 7 days verified by exhaled carbon monoxide (CO) <10 ppm. The oral nicotine solution was well tolerated when mixed with an individual's chosen beverage. Subjects controlled the concentration of nicotine consumed, which ranged from 0.25 to 10 mg nicotine base per 170-354 ml of beverage. One week after the quit date the mean venous nicotine level was 13.4 ng/ml and mean serum cotinine level was 418.0 ng/ml in six non-smokers. Abstinence rates at 4 weeks, 3 months, and 6 months were 28.0%, 24.0%, and 20.0%, respectively. It was concluded that an oral nicotine solution was tolerable and provided nicotine replacement at levels that may prove useful for smoking cessation. Further research to clarify appropriate dosages and optimal beverages for mixture, and controlled trials to assess safety and efficacy, appear in order.