The first question a patient often asks their FP after receiving a diagnosis of breast cancer (BC) is “What will my treatment be?” This article will help FPs answer this complex question by reviewing multimodal therapy for BC, which is contingent on molecular subtype and stage.
Polyneuropathy is a common neurologic condition with an overall prevalence in the general population of about 1%–3%, increasing to roughly 7% among people older than 65 years. Polyneuropathy has many causes, and can present in many different ways; thus, it requires a logical clinical approach for evaluation, diagnosis and management. We review the approach to evaluating a patient with polyneuropathy by highlighting important aspects of the history and neurologic examination. We focus on the role of diagnostic investigations for distal symmetric polyneuropathy (DSP), the most common subtype, and an approach to the symptomatic treatment of painful diabetic polyneuropathy (PDN). We draw on practice based guidelines, meta-analyses and systematic reviews, where
possible, as they represent the highest levels of evidence (Box 1).
GUIDELINE TITLE Global Strategy for Asthma Management
and Prevention (GINA Strategy Report)
RELEASE DATE April 26, 2021
PRIOR VERSION April 3, 2020
DEVELOPER AND FUNDING SOURCE The Global Initiative for
Asthma (GINA)
TARGET POPULATION Patients aged 12 y with asthma
MAJOR RECOMMENDATIONS
• Short-acting β-agonist (SABA) monotherapy is no longer
recommended (level of evidence: A).
• There is no distinction between mild-intermittent
and mild-persistent asthma; inhaled corticosteroid
(ICS)–containing therapies are recommended for
both. ICS-formoterol is recommended as the preferred
reliever inhaler (level of evidence: A).
• For treatment of moderate asthma, GINA recommends
ICS-formoterol maintenance and reliever therapy in
the preferred track (level of evidence: A).
Importance: The Global Initiative for Asthma (GINA) recommends 2 alternative treatments for patients receiving treatment at steps 3 to 5: single inhaler combination inhaled corticosteroid-formoterol as both maintenance and reliever (SMART) or inhaled corticosteroid-long-acting β2-agonist as maintenance plus short-acting β2-agonist as reliever.
Objective: To assess whether switching to SMART is associated with longer time to first severe asthma exacerbation compared with a step up or continuation of GINA treatment step with maintenance inhaled corticosteroid-long-acting β2-agonist plus short-acting β2-agonist reliever among patients with poorly controlled asthma.
Data sources: For this systematic review and meta-analysis, the literature, internal study databases at AstraZeneca and the Medical Research Institute of New Zealand, and references from a previous systematic review and meta-analysis on SMART were searched to identify randomized clinical trials published from January 1990 to February 2018, that compared budesonide-formoterol by SMART with maintenance inhaled corticosteroid-long-acting β2-agonist plus short-acting β2-agonist reliever.
Study selection: Trials of at least 24 weeks' duration were included if they reported baseline data on GINA treatment step, asthma control status, and efficacy measures of severe exacerbations. Included patients were adults and adolescents with asthma and baseline Asthma Control Questionnaire 5-item version scores of 1.5 or higher.
Data extraction and synthesis: Patient-level data were identified by independent extraction, and analyses were performed using a fixed-effect model. Data analysis was performed from August 2018 to November 2021.
Main outcomes and measures: The primary outcome was time to first severe asthma exacerbation associated with each treatment, analyzed by Cox proportional hazards regression.
Results: Overall, 4863 patients were included (3034 [62.4%] female; mean [SD] age, 39.8 [16.3] years). Switching patients with uncontrolled asthma at GINA step 3 (n = 1950) to SMART at either step 3 or 4 was associated with a prolonged time to first severe asthma exacerbation, with a 29% reduced risk compared with stepping up to step 4 inhaled corticosteroid-long-acting β2-agonist maintenance plus short-acting β2-agonist reliever (hazard ratio, 0.71; 95% CI, 0.52-0.97). For patients with uncontrolled asthma at step 3 and step 4 (n = 2913), switching to SMART was associated with a prolonged time to first severe asthma exacerbation and a 30% reduced risk compared with remaining at the same treatment step (hazard ratio, 0.70; 95% CI, 0.58-0.85).
Conclusions and relevance: In this systematic review and meta-analysis, for patients with poorly controlled asthma, SMART was associated with longer time to first severe asthma exacerbation compared with a step up or continuation of GINA step with maintenance inhaled corticosteroid-long-acting β2-agonist plus short-acting β2-agonist reliever. These findings suggest that if an adult or adolescent receiving treatment at GINA step 3 or 4 has poorly controlled asthma, it is preferable to switch to the SMART regimen rather than to step up or continue the GINA treatment step with maintenance inhaled corticosteroid-long-acting β2-agonist plus short-acting β2-agonist reliever therapy.
Objectives. To synthesize existing knowledge about the effectiveness and harms of pharmacologic and nonpharmacologic treatments for exacerbations of chronic obstructive pulmonary disease (ECOPD).
Data sources. Embase®, Epub Ahead of Print, In-Process & Other Non-Indexed Citations, MEDLINE® Daily, MEDLINE, Cochrane Central Registrar of Controlled Trials, Ovid Cochrane Database of Systematic Reviews, and Scopus from database inception to January 2, 2019.
Review methods. We included randomized controlled trials (RCTs) that evaluated pharmacologic intervention or nonpharmacologic interventions for ECOPD. The strength of evidence (SOE) was graded for critical final health outcomes.
Results. We included 98 RCTs (13,401 patients, mean treatment duration 9.9 days, mean followup 3.7 months). Final health outcomes, including mortality, resolution of exacerbation, hospital readmissions, repeat exacerbations, and need for intubation, were infrequently evaluated and often showed no statistically significant differences between groups. Antibiotic therapy increases the clinical cure rate and reduces the clinical failure rate regardless of the severity of ECOPD (moderate SOE). There is insufficient evidence to support a particular antibiotic regimen. Oral and intravenous corticosteroids improve dyspnea and reduce the clinical failure rate (low SOE). Despite the ubiquitous use of inhaled bronchodilators in ECOPD, we found only a small number of trials that assessed lung function tests, and not final health outcomes. The evidence is insufficient to support the effect of aminophyllines, magnesium sulfate, mucolytics, inhaled corticosteroids, inhaled antibiotics, 5-lipoxygenase inhibitor, and statins on final health outcomes. Titrated oxygen reduces mortality compared with high flow oxygen (low SOE). Low SOE suggested benefit from some nonpharmacologic interventions such as chest physiotherapy using vibration/percussion/massage or breathing technique (on dyspnea), resistance training (on dyspnea and quality of life), early pulmonary rehabilitation commenced before hospital discharge during the initial most acute phase of exacerbation rather than the convalescence period (on dyspnea) and whole body vibration training (on quality of life). Vitamin D supplementation may improve quality of life (low SOE).
Conclusions. Although chronic obstructive pulmonary disease is a common condition, the evidence base for most interventions in ECOPD remains limited. Systemic antibiotics and corticosteroids are associated with improved outcomes in mild and moderate to severe ECOPD. Titrated oxygen reduces mortality. Future research is required to assess the effectiveness of several emerging nonpharmacologic and dietary treatments.
Background
Excessive drinking is a significant cause of mortality, morbidity and social problems in many countries. Brief interventions aim to reduce alcohol consumption and related harm in hazardous and harmful drinkers who are not actively seeking help for alcohol problems. Interventions usually take the form of a conversation with a primary care provider and may include feedback on the person’s alcohol use, information about potential harms and benefits of reducing intake, and advice on how to reduce consumption. Discussion informs the development of a personal plan to help reduce consumption. Brief interventions can also include behaviour change or motivationally-focused counselling.
This is an update of a Cochrane Review published in 2007.
Objective. To assess efficacy, comparative effectiveness, and harms of psychological and pharmacological treatments for adults with posttraumatic stress disorder (PTSD) and to update the original 2013 review.
Data sources. MEDLINE®, CINAHL®, Cochrane Library, Cochrane Clinical Trials Registry, PILOTS (Published International Literature on Traumatic Stress), PsycINFO®, and reference lists of published literature (May 2012–September 2017).
Review methods. Two investigators independently selected, extracted data from, and rated risk of bias of relevant studies. We conducted meta-analyses or network meta-analyses using random-effects models when we had evidence from three or more studies with low heterogeneity. We graded strength of evidence (SOE) following established Agency for Healthcare Research and Quality guidance.
Results. We included 193 randomized controlled trials (207 articles) for this review.
Several psychological treatments were associated with the reduction of PTSD symptoms and loss of PTSD diagnosis compared with inactive comparators; high SOE supports efficacy of cognitive behavioral therapy (CBT)-exposure and CBT-mixed treatments, and moderate SOE supports efficacy of cognitive processing therapy (CPT), cognitive therapy (CT), eye movement desensitization and reprocessing (EMDR), and narrative exposure therapy (NET). When directly comparing two treatments of interest, moderate SOE favors CBT-exposure over relaxation therapy.
Several pharmacological treatments reduced PTSD symptoms; moderate SOE supports the efficacy of fluoxetine, paroxetine, and venlafaxine compared with placebo. Our network meta-analysis (33 trials; N=4,817) of Clinician-Administered PTSD Scale (CAPS)-measured PTSD symptoms showed no differences in effectiveness between medications with at least moderate SOE of efficacy (fluoxetine, paroxetine, and venlafaxine) (low SOE for no difference).
Studies provided insufficient strength of evidence for serious adverse events associated with any treatments of interest. The majority of psychological studies reported no information about adverse events. Among pharmacological treatments with evidence of efficacy (moderate SOE), we found increased risk of nausea with venlafaxine compared with placebo (moderate SOE).
Our review found insufficient strength of evidence for the comparative effectiveness of any psychological versus pharmacological treatment and for differences in the efficacy or comparative effectiveness of treatments by patient characteristics (e.g., co-occurring conditions) or type, number, severity, or chronicity of trauma exposure(s). We did not find evidence for many of our outcomes of interest or interventions of interest, including the newer treatments added since our prior review.
Conclusions. Several psychological and pharmacological treatments have moderate to high SOE of efficacy for treating adults with PTSD. Future research is needed on the comparative effectiveness of treatments (including different comparisons of psychological and pharmacological treatments), differences in treatment benefits by trauma type or other patient characteristics, and adverse events associated with treatments.
