Chronic Obstructive Pulmonary Disease Self-Management in Three Low- and Middle-Income Countries: A Pilot Randomized Trial.

Objectives: Chronic obstructive pulmonary disease (COPD) disproportionately affects low- and middle-income countries. Health systems are ill prepared to manage the increase in COPD cases. Methods: We performed a pilot effectiveness-implementation randomized field trial of a community health worker (CHW)-supported, 1-year self-management intervention in individuals with COPD grades B-D. The study took place in low-resource settings of Nepal, Peru, and Uganda. The primary outcome was the St. George's Respiratory Questionnaire (SGRQ) score at 1 year. We evaluated differences in moderate to severe exacerbations, all-cause hospitalizations, and the EuroQol score (EQ-5D-3 L) at 12 months. Measurements and Main Results: We randomly assigned 239 participants (119 control arm, 120 intervention arm) with grades B-D COPD to a multicomponent, CHW-supported intervention or standard of care and COPD education. Twenty-five participants (21%) died or were lost to follow-up in the control arm compared with 11 (9%) in the intervention arm. At 12 months, there was no difference in mean total SGRQ score between the intervention and control arms (34.7 vs. 34.0 points; adjusted mean difference, 1.0; 95% confidence interval, -4.2, 6.1; P = 0.71). The intervention arm had a higher proportion of hospitalizations than the control arm (10% vs. 5.2%; adjusted odds ratio, 2.2; 95% confidence interval, 0.8, 7.5; P = 0.15) at 12 months. Conclusions: A CHW-based intervention to support self-management of acute exacerbations of COPD in three resource-poor settings did not result in differences in SGRQ scores at 1 year. Fidelity was high, and intervention engagement was moderate. Although these results cannot differentiate between a failed intervention or implementation, they nonetheless suggest that we need to revisit our strategy. Clinical trial registered with www.clinicaltrials.gov (NCT03359915).

Impact of prophylactic and 'rescue pack' antibiotics on the airway microbiome in chronic lung disease.

The management of many chronic lung diseases involves multiple antibiotic prescriptions either to treat acute exacerbations or as prophylactic therapy to reduce the frequency of exacerbations and improve patients' quality of life. AIM: To investigate the effects of antibiotics on the homeostasis of bacterial communities in the airways, and how this may contribute to antimicrobial resistance (AMR) among respiratory pathogens and microbiota. METHODS: Within an observational cohort study, sputum was collected from 84 patients with chronic obstructive pulmonary disease and/or bronchiectasis at stable state: 47 were receiving antibiotic prophylaxis therapy. V3-V4 16S-rRNA sequencing on Illumina MiSeq, quantitative PCR for typical respiratory pathogens, bacteriology cultures and antimicrobial susceptibility testing of sputum isolates, resistome analysis on a subset of 17 sputum samples using MinION metagenomics sequencing were performed. FINDING: The phylogenetic α-diversity and the total bacterial density in sputum were significantly lower in patients receiving prophylactic antibiotics (p=0.014 and 0.029, respectively). Antibiotic prophylaxis was associated with significantly lower relative abundance of respiratory pathogens such as Pseudomonas aeruginosa, Moraxella catarrhalis and members of family Enterobacteriaceae in the airway microbiome, but not Haemophilus influenzae and Streptococcus pneumoniae. No major definite directional shifts in the microbiota composition were identified with prophylactic antibiotic use at the cohort level. Surveillance of AMR and resistome analysis revealed a high frequency of resistance to macrolide and tetracycline in the cohort. AMR expressed by pathogenic bacterial isolates was associated with antibiotics prescribed as 'rescue packs' for prompt initiation of self-treatment of exacerbations (Spearman's rho=0.408, p=0.02). CONCLUSIONS: Antibiotic prophylactic therapy suppresses recognised pathogenic bacteria in the sputum of patients with chronic lung disease. The use of antibiotic rescue packs may be driving AMR in this cohort rather than prophylactic antibiotics.

A multi-centre observational study of HIV, tuberculosis and risk of chronic lung disease in urban West Africa.

OBJECTIVE: HIV and tuberculosis (TB) are risk factors for non-communicable chronic lung disease (CLD). Despite the high prevalence of these infections in West Africa, there are no studies that compare CLD between people with HIV and HIV-negative populations in this setting. This study sought to quantify the contribution of HIV and TB infection in addition to conventional CLD risk factors, such as tobacco and biofuel exposure, to CLD in urban West Africa. DESIGN: A multi-centre cross-sectional study was conducted in three community clinics in Lagos, Nigeria between 2018 and 2019. METHODS: Spirometry, questionnaires and clinical records were used to estimate prevalence of CLD and association with risk factors. RESULTS: In total, 148 HIV-negative individuals and 170 HIV-positive individuals completed the study. Current cigarette (11 of 318, 3.5%) and lifetime domestic biofuel (6 of 318, 1.8%) exposures were low. Airway obstruction (33 of 170, 19.4% vs. 12 of 148, 8.1%, P  = 0.004) and CLD (73 of 170, 42.9% vs. 34 of 148, 23%, P  < 0.0001) were more prevalent in people with HIV compared with the HIV-negative group. HIV infection [odds ratio 2.35 (1.33, 4.17), P  = 0.003] and history of TB [odds ratio 2.09 (1.04, 4.20), P  = 0.038] were independently associated with increased risk of CLD. CONCLUSION: HIV and TB far outweigh conventional risk factors, including tobacco and domestic biofuel exposure, as drivers of non-communicable CLD in urban West Africa. Current global policy for CLD may have limited impact on CLD in this setting. Enhanced prevention, diagnosis and management strategies for incident HIV and TB infections are likely to have a significant impact on long-term lung health in sub-Saharan Africa.

Discriminative Accuracy of Chronic Obstructive Pulmonary Disease Screening Instruments in 3 Low- and Middle-Income Country Settings.

Importance: Most of the global morbidity and mortality in chronic obstructive pulmonary disease (COPD) occurs in low- and middle-income countries (LMICs), with significant economic effects. Objective: To assess the discriminative accuracy of 3 instruments using questionnaires and peak expiratory flow (PEF) to screen for COPD in 3 LMIC settings. Design, Setting, and Participants: A cross-sectional analysis of discriminative accuracy, conducted between January 2018 and March 2020 in semiurban Bhaktapur, Nepal; urban Lima, Peru; and rural Nakaseke, Uganda, using a random age- and sex-stratified sample of the population 40 years or older. Exposures: Three screening tools, the COPD Assessment in Primary Care to Identify Undiagnosed Respiratory Disease and Exacerbation Risk (CAPTURE; range, 0-6; high risk indicated by a score of 5 or more or score 2-5 with low PEF [<250 L/min for females and <350 L/min for males]), the COPD in LMICs Assessment questionnaire (COLA-6; range, 0-5; high risk indicated by a score of 4 or more), and the Lung Function Questionnaire (LFQ; range, 0-25; high risk indicated by a score of 18 or less) were assessed against a reference standard diagnosis of COPD using quality-assured postbronchodilator spirometry. CAPTURE and COLA-6 include a measure of PEF. Main Outcomes and Measures: The primary outcome was discriminative accuracy of the tools in identifying COPD as measured by area under receiver operating characteristic curves (AUCs) with 95% CIs. Secondary outcomes included sensitivity, specificity, positive predictive value, and negative predictive value. Results: Among 10 709 adults who consented to participate in the study (mean age, 56.3 years (SD, 11.7); 50% female), 35% had ever smoked, and 30% were currently exposed to biomass smoke. The unweighted prevalence of COPD at the 3 sites was 18.2% (642/3534 participants) in Nepal, 2.7% (97/3550) in Peru, and 7.4% (264/3580) in Uganda. Among 1000 COPD cases, 49.3% had clinically important disease (Global Initiative for Chronic Obstructive Lung Disease classification B-D), 16.4% had severe or very severe airflow obstruction (forced expiratory volume in 1 second <50% predicted), and 95.3% of cases were previously undiagnosed. The AUC for the screening instruments ranged from 0.717 (95% CI, 0.677-0.774) for LFQ in Peru to 0.791 (95% CI, 0.770-0.809) for COLA-6 in Nepal. The sensitivity ranged from 34.8% (95% CI, 25.3%-45.2%) for COLA-6 in Nepal to 64.2% (95% CI, 60.3%-67.9%) for CAPTURE in Nepal. The mean time to administer the instruments was 7.6 minutes (SD 1.11), and data completeness was 99.5%. Conclusions and Relevance: This study demonstrated that screening instruments for COPD were feasible to administer in 3 low- and middle-income settings. Further research is needed to assess instrument performance in other low- and middle-income settings and to determine whether implementation is associated with improved clinical outcomes.

Availability, affordability and access to essential medications for asthma and chronic obstructive pulmonary disease in three low- and middle-income country settings.

INTRODUCTION: Despite the rising burden of chronic respiratory disease globally, and although many respiratory medications are included in the World Health Organization Essential Medications List (WHO-EML), there is limited information concerning the availability and affordability of treatment drugs for respiratory conditions in low- and middle-income countries (LMICs). METHODS: All public and private pharmacies in catchment areas of the Global Excellence in COPD outcomes (GECo) study sites in Bhaktapur, Nepal, Lima, Peru, and Nakaseke, Uganda, were approached in 2017-2019 to assess pricing and availability of medications for the management of asthma and COPD. RESULTS: We surveyed all 63 pharmacies in respective study areas in Nepal (95.2% private), 104 pharmacies in Peru (94.2% private) and 53 pharmacies in Uganda (98.1% private). The availability of any medication for respiratory disease was higher in private (93.3%) compared to public (73.3%) pharmacies. Salbutamol (WHO-EML) monotherapy in any formulation was the most commonly available respiratory medication among the three sites (93.7% Nepal, 86.5% Peru and 79.2% Uganda) while beclomethasone (WHO-EML) was only available in Peru (33.7%) and Nepal (22%). LABA-LAMA combination therapy was only available in Nepal (14.3% of pharmacies surveyed). The monthly treatment cost of respiratory medications was lowest in Nepal according to several cost metrics: the overall monthly cost, the median price ratio comparing medication costs to international reference prices at time of survey in dollars, and in terms of days' wages of the lowest-paid government worker. For the treatment of intermittent asthma, defined as 100 mcg Salbutamol/Albuterol inhaler, days' wages ranged from 0.47 days in Nepal and Peru to 3.33 days in Uganda. CONCLUSION: The availability and pricing of respiratory medications varied across LMIC settings, with medications for acute care of respiratory diseases being more widely available than those for long-term management.

Development and Validity Assessment of a Chronic Obstructive Pulmonary Disease Knowledge Questionnaire in Low- and Middle-Income Countries.

Rationale: The majority of the morbidity and mortality related to chronic obstructive pulmonary disease (COPD) occurs in low- and middle-income countries (LMICs). Despite the increasing burden of COPD, disease-specific knowledge among healthcare workers and patients in LMICs remains limited. COPD knowledge questionnaires (COPD-KQ) are valid and reliable tools to assess COPD knowledge and can be employed in settings with limited health literacy. Objectives: To develop and assess the validity and reliability of a COPD-KQ among individuals with COPD in three LMIC settings. Methods: Twelve questions were generated by an expert team of 16 researchers, physicians, and public health professionals to create an LMIC-specific COPD-KQ. The content was based on previous instruments, clinical guidelines, focus-group discussions, and questionnaire piloting. Participants with COPD completed the questionnaire across three diverse LMIC settings before and 3 months after delivery of a standardized COPD-specific education package by a local community health worker trained to deliver the education to an appropriate standard. We used paired t tests to assess improvement in knowledge after intervention. Results: Questionnaire development initially yielded 52 items. On the basis of community feedback and expertise, items were eliminated and added, yielding a final 12-item questionnaire, with a maximum total score of 12. A total of 196 participants with COPD were included in this study in Nepal (n = 86), Peru (n = 35), and Uganda (n = 75). The mean ± standard deviation baseline score was 8.0 ± 2.5, and 3 months after education, the mean score was 10.2 ± 1.7. The community health worker-led COPD educational intervention improved COPD knowledge among community members by 2.2 points (95% confidence interval, 1.8-2.6 points; t = 10.9; P < 0.001). Internal consistency using Cronbach's α was 0.75. Conclusions: The LMIC COPD-KQ demonstrates face and content validity and acceptable internal consistency through development phases, suggesting a reliable and valid COPD education instrument that can be used to assess educational interventions across LMIC settings. Clinical trial registered with www.clinicaltrials.gov (NCT03365713).

Once Daily Versus Overnight and Symptom Versus Physiological Monitoring to Detect Exacerbations of Chronic Obstructive Pulmonary Disease: Pilot Randomized Controlled Trial.

BACKGROUND: Earlier detection of chronic obstructive pulmonary disease (COPD) exacerbations may facilitate more rapid treatment with reduced risk of hospitalization. Changes in pulse oximetry may permit early detection of exacerbations. We hypothesized that overnight pulse oximetry would be superior to once-daily monitoring for the early detection of exacerbations. OBJECTIVE: This study aims to evaluate whether measuring changes in heart rate and oxygen saturation overnight is superior to once-daily monitoring of both parameters and to assess symptom changes in facilitating earlier detection of COPD exacerbations. METHODS: A total of 83 patients with COPD were randomized to once-daily or overnight pulse oximetry. Both groups completed the COPD assessment test questionnaire daily. The baseline mean and SD for each pulse oximetry variable were calculated from 14 days of stable monitoring. Changes in exacerbation were expressed as Z scores from this baseline. RESULTS: The mean age of the patients was 70.6 (SD 8.1) years, 52% (43/83) were female, and the mean FEV1 was 53.0% (SD 18.5%) predicted. Of the 83 patients, 27 experienced an exacerbation. Symptoms were significantly elevated above baseline from 5 days before to 12 days after treatment initiation. Day-to-day variation in pulse oximetry during the stable state was significantly less in the overnight group than in the once-daily group. There were greater relative changes at exacerbation in heart rate than oxygen saturation. An overnight composite score of change in heart rate and oxygen saturation changed significantly from 7 days before initiation of treatment for exacerbation and had a positive predictive value for exacerbation of 91.2%. However, this was not statistically better than examining changes in symptoms alone. CONCLUSIONS: Overnight pulse oximetry permits earlier detection of COPD exacerbations compared with once-daily monitoring. Monitoring physiological variables was not superior to monitoring symptoms, and the latter would be a simpler approach, except where there is a need for objective verification of exacerbations. TRIAL REGISTRATION: ClinicalTrials.gov NCT03003702; https://clinicaltrials.gov/ct2/show/NCT03003702.

A Novel Case-Finding Instrument for Chronic Obstructive Pulmonary Disease in Low- and Middle-Income Country Settings.

Background: Low- and middle-income countries (LMICs) account for >90% of deaths and illness episodes related to COPD; however, this condition is commonly underdiagnosed in these settings. Case-finding instruments for COPD may improve diagnosis and identify individuals that need treatment, but few have been validated in resource-limited settings. Methods: We conducted a population-based cross-sectional study in Uganda to assess the diagnostic accuracy of a respiratory symptom, exposure and functional questionnaire in combination with peak expiratory flow for COPD diagnosis using post-bronchodilator FEV1/FVC z-score below the 5th percentile as the gold standard. We included locally relevant exposure questions and statistical learning techniques to identify the most important risk factors for COPD. We used 80% of the data to develop the case-finding instrument and validated it in the remaining 20%. We evaluated for calibration and discrimination using standard approaches. The final score, COLA (COPD in LMICs Assessment), included seven questions, age and pre-bronchodilator peak expiratory flow. Results: We analyzed data from 1,173 participants (average age 47 years, 46.9% male, 4.5% with COPD) with acceptable and reproducible spirometry. The seven questions yielded a cross-validated area-under-the-curve [AUC] of 0.68 (95% CI 0.61-0.75) with higher scores conferring greater odds of COPD. The inclusion of peak expiratory flow and age improved prediction in a validation sample (AUC=0.83, 95% CI 0.78-0.88) with a positive predictive value of 50% and a negative predictive value of 96%. The final instrument (COLA) included seven questions, age and pre-bronchodilator peak expiratory flow. Conclusion: COLA predicted COPD in urban and rural settings in Uganda has high calibration and discrimination, and could serve as a simple, low-cost screening tool in resource-limited settings.

Illness representations of chronic obstructive pulmonary disease (COPD) to inform health education strategies and research design-learning from rural Uganda.

More than 90% of chronic obstructive pulmonary disease (COPD)-related deaths occur in low- and middle-income countries; however, few studies have examined the illness experiences of individuals living with and providing treatment for COPD in these settings. This study characterizes illness representations for COPD in Nakaseke, Uganda from the perspectives of health care providers, village health teams and community members (CMs) with COPD. We conducted 40 in-depth, semi-structured interviews (16 health care providers, 12 village health teams and 12 CMs, aged 25-80 years). Interviews were analyzed using inductive coding, and the Illness Representations Model guided our analysis. Stakeholder groups showed concordance in identifying causal mechanisms of COPD, but showed disagreement in reasons for care seeking behaviors and treatment preferences. CMs did not use a distinct label to differentiate COPD from other respiratory illnesses, and described both the physical and social consequences of COPD. Local representations can inform development of adapted educational and self-management tools for COPD.

Prevalence, Severity and Mortality associated with COPD and Smoking in patients with COVID-19: A Rapid Systematic Review and Meta-Analysis.

BACKGROUND: Coronavirus disease 2019 (COVID-19) is an evolving infectious disease that dramatically spread all over the world in the early part of 2020. No studies have yet summarized the potential severity and mortality risks caused by COVID-19 in patients with chronic obstructive pulmonary disease (COPD), and we update information in smokers. METHODS: We systematically searched electronic databases from inception to March 24, 2020. Data were extracted by two independent authors in accordance with the Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines. Study quality was assessed using a modified version of the Newcastle-Ottawa Scale. We synthesized a narrative from eligible studies and conducted a meta-analysis using a random-effects model to calculate pooled prevalence rates and 95% confidence intervals (95%CI). RESULTS: In total, 123 abstracts were screened and 61 full-text manuscripts were reviewed. A total of 15 studies met the inclusion criteria, which included a total of 2473 confirmed COVID-19 patients. All studies were included in the meta-analysis. The crude case fatality rate of COVID-19 was 7.4%. The pooled prevalence rates of COPD patients and smokers in COVID-19 cases were 2% (95% CI, 1%-3%) and 9% (95% CI, 4%-14%) respectively. COPD patients were at a higher risk of more severe disease (risk of severity = 63%, (22/35) compared to patients without COPD 33.4% (409/1224) [calculated RR, 1.88 (95% CI, 1.4-2.4)]. This was associated with higher mortality (60%). Our results showed that 22% (31/139) of current smokers and 46% (13/28) of ex-smokers had severe complications. The calculated RR showed that current smokers were 1.45 times more likely [95% CI: 1.03-2.04] to have severe complications compared to former and never smokers. Current smokers also had a higher mortality rate of 38.5%. CONCLUSION: Although COPD prevalence in COVID-19 cases was low in current reports, COVID-19 infection was associated with substantial severity and mortality rates in COPD. Compared to former and never smokers, current smokers were at greater risk of severe complications and higher mortality rate. Effective preventive measures are required to reduce COVID-19 risk in COPD patients and current smokers.

Global use, utility, and methods of tele-health in COPD: a health care provider survey.

Introduction: Advances in technology offer various solutions that might help optimize the care provided to patients living with chronic non-communicable diseases such as chronic obstructive pulmonary disease (COPD). However, the efficacy of tele-health in COPD is still controversial. Despite this, there appears to be widespread adoption of this technology. Aim: To explore the international use of tele-heath for COPD, to assess the perceptions of clinicians employing tele-health in COPD, and to summarize the techniques that have been used by health care providers to personalize alarm limits for patients with COPD enrolled on tele-health programs. Methods: A cross-sectional survey consisting of 15 questions was distributed and advertised to health care professionals worldwide. Questions were designed to cover five different aspects of tele-health in COPD: purpose of use, equipment type, clinician perceptions, variables monitored, and personalization of alarm limits. Results: A total of 138 participants completed the survey from 29 different countries. As high as 59% of the participants had ever used tele-health for COPD, and 33% still provided tele-health services to patients with COPD. Tele-health was most commonly used for baseline monitoring, with 90% believing it to be effective. The three most commonly monitored variables were oxygen saturation, heart rate, and the use of rescue medication. Conclusion: Twenty-nine different countries use tele-health for managing COPD and therefore there is widespread international use of tele-health in COPD. The majority of providers thought tele-health was effective despite evidence to the contrary.

Use, utility and methods of telehealth for patients with COPD in England and Wales: a healthcare provider survey.

Introduction: Although the effectiveness of domiciliary monitoring (telehealth) to improve outcomes in chronic obstructive pulmonary disease (COPD) is controversial, it is being used in the National Health Service (NHS). Aim: To explore the use of teleheath for COPD across England and Wales, to assess the perceptions of clinicians employing telehealth in COPD and to summarise the techniques that have been used by healthcare providers to personalise alarm limits for patients with COPD enrolled in telehealth programmes. Methods: A cross-sectional survey consisting of 14 questions was sent to 230 COPD community services in England and Wales. Questions were designed to cover five aspects of telehealth in COPD: purpose of use, equipment type, clinician perceptions, variables monitored and personalisation of alarm limits. Results: 65 participants completed the survey from 52 different NHS Trusts. 46% of Trusts had used telehealth for COPD, and currently, 31% still provided telehealth services to patients with COPD. Telehealth is most commonly used for baseline monitoring and to allow early detection of exacerbations, with 54% believing it to be effective. The three most commonly monitored variables were oxygen saturation, heart rate and breathlessness. A variety of methods were used to set alarm limits with the majority of respondents believing that at least 40% of alarms were false. Conclusion: Around one-third of responded community COPD services are using telehealth, believing it to be effective without robust evidence, with a variety of variables monitored, a variety of hardware and varying techniques to set alarm limits with high false alarm frequencies.

Effectiveness-implementation of COPD case finding and self-management action plans in low- and middle-income countries: global excellence in COPD outcomes (GECo) study protocol.

BACKGROUND: Chronic obstructive pulmonary disease (COPD) is the end result of a susceptible individual being exposed to sufficiently deleterious environmental stimuli. More than 90% of COPD-related deaths occur in low- and middle-income countries (LMICs). LMICs face unique challenges in managing COPD; for example, deficient primary care systems present challenges for proper diagnosis and management. Formal diagnosis of COPD requires quality-assured spirometry, which is often limited to urban health centres. Similarly, standard treatment options for COPD remain limited where few providers are trained to manage COPD. The Global Excellence in COPD Outcomes (GECo) studies aim to assess the performance of a COPD case-finding questionnaire with and without peak expiratory flow (PEF) to diagnose COPD, and inform the effectiveness and implementation of COPD self-management Action Plans in LMIC settings. The ultimate goal is to develop simple, low-cost models of care that can be implemented in LMICs. This study will be carried out in Nepal, Peru and Uganda, three distinct LMIC settings. METHODS/DESIGN: We aim to assess the diagnostic accuracy of a simple questionnaire with and without PEF to case-find COPD (GECo1), and examine the effectiveness, cost-effectiveness and implementation of a community-health-worker-supported self-management Action Plan strategy for managing exacerbations of COPD (GECo2). To achieve the first aim, we will enrol a randomly selected sample of up to 10,500 adults aged ≥ 40 years across our three sites, with the goal to enrol 240 participants with moderate-to-severe COPD in to GECo2. We will apply two case-finding questionnaires (Lung Function Questionnaire and CAPTURE) with and without PEF and compare performance against spirometry. We will report ROC areas, sensitivity and specificity. Individuals who are identified as having COPD grades B-D will be invited to enrol in an effectiveness-implementation hybrid randomised trial of a multi-faceted COPD self-management Action Plan intervention delivered by CHWs. The intervention group will receive (1) COPD education, (2) facilitated-self management Action Plans for COPD exacerbations and (3) monthly visits by community health workers. The control group will receive COPD education and standard of care treatment provided by local health providers. Beginning at baseline, we will measure quality of life with the EuroQol-5D (EQ-5D) and St. George's Respiratory Questionnaire (SGRQ) every 3 months over a period of 1 year. The primary endpoint is SGRQ at 12 months. Quality-adjusted life years (QALYs) using the Short-Form 36 version 2 will also be calculated. We will additionally assess the acceptability and feasibility of implementing COPD Action Plans in each setting among providers and individuals with COPD. DISCUSSION: This study should provide evidence to inform the use of pragmatic models of COPD diagnosis and management in LMIC settings. TRIAL REGISTRATION: NCT03359915 (GECo1). Registered on 2 December 2017 and NCT03365713 (GECo2). Registered on 7 December 2017. Trial acronym: Global Excellence in COPD Outcomes (GECo1; GECo2).

Implementation of NICE Clinical Guideline 95 for assessment of stable chest pain in a rapid access chest pain clinic reduces the mean number of investigations and cost per patient.

OBJECTIVE: In 2010, the National Institute for Health and Care Excellence (NICE) in the UK published Clinical Guideline 95 (CG95) advocating risk stratification of patients using 'CADScore' to guide appropriate cardiac investigations for chest pain of recent onset. Implementation of the guideline in the University College London Hospitals NHS Foundation Trust was evaluated to see if it led to a reduction in the average cost of the diagnostic journey per patient and fewer investigations per patient in order to confirm a diagnosis. METHODS: This was a single centre study at a Tertiary Centre in Central London. The investigative journey for each patient presenting to the Rapid Access Chest Pain Clinic (RACPC) at University College London Hospitals NHS Foundation Trust was recorded. Retrospective analysis on this data was performed. RESULTS: Data for 4968 patients presenting to the RACPC from 2004 to 2012 was analysed and a size-matched cohort of 1503 patients preimplementation and postimplementation of the guidelines was compared. The mean cost of investigations postimplementation was £291.83 as compared to £319.54 preimplementation of the guidelines despite higher costs associated with some of the recommended initial investigations. The mean number of tests per patient postguidelines was 0.78 compared to 0.97 for preguidelines. An approximate twofold increase in patients not requiring tests was seen post-CG95 implementation (245 pre-CG95 vs 476 post-CG95). CONCLUSIONS: The implementation of the NICE guidelines in our trust has reduced the average cost of the investigative journey and the number of investigations required per patient.

Diagnosis, management and post-mortem findings of a human case of rabies imported into the United Kingdom from India: a case report.

BACKGROUND: Human rabies infection continues to be a significant public health burden globally, and is occasionally imported to high income settings where the Milwaukee Protocol for intensive care management has recently been employed, with limited success in improving survival. Access to molecular diagnostics, pre- and post-mortem, and documentation of pathophysiological responses while using the Milwaukee protocol, can add useful insights for the future of rabies management. CASE PRESENTATION: A 58-year-old British Asian woman was referred to a regional general hospital in the UK with hydrophobia, anxiety and confusion nine weeks after receiving a dog bite in North West India. Nuchal skin biopsy, saliva, and a skin biopsy from the site of the dog bite wound, taken on the day of admission, all demonstrated the presence of rabies virus RNA. Within 48 hours sequence analysis of viral RNA confirmed the diagnosis and demonstrated that the virus was a strain closely related to canine rabies viruses circulating in South Asia. Her condition deteriorated rapidly with increased agitation and autonomic dysfunction. She was heavily sedated and intubated on the day after admission, treated according to a modified Milwaukee protocol, and remained stable until she developed heart block and profound acidosis and died on the eighth day. Analysis of autopsy samples showed a complete absence of rabies neutralizing antibody in cerebrospinal fluid and serum, and corresponding high levels of virus antigen and nucleic acid in brain and cerebrospinal fluid. Quantitative PCR showed virus was also distributed widely in peripheral tissues despite mild or undetectable histopathological changes. Vagus nerve branches in the heart showed neuritis, a probable Negri body but no demonstrable rabies antigen. CONCLUSION: Rapid molecular diagnosis and strain typing is helpful in the management of human rabies infection. Post-mortem findings such as vagal neuritis highlight clinically important effects on the cardiovascular system which are typical for the clinical course of rabies in humans. Management guided by the Milwaukee protocol is feasible within well-resourced intensive care units, but its role in improving outcome for canine-derived rabies remains theoretical.