Inhaled corticosteroids versus placebo for stable chronic obstructive pulmonary disease.

BACKGROUND: The role of inhaled corticosteroids (ICS) in chronic obstructive pulmonary disease (COPD) has been the subject of much uncertainty. COPD clinical guidelines currently recommend selective use of ICS. ICS are not recommended as monotherapy for people with COPD, and are only given in combination with long-acting bronchodilators due to greater efficacy of combination therapy. Incorporating and critiquing newly published placebo-controlled trials into the monotherapy evidence base may help to resolve ongoing uncertainties and conflicting findings about their role in this population. OBJECTIVES: To evaluate the benefits and harms of inhaled corticosteroids, used as monotherapy versus placebo, in people with stable COPD, in terms of objective and subjective outcomes. SEARCH METHODS: We used standard, extensive Cochrane search methods. The latest search date was October 2022. SELECTION CRITERIA: We included randomised trials comparing any dose of any type of ICS, given as monotherapy, with a placebo control in people with stable COPD. We excluded studies of less than 12 weeks' duration and studies of populations with known bronchial hyper-responsiveness (BHR) or bronchodilator reversibility. DATA COLLECTION AND ANALYSIS: We used standard Cochrane methods. Our a priori primary outcomes were 1. exacerbations of COPD and 2. quality of life. Our secondary outcomes were 3. all-cause mortality, 4. lung function (rate of decline of forced expiratory volume in one second (FEV1)), 5. rescue bronchodilator use, 6. exercise capacity, 7. pneumonia and 8. adverse events including pneumonia. ]. We used GRADE to assess certainty of evidence. MAIN RESULTS: Thirty-six primary studies with 23,139 participants met the inclusion criteria. Mean age ranged from 52 to 67 years, and females were 0% to 46% of participants. Studies recruited across the severities of COPD. Seventeen studies were of duration longer than three months and up to six months and 19 studies were of duration longer than six months. We judged the overall risk of bias as low.  Long-term (more than six months) use of ICS as monotherapy reduced the mean rate of exacerbations in those studies where pooling of data was possible (generic inverse variance analysis: rate ratio 0.88 exacerbations per participant per year, 95% confidence interval (CI) 0.82 to 0.94; I2 = 48%, 5 studies, 10,097 participants; moderate-certainty evidence; pooled means analysis: mean difference (MD) -0.05 exacerbations per participant per year, 95% CI -0.07 to -0.02; I2 = 78%, 5 studies, 10,316 participants; moderate-certainty evidence). ICS slowed the rate of decline in quality of life, as measured by the St George's Respiratory Questionnaire (MD -1.22 units/year, 95% CI -1.83 to -0.60; I2 = 0%; 5 studies, 2507 participants; moderate-certainty evidence; minimal clinically importance difference 4 points). There was no evidence of a difference in all-cause mortality in people with COPD (odds ratio (OR) 0.94, 95% CI 0.84 to 1.07; I2 = 0%; 10 studies, 16,636 participants; moderate-certainty evidence). Long-term use of ICS  reduced the rate of decline in FEV1 in people with COPD (generic inverse variance analysis: MD 6.31 mL/year benefit, 95% CI 1.76 to 10.85; I2 = 0%; 6 studies, 9829 participants; moderate-certainty evidence; pooled means analysis: 7.28 mL/year, 95% CI 3.21 to 11.35; I2 = 0%; 6 studies, 12,502 participants; moderate-certainty evidence). ADVERSE EVENTS: in the long-term studies, the rate of pneumonia was increased in the ICS group, compared to placebo, in studies that reported pneumonia as an adverse event (OR 1.38, 95% CI 1.02 to 1.88; I2 = 55%; 9 studies, 14,831 participants; low-certainty evidence). There was an increased risk of oropharyngeal candidiasis (OR 2.66, 95% CI 1.91 to 3.68; 5547 participants) and hoarseness (OR 1.98, 95% CI 1.44 to 2.74; 3523 participants). The long-term studies that measured bone effects generally showed no major effect on fractures or bone mineral density over three years. We downgraded the certainty of evidence to moderate for imprecision and low for imprecision and inconsistency. AUTHORS' CONCLUSIONS: This systematic review updates the evidence base for ICS monotherapy with newly published trials to aid the ongoing assessment of their role for people with COPD. Use of ICS alone for COPD likely results in a reduction of exacerbation rates of clinical relevance, probably results in a reduction in the rate of decline of FEV1 of uncertain clinical relevance and likely results in a small improvement in health-related quality of life not meeting the threshold for a minimally clinically important difference. These potential benefits should be weighed up against adverse events (likely to increase local oropharyngeal adverse effects and may increase the risk of pneumonia) and probably no reduction in mortality. Though not recommended as monotherapy, the probable benefits of ICS highlighted in this review support their continued consideration in combination with long-acting bronchodilators. Future research and evidence syntheses should be focused in that area.

Pharmacogenomics-guided policy in opioid use disorder (OUD) management: An ethnically-diverse case-based approach.

INTRODUCTION: Opioid use disorder (OUD) is characterized by a problematic pattern of opioid use leading to clinically-significant impairment or distress. Opioid agonist treatment is an integral component of OUD management, and buprenorphine is often utilized in OUD management due to strong clinical evidence for efficacy. However, interindividual genetic differences in buprenorphine metabolism may result in variable treatment response, leaving some patients undertreated and at increased risk for relapse. Clinical pharmacogenomics studies the effect that inherited genetic variations have on drug response. Our objective is to demonstrate the impact of pharmacogenetic testing on OUD management outcomes. METHODS: We analyzed a patient who reported discomfort at daily buprenorphine dose of 24 mg, which was a mandated daily maximum by the pharmacy benefits manager. Regular urine screenings were conducted to detect the presence of unauthorized substances, and pharmacogenetic testing was used to determine the appropriate dose of buprenorphine for OUD management. RESULTS: At the 24 mg buprenorphine daily dose, the patient had multiple relapses with unauthorized substances. Pharmacogenetic testing revealed that the patient exhibited a cytochrome P450 3A4 ultrarapid metabolizer phenotype, which necessitated a higher than recommended daily dose of buprenorphine (32 mg) for adequate OUD management. The patient exhibited a reduction in the number of relapses on the pharmacogenetic-based dose recommendation compared to standard dosing. CONCLUSION: Pharmacogenomic testing as clinical decision support helped to individualize OUD management. Collaboration by key stakeholders is essential to establishing pharmacogenetic testing as standard of care in OUD management.

Use of inhaled corticosteroids in COPD: improving efficacy.

Chronic obstructive pulmonary disease (COPD) is a chronic, inflammatory lung disease characterized by airflow limitation that is not fully reversible. The pathological changes in COPD lead to alveolar destruction (emphysema) and chronic airway inflammation, resulting in airflow obstruction and recurrent exacerbations. Inhaled corticosteroids (ICS) are anti-inflammatory agents that are widely used, especially in combination with long-acting beta-agonists, in patients with COPD. Here, we will summarize the benefits and risks of ICS use for COPD, and discuss approaches to more personalized medicine when selecting COPD patients to commence (or withdraw) ICS use. The conclusion arising is that further validation of clinical and biological markers should be undertaken in COPD, in order to individualize ICS therapy to maximize efficacy for patients.

Characteristics of patients at risk for adverse drug events: designing for patient safety and decision support.

Adverse drug events are a significant global health issue. In this paper we describe our research work to date in identifying the characteristics of patients who are at risk for adverse drug events. We conducted a focus group study with health professionals to identify those characteristics of patients that health professionals attend to if they believe a patient is at risk for an adverse drug event. This work is being undertaken in order to develop an electronic decision support system that will alert health professionals to the presence of such patient characteristics in order to support their clinical decision making.

Inhaled corticosteroids for stable chronic obstructive pulmonary disease.

BACKGROUND: The role of inhaled corticosteroids (ICS) in chronic obstructive pulmonary disease (COPD) has been the subject of much controversy. Major international guidelines recommend selective use of ICS. Recently published meta-analyses have reported conflicting findings on the effects of inhaled steroid therapy in COPD. OBJECTIVES: To determine the efficacy and safety of inhaled corticosteroids in stable patients with COPD, in terms of objective and subjective outcomes. SEARCH METHODS: A pre-defined search strategy was used to search the Cochrane Airways Group Specialised Register for relevant literature. Searches are current as of July 2011. SELECTION CRITERIA: We included randomised trials comparing any dose of any type of inhaled steroid with a placebo control in patients with COPD. Acute bronchodilator reversibility to short-term beta(2)-agonists and bronchial hyper-responsiveness were not exclusion criteria. The a priori primary outcome was change in lung function. We also analysed data on mortality, exacerbations, quality of life and symptoms, rescue bronchodilator use, exercise capacity, biomarkers and safety. DATA COLLECTION AND ANALYSIS: Two review authors independently assessed trial quality and extracted data. We contacted study authors for additional information. We collected adverse effects information from the trials. MAIN RESULTS: Fifty-five primary studies with 16,154 participants met the inclusion criteria. Long-term use of ICS (more than six months) did not consistently reduce the rate of decline in forced expiratory volume in one second (FEV(1)) in COPD patients (generic inverse variance analysis: mean difference (MD) 5.80 mL/year with ICS over placebo, 95% confidence interval (CI) -0.28 to 11.88, 2333 participants; pooled means analysis: 6.88 mL/year, 95% CI 1.80 to 11.96, 4823 participants), although one major trial demonstrated a statistically significant difference. There was no statistically significant effect on mortality in COPD patients (odds ratio (OR) 0.98, 95% CI 0.83 to 1.16, 8390 participants). Long-term use of ICS reduced the mean rate of exacerbations in those studies where pooling of data was possible (generic inverse variance analysis: MD -0.26 exacerbations per patient per year, 95% CI -0.37 to -0.14, 2586 participants; pooled means analysis: MD -0.19 exacerbations per patient per year, 95% CI -0.30 to -0.08, 2253 participants). ICS slowed the rate of decline in quality of life, as measured by the St George's Respiratory Questionnaire (MD -1.22 units/year, 95% CI -1.83 to -0.60, 2507 participants). Response to ICS was not predicted by oral steroid response, bronchodilator reversibility or bronchial hyper-responsiveness in COPD patients. There was an increased risk of oropharyngeal candidiasis (OR 2.65, 95% CI 2.03 to 3.46, 5586 participants) and hoarseness. In the long-term studies, the rate of pneumonia was increased in the ICS group compared to placebo, in studies that reported pneumonia as an adverse event (OR 1.56, 95% CI 1.30 to 1.86, 6235 participants). The long-term studies that measured bone effects generally showed no major effect on fractures and bone mineral density over three years. AUTHORS' CONCLUSIONS: Patients and clinicians should balance the potential benefits of inhaled steroids in COPD (reduced rate of exacerbations, reduced rate of decline in quality of life and possibly reduced rate of decline in FEV(1)) against the potential side effects (oropharyngeal candidiasis and hoarseness, and risk of pneumonia).

Teleoncology uptake in British Columbia.

Telehealth enables the delivery of specialized health care to patients living in isolated and remote regions. The purpose of this analysis is to determine the current uptake of teleoncology in mainland British Columbia. Patient appointment data was extracted from the Cancer Agency Information System (CAIS) for the 2009 calendar year. Three types of practitioners used teleoncology in 2009: Medical Oncologists, Genetic Counsellors and Medical Geneticists. In total, 712 telehealth encounters were conducted; Medical Oncologists conducted 595 encounters (83.6%), Genetic Counsellors conducted 112 encounters (15.7%) and Medical Geneticists conducted 5 encounters (0.7%). The most common oncology appointments were Gastro-Intestinal (11.4%) and Lymphoma (11.0%) follow-up appointments with a Medical Oncologist. Telehealth encounters were conducted by 46 individual health care providers however, a single Medical Oncologist conducted 418 encounters and this accounts for more than half (58.7%) of all telehealth appointments in 2009. Radiation Oncologists on the mainland up to this point are not using the technology. The Local Health Areas with the highest number of oncology telehealth appointments were: Kamloops: 203 encounters (34.1%), Penticton: 84 encounters (14.1%), Cranbrook: 58 encounters (9.7%) and the Southern Okanagan: 33 encounter (5.5%). Use of telehealth in rural and remote areas of BC is limited and there is significant room for growth. Further research will be required to identify barriers and restrictions to the use of telehealth in order to increase teleoncology adoption in British Columbia.