A randomised controlled trial of energetic activity for depression in young people (READY): a multi-site feasibility trial protocol.

BACKGROUND: Prevalence of depression is increasing in young people, and there is a need to develop and evaluate behavioural interventions which may provide benefits equal to or greater than talking therapies or pharmacological alternatives. Exercise could be beneficial for young people living with depression, but robust, large-scale trials of effectiveness and the impact of exercise intensity are lacking. This study aims to test whether a randomised controlled trial (RCT) of an intervention targeting young people living with depression is feasible by determining whether it is possible to recruit and retain young people, develop and deliver the intervention as planned, and evaluate training and delivery. METHODS: The design is a three-arm cluster randomised controlled feasibility trial with embedded process evaluation. Participants will be help-seeking young people, aged 13-17 years experiencing mild to moderate low mood or depression, referred from three counties in England. The intervention will be delivered by registered exercise professionals, supported by mental health support workers, twice a week for 12 weeks. The three arms will be high-intensity exercise, low-intensity exercise, and a social activity control. All arms will receive a 'healthy living' behaviour change session prior to each exercise session and the two exercise groups are energy matched. The outcomes are referral, recruitment, and retention rates; attendance at exercise sessions; adherence to and ability to reach intensity during exercise sessions; proportions of missing data; adverse events, all measured at baseline, 3, and 6 months; resource use; and reach and representativeness. DISCUSSION: UK National Health Service (NHS) policy is to provide young people with advice about using exercise to help depression but there is no evidence-based exercise intervention to either complement or as an alternative to medication or talking therapies. UK National Institute for Health and Care Excellence (NICE) guidelines suggest that exercise can be an effective treatment, but the evidence base is relatively weak. This feasibility trial will provide evidence about whether it is feasible to recruit and retain young people to a full RCT to assess the effectiveness and cost-effectiveness of an exercise intervention for depression. TRIAL REGISTRATION: ISRCTN, ISRCTN66452702 . Registered 9 April 2020.

Diagnostic accuracy of a prototype rapid chlamydia and gonorrhoea recombinase polymerase amplification assay: a multicentre cross-sectional preclinical evaluation.

OBJECTIVES: Rapid and accurate sexually transmitted infection diagnosis can reduce onward transmission and improve treatment efficacy. We evaluated the accuracy of a 15-minute run-time recombinase polymerase amplification-based prototype point-of-care test (TwistDx) for Chlamydia trachomatis (CT) and Neisseria gonorrhoeae (NG). METHODS: Prospective, multicentre study of symptomatic and asymptomatic patients attending three English sexual health clinics. Research samples provided were additional self-collected vulvovaginal swab (SCVS) (female participants) and first-catch urine (FCU) aliquot (female and male participants). Samples were processed blind to the comparator (routine clinic CT/NG nucleic acid amplification test (NAAT)) results. Discrepancies were resolved using Cepheid CT/NG GeneXpert. RESULTS: Both recombinase polymerase amplification and routine clinic NAAT results were available for 392 male and 395 female participants. CT positivity was 8.9% (35/392) (male FCU), 7.3% (29/395) (female FCU) and 7.1% (28/395) (SCVS). Corresponding NG positivity was 3.1% (12/392), 0.8% (3/395) and 0.8% (3/395). Specificity and positive predictive values were 100% for all sample types and both organisms, except male CT FCU (99.7% specificity (95% confidence interval (CI) 98.4-100.0; 356/357), 97.1% positive predictive value (95% CI 84.7-99.9; 33/34)). For CT, sensitivity was ≥94.3% for FCU and SCVS. CT sensitivity for female FCU was higher (100%; 95% CI, 88.1-100; 29/29) than for SCVS (96.4%; 95% CI, 81.7-99.9; 27/28). NG sensitivity and negative predictive values were 100% in FCU (male and female). CONCLUSIONS: This prototype test has excellent performance characteristics, comparable to currently used NAATs, and fulfils several World Health Organization ASSURED criteria. Its rapidity without loss of performance suggests that once further developed and commercialized, this test could positively affect clinical practice and public health.

Differential characterization of emerging skin diseases of rainbow trout--a standardized approach to capturing disease characteristics and development of case definitions.

Farmed and wild salmonids are affected by a variety of skin conditions, some of which have significant economic and welfare implications. In many cases, the causes are not well understood, and one example is cold water strawberry disease of rainbow trout, also called red mark syndrome, which has been recorded in the UK since 2003. To date, there are no internationally agreed methods for describing these conditions, which has caused confusion for farmers and health professionals, who are often unclear as to whether they are dealing with a new or a previously described condition. This has resulted, inevitably, in delays to both accurate diagnosis and effective treatment regimes. Here, we provide a standardized methodology for the description of skin conditions of rainbow trout of uncertain aetiology. We demonstrate how the approach can be used to develop case definitions, using coldwater strawberry disease as an example.

Limited prevalence of gaffkaemia (Aerococcus viridans var. homari) isolated from wild-caught European lobsters Homarus gammarus in England and Wales.

Gaffkaemia, caused by Aerococcus viridans var. homari, causes fatal infections in Homarus spp. (clawed lobsters). Despite its high economic significance to the lobster fisheries in the USA and northern Europe, data on its prevalence in captured and wild populations, particularly in Europe, is scarce. Following an outbreak of gaffkaemia in a European lobster holding facility in South Wales (UK), a base-line survey was conducted for gaffkaemia in wild populations of European lobster Homarus gammarus around the coast of England and Wales. In addition, isolates recovered from the original outbreak and the survey were typed using pulsed-field gel electrophoresis (PFGE) and compared with previously characterised isolates from the USA, UK and Canada. Locally caught H. gammarus were sampled at 30 sites from around the coast of England and Wales between March 2006 and October 2008. Results confirmed that the prevalence of gaffkaemia in populations of H. gammarus was low, with only 9 positive isolates recovered from 952 samples examined. PFGE analysis showed that the isolates from the outbreak investigation shared the same pulsotype as A. viridans var. homari isolates from the USA, Norway and Canada, as well as an isolate (NCIMB 1119) reportedly recovered from an outbreak of European lobsters in England in the 1960s. This confirms earlier studies that suggest virulent strains of A. viridans var. homari show very limited geographical or temporal genetic variation and were introduced into the UK with American lobsters H. americanus.

Moxifloxacin and pyrazinamide susceptibility testing in a complex case of multidrug-resistant tuberculosis.

Multidrug-resistant tuberculosis (MDR-TB) is a public health problem of global concern. It is critical that drug susceptibility testing (DST) methods accurately predict clinical response. We present a patient with a challenging case of MDR-TB with additional resistance to quinolones and pyrazinamide. Treatment with a regimen including high-dosage moxifloxacin, based on additional genotypic and phenotypic DST, produced excellent results. This case highlights the possibility of treatment with high-dose fluoroquinolones despite apparent bacterial resistance to these agents. Improved DST methods are necessary for both agents. Development of genotypic approaches may offer a susceptibility profile rapidly, enabling early introduction of individualised treatments.

Emergence of cold water strawberry disease of rainbow trout Oncorynchus mykiss in England and Wales: outbreak investigations and transmission studies.

Cold water strawberry disease (CWSD), or red mark syndrome (RMS), is a severe dermatitis affecting the rainbow trout Oncorynchus mykiss. The condition, which presents as multifocal, raised lesions on the flanks of affected fish, was first diagnosed in Scotland in 2003 and has since spread to England and Wales. Results of field investigations indicated the condition had an infectious aetiology, with outbreaks in England linked to movements of live fish from affected sites in Scotland. Transmission trials confirmed these results, with 11 of 149 and 106 of 159 naive rainbow trout displaying CWSD-characteristic lesions 104 to 106 d after being cohabited with CWSD-affected fish from 2 farms (Farm B from England and Farm C from Wales, respectively). The condition apparently has a long latency, with the first characteristic lesions in the previously naive fish not definitively observed until 65 d (650 day-degrees) post-contact with affected fish. Affected fish from both outbreak investigations and the infection trial were examined for the presence of viruses, oomycetes, parasites and bacteria using a combination of techniques and methodologies (including culture-independent cloning of PCR-amplified bacterial 16S rRNA genes from lesions), with no potentially causative infectious agent consistently identified. The majority of the cloned phylotypes from both lesion and negative control skin samples were assigned to Acidovorax-like beta-Proteobacteria and Methylobacterium-like alpha-Proteobacteria.

The development of selective attention in children with attention deficit hyperactivity disorder.

The influence of age on a selective attention task was studied in a sample of children with and without Attention Deficit Hyperactivity Disorder (ADHD). The impact of methylphenidate (MPH) treatment on selective attention was also investigated in the children with ADHD. Two age groups of children with ADHD and two age groups of control children were tested using a timed computer task. The task consisted of identifying visual target stimuli under various distracter conditions. Distracters varied on the basis of modality (i.e., visual, auditory, or both) and task relevance (i.e., meaningful or irrelevant). Reaction times and accuracy were measured. Children with ADHD were less efficient on the selective attention task than were children without ADHD, and older children were more efficient than younger children in both groups. Children without ADHD were influenced more by the nature of distracters than were children with ADHD. For children with ADHD, MPH improved performance overall.

Effect of hoof characteristics on the propensity of cattle to slip.

Bovine hooves were assessed for their linear and volumetric characteristics and ranked in sets of four for hoof volume. An artificial cow was constructed with the hooves set into metal cylinders underneath a platform containing a known weight. The device was connected via a strain gauge to a pulling handle operated by two people, and the horizontal force required to move each set of hooves was determined three times. The coefficient of friction, calculated as the horizontal force divided by the fixed vertical force, was positively correlated with hoof volume. The same exercise was repeated with the hooves ranked for toe angle, and the hooves with steep toe angles had a lower coefficient of friction than the hooves with shallow toe angles. However, since both hoof volume and toe angle were related to toe length, the relationship between friction and toe angle was believed to derive from the larger size of claws with shallow toe angles. The results indicate that young cattle that have small claws with smooth surfaces and steep toe angles are more likely to slip.

Development and implementation of clinical pathways for stroke on a multihospital basis.

This study describes the development and implementation of clinical pathways for stroke on a cooperative basis by three hospitals in the same community. The participating institutions developed separate pathways which met their respective organizational needs. This process occurred within separate hospital management structures with coordination among the institutions. They employed a common set of length of stay, quality and resource variables to evaluate the impact of the pathways.

Intravenous colistin sulphomethate in acute respiratory exacerbations in adult patients with cystic fibrosis.

BACKGROUND: Patients with cystic fibrosis have received more intravenous antibiotic courses as median survival has steadily increased. A number of centres have adopted a policy of regular (three monthly) rather than on demand intravenous antipseudomonal antibiotics. More widespread bacterial antibiotic resistance has resulted from this increased antibiotic use. Most Pseudomonas aeruginosa strains remain fully sensitive to colistin but its use has been resisted owing to concerns about neurotoxicity and nephrotoxicity. A study was carried out to assess the safety and efficacy of intravenous colistin in the treatment of acute respiratory exacerbations in adult patients with cystic fibrosis. METHODS: Patients with chronic Pseudomonas aeruginosa colonisation who presented with protocol defined respiratory tract exacerbations were randomised to receive treatment for 12 days with either colistin (2 MU tds intravenously) alone or with a second anti-pseudomonal antibiotic. Comparisons of the absolute values of respiratory function tests on days 1, 5, and 12 and of overnight oxygen saturation on days 1 and 12 were the primary outcome measures. Patient's weight, clinical and chest radiographic scores, and peripheral blood markers of inflammation were also documented. The effect of each treatment regimen individually was assessed by the change in clinical measurements from baseline values. Adverse renal effects were monitored by measurement of serum levels of urea and electrolytes, creatinine clearance, and ward urine testing. Neurotoxicity was monitored by direct questioning for symptoms. RESULTS: Fifty three patients, 18 of whom entered the study twice, were enrolled. The mean forced expiratory volume in one second (FEV1) increased significantly in both groups, mean forced vital capacity (FVC) only with dual therapy. Both groups showed a non-significant increase in overnight oxygen saturation. All patients showed clinical improvement. Thirty seven adverse neurological events (two severe) were reported in 33 patients in the monotherapy group and 37 (none severe) in 36 patients in the dual therapy group. One patient withdrew because of severe weakness and dizziness. All other adverse neurological events were well tolerated and resolved during or shortly after treatment. Significant changes were seen in mean serum urea levels in both groups, but in only four patients to a level above the normal range, and in creatinine clearance in the dual therapy group. At 24 month follow up no long term adverse consequences from intravenous colistin were found in patients who completed the study. CONCLUSIONS: Intravenous colistin is an effective treatment for Pseudomonas aeruginosa associated pulmonary exacerbations in patients with cystic fibrosis. Assessment of the individual effect of each treatment regimen suggests a greater efficacy when colistin is combined with a second antibiotic to which the pseudomonas shows in vitro sensitivity. Changes in renal function should be monitored.

Functional iron deficiency in adults with cystic fibrosis.

Functional iron deficiency (transferrin saturation < 16%) was found in 44 (62%) of 71 adult cystic fibrosis (CF) patients. Haemoglobin concentration and mean cell volume were lower in iron-deficient patients, in whom there was a non-significant trend for lower serum ferritin. Ten iron-deficient patients and two patients with transferrin saturation > = 16% (normal iron) were anaemic. There were no significant differences between iron-deficient and normal-iron patients in intake of calories, protein, iron and vitamin C as determined by 4-day records of dietary intake. Dietary iron deficiency is not an important factor in functional iron deficiency in adult CF patients. Impairment of absorption by exogenous pancreatic enzyme supplements is unlikely to be significant as enzyme intake was the same in the two groups. Iron-deficient patients had lower Shwachman-Kulczycki scores and lower percent predicted forced expiratory volume in 1 s (FEV1% predicted) and forced vital capacity (FVC% predicted). There was a non-significant trend for higher values of white cell count and plasma viscosity in the iron-deficient group. Chronic inflammation is likely to be the primary cause of functional iron deficiency in adult CF patients. Fifteen patients completed 3-month courses of oral iron replacement with no deterioration in pulmonary function, but with no effect on haemoglobin concentration.

An examination of differential follow-up rates in breast cancer screening.

This study was designed to test the hypothesis that follow-up rates for women with abnormal breast screening results would vary by age, ethnicity and initial screening results in California's Breast Cervical Cancer Control Program. The sample was composed of women in this screening program who had received abnormal clinical breast exam (N = 5239) or mammography results (N = 1202). Chi-squared analysis showed significant differences by age and initial screening results but in logistic regression analysis the only demographic variable to retain significance in analysis was age, although size of the clinic was also highly significant. Older women should be targeted as a group needing assistance with compliance with follow-up recommendations.

Compliance with treatment in adult patients with cystic fibrosis.

BACKGROUND: Patients with chronic disease comply with about 50% of their treatment. The complex and time consuming daily drug regimens needed in the care of adult patients with cystic fibrosis encourage non-compliance with prescribed treatments. Understanding the reasons for, and the extent of, non-compliance is essential for a realistic appraisal of the patient's condition and sensible planning of future treatment programmes. METHODS: Patients were invited to complete a questionnaire which asked about their compliance with daily treatment. The data were used to calculate a compliance score, the percentage of prescribed treatment taken, and to examine patient attitudes to each individual prescription. An assessment score derived from consultant, cystic fibrosis research fellow, specialist nurse, and physiotherapist ratings of patient compliance was compared with the compliance score. Both scores were correlated with patient characteristics and disease severity, and the compliance score was also correlated with the patient's knowledge of cystic fibrosis. RESULTS: More than half the patients claimed to take more than 80% of their treatments. Compliance with individual treatments varied according to their perceived unpleasantness and degree of infringement on daily activities. The most common reason given for omitting treatment was forgetfulness. Professional carers were poor judges of patient compliance. There was no correlation between compliance and patients' sociodemographic characteristics or their knowledge about cystic fibrosis. CONCLUSIONS: Non-compliance is universal and should be recognised as normal behaviour. There are no reliable criteria for predicting any patient's level of compliance. Treatment protocols should be planned around individual patient's requirements, modifying treatment ideals where necessary according to the exigency and pattern of that patient's lifestyle.

Knowledge of adult patients with cystic fibrosis about their illness.

BACKGROUND: Adult patients need to understand their illness if the locus of control is to move from doctor to patient. Previous studies have shown important misconceptions and gaps in patients' knowledge about cystic fibrosis. METHODS: Patients were invited to complete a multiple choice questionnaire covering all major aspects of cystic fibrosis. The questionnaire score was compared with a predicted score derived from the consultant, cystic fibrosis fellow, nurse, and physiotherapist ratings of patient knowledge. Data were obtained to provide a comprehensive patient profile and disease severity score. Both scores were tested for any associations with patient characteristics. RESULTS: Although patients had good general knowledge about the aspects of cystic fibrosis that impacted most on their daily lives--that is, respiratory and gastrointestinal problems--important gaps and misconceptions in these areas were still present. Knowledge and understanding of genetic and reproductive issues and the less common complications of cystic fibrosis were only moderate. Older more severely affected patients, and those who had more contact with the hospital caring team, had better multiple choice questionnaire knowledge scores. Professional carers were poor judges of the knowledge of individual patients. CONCLUSIONS: Important gaps persist into adult life in the knowledge patients with cystic fibrosis have about their illness. Objective assessment of these deficits is required so that each patient can be counselled according to his or her needs.

Munchausen syndrome by proxy abuse: a foundation for adult Munchausen syndrome.

Symptoms fabricated by the mother, and abnormal maternal pressurising of medical staff, resulted in misinterpretation of sweat test results and a diagnosis of cystic fibrosis in a two year old child. Her mother refused to accept later medical evidence which irrefutably showed this diagnosis to be wrong. The child was extensively investigated and for most of her childhood was treated for pancreatic malabsorption. She progressed from an innocent child victim of Munchausen Syndrome by Proxy abuse to an accomplice in her mother's deception, and finally to adult Munchausen Syndrome behaviour. Munchausen Syndrome by Proxy abuse may programme a child into developing adult Munchausen Syndrome.

Nocturnal oxygen desaturation and spirometric parameters in adults with cystic fibrosis.

BACKGROUND: Correction of nocturnal hypoxaemia in patients with cystic fibrosis may delay the development of pulmonary hypertension. Descriptive statistics used for nocturnal arterial oxygen saturation (SpO2) lack uniformity. The relationship between SpO2 and spirometric parameters has not previously been explored in a large number of exacerbations in adult patients with cystic fibrosis. METHODS: Over a 21 month period overnight SpO2, forced expiratory volume in one second (FEV1), and forced vital capacity (FVC) were recorded on admission and discharge in 120 treatments of pulmonary exacerbations in 47 patients with cystic fibrosis who did not receive supplemental oxygen during recording. Nocturnal SpO2 was related to spirometric parameters for the whole group and individually in 11 patients, each of whom had at least five treatments. RESULTS: There was a close linear relationship between the percentage of the recording spent with SpO2 < 90% and mean overnight SpO2. Mean SpO2 correlated moderately with percentage predicted FEV1(%FEV1), r = 0.6, and poorly with percentage predicted FVC (%FVC), r = 0.34. The relationship between mean SpO2 and % FEV1 was non-linear at mean SpO2 < 89%, but approximated to linearity above this value. After exclusion of treatments with mean SpO2 < 89% the regression relationship between mean SpO2 and %FEV1 was the same on admission and discharge. Individual correlation coefficients of mean SpO2 versus % FEV1 in the 11 patients with repeated treatments ranged from 0.57 to 0.77. The slopes of the regression lines did not differ, with a pooled slope of 0.116, but the intercepts varied widely. CONCLUSIONS: In patients with cystic fibrosis mean overnight SpO2 can be substituted for percentage of recording < 90%. The relationship between mean SpO2 and percentage predicted FEV1 is non-linear at low values of SpO2 and is not influenced by treatment of pulmonary exacerbations. Patients with cystic fibrosis desaturate at a uniform rate compared with percentage predicted FEV1, but the value of FEV1 at which desaturation first occurs varies between patients. The spirometric values do not accurately predict nocturnal desaturation in a cystic fibrosis population, but FEV1 is a useful guide in individual patients with moderate desaturation.

Home versus hospital intravenous antibiotic therapy in the treatment of young adults with cystic fibrosis.

We wanted to investigate whether home intravenous antibiotic treatment of pulmonary exacerbations of cystic fibrosis is as effective as treatment in hospital. The case records of all patients attending the Leeds adult cystic fibrosis clinic were reviewed to identify those who had received home intravenous antibiotic treatment. All home treatments undertaken were included. For each home treatment, the temporally closest hospital treatment for that patient was then selected for comparison and the changes with treatment in peak expiratory flow rate (PEFR), forced vital capacity (FVC), forced expiratory volume in one second (FEV1), C-reactive protein (CRP), plasma viscosity, total white cell count, absolute neutrophil count, total immunoglobulin G (IgG) concentration, chest X-ray score (Northern), clinical score, Shwachman-Kulczyki score and weight were analysed for differences between home treatment and hospital treatment. Fifty one paired home/hospital treatments in 25 patients were compared. The improvement in total white cell count was found to be significantly greater in the hospital group, but the difference was very small. The improvements in absolute neutrophil count, and all the other measured variables, were the same in the two groups. Treatment of exacerbations of cystic fibrosis at home or in hospital is, thus, equally effective given proper patient selection and adequate monitoring of the response to treatment.

The chest radiograph in cystic fibrosis: a new scoring system compared with the Chrispin-Norman and Brasfield scores.

BACKGROUND: Scoring systems for the chest radiograph in cystic fibrosis are used to compare patients and different treatment regimens, and to monitor respiratory disease in individual patients. The Northern chest radiograph score was designed to allow one person to assess the radiological features of lung involvement in cystic fibrosis in as simple, rapid and equally reproducible manner as the established Chrispin and Norman, and Brasfield scoring systems. METHODS: Forty five chest radiographs were scored by 10 physicians with a special interest in cystic fibrosis according to the Brasfield and Northern methods, and by five pairs of physicians according to the Chrispin-Norman criteria. Three individuals and two pairs rescored the radiographs after an interval of 3-5 months. The Northern score was performed with and without a lateral view, using the original posteroanterior radiograph. RESULTS: The Northern score showed a better agreement between observers for the ranking of the radiographs. It was equally well related to respiratory function tests, the Shwachman-Kulczycki score of overall clinical status, and in its discrimination between different radiographs as the other two scoring systems. The Northern score performed equally well with or without a lateral film. CONCLUSIONS: The Northern system fulfils the requirements of a chest radiograph score more successfully than the Chrispin-Norman or Brasfield systems, and does not require a lateral film.