Predicting CPAP failure in patients with suspected sleep hypoventilation identified on ambulatory testing.

STUDY OBJECTIVES: Home sleep apnea testing (HSAT) is commonly used to diagnose obstructive sleep apnea, but its role in identifying patients with suspected hypoventilation or predicting their response to continuous positive airway pressure (CPAP) therapy has not been assessed. The primary objective was to determine if HSAT, combined with clinical variables, could predict the failure of CPAP to correct nocturnal hypoxemia during polysomnography in a population with suspected hypoventilation. Secondary objectives were to determine if HSAT and clinical parameters could predict awake or sleep hypoventilation. METHODS: A retrospective review was performed of 142 consecutive patients who underwent split-night polysomnography for suspected hypoventilation after clinical assessment by a sleep physician and review of HSAT. We collected quantitative indices of nocturnal hypoxemia, patient demographics, medications, pulmonary function tests, as well as arterial blood gas data from the night of the polysomnography . CPAP failure was defined as persistent obstructive sleep apnea, hypoxemia (oxygen saturation measured by pulse oximetry < 85%), or hypercapnia despite maximal CPAP. RESULTS: Failure of CPAP was predicted by awake oxygen saturation and arterial blood gas results but not by HSAT indices of nocturnal hypoxemia. Awake oxygen saturation ≥ 94% ruled out CPAP failure, and partial pressure of oxygen measured by arterial blood gas ≥ 68 mmHg decreased the likelihood of CPAP failure significantly. CONCLUSIONS: In patients with suspected hypoventilation based on clinical review and HSAT interpretation by a sleep physician, awake oxygen saturation measured by pulse oximetry and partial pressure of oxygen measured by arterial blood gas can reliably identify patients in whom CPAP is likely to fail. Additional research is required to determine the role of HSAT in the identification and treatment of patients with hypoventilation.

Statin discontinuation in high-risk patients: a systematic review of the evidence.

Hypercholesterolemia is a major risk factor for cardiovascular disease (CVD), the leading cause of death worldwide. Since the late 1980s, statins have emerged as effective lipid-lowering therapies and are now widely used to protect against and slow the progression of CVD and cerebrovascular disease. However, there is a significant gap between disease improvement in clinical trials and daily practice possibly attributable to poor adherence with statin therapy. High discontinuation rates were reported in primary and secondary prevention. This systematic review aims to summarize the current literature regarding the association between statin therapy discontinuation and cardiovascular and cerebrovascular events and all-cause mortality in high-risk patients. Available English literature was reviewed using Medline, Embase, Web of Sciences and the Cochrane Library; 39 studies were identified. In primary and secondary prevention, as well as perioperatively, non-adherence or discontinuation of statin therapy was associated with detrimental effects on cardiovascular and cerebrovascular outcomes, including disease severity and mortality. Importantly, some studies reported that very low adherence and discontinuation was associated with worse outcomes than never using statins. In conclusion, non-adherence and discontinuation of statin therapy significantly increased the incidence of cardiovascular and cerebrovascular events as well as all-cause mortality in high-risk patients. Patients would therefore benefit from closer adherence assessment and education programs aimed at increasing awareness of the risk associated with discontinuation of statin therapy.

Insights into the effect of detergents on the full-length rhomboid protease from Pseudomonas aeruginosa and its cytosolic domain.

Rhomboids comprise a family of intramembrane serine proteases that catalyze the cleavage of transmembrane segments within the lipid membrane to achieve a wide range of biological functions. A subset of bacterial rhomboids possesses an N-terminal cytosolic domain that appears to enhance proteolytic activity via an unknown mechanism. Structural analysis of a full-length rhomboid would provide new insights into this mechanism, an objective that solution NMR has the potential to realize. For this purpose we purified the rhomboid from Pseudomonas aeruginosa in a range of membrane-mimetic media, evaluated its functional status in vitro and investigated the NMR spectroscopic properties of these samples. In general, NMR signals could only be observed from the cytosolic domain, and only in detergents that did not support rhomboid activity. In contrast, media that supported rhomboid function did not show these resonances, suggesting an association between the cytosolic domain and the protein-detergent complex. Investigations into the ability of the isolated cytosolic domain to bind detergent micelles revealed a denaturing interaction, whereas no interaction occurred with micelles that supported rhomboid activity. The cytosolic domain also did not show any tendency to interact with lipid bilayers found in small bicelles or vesicles made from Escherichia coli phospholipid extracts. Based on these data we propose that the cytosolic domain does not interact with the lipid membrane, but instead enhances rhomboid activity through interactions with some other part of the rhomboid, such as the catalytic core domain.