Refractory gout: what is it and what to do about it?

PURPOSE OF REVIEW: The purpose of this review is to discuss the defining characteristics of refractory gout and the pharmacological management of this problem. RECENT FINDINGS: Refractory gout refers to those patients who have ongoing symptoms of active disease and cannot maintain a target serum urate less than 6 mg/dl. Patients with refractory gout have reduced quality of life, functional impairment, and joint destruction. Multiple factors contribute to refractory gout, and they often relate to delayed or insufficient dosing with allopurinol. Chronic kidney disease imparts a dose limitation on allopurinol that further impairs the effectiveness of urate-lowering therapy. Febuxostat, a novel xanthine oxidase inhibitor, represents a potential alternative to allopurinol in refractory gout patients. Uricase, the enzyme that catalyzes conversion of uric acid into allantoin, is showing promise with its ability to rapidly diminish serum urate levels. The recently defined role of the NALP3 inflammasome in the inflammatory phase of gout suggests a potential role for interleukin-1 inhibition in urate crystal-induced inflammation. SUMMARY: Refractory gout occurs when urate levels are not adequately controlled. Emerging therapies may improve the clinical course of patients with recalcitrant disease.     

"Refractory GERD": acid, nonacid, or not GERD?

Gastroesophageal reflux disease (GERD) is a common condition with 44% of Americans surveyed reporting heartburn at least once a month and 20% once a week (1, 2). However, despite major advances in our understanding of this disease, management of GERD is still a challenge. Proton pump inhibitors (PPIs) are more effective than H2-receptor antagonists (H2RA) in the initial healing of erosive esophagitis, which provide symptom relief and maintenance (3). Due to its established efficacy and safety, PPI treatment is used as the initial "test" in diagnosing GERD in the absence of bleeding, anemia, weight loss, or dysphagia. A single dose of PPI provides adequate symptom relief in most patients; however, dose escalation to twice a day may be needed in some. Patients unresponsive to PPI therapy are often labeled as having "refractory GERD." However, this term is poorly defined and has a different meaning in different countries. More importantly, the cause of "refractory GERD" is poorly understood.     

What is healthcare-associated pneumonia and how is it managed?

PURPOSE OF REVIEW: Pneumonia developing before hospital admission in patients in close contact with the health system was recently termed 'healthcare-associated pneumonia' and proposed as a new category of respiratory infection. We focus on the recent literature concerning the epidemiology, causative organisms, antibiotic susceptibilities, and outcomes of and empirical antibiotic therapy for this condition. RECENT FINDINGS: The reported incidence of healthcare-associated pneumonia among patients requiring hospitalization for pneumonia ranges from 17% to 67%. Hospitalization within 90 days before pneumonia, attending a dialysis clinic and residing in a nursing home were the most common criteria for healthcare-associated pneumonia. Compared with patients with community-acquired pneumonia, those with healthcare-associated pneumonia are older, have greater co-morbidity, and are more likely to have aspiration pneumonia and pneumonia caused by antibiotic-resistant pathogens. Patients with healthcare-associated pneumonia also more frequently initially receive an inappropriate antibiotic therapy, have higher case fatality rates and have longer hospital stay. SUMMARY: Many patients hospitalized with pneumonia via the emergency department have healthcare-associated pneumonia. There are significant differences in the spectrum of causative organisms and antibiotic susceptibilities between healthcare-associated and community-acquired pneumonia. Physicians should differentiate patients with healthcare-associated pneumonia from those with community-acquired pneumonia to promote a targeted approach when selecting initial antibiotic therapy.     

Exercise training in COPD: What is it about intensity?

Most of the current guidelines for pulmonary rehabilitation recommend higher, over lower, intensity exercise training for COPD. Typically, we consider intensity of exercise training to be a key component of any exercise training programme. Whilst studies of young individuals have demonstrated that higher exercise training intensity results in greater improvements in exercise capacity, the evidence for older patients is not so clear cut. In COPD, there is limited evidence regarding the optimal intensity of exercise training. Using both physiological (peak exercise capacity) and patient‐centred (e.g. quality of life) outcomes, it remains inconclusive if higher intensity exercise training bestows any greater benefit than low‐intensity exercise. If we examine the data from interval training studies, which used both high‐ and low‐intensity interval and continuous exercise, we are able to generate more data for comparison. Unfortunately, these data are challenging to interpret due to heterogeneity in how interval training was prescribed. However, when we normalize the interval training data for training volume and examine the change in peak cycling power, there is a relationship between training intensity and increase in peak power (W_peak, r = 0.68, P < 0.05). Hence, whilst there is an inconclusive amount of evidence to support this intervention based on studies that only examined high‐ versus low‐intensity continuous exercise, the additional data from interval training studies would suggest that higher intensity may be superior in terms of increases in W_peak. Future studies should focus on establishing a threshold and an optimal training intensity for COPD.     

GERD and complications: when is surgery necessary?

Esophagitis, ulcer with potential for bleeding and peptic stenosis are typical complications of gastroesophageal reflux disease (GERD). Whereas GERD is frequent with symptom prevalence of 30 % in the normal population, ulcer and peptic stenosis have become very rare. Consequently surgical interventions due to these complications are only necessary in exceptional cases. After successful bougienage and response to adequate medical treatment, surgical indications for peptic stenosis or ulcer are not different to those for other forms of reflux disease. GERD patients with a "short esophagus" and axial hiatal hernia are difficult to treat either by medication or surgery. However, intrathoracic fundoplication may lead to acceptable results. Extraesophageal manifestations of GERD are caused by a severe reflux up to the cervical esophagus. The resulting laryngitis or pulmonary problems require antireflux surgery more often than in the absence of these symptoms. Long-standing reflux can lead to the development of Barrett mucosa, which represents a precancerous for esophageal adenocarcinoma and can be considered as a special complication of GERD. Retrospective data show that progression of Barrett mucosa or its malignant degeneration cannot be prevented by fundoplication. However, in a comparative study concerning low-grade neoplasia fundoplication leads to significantly more cases with regression than medication. High-grade neoplasia has to be removed in all cases. With regard to the prerequisite for correct indications the long-term results of endoscopic or surgical procedures are equal, but endoscopic mucosectomy is favoured due to its lower invasiveness. Indications for surgery by limited or radical esophagectomy are incomplete removal of neoplasia after mucosectomy, long Barrett's esophagus with multifocal lesions or suspicion of submucosal carcinoma.     

What is empathy and can it be taught?

Empathy is the "almost magical" emotion that persons or objects arouse in us as projections of our feelings. Empathy requires passion, more so than does equanimity, so long cherished by physicians. Medical students lose some of their empathy as they learn science and detachment, and hospital residents lose the remainder in the weariness of overwork and in the isolation of the intensive care units that modern hospitals have become. Conversations about experiences, discussions of patients and their human stories, more leisure and unstructured contemplation of the humanities help physicians to cherish empathy and to retain their passion. Physicians need rhetoric as much as knowledge, and they need stories as much as journals if they are to be more empathetic than computers.     

H. pylori and GERD: is less more?

Does chronic Helicobacter pylori gastritis prevent gastroesophageal reflux disease (GERD) and its sequelae? Yes, no, life should be so simple. A quick Medline search on the paired terms identified 527 citations since 1988 and that tells you something right there. Evidently, this is a complex relationship and attempting to reduce it to a yes/no answer is just not going to work. Perusing the literature, it becomes apparent that some combination of three component questions are in fact being asked: (i) Is it biologically plausible that H. pylori gastritis will reduce the occurrence of GERD? (ii) Is there an inverse epidemiological relationship between H. pylori infection and GERD? and (iii) Will the eradication of H. pylori unleash an epidemic of GERD? Each of these questions entails a unique set of consideration. We will consider each in turn.     

Bone quality: what is it and how is it measured?

Bone quality describes aspects of bone composition and structure that contribute to bone strength independently of bone mineral density. These include bone turnover, microarchitecture, mineralisation, microdamage and the composition of bone matrix and mineral. New techniques to assess these components of bone quality are being developed and should produce important insights into determinants of fracture risk in untreated and treated disease.     

Endoscopic therapy for GERD: Does it have a future?

Approximately 20% of patients with gastroesophageal reflux disease (GERD) have symptoms refractory to long-term proton pump inhibitor (PPI) therapy. Furthermore, PPI therapy is expensive. Fundoplication is considered the gold standard of GERD therapy in terms of normalization of esophageal acid exposure and symptom control; however, this exposes the patient to the risks of surgery and anesthesia. Therefore, an endoscopic approach to treating GERD that obviates the need for PPIs and avoids surgical morbidity is desirable. Several endoscopic methods have been used, including radiofrequency ablation, implantation of foreign substances as bulking agents, and various tissue apposition strategies. The emerging field of GERD endotherapy is promising, but more rigorous, sham-controlled, long-term studies are required to elucidate its exact role in clinical practice. This review discusses the evolution of these concepts, describes specific endoscopic devices that have been developed, and explores the future of endotherapies as viable treatment alternatives for GERD.