Assessment of Intervention Fidelity and Recommendations for Researchers Conducting Studies on the Diagnosis and Treatment of Chronic Cough in the Adult: CHEST Guideline and Expert Panel Report

BACKGROUND: Successful management of chronic cough has varied in the primary research studies in the reported literature. One of the potential reasons relates to a lack of intervention fidelity to the core elements of the diagnostic and/or therapeutic interventions that were meant to be used by the investigators.

METHODS: We conducted a systematic review to summarize the evidence supporting intervention fidelity as an important methodologic consideration in assessing the effectiveness of clinical practice guidelines used for the diagnosis and management of chronic cough. We developed and used a tool to assess for five areas of intervention fidelity. Medline (PubMed), Scopus, and the Cochrane Database of Systematic Reviews were searched from January 1998 to May 2014. Guideline recommendations and suggestions for those conducting research using guidelines or protocols to diagnose and manage chronic cough in the adult were developed and voted upon using CHEST Organization methodology.

RESULTS: A total of 23 studies (17 uncontrolled prospective observational, two randomized controlled, and four retrospective observational) met our inclusion criteria. These articles included 3,636 patients. Data could not be pooled for meta-analysis because of heterogeneity. Findings related to the five areas of intervention fidelity included three areas primarily related to the provider and two primarily related to the patients. In the area of study design, 11 of 23 studies appeared to be underpinned by a single guideline/protocol; for training of providers, two of 23 studies reported training, and zero of 23 reported the use of an intervention manual; and for the area of delivery of treatment, when assessing the treatment of gastroesophageal reflux disease, three of 23 studies appeared consistent with the most recent guideline/protocol referenced by the authors. For receipt of treatment, zero of 23 studies mentioned measuring concordance of patient-interventionist understanding of the treatment recommended, and zero of 23 mentioned measuring enactment of treatment, with three of 23 measuring side effects and two of 23 measuring adherence. The overall average intervention fidelity score for all 23 studies was poor (20.74 out of 48).

CONCLUSIONS: Only low-quality evidence supports that intervention fidelity strategies were used when conducting primary research in diagnosing and managing chronic cough in adults. This supports the contention that some of the variability in the reporting of patients with unexplained or unresolved chronic cough may be due to lack of intervention fidelity. By following the recommendations and suggestions in this article, researchers will likely be better able to incorporate strategies to address intervention fidelity, thereby strengthening the validity and generalizability of their results that provide the basis for the development of trustworthy guidelines.

Metastatic melanoma:A regional review and future directions

Aims and background. The incidence of malignant melanoma has risen steadily over recent decades. NCI data from 2005-2007 have suggested that 1.93% of individuals born today in the US will develop melanoma at some stage. Approximately 15% of patients with MM either present with metastatic disease or develop metastases during the course of their illness. Unfortunately, metastatic MM remains a challenge with limited treatment options, and median overall survival is 6-9 months. Methods. We reviewed our data for the treatment of metastatic MM over a period of four years. Data from all patients with metastatic MM treated with systemic therapy without clinical trials from 2006 to 2009 were reviewed. Response rate was determined as per RECIST criteria. Results. Sixty four patients were treated with one or more lines of cytotoxic therapy. Median age was 62 years (range, 23-82) with 53% males. Primary site of the disease was the skin in 75%, mucosal in 12.5%, ocular in 9.4% and nodal with an occult primary in 3.1%. Visceral metastases were present in 75% of patients at the start of treatment, including pulmonary (39.6%) and hepatic (34.4%). All patients were screened for brain metastases, which were present in 26.5% of patients. ECOG performance status was 0 in 7.8%, 1 in 68.7%, 2 in 9.4% and undocumented in the remaining 14%. Patients without brain metastases received single agent DTIC as first line; those with brain metastases received temozolomide. Response rate was 7% for DTIC and 28% for temozolomide, with median progression-free survival of 2.4 and 3.2 months, respectively. Seven patients who received DTIC are alive on follow-up, 2 have ongoing stable disease post-DTIC at 41 months and 18 months. Second line therapy with vinblastine was given to 21 patients (32%), with a response rate of 9.5% and median progression-free survival of 3.4 months. Median overall survival from initiation of therapy was 7.7 months for DTIC and 3.6 months for patients with brain metastases receiving temozolomide. A performance status of 2 was associated with shorter median overall survival (2.0 months). Conclusions. Our results are comparable to published data. Malignant melanoma is a disease with rising incidence and limited treatment options. These patients are best treated in the context of clinical trials as new targeted therapies are promising as future strategies. © Il Pensiero Scientifico Editore.

Molecular classification of non-invasive breast lesions for personalised therapy and chemoprevention

Breast cancer screening has led to a dramatic increase in the detection of pre-invasive breast lesions. While mastectomy is almost guaranteed to treat the disease, more conservative approaches could be as effective if patients can be stratified based on risk of co-existing or recurrent invasive disease.Here we use a range of biomarkers to interrogate and classify purely non-invasive lesions (PNL) and those with co-existing invasive breast cancer (CEIN). Apart from Ductal Carcinoma In Situ (DCIS), relative homogeneity is observed. DCIS contained a greater spread of molecular subtypes. Interestingly, high expression of p-mTOR was observed in all PNL with lower expression in DCIS and invasive carcinoma while the opposite expression pattern was observed for TOP2A.Comparing PNL with CEIN, we have identified p53 and Ki67 as predictors of CEIN with a combined PPV and NPV of 90.48% and 43.3% respectively. Furthermore, HER2 expression showed the best concordance between DCIS and its invasive counterpart.We propose that these biomarkers can be used to improve the management of patients with pre-invasive breast lesions following further validation and clinical trials. p53 and Ki67 could be used to stratify patients into low and high-risk groups for co-existing disease. Knowledge of expression of more actionable targets such as HER2 or TOP2A can be used to design chemoprevention or neo-adjuvant strategies. Increased knowledge of the molecular profile of pre-invasive lesions can only serve to enhance our understanding of the disease and, in the era of personalised medicine, bring us closer to improving breast cancer care.

Personalised and Precision Medicine in Cancer Clinical Trials: Panacea for Progress or Pandora's Box?

Cancer clinical trials have been one of the key foundations for significant advances in oncology. However, there is a clear recognition within the academic, care delivery and pharmaceutical/biotech communities that our current model of clinical trial discovery and development is no longer fit for purpose. Delivering transformative cancer care should increasingly be our mantra, rather than maintaining the status quo of, at best, the often miniscule incremental benefits that are observed with many current clinical trials. As we enter the era of precision medicine for personalised cancer care (precision and personalised medicine), it is important that we capture and utilise our greater understanding of the biology of disease to drive innovative approaches in clinical trial design and implementation that can lead to a step change in cancer care delivery. A number of advances have been practice changing (e.g. imatinib mesylate in chronic myeloid leukaemia, Herceptin in erb-B2-positive breast cancer), and increasingly we are seeing the promise of a number of newer approaches, particularly in diseases like lung cancer and melanoma. Targeting immune checkpoints has recently yielded some highly promising results. New algorithms that maximise the effectiveness of clinical trials, through for example a multi-stage, multi-arm type design are increasingly gaining traction. However, our enthusiasm for the undoubted advances that have been achieved are being tempered by a realisation that these new approaches may have significant cost implications. This article will address these competing issues, mainly from a European perspective, highlight the problems and challenges to healthcare systems and suggest potential solutions that will ensure that the cost/value rubicon is addressed in a way that allows stakeholders to work together to deliver optimal cost-effective cancer care, the benefits of which can be transferred directly to our patients.

Sources of patient knowledge and financing of cataract surgery in rural China: the Sanrao Study of Cataract Outcomes and Up-Take of Services (SCOUTS), report 6.

AIM: To study patient sources of knowledge about cataract surgical services, and strategies for financing surgery in rural China. DESIGN: Cross-sectional case series. METHODS: Patients undergoing cataract surgery by local surgeons in a government, village-level facility in Sanrao, Guangdong between 8 August and 31 December 2005 were examined and had standardised interviews an average of 12 months after surgery. RESULTS: Of 313 eligible patients, 239 (76%) completed the questionnaire. Subjects had a mean (SD) age of 69.9 (10.2) years, 36.4% (87/239) were male, and 87.0% (208/239) had been blind (presenting visual acuity < or = 6/60) before surgery. Word-of-mouth advertising was particularly important: 198 (85.0%) of the subjects knew a person who had undergone cataract surgery, of whom 191 (96.5%) had had cataract surgery at Sanrao itself. Over 70% of subjects (166/239) watched TV daily, whereas 80.0% (188/239) "never" read the newspaper. Nearly two-thirds of suggestions from participants (n = 211, 59.6%) favoured either TV advertisements or word-of-mouth to publicise the programme. While the son or daughter had paid for surgery in over 70% of cases (164/233), the patient's having paid without help was the sole predictor of undergoing second-eye surgery (OR 2.27 (95% CI 1.01 to 5.0, p = 0.04)). DISCUSSION: Strategies to increase uptake of cataract surgery in rural China may benefit from enhancing word-of-mouth advertising (such as with pseudophakic motivators), using television advertising where affordable, and micro-credit or other programmes to enable patients to pay their own fees, thus increasing uptake of second-eye surgery.

Impact of cataract screening outreach in rural China.

PURPOSE: To examine differences between patients with cataract detected during screening and presenting to clinic in rural China. METHODS: Subjects were recruited from 27 screenings and an eye clinic in the same town. All had pinhole-corrected vision < or =6/18 in > or =1 eye due to ophthalmologist-diagnosed cataract. Subjects were administered a previously validated questionnaire on barriers to surgery in four areas: knowledge (K), perceptions of quality (Q), transportation (T), and cost (C). RESULTS: Screening group (SG; n = 120) and clinic group (CG; n = 120) participants did not differ from eligible, examined screening and clinic patients respectively in age, gender, or vision. SG participants were significantly more likely to be female (P = 0.002) and had a smaller housing area and less education (P < 0.001 for both) than those in the CG. Those in the CG were more likely to be blind (habitual VA < or = 6/60) in the better-seeing eye (P = 0.05) and more willing to undergo and pay for cataract surgery (P < 0.001 for both) than SG. In logistic regression models, SG subjects had significantly lower quality scores (P < 0.001) and better habitual vision (P = 0.02) than did CG participants, and SG subjects who agreed to cataract surgery (78.3%) had significantly higher knowledge scores (P < 0.001) than those who refused. DISCUSSION: Screening outreach has the potential to ameliorate disparities in access to cataract surgery in rural China, as it appears more likely to detect patients with cataract with gender-related, economic, educational, and attitudinal barriers to surgery. However, education may be needed to convince screening subjects to undergo surgery.

Community dynamics and the lower airway microbiota in stable chronic obstructive pulmonary disease, smokers and healthy non-smokers

RATIONALE: The role bacteria play in the progression of COPD has increasingly been highlighted in recent years. However, the microbial community complexity in the lower airways of patients with COPD is poorly characterised.

OBJECTIVES: To compare the lower airway microbiota in patients with COPD, smokers and non-smokers.

METHODS: Bronchial wash samples from adults with COPD (n=18), smokers with no airways disease (n=8) and healthy individuals (n=11) were analysed by extended-culture and culture-independent Illumina MiSeq sequencing. We determined aerobic and anaerobic microbiota load and evaluated differences in bacteria associated with the three cohorts. Culture-independent analysis was used to determine differences in microbiota between comparison groups including taxonomic richness, diversity, relative abundance, 'core' microbiota and co-occurrence.

MEASUREMENT AND MAIN RESULTS: Extended-culture showed no difference in total load of aerobic and anaerobic bacteria between the three cohorts. Culture-independent analysis revealed that the prevalence of members of Pseudomonas spp. was greater in the lower airways of patients with COPD; however, the majority of the sequence reads for this taxa were attributed to three patients. Furthermore, members of Bacteroidetes, such as Prevotella spp., were observed to be greater in the 'healthy' comparison groups. Community diversity (α and β) was significantly less in COPD compared with healthy groups. Co-occurrence of bacterial taxa and the observation of a putative 'core' community within the lower airways were also observed.

CONCLUSIONS: Microbial community composition in the lower airways of patients with COPD is significantly different to that found in smokers and non-smokers, indicating that a component of the disease is associated with changes in microbiological status.

A vivência emocional dos enfermeiros nos cenários da prestação de cuidados ao doente oncológico: o caso dos enfermeiros de um serviço de oncologia médica do Instituto Português de Oncologia de Lisboa Francisco Gentil, E.P.E.

Com a presente investigação pretendemos conhecer a vivência das emoções dos enfermeiros nos cenários da prestação de cuidados ao doente oncológico e simultaneamente contribuir para uma melhoria das práticas de intervenção e de gestão emocional em enfermagem nos contextos de trabalho em Oncologia, procurando dar resposta à pergunta inicial de investigação: Qual a vivência emocional dos enfermeiros nos cenários da prestação de cuidados ao doente oncológico? Nas opções metodológicas optámos pelo paradigma qualitativo, onde a entrevista narrativa foi a técnica privilegiada de recolha de informação, tendo permitido compreender com profundidade a forma como os enfermeiros vivem a prestação de cuidados ao doente oncológico. As experiências emocionais consideradas mais marcantes foram na generalidade aquelas que mais penosas se constituíram para os entrevistados, relacionadas com uma relação mais próxima e profunda com o doente e com situações de morte e sofrimento. Consequentemente os sentimentos e emoções referidos foram na sua maioria negativa. Na prática de cuidar do doente oncológico verificou-se a influência marcada dos mitos sociais e pessoais associados à doença cancro, tendo sido reconhecida de forma global a complexidade e especificidade inerentes a esta prestação de cuidados, tão gratificante, quanto desgastante. O uso de mecanismos de gestão das experiências emocionais refletiu-se no recurso a estratégias pessoais e externas, usadas na sua maioria com o objetivo de o desgaste emocional. Foram sugeridas várias medidas de intervenção organizacional no reconhecer uníssono da necessidade de acompanhamento e suporte por parte da organização de saúde. Os resultados desta investigação acrescentam assim todo um conjunto de novos dados que ajudam na compreensão da problemática da vivência emocional dos enfermeiros, na certeza de que esta melhorará a prestação de cuidados ao doente oncológico, com consequente otimização organizacional. /ABSTRACT - With this present investigation we intend to study the emocional life of nurses while providing health care to oncological patients and simultaneously contribute to an improvement of the intervention and emotional management practices in nursing in the contexts of working in Oncology, trying to answer the initial question of the inquiry: What is the emotional life of nurses in health care scenerjy to oncological patients? As far as the methodology is concerned we chose the qualitative paradigm, in which the narrative interview was the privileged technique to gather information. That allowed us to deeply understand the way nurses live the providing of health care to the oncological patient, their emotional experiences, what they feel and express, what moves and consumes them, as well as the forms of emotional management. The most striking emotional experiences have, in general, been those considered most painful by the interviewed nurses, usually related to a closer and deeper relation with the patient and situations of death and suffering. The consequent feelings and emotions have been mostly negative. Health care provided to oncologic patients is strongly influenced by social and personal myths related to cancer and both the complexity and specificity inherent to this kind of health care has been acknowledged as rewarding, as consuming. The use of means of emotional management is visible in the resource to personal and external strategies, used to diminish the emotional consumption. They have also suggested some measures of organizational intervention in the unison recognition of the need of accompaniment and support from the health care institution. The results of this investigation, thus add whole a set of new data that helps in the understanding of the problematic of the emotional life of nurses, in the certainty that this will improve the providing of care to the oncolologically sick person, with consequent organizational optimization.

Study of predictive biomarkers of manganese toxicity : control and prevention of neurotoxicity associated with parenteral nutrition

Tese de doutoramento, Farmácia (Toxicologia), Universidade de Lisboa, Faculdade de Farmácia, 2014

Using genomics for drug discovery in medulloblastoma

Tese de doutoramento, Medicina (Neurocirurgia), Universidade de Lisboa, Faculdade de Medicina, 2014

The Long Range Transport of Birch (Betula) Pollen from Poland and Germany Causes Significant Pre-season Concentrations in Denmark

Background Birch pollen is highly allergic and has the potential for episodically long range transport. Such episodes will in general occur out of the main pollen season. During that time allergy patients are unprotected and high pollen concentrations will therefore have a full allergenic impact. Objective To show that Denmark obtains significant quantities of birch pollen from Poland or Germany before the local trees start to flower. Methods Simultaneous observations of pollen concentrations and phenology in the potential source area in Poland as well as in Denmark were performed in 2006. The Danish pollen records from 2000-2006 were analysed for possible long range transport episodes and analysed with trajectories in combination with a birch tree source map. Results In 2006 high pollen concentrations were observed in Denmark with bi-hourly concentrations above 500 grains/ m3 before the local trees began to flower. Poland was identified as a source region. The analysis of the historical pollen record from Copenhagen shows significant pre-seasonal pollen episodes almost every year from 2000-2006. In all episodes trajectory analysis identified Germany or Poland as source regions. Conclusion Denmark obtains significant pre-seasonal quantities of birch pollen from either Poland or Germany almost every year. Forecasting of birch pollen quantities relevant to allergy patients must therefore take into account long-range transport. This cannot be based on measured concentrations in Denmark. The most effective way to improve the current Danish pollen forecasts is to extend the current forecasts with atmospheric transport models that take into account pollen emission and transport from countries such as Germany and Poland. Unless long range transport is taken into account pre-seasonal pollen episodes will have a full allergic impact, as the allergy patients in general will be unprotected during that time.

Understanding the Needs of People with Dementia and Family Carers

This is the first in a short series that presents case study examples of the positive work achieved by trusts who participated in the Royal College of Nursing's development programme to improve dementia care in acute hospitals. When a person with dementia is in hospital, poor understanding of individual needs and preferences can contribute to a lack of person-centred care. Similarly, the needs of family carers can often be overlooked and staff do not always appreciate these needs at such a stressful time. This article illustrates how three NHS trusts have addressed these issues. To help staff get to know patients with dementia, Salford Royal NHS Foundation Trust has implemented a patient passport. Similarly, The Shrewsbury and Telford Hospital NHS Trust has implemented a carer passport that overcomes the restrictions imposed by hospital visiting hours. Royal Devon and Exeter NHS Foundation Trust also focused on carers, holding a workshop to elicit feedback on what was important to them. This was a useful means of engaging with carers and helped staff to realise that even simple changes can have a significant effect.

Investigating Behaviour and Face Encoding in a Hypothetical Real-World Social Contract: Handwashing in Hazardous Health Settings

Investigations into the evolutionary origins of human cognition has shown that individuals’ memory for others is influenced by the latter’s behaviour in social contracts. Such research is primarily based on hypothetical or more abstract forms of social contracts, whereas an application of this knowledge to everyday health behaviours can be of great value. To address this, the current study investigated whether participants who were asked to imagine themselves in a hypothetical hazardous health scenario showed differential response sensitivity (d’) and latency (RT) to faces of hospital staff tagged with contrasting hand hygiene before touching patients: clean hands, dirty hands, or unknown hand-washing behaviour (control). The test used a two alternative forced-choice (2AFC: “old/new”) face recognition paradigm. The findings showed that d’ to dirty and clean hands was similar, but higher than for controls. Moreover, d’ was not affected by the occupation of hospital staff (nurses vs porters). The absence of memory gains towards clean or dirty hands points to the need for new strategies to remind patients to observe (and remember) the hand hygiene of others when exposed to hazardous health environments.

Starting antidepressant use: a qualitative synthesis of UK and Australian data

Objective To explore people's experiences of starting antidepressant treatment. Design Qualitative interpretive approach combining thematic analysis with constant comparison. Relevant coding reports from the original studies (generated using NVivo) relating to initial experiences of antidepressants were explored in further detail, focusing on the ways in which participants discussed their experiences of taking or being prescribed an antidepressant for the first time. Participants 108 men and women aged 22–84 who had taken antidepressants for depression. Setting Respondents recruited throughout the UK during 2003–2004 and 2008 and 2012–2013 and in Australia during 2010–2011. Results People expressed a wide range of feelings about initiating antidepressant use. People's attitudes towards starting antidepressant use were shaped by stereotypes and stigmas related to perceived drug dependency and potentially extreme side effects. Anxieties were expressed about starting use, and about how long the antidepressant might begin to take effect, how much it might help or hinder them, and about what to expect in the initial weeks. People worried about the possibility of experiencing adverse effects and implications for their senses of self. Where people felt they had not been given sufficient time during their consultation information or support to take the medicines, the uncertainty could be particularly unsettling and impact on their ongoing views on and use of antidepressants as a viable treatment option. Conclusions Our paper is the first to explore in-depth patient existential concerns about start of antidepressant use using multicountry data. People need additional support when they make decisions about starting antidepressants. Health professionals can use our findings to better understand and explore with patients��� their concerns before their patients start antidepressants. These insights are key to supporting patients, many of whom feel intimidated by the prospect of taking antidepressants, especially during the uncertain first few weeks of treatment.

Avaliação da dispneia e padrões ventílatórios num grupo de doentes com limitação crónica do débito aéreo candidatos a um programa de reabilitação

Revista Portuguesa de Pneumologia 1995; 1:p. 119-127.