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1.  Telemedicine in Alentejo 
Alentejo covers a third of Portugal, yet it is home to only 5% of the population. Residents of the region are poorer, older, and less educated than the rest of the country. There is a shortage of physicians in several specialties. The low population density, a concentration of specialized services, and a poor public transportation network all create barriers to access. Telemedicine was introduced in 1998 to help address these challenges. In this article, we provide an overview of the program and its current status, focusing on infrastructure, services, and activity volume. We also discuss the impact the program has had from the perspectives of patients and healthcare professionals. From 1998 to 2011, there were 132,546 episodes of service using telemedicine, including real-time teleconsultations, teleradiology, teleultrasound, and telepathology. At present, the network includes 20 primary care units and five hospitals, covering almost 30,000 km2 and 500,000 people. Units have high-resolution videoconferencing equipment, access to patients' clinical records, an image archive, and peripherals, such as electronic dermatoscopes and phonendoscopes. Teleconsultations are available in 15 medical specialties and areas, ranging from neurology to pediatric surgery. In 2008, regional health authorities started a tele-education program, and by the end of 2011, 876 healthcare professionals, across 52 locations, had participated in remote learning sessions. More than a decade since telemedicine was introduced in Alentejo, it is now an integral part of everyday service provision. A comprehensive assessment of the costs and consequences of the program is currently underway.
PMCID: PMC3880063  PMID: 24180419
telemedicine; teleradiology; distance learning
2.  Cost-effectiveness of telecare for people with social care needs: the Whole Systems Demonstrator cluster randomised trial 
Age and Ageing  2014;43(6):794-800.
Purpose of the study: to examine the costs and cost-effectiveness of ‘second-generation’ telecare, in addition to standard support and care that could include ‘first-generation’ forms of telecare, compared with standard support and care that could include ‘first-generation’ forms of telecare.
Design and methods: a pragmatic cluster-randomised controlled trial with nested economic evaluation. A total of 2,600 people with social care needs participated in a trial of community-based telecare in three English local authority areas. In the Whole Systems Demonstrator Telecare Questionnaire Study, 550 participants were randomised to intervention and 639 to control. Participants who were offered the telecare intervention received a package of equipment and monitoring services for 12 months, additional to their standard health and social care services. The control group received usual health and social care.
Primary outcome measure: incremental cost per quality-adjusted life year (QALY) gained. The analyses took a health and social care perspective.
Results: cost per additional QALY was £297,000. Cost-effectiveness acceptability curves indicated that the probability of cost-effectiveness at a willingness-to-pay of £30,000 per QALY gained was only 16%. Sensitivity analyses combining variations in equipment price and support cost parameters yielded a cost-effectiveness ratio of £161,000 per QALY.
Implications: while QALY gain in the intervention group was similar to that for controls, social and health services costs were higher. Second-generation telecare did not appear to be a cost-effective addition to usual care, assuming a commonly accepted willingness to pay for QALYs.
Trial registration number: ISRCTN 43002091.
PMCID: PMC4204660  PMID: 24950690
telecare; economic evaluation; social care; older people
3.  Perceptions and experiences of financial incentives: a qualitative study of dialysis care in England 
BMJ Open  2014;4(2):e004249.
The objective of the study was to understand the extent to which financial incentives such as Payment by Results and other payment mechanisms motivate kidney centres in England to change their practices.
The study followed a qualitative design. Data collection involved 32 in-depth semistructured interviews with healthcare professionals and managers, focusing on their subjective experience of payment structures.
Participants were kidney healthcare professionals, clinical directors, kidney centre managers and finance managers. Healthcare commissioners from different parts of England were also interviewed.
Participants worked at five kidney centres from across England. The selection was based on the prevalence of home haemodialysis, ranging from low (<3%), medium (5–8%) and high (>8%) prevalence, with at least one centre in each one of these categories at the time of selection.
While the tariff for home haemodialysis is not a clear incentive for its adoption due to uncertainty about operational costs, Commissioning for Quality and Innovation (CQUIN) targets and the Best Practice Tariff for vascular access were seen by our case study centres as a motivator to change practices.
The impact of financial incentives designed at a policy level is influenced by the understanding of cost and benefits at the local operational level. In a situation where costs are unclear, incentives which are based on the improvement of profit margins have a smaller impact than incentives which provide an additional direct payment, even if this extra financial support is relatively small.
PMCID: PMC3927715  PMID: 24523426
4.  Barriers to successful implementation of care in home haemodialysis (BASIC-HHD):1. Study design, methods and rationale 
BMC Nephrology  2013;14:197.
Ten years on from the National Institute of Health and Clinical Excellence’ technology appraisal guideline on haemodialysis in 2002; the clinical community is yet to rise to the challenge of providing home haemodialysis (HHD) to 10-15% of the dialysis cohort. The renal registry report, suggests underutilization of a treatment type that has had a lot of research interest and several publications worldwide on its apparent benefit for both physical and mental health of patients. An understanding of the drivers to introducing and sustaining the modality, from organizational, economic, clinical and patient perspectives is fundamental to realizing the full benefits of the therapy with the potential to provide evidence base for effective care models. Through the BASIC-HHD study, we seek to understand the clinical, patient and carer related psychosocial, economic and organisational determinants of successful uptake and maintenance of home haemodialysis and thereby, engage all major stakeholders in the process.
Design and methods
We have adopted an integrated mixed methodology (convergent, parallel design) for this study. The study arms include a. patient; b. organization; c. carer and d. economic evaluation. The three patient study cohorts (n = 500) include pre-dialysis patients (200), hospital haemodialysis (200) and home haemodialysis patients (100) from geographically distinct NHS sites, across the country and with variable prevalence of home haemodialysis. The pre-dialysis patients will also be prospectively followed up for a period of 12 months from study entry to understand their journey to renal replacement therapy and subsequently, before and after studies will be carried out for a select few who do commence dialysis in the study period. The process will entail quantitative methods and ethnographic interviews of all groups in the study. Data collection will involve clinical and biomarkers, psychosocial quantitative assessments and neuropsychometric tests in patients. Organizational attitudes and dialysis unit practices will be studied together with perceptions of healthcare providers on provision of home HD. Economic evaluation of home and hospital haemodialysis practices will also be undertaken and we will apply scenario ("what … if") analysis using system dynamics modeling to investigate the impact of different policy choices and financial models on dialysis technology adoption, care pathways and costs. Less attention is often given to the patient’s carers who provide informal support, often of a complex nature to patients afflicted by chronic ailments such as end stage kidney disease. Engaging the carers is fundamental to realizing the full benefits of a complex, home-based intervention and a qualitative study of the carers will be undertaken to elicit their fears, concerns and perception of home HD before and after patient’s commencement of the treatment. The data sets will be analysed independently and the findings will be mixed at the stage of interpretation to form a coherent message that will be informing practice in the future.
The BASIC-HHD study is designed to assemble pivotal information on dialysis modality choice and uptake, investigating users, care-givers and care delivery processes and study their variation in a multi-layered analytical approach within a single health care system. The study results would define modality specific service and patient pathway redesign.
Study Registration
This study has been reviewed and approved by the Greater Manchester West Health Research Authority National Research Ethics Service (NRES) The study is on the NIHR (CLRN) portfolio.
PMCID: PMC3851985  PMID: 24044499
Barriers; Home haemodialysis; Mixed methods; Qualitative; Organisation; Adoption; Quality of life
6.  An organisational analysis of the implementation of telecare and telehealth: the whole systems demonstrator 
To investigate organisational factors influencing the implementation challenges of redesigning services for people with long term conditions in three locations in England, using remote care (telehealth and telecare).
Case-studies of three sites forming the UK Department of Health’s Whole Systems Demonstrator (WSD) Programme. Qualitative research techniques were used to obtain data from various sources, including semi-structured interviews, observation of meetings over the course programme and prior to its launch, and document review. Participants were managers and practitioners involved in the implementation of remote care services.
The implementation of remote care was nested within a large pragmatic cluster randomised controlled trial (RCT), which formed a core element of the WSD programme. To produce robust benefits evidence, many aspect of the trial design could not be easily adapted to local circumstances. While remote care was successfully rolled-out, wider implementation lessons and levels of organisational learning across the sites were hindered by the requirements of the RCT.
The implementation of a complex innovation such as remote care requires it to organically evolve, be responsive and adaptable to the local health and social care system, driven by support from front-line staff and management. This need for evolution was not always aligned with the imperative to gather robust benefits evidence. This tension needs to be resolved if government ambitions for the evidence-based scaling-up of remote care are to be realised.
PMCID: PMC3532839  PMID: 23153014
Telecare; Telehealth; Whole system redesign; Organisational change; Adoption; Implementation; Ethnographic methods
7.  Exploring barriers to participation and adoption of telehealth and telecare within the Whole System Demonstrator trial: a qualitative study 
Telehealth (TH) and telecare (TC) interventions are increasingly valued for supporting self-care in ageing populations; however, evaluation studies often report high rates of non-participation that are not well understood. This paper reports from a qualitative study nested within a large randomised controlled trial in the UK: the Whole System Demonstrator (WSD) project. It explores barriers to participation and adoption of TH and TC from the perspective of people who declined to participate or withdrew from the trial.
Qualitative semi-structured interviews were conducted with 22 people who declined to participate in the trial following explanations of the intervention (n = 19), or who withdrew from the intervention arm (n = 3). Participants were recruited from the four trial groups (with diabetes, chronic obstructive pulmonary disease, heart failure, or social care needs); and all came from the three trial areas (Cornwall, Kent, east London). Observations of home visits where the trial and interventions were first explained were also conducted by shadowing 8 members of health and social care staff visiting 23 people at home. Field notes were made of observational visits and explored alongside interview transcripts to elicit key themes.
Barriers to adoption of TH and TC associated with non-participation and withdrawal from the trial were identified within the following themes: requirements for technical competence and operation of equipment; threats to identity, independence and self-care; expectations and experiences of disruption to services. Respondents held concerns that special skills were needed to operate equipment but these were often based on misunderstandings. Respondents’ views were often explained in terms of potential threats to identity associated with positive ageing and self-reliance, and views that interventions could undermine self-care and coping. Finally, participants were reluctant to risk potentially disruptive changes to existing services that were often highly valued.
These findings regarding perceptions of potential disruption of interventions to identity and services go beyond more common expectations that concerns about privacy and dislike of technology deter uptake. These insights have implications for health and social care staff indicating that more detailed information and time for discussion could be valuable especially on introduction. It seems especially important for potential recipients to have the opportunity to discuss their expectations and such views might usefully feed back into design and implementation.
PMCID: PMC3413558  PMID: 22834978
Telehealth; Telecare; Patients’ perspectives; Non-adoption; Non-participation; Barriers; Qualitative research; Whole System Demonstrator
8.  A comprehensive evaluation of the impact of telemonitoring in patients with long-term conditions and social care needs: protocol for the whole systems demonstrator cluster randomised trial 
It is expected that increased demands on services will result from expanding numbers of older people with long-term conditions and social care needs. There is significant interest in the potential for technology to reduce utilisation of health services in these patient populations, including telecare (the remote, automatic and passive monitoring of changes in an individual's condition or lifestyle) and telehealth (the remote exchange of data between a patient and health care professional). The potential of telehealth and telecare technology to improve care and reduce costs is limited by a lack of rigorous evidence of actual impact.
We are conducting a large scale, multi-site study of the implementation, impact and acceptability of these new technologies. A major part of the evaluation is a cluster-randomised controlled trial of telehealth and telecare versus usual care in patients with long-term conditions or social care needs. The trial involves a number of outcomes, including health care utilisation and quality of life. We describe the broad evaluation and the methods of the cluster randomised trial
If telehealth and telecare technology proves effective, it will provide additional options for health services worldwide to deliver care for populations with high levels of need.
Trial Registration
Current Controlled Trials ISRCTN43002091
PMCID: PMC3169462  PMID: 21819569
9.  Effect of telehealth on quality of life and psychological outcomes over 12 months (Whole Systems Demonstrator telehealth questionnaire study): nested study of patient reported outcomes in a pragmatic, cluster randomised controlled trial  
Objective To assess the effect of second generation, home based telehealth on health related quality of life, anxiety, and depressive symptoms over 12 months in patients with long term conditions.
Design A study of patient reported outcomes (the Whole Systems Demonstrator telehealth questionnaire study; baseline n=1573) was nested in a pragmatic, cluster randomised trial of telehealth (the Whole Systems Demonstrator telehealth trial, n=3230). General practice was the unit of randomisation, and telehealth was compared with usual care. Data were collected at baseline, four months (short term), and 12 months (long term). Primary intention to treat analyses tested treatment effectiveness; multilevel models controlled for clustering by general practice and a range of covariates. Analyses were conducted for 759 participants who completed questionnaire measures at all three time points (complete case cohort) and 1201 who completed the baseline assessment plus at least one other assessment (available case cohort). Secondary per protocol analyses tested treatment efficacy and included 633 and 1108 participants in the complete case and available case cohorts, respectively.
Setting Provision of primary and secondary care via general practices, specialist nurses, and hospital clinics in three diverse regions of England (Cornwall, Kent, and Newham), with established integrated health and social care systems.
Participants Patients with chronic obstructive pulmonary disease (COPD), diabetes, or heart failure recruited between May 2008 and December 2009.
Main outcome measures Generic, health related quality of life (assessed by physical and mental health component scores of the SF-12, and the EQ-5D), anxiety (assessed by the six item Brief State-Trait Anxiety Inventory), and depressive symptoms (assessed by the 10 item Centre for Epidemiological Studies Depression Scale).
Results In the intention to treat analyses, differences between treatment groups were small and non-significant for all outcomes in the complete case (0.480≤P≤0.904) or available case (0.181≤P≤0.905) cohorts. The magnitude of differences between trial arms did not reach the trial defined, minimal clinically important difference (0.3 standardised mean difference) for any outcome in either cohort at four or 12 months. Per protocol analyses replicated the primary analyses; the main effect of trial arm (telehealth v usual care) was non-significant for any outcome (complete case cohort 0.273≤P≤0.761; available case cohort 0.145≤P≤0.696).
Conclusions Second generation, home based telehealth as implemented in the Whole Systems Demonstrator Evaluation was not effective or efficacious compared with usual care only. Telehealth did not improve quality of life or psychological outcomes for patients with chronic obstructive pulmonary disease, diabetes, or heart failure over 12 months. The findings suggest that concerns about potentially deleterious effect of telehealth are unfounded for most patients.
Trial Registration ISRCTN43002091.
PMCID: PMC3582704  PMID: 23444424
The Journal of General Physiology  1957;41(2):307-331.
Phage coats or ghosts, composed entirely of protein, appear to be responsible for protecting the phage nucleic acid from degradation by factors in the surrounding medium; attachment of the virus to its susceptible host; and delivering the nucleic acid to the interior of the cell. In addition, the ghosts have a number of biological actions which resemble similar actions of the parent phage. Thus, they both "kill" cells, inhibit pentosenucleic acid formation, interfere with subsequent infection by other virus particles, block adaptive enzyme formation, induce or trigger lysis of the host, and cause a leakage of phosphorus-containing fragments from the cell. Results to date fail to demonstrate a direct involvement of the ghosts in the passage of genetic information to the progeny. Several of the above changes induced in the host cell following attachment of ghosts could be derived from an alteration in but a single metabolic reaction. The stoichiometry of the ghost-bacterial cell interaction is different from that of the parent phage. Experiments to distinguish between a variable response of the host cell to reaction at different sites and a state of heterogeneity in the ghost preparations suggest the former but they are not decisive.
PMCID: PMC2194826  PMID: 13475694
The Journal of General Physiology  1957;40(5):809-825.
A method of preparing the protein coats or ghosts of phage T2 is described along with proof that the lytic action is a property of the ghost. An assay based on the lytic action toward host cells has been developed which permits a rapid evaluation of the number of ghosts with a reliability of ±15 per cent. The antigenic and certain physicochemical properties of the ghost have been determined.
PMCID: PMC2147644  PMID: 13428990
1. A method for the preparation of 8 to 10 liter quantities of T2 virus lysates, titering 2 to 5 x 1011 infectious units per ml. has been described. 2. Procedures have been developed for the concentration and purification of virus to a high specific infectivity. No fractionation procedure of the several used succeeded in further raising the specific infectivity of these purified preparations. 3. Some of the general properties of the better preparations have been determined. They exhibited titers of 2 x 1015 infective units per gm. of material or 1.2 x 1016 per gm. of nitrogen. 4. A study of the distribution of nitrogen among the various fractions of the virus showed that about 6 per cent of the total nitrogen is soluble in 4 per cent trichloracetic acid; that the protein nitrogen is about 40 per cent of the total and the nucleic acid nitrogen is 53 per cent. At least 96 per cent of the total phosphorus is in the nucleic acid fraction. Less than 0.5 per cent quantities of lipid and PNA were found.
PMCID: PMC2147345  PMID: 12981232

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