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2.  Improvement in obstructive sleep apnea diagnosis and management wait times: A retrospective analysis of a home management pathway for obstructive sleep apnea 
Despite the estimated prevalence of obstructive sleep apnea in the Canadian population, many adults with the condition are undiagnosed. Moreover, limited access to polysomnography testing and increasing obesity rates only compound the problem. Recently, however, home diagnosis and management pathways using emerging portable technology has garnered significant interest. This retrospective analysis compared a home management program running in parallel with an in-laboratory system to determine whether it is a viable alternative in patients who meet strict criteria.
Obstructive sleep apnea is a common condition within the Canadian population. The current gold standard for diagnosis and management of patients is in-laboratory (in-lab) polysomnography; however, the limited availability of testing options for patients has led to long wait times and increased disease burden within the population. The Sleep Research Laboratory in Saskatoon (Saskatchewan) implemented a home management program to run in parallel with the in-lab system several years ago in an effort to increase their capacity and reduce wait times. The present study was a retrospective analysis of all patients referred to the program between 2009 and 2012. The home management system has improved wait times by diagnosing and managing up to one-half of the referred patient population, reducing the wait for in-lab treatment from a median of 152 days in 2009 to 92 days in 2012 (P<0.0001). Moving forward, home management can provide a viable alternative to in-lab testing for patients who meet strict entry criteria, reducing the in-lab workload and, ultimately, reducing wait times.
PMCID: PMC4470551  PMID: 25751031
Monitoring, physiological; Polysomnography; Saskatchewan; Sleep apnea; Time factors; Time to treatment
3.  Dementia priority setting partnership with the James Lind Alliance: using patient and public involvement and the evidence base to inform the research agenda 
Age and Ageing  2015;44(6):985-993.
Background: the James Lind Alliance (JLA) created an approach to elicit the views of those under-represented in research priority exercises. Building on this, the JLA Dementia Priority Setting Partnership was set up as an independent and evidence-based project to identify and prioritise unanswered questions (‘uncertainties') about prevention, diagnosis, treatment and care relating to dementia.
Methods: a survey was widely disseminated to stakeholders with an interest in the needs of the older population. Thematic analysis was used to identify themes from the large amount of questions collected from which research questions were developed using PICO framework (Population, Intervention, Comparator, Outcome). Each question was checked against an extensive evidence base of high-quality systematic reviews to verify whether they were true uncertainties.
Findings: one thousand five hundred and sixty-three questionnaires were received, from people with dementia, carers/relatives, and health and care professionals; 85 uncertainties were identified from other sources. Questions were refined and formatted iteratively into 146 unique uncertainties. An interim prioritisation process involving diverse organisations identified the top 25 ranked questions. At a final face-to-face prioritisation workshop, 18 people representing the above constituencies arrived by consensus at the top 10 priority questions. The impact of patient and public involvement on the priorities is discussed.
Interpretation: the long (146 questions) and top 10 lists of dementia research priorities provide a focus for researchers, funders and commissioners. They highlight a need for more research into care for people with dementia and carers, and a need for high-quality effectiveness trials in all aspects of dementia research.
PMCID: PMC4621237  PMID: 26504119
dementia; survey; priority setting; James Lind Alliance; public health; prevention; treatment; diagnosis; care; patient and public involvement; carer; PPI; older people
4.  Identifying acne treatment uncertainties via a James Lind Alliance Priority Setting Partnership 
BMJ Open  2015;5(7):e008085.
The Acne Priority Setting Partnership (PSP) was set up to identify and rank treatment uncertainties by bringing together people with acne, and professionals providing care within and beyond the National Health Service (NHS).
The UK with international participation.
Teenagers and adults with acne, parents, partners, nurses, clinicians, pharmacists, private practitioners.
Treatment uncertainties were collected via separate online harvesting surveys, embedded within the PSP website, for patients and professionals. A wide variety of approaches were used to promote the surveys to stakeholder groups with a particular emphasis on teenagers and young adults. Survey submissions were collated using keywords and verified as uncertainties by appraising existing evidence. The 30 most popular themes were ranked via weighted scores from an online vote. At a priority setting workshop, patients and professionals discussed the 18 highest-scoring questions from the vote, and reached consensus on the top 10.
In the harvesting survey, 2310 people, including 652 professionals and 1456 patients (58% aged 24 y or younger), made submissions containing at least one research question. After checking for relevance and rephrasing, a total of 6255 questions were collated into themes. Valid votes ranking the 30 most common themes were obtained from 2807 participants. The top 10 uncertainties prioritised at the workshop were largely focused on management strategies, optimum use of common prescription medications and the role of non-drug based interventions. More female than male patients took part in the harvesting surveys and vote. A wider range of uncertainties were provided by patients compared to professionals.
Engaging teenagers and young adults in priority setting is achievable using a variety of promotional methods. The top 10 uncertainties reveal an extensive knowledge gap about widely used interventions and the relative merits of drug versus non-drug based treatments in acne management.
PMCID: PMC4513497  PMID: 26187120
5.  A community-based participatory research methodology to address, redress, and reassess disparities in respiratory health among First Nations 
BMC Research Notes  2015;8:199.
To date, determinants of respiratory health in First Nations people living on reserves and means of addressing and redressing those determinants have not been well established. Hence the Saskatchewan First Nations Lung Health Project (FNLHP) is a new prospective cohort study of aboriginal people being conducted in two First Nations reserves to evaluate potential health determinants associated with respiratory outcomes. Using the population health framework (PHF) of Health Canada, instruments designed with the communities, joint ownership of data, and based on the 4-phase concept of the First Nations Regional Longitudinal Health Survey, the project aims to evaluate individual factors, contextual factors, and principal covariates on respiratory outcomes. The objective of this report is to clearly describe the methodology of (i) the baseline survey that consists of two components, an interviewer-administered questionnaire and clinical assessment; and (ii) potential intervention programs; and present descriptive results of the baseline data of longitudinal FNLHP.
The study is being conducted over 5 years (2012–2017) in two phases, baseline and longitudinal. Baseline survey has been completed and consisted of (i) an interviewer-administered questionnaire-based evaluation of individual and contextual factors of importance to respiratory health (with special focus on chronic bronchitis, chronic obstructive pulmonary disease, asthma and obstructive sleep apnea), and (ii) clinical lung function and allergy tests with the consent of study participants. The address-redress phase consists of potential intervention programs and is currently being rolled out to address-at community level (via green light program and environmental study), and redress-at policy level (via obesity reduction and improved diagnosis and treatment of obstructive sleep apnea) the issues that have been identified by the baseline data.
Interviewer-administered surveys were conducted in 2012–2013 and collected data on 874 individuals living in 406 households from two reserve communities located in Saskatchewan, Canada. Four hundred and forty six (51%) females and 428 (49%) males participated in the FNLHP.
The information from this project will assist in addressing and redressing many of the issues involved including the provision of adequate housing, health lifestyle practices, and in planning for health service delivery.
Electronic supplementary material
The online version of this article (doi:10.1186/s13104-015-1137-5) contains supplementary material, which is available to authorized users.
PMCID: PMC4440281  PMID: 25981585
6.  Setting research priorities to improve the health of children and young people with neurodisability: a British Academy of Childhood Disability-James Lind Alliance Research Priority Setting Partnership 
BMJ Open  2015;5(1):e006233.
To engage young people, parent carers and clinicians in a systematic process to identify and prioritise research questions regarding ways to improve the health and well-being of children and young people with neurodisability.
British Academy of Childhood Disability (BACD)-James Lind Alliance research priority setting partnership bringing together patients, carers and clinicians as equal stakeholders.
UK health service and community.
The BACD Strategic Research Group formed the partnership. A Steering Group was established; charity and professional partner organisations were recruited. Suggestions were gathered in an open survey and from research recommendations for statutory guidance. Items were aggregated to formulate indicative research questions and verified as uncertainties from research evidence. An interim survey was used to rank the questions to shortlist topics. A mixed group of stakeholders discussed the top 25 questions at the final priority setting workshop agreeing a final rank order and the top 10 research priorities.
Partner organisations were 13 charities and 8 professional societies. 369 people submitted suggestions (40% non-clinicians). 76 people participated in the interim prioritisation (26 parents, 1 young person, 10 charity representatives, 39 clinicians); 22 took part in the final workshop (3 young people, 7 parents, 3 charity representatives, 9 professionals).
The top three research priorities related to (1) establishing the optimal frequency and intensity (dose) for mainstream therapies, (2) means for selecting and encouraging use of communication strategies and (3) ways to improve children's attitudes towards disability. The top 10 included evaluating interventions to promote mobility, self-efficacy, mental health, continence, physical fitness, educational inclusion and reduce impacts of sleep disturbance.
The methodology provided a systematic and transparent process to identify research priorities that included stakeholders that have typically not contributed to setting the research agenda. The top 10 and other topics identified provide a resource for researchers and agencies that fund research
PMCID: PMC4316435  PMID: 25631309
7.  The StrongWomen Change Clubs: Engaging Residents to Catalyze Positive Change in Food and Physical Activity Environments 
Introduction. The epidemic of obesity is a multifaceted public health issue. Positive policy and environmental changes are needed to support healthier eating and increased physical activity. Methods. StrongWomen Change Clubs (SWCCs) were developed through an academic-community research partnership between researchers at Cornell University and Tufts University and community partners (cooperative extension educators) in rural towns in seven U.S. states. Extension educators served as the local leader and each recruited 10–15 residents to undertake a project to improve some aspect of the nutrition or physical activity environment. Most residents had limited (or no) experience in civic engagement. At 6 and 12 months after implementation, the research team conducted key informant interviews with SWCC leaders to capture their perceptions of program process, benchmark achievement, and self-efficacy. Results. At 12 months, each SWCC had accomplished one benchmark; the majority had completed three or more benchmarks. They described common processes for achieving benchmarks such as building relationships and leveraging stakeholder partnerships. Barriers to benchmark achievement included busy schedules and resistance to and slow pace of change. Conclusion. Findings suggest that community change initiatives that involve stakeholders, build upon existing activities and organizational resources, and establish feasible timelines and goals can successfully catalyze environmental change.
PMCID: PMC4265724  PMID: 25525441
8.  Individual psychodynamic psychotherapy and psychoanalysis for schizophrenia and severe mental illness 
People with schizophrenia and severe mental illness may require considerable support from health care professionals, in most cases over a long period of time. Research on the effects of psychotherapy for schizophrenia has shown mixed results. Although pharmacological interventions remain the treatment of choice, the effects of treatments focusing on psychosocial factors affecting schizophrenia are important.
To review the effects of psychodynamic psychotherapy, psychoanalysis, or both, for people with schizophrenia or severe mental illness.
Search methods
For the updated review, we searched the Cochrane Schizophrenia Group Trials Register (June 2008) which is based on regular searches of BIOSIS, CENTRAL, CINAHL, EMBASE, MEDLINE and PsycINFO.
Selection criteria
We sought all randomised trials of individual psychodynamic psychotherapy or psychoanalysis for people with schizophrenia or severe mental illness.
Data collection and analysis
We extracted data independently. For dichotomous data we calculated relative risks (RR) and their 95% confidence intervals (CI) on an intention-to-treat basis using a fixed-effect model. We calculated numbers needed to treat/harm (NNT/NNH) where appropriate. For continuous data, we calculated mean differences (MD) and weighted mean differences (WMD) using a fixed-effect model.
Main results
We included four randomised trials (total 528 participants, 5 comparisons). All used a psychodynamic approach and reported limited data.
For individual psychodynamic therapy versus medication alone we found significantly more participants in the therapy group were unable to be discharged (n=92, RR 8.35 CI 2.0 to 34.3, NNH 3 CI 2 to 6). We found no significant difference between groups in the number of participants who were re-hospitalised (n=24, RR 0.63 CI 0.3 to 1.4) during long-term analyses. At 12 months, fewer participants in the psychotherapy groups needed additional medications compared with those who did receive medication (n=74, RR 0.64 CI 0.5 to 0.8, NNT 3 CI 3 to 6), and also at three years follow up (n=87, RR 0.85 CI 0.8 to 1.0, NNT 7 CI 5 to 26).
For individual psychodynamic therapy plus medication versus medication alone we found no significant difference in suicide (n=92, RR 0.16 CI 0.01 to 2.9) or suitability for discharge (n=92, RR 1.09 CI 0.2 to 7.4). Also, we found re-hospitalisation rates in long-term analyses were equivocal (n=24, RR 1.00 CI 0.4 to 2.6). For insight-orientated psychodynamic psychotherapy versus reality adaptive psychotherapy we found no significant difference in re-hospitalisation rates (n=164, RR 1.20 CI 0.9 to 1.6), but we found study attrition favoured the insight-orientated psychodynamic psychotherapy group at 12 months (n=164, RR 0.46 CI 0.3 to 0.6, NNT 2 CI 2 to 4). For individual psychodynamic psychotherapy versus group psychotherapy we found no significant difference in global state ‘not improved’ (n=100, RR 1.27 CI 1.0 to 1.7). For individual psychodynamic therapy plus medication versus individual psychodynamic therapy we found rates of re-hospitalisation during long-term analyses were equivocal (n=24, RR 1.00 CI 0.4 to 2.6). There is no clear evidence of any positive effect of psychodynamic therapy and the possibility of adverse effects seems never to have been considered. We did not identify any trials using a psychoanalytic approach.
Authors’ conclusions
Current data do not support the use of psychodynamic psychotherapy techniques for hospitalised people with schizophrenia. If psychoanalytic therapy is being used for people with schizophrenia there is an urgent need for trials.
PMCID: PMC4171459  PMID: 11686988
*Psychoanalytic Therapy; *Psychotherapy; Hospitalization; Mental Disorders [therapy]; Randomized Controlled Trials as Topic; Schizophrenia [*therapy]; Humans
9.  The Sight Loss and Vision Priority Setting Partnership (SLV-PSP): overview and results of the research prioritisation survey process 
BMJ Open  2014;4(7):e004905.
The Sight Loss and Vision Priority Setting Partnership aimed to identify research priorities relating to sight loss and vision through consultation with patients, carers and clinicians. These priorities can be used to inform funding bodies’ decisions and enhance the case for additional research funding.
Prospective survey with support from the James Lind Alliance.
UK-wide National Health Service (NHS) and non-NHS.
Patients, carers and eye health professionals. Academic researchers were excluded solely from the prioritisation process. The survey was disseminated by patient groups, professional bodies, at conferences and through the media, and was available for completion online, by phone, by post and by alternative formats (Braille and audio).
Outcome measure
People were asked to submit the questions about prevention, diagnosis and treatment of sight loss and eye conditions that they most wanted to see answered by research. Returned survey questions were reviewed by a data assessment group. Priorities were established across eye disease categories at final workshops.
2220 people responded generating 4461 submissions. Sixty-five per cent of respondents had sight loss and/or an eye condition. Following initial data analysis, 686 submissions remained which were circulated for interim prioritisation (excluding cataract and ocular cancer questions) to 446 patients/carers and 218 professionals. The remaining 346 questions were discussed at final prioritisation workshops to reach agreement of top questions per category.
The exercise engaged a diverse community of stakeholders generating a wide range of conditions and research questions. Top priority questions were established across 12 eye disease categories.
PMCID: PMC4120376  PMID: 25056971
Sight loss; Vision; Research; Priorities; Partnership; James Lind Alliance
10.  Bacteriophage-Derived Peptidase CHAPK Eliminates and Prevents Staphylococcal Biofilms 
New antibacterial agents are urgently needed for the elimination of biofilm-forming bacteria that are highly resistant to traditional antimicrobial agents. Proliferation of such bacteria can lead to significant economic losses in the agri-food sector. This study demonstrates the potential of the bacteriophage-derived peptidase, CHAPK, as a biocidal agent for the rapid disruption of biofilm-forming staphylococci, commonly associated with bovine mastitis. Purified CHAPK applied to biofilms of Staphylococcus aureus DPC5246 completely eliminated the staphylococcal biofilms within 4 h. In addition, CHAPK was able to prevent biofilm formation by this strain. The CHAPK lysin also reduced S. aureus in a skin decolonization model. Our data demonstrates the potential of CHAPK as a biocidal agent for prevention and treatment of biofilm-associated staphylococcal infections or as a decontaminating agent in the food and healthcare sectors.
PMCID: PMC3574654  PMID: 23431312
11.  Normal expiratory flow rate and lung volumes in patients with combined emphysema and interstitial lung disease: A case series and literature review 
Pulmonary function tests in patients with idiopathic pulmonary fibrosis characteristically show a restrictive pattern including small lung volumes and increased expiratory flow rates resulting from a reduction in pulmonary compliance due to diffuse fibrosis. Conversely, an obstructive pattern with hyperinflation results in emphysema by loss of elastic recoil, expiratory collapse of the peripheral airways and air trapping. When the diseases coexist, pulmonary volumes are compensated, and a smaller than expected reduction or even normal lung volumes can be found. The present report describes 10 patients with progressive breathlessness, three of whom experienced severe limitation in their quality of life. All patients showed lung interstitial involvement and emphysema on computed tomography scan of the chest. The 10 patients showed normal spirometry and lung volumes with severe compromise of gas exchange. Normal lung volumes do not exclude diagnosis of idiopathic pulmonary fibrosis in patients with concomitant emphysema. The relatively preserved lung volumes may underestimate the severity of idiopathic pulmonary fibrosis and attenuate its effects on lung function parameters.
PMCID: PMC3267611  PMID: 21969934
Emphysema; Expiratory flow rates; Intersitial lung disease; Lung volumes
12.  In silico modeling of the staphylococcal bacteriophage-derived peptidase CHAPK 
Bacteriophage  2011;1(4):198-206.
The aim of this study was to use comparative modeling to predict the three-dimensional structure of the CHAPK protein (cysteine, histidine-dependent amidohydrolase/peptidase domain of the LysK endolysin, derived from bacteriophage K). Iterative PSI-BLAST searches against the Protein Data Bank (PDB) and nonredundant (nr) databases were used to populate a multiple alignment for analysis using the T-Coffee Expresso server. A consensus Maximum Parsimony phylogenetic tree with a bootstrap analysis setting of 1,000 replicates was constructed using MEGA4. Structural templates relevant to our target (CHAPK) were identified, processed in Expresso and used to generate a 3D model in the alignment mode of SWISS-MODEL. These templates were also processed in the I-TASSER web server. A Staphylococcus saprophyticus CHAP domain protein, 2K3A, was identified as the structural template in both servers. The I-TASSER server generated the CHAPK model with the best bond geometries when analyzed using PROCHECK and the most logical organization of the structure. The predicted 3D model indicates that CHAPK has a papain-like fold. Circular dichroism spectropolarimetry also indicated that CHAPK has an αβ fold, which is consistent with the model presented. The putative active site maintained a highly conserved Cys54-His117-Glu134 charge relay and an oxyanion hole residue Asn136. The residue triplet, Cys-His-Glu, is known to be a viable proteolytic triad in which we predict the Cys residue is used in a nucleophilic attack on peptide bonds at a specific site in the pentaglycine cross bridge of staphylococcal cell wall peptidoglycan. Use of comparative modeling has allowed approximation of the 3D structure of CHAPK giving information on the structure and an insight into the binding and active site of the catalytic domain. This may facilitate its development as an alternative antibacterial agent.
PMCID: PMC3448105  PMID: 23050213
bacteriophage; CHAP; endolysin; in silico; peptidase; staphylococcus
13.  Sulpiride Augmentation for Schizophrenia 
Schizophrenia Bulletin  2010;36(2):229-230.
PMCID: PMC2833130  PMID: 20061345
cochrane; sulpiride; schizophrenia
14.  Recombinant bacteriophage lysins as antibacterials 
Bioengineered Bugs  2010;1(1):9-16.
With the increasing worldwide prevalence of antibiotic resistant bacteria, bacteriophage endolysins (lysins) represent a very promising novel alternative class of antibacterial in the fight against infectious disease. Lysins are phage-encoded peptidoglycan hydrolases which, when applied exogenously (as purified recombinant proteins) to Gram-positive bacteria, bring about rapid lysis and death of the bacterial cell. A number of studies have recently demonstrated the strong potential of these enzymes in human and veterinary medicine to control and treat pathogens on mucosal surfaces and in systemic infections. They also have potential in diagnostics and detection, bio-defence, elimination of food pathogens and control of phytopathogens. This review discusses the extensive research on recombinant bacteriophage lysins in the context of antibacterials, and looks forward to future development and potential.
PMCID: PMC3035150  PMID: 21327123
lysin; endolysin; bacteriophage; pathogen; antibacterial; infection; lytic; enzyme
15.  The truncated phage lysin CHAPk eliminates Staphylococcus aureus in the nares of mice 
Bioengineered Bugs  2010;1(6):404-407.
The endolysin LysK derived from staphylococcal phage K has previously been shown to have two enzymatic domains, one of which is an N-acetylmuramoyl-L-alanine amidase and the other a cysteine/histidine-dependant amidohydrolase/peptidase designated CHAPk. The latter, when cloned as a single-domain truncated enzyme, is conveniently overexpressed in a highly-soluble form. This enzyme was shown to be highly active in vitro against live cell suspensions of S. aureus. In the current study, the IVIS imaging system was used to demonstrate the effective elimination of a lux labeled S. aureus from the nares of BALB/c mice.
PMCID: PMC3056090  PMID: 21468207
Staphylococcus; decolonization; lysin; bacteriophage; nasal
16.  Nitrofurantoin-associated bronchiolitis obliterans organizing pneumonia: Report of a case 
Bronchiolitis obliterans organizing pneumonia due to nitrofurantoin has rarely been reported and is associated with poor outcomes. A case of nitrofurantoin-associated bronchiolitis obliterans organizing pneumonia responsive to drug withdrawal and corticosteroids is presented.
PMCID: PMC2679562  PMID: 18818785
Bronchiolitis obliterans organizing pneumonia; Nitrofurantoin pulmonary toxicity
17.  Intracerebral abscess: A complication of severe cystic fibrosis lung disease 
Intracerebral abscess is an uncommon complication of severe cystic fibrosis lung disease. The present report describes a case of fatal multiple intracerebral abscesses in a patient with a severely bronchiectatic, nonfunctioning right lung and chronic low-grade infection. The patient was previously turned down for pneumonectomy. Intracerebral abscess in cystic fibrosis and the potential role of pneumonectomy in the present patient are discussed.
PMCID: PMC2677856  PMID: 18292854
Cystic fibrosis; Intracerebral abscess; Pneumonectomy
18.  How to formulate research recommendations 
BMJ : British Medical Journal  2006;333(7572):804-806.
“More research is needed” is a conclusion that fits most systematic reviews. But authors need to be more specific about what exactly is required
PMCID: PMC1602035  PMID: 17038740
19.  Gross Domestic Product (GDP) and productivity of schizophrenia trials: an ecological study 
BMC Psychiatry  2003;3:18.
The 5000 randomised controlled trials (RCTs) in the Cochrane Schizophrenia Group's database affords an opportunity to research for variables related to the differences between nations of their output of schizophrenia trials.
Ecological study – investigating the relationship between four economic/demographic variables and number of schizophrenia RCTs per country. The variable with closest correlation was used to predict the expected number of studies.
GDP closely correlated with schizophrenia trial output, with 76% of the total variation about the Y explained by the regression line (r = 0.87, 95% CI 0.79 to 0.92, r2 = 0.76). Many countries have a strong tradition of schizophrenia trials, exceeding their predicted output. All nations with no identified trial output had GDPs that predicted zero trial activity. Several nations with relatively small GDPs are, nevertheless, highly productive of trials. Some wealthy countries seem either not to have produced the expected number of randomised trials or not to have disseminated them to the English-speaking world.
This hypothesis-generating study could not investigate causal relationships, but suggests, that for those seeking all relevant studies, expending effort searching the scientific literature of Germany, Italy, France, Brazil and Japan may be a good investment.
PMCID: PMC305357  PMID: 14656379

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