• How the Gut Microbiome Affects Outcomes in Cirrhosis: A Review
• PPI Use and Changes in Bacterial Flora Associated with C. difficile Infection
• Chinese Pfizer Plant Problems: First India, Now China
• What Do Victims of Sexual Assault Expect from Providers?
• Adding Coronary Artery Calcium to Risk Scores Aids Cardiovascular Risk Prediction
• Medical Marijuana for Post-Traumatic Stress Disorder? No Way!
• Can Sleep Apnea Cause Depressive Symptoms in Some Patients?
Am J Gastroenterol 2015 Oct; 110:1399
How the Gut Microbiome Affects Outcomes in Cirrhosis: A Review
Pathophysiological effects of dysbiosis are becoming clearer, but knowledge has not yet translated to development of new therapies.
Emerging evidence supports a role for gut microbiota in shaping immune and metabolic functions. In patients with cirrhosis, we know that dysbiosis is associated with adverse effects on metabolism and immunity that can lead to complications such as spontaneous bacterial peritonitis, hepatic encephalopathy, and variceal hemorrhage.
To assess the current evidence on the effects of dysbiosis on outcomes of cirrhosis, researchers conducted a review of relevant studies published through April 2015. Key findings include:
- Alterations found in the composition of enteric flora in patients with cirrhosis include elevated Enterobacter and Enterococcus and reduced Bifidobacteria. In addition, microbial and genetic diversity is lower compared with healthy patients.
- The process by which dysbiosis contributes to hepatic encephalopathy is production of ammonia and endotoxin-driven inflammation.
- The process by which dysbiosis contributes to spontaneous bacterial peritonitis is bacterial translocation, resulting from bacterial overgrowth, increased intestinal permeability, and integrity of immune surveillance mechanisms.
- The success of gut decontamination to treat cirrhosis-related events (e.g., rifaximin use in treating hepatic encephalopathy) highlights the central role of the gut microbiota in their pathogenesis.
- The possible role of probiotics in treating complications of cirrhosis such as hepatic encephalopathy is inconclusive due to substantial heterogeneity of clinical trials.
COMMENT: The authors provide an excellent summary of the established and evolving knowledge of the role of the gut microbiome — and the clinical consequences of dysbiosis — in cirrhosis. Hopefully, recent advances in culture-independent techniques to describe the composition of the gut microbiome will continue to drive us towards a deeper understanding of the pathophysiology of cirrhosis and identification of novel treatments. For now, interventions such as probiotics should not be used routinely in patients with cirrhosis until we have a better understanding of their therapeutic potential.
CITATION(S): Macnaughtan J and Jalan R.Clinical and pathophysiological consequences of alterations in the microbiome in cirrhosis. Am J Gastroenterol 2015 Oct; 110:1399. (http://dx.doi.org/10.1038/ajg.2015.313)
http://www.ncbi.nlm.nih.gov/pubmed/26416191?access_num=26416191&link_type=
MED&dopt=Abstract
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Gastroenterology 2015 Oct; 149:883
PPI Use and Changes in Bacterial Flora Associated with C. difficile Infection
Although overall bacterial diversity remained unaltered after 4 weeks of high-dose proton-pump inhibitor treatment, certain taxa that may affect CDI risk showed changes in relative abundance.
Proton-pump inhibitor (PPI) use is believed to increase the risk for Clostridium difficile infection (CDI), presumably by altering the bacteria normally found in the gut. To further investigate this presumption, researchers conducted a prospective, open-label trial involving 12 healthy volunteers.
Stool samples were obtained at baseline and 4 weeks, after which all participants received 40 mg of omeprazole twice daily for 4 weeks, and another stool sample was obtained. Half of the participants then stopped the PPI, and half continued it for an additional 4 weeks. A final stool sample was collected from all at 12 weeks. Samples were analyzed using 16S ribosomal RNA gene sequencing.
Although PPI therapy did not affect overall bacterial diversity in stool, certain taxa that have been associated with antibiotic exposure and increased CDI risk (specifically, enterococci and streptococci) were increased in relative abundance, and Clostridiales species were decreased. PPI treatment also increased bacterial genes associated with epithelial invasion and the renin-angiotensin pathway. There were no changes in bile salts.
COMMENT: This is a very small, open-label study in volunteers whose diet was not controlled or recorded. The changes noted in particular bacterial taxa and in genes associated with epithelial invasion suggest a potential mechanism by which PPI use could affect CDI risk. Further studies are needed to replicate these results and clarify the mechanism. Large, prospective trials are necessary to determine whether these changes translate into clinically significant changes in CDI risk in particular patient groups.
CITATION(S): Freedberg DE et al. Proton pump inhibitors alter specific taxa in the human gastrointestinal microbiome: A crossover trial. Gastroenterology 2015 Oct; 149:883. (http://dx.doi.org/10.1053/j.gastro.2015.06.043)
http://www.ncbi.nlm.nih.gov/pubmed/26164495?access_num=26164495&link_
type=MED&dopt=Abstract
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Chinese Pfizer Plant Problems: First India, Now China
A Pfizer Inc. plant in China that was being inspected by FDA regulators in order to ship drugs to the U.S. kept a second set of quality and manufacturing records that didn't match official ones. During an inspection of Pfizer's plant in Dalian, FDA inspectors said in their report that employees hid quality failures, used expired manufacturing materials or ones that hadn't been recently checked, moved around records during the investigation, and retested failing products until they passed. In another plant, the FDA inspectors noticed that one manufacturing unit had only one stand-alone toilet in significant disrepair 50 yards from the aseptic manufacturing unit. Inside the facility inspectors saw no hand-washing station and an open pit that appeared to be used as a urinal.
http://www.bloomberg.com/news/articles/2015-10-30/fda-says-chinese-pfizer-plant-hid-failures-used-old-ingredients
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Emerg Med J 2015 Oct 19
What Do Victims of Sexual Assault Expect from Providers?
Sexual assault patients expect that both their physical and mental health will be assessed on their initial visit, but that rarely occurs.
Sexual assault survivors may seek care through multiple avenues, including primary care physicians, emergency physicians, and gynecologists. In Europe, these providers have no specific training to deal with the psychological trauma caused by the event. In this prospective study, 232 survivors of sexual assault who presented to a Department of Forensic Medicine near Paris after seeking medical care at another facility were surveyed about their initial experience.
On the initial visit, the care patients received matched the care they expected for trauma care (40% received trauma care; 44% expected it) and gynecologic care (31% received; 28% expected). Forensic support services were provided more often than patients expected (54% received; 21% expected), and psychological support was provided less often than expected (21% received; 31% expected). Patients more often considered their care to have provided crucial support when they received forensic support services plus medical care than when they received medical care alone (25% vs. 3%).
COMMENT: Sexual assault is as much a psychological assault as it is physical, and not surprisingly, initial providers of care to victims of sexual assault in this study failed to meet patient expectations. To meet the needs of our patients, emergency departments must be prepared to address not only their physical but also their psychological and forensic needs. Sexual Assault Nurse Examiner (SANE) programs have helped to address this in the U.S., but emergency departments without a SANE program must include mental health in the initial assessment.
CITATION(S): Denis C et al. Expectations and perceptions of care among victims of sexual assault who first seek care from emergency, primary care and gynaecological doctors. Emerg Med J 2015 Oct 19; [e-pub].
(http://dx.doi.org/10.1136/emermed-2015-204655)
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J Am Coll Cardiol 2015 Oct 13; 66:1643
Adding Coronary Artery Calcium to Risk Scores Aids Cardiovascular Risk Prediction
Two studies show how CAC scoring can further refine risk.
Coronary artery calcium (CAC) screening can identify individuals with subclinical atherosclerosis who are at higher risk for cardiac events than otherwise expected. Two separate studies were reported simultaneously using data from the Multi-Ethnic Study of Atherosclerosis (MESA).
McClelland and colleagues sought to evaluate 10-year heart disease risk prediction using coronary artery calcium and traditional risk factors, derived in the MESA cohort. They assessed the utility of a novel risk equation in two well-described, similar external cohorts, which demonstrated good-to-excellent discrimination and calibration in these cohorts. The authors found that the inclusion of CAC measurements in the MESA risk score offered significant improvement in risk prediction, even over the additive effect of CAC and traditional risk scores.
Nasir and colleagues examined the circumstances in which the absence of CAC would lead to reclassifying patients from a risk stratum in which statins are recommended to one in which statins would not be recommended. The researchers followed 4758 participants (aged 59±9 years) for a median of 10.3 years. Most (77%) of the 2377 MESA participants were classified by American College of Cardiology/American Heart Association guidelines as recommended for moderate- or high-intensity statins because their 10-year risk was ≥7.5%. Of statin-eligible patients, 41% had a CAC score of 0 and had fewer cardiac events than expected for their risk-factor level (5.2 per 1000 person-years). Among 589 participants (12%) for moderate-intensity statin therapy would be considered based on risk assessment, 338 (57%) had a CAC score of 0 and a cardiac event rate of 1.5 per 1000 person-years.
COMMENT: These studies suggest that CAC provides a useful means of both better identifying patients at risk for cardiac events and, alternately, to reclassify patients from being recommended for statin therapy to not being recommended. As an editorialist points out, the optimal approach for now appears to be sequential screening with quantitative risk assessment, followed by selective CAC screening mainly for those with risk scores of 5% to 20%, rather than universal CAC screening.
CITATION(S):McClelland RL et al. 10-year coronary heart disease risk prediction using coronary artery calcium and traditional risk factors: Derivation in the MESA (Multi-Ethnic Study of Atherosclerosis) with validation in the HNR (Heinz Nixdorf Recall) study and the DHS (Dallas Heart Study). J Am Coll Cardiol 2015 Oct 13; 66:1643. (http://dx.doi.org/10.1016/j.jacc.2015.08.035)
http://www.ncbi.nlm.nih.gov/pubmed/26449133?access_num=26449133&link_
type=MED&dopt=Abstract
• Nasir K et al. Implications of coronary artery calcium testing among statin candidates according to American College of Cardiology/American Heart Association cholesterol management guidelines: MESA (Multi-Ethnic Study of Atherosclerosis). J Am Coll Cardiol 2015 Oct 13; 66:1657. (http://dx.doi.org/10.1016/j.jacc.2015.07.066)
http://www.ncbi.nlm.nih.gov/pubmed/26449135?access_num=26449135&link_
type=MED&dopt=Abstract
• Sanz J.Coronary calcium score and the new guidelines: Back to square one? J Am Coll Cardiol 2015 Oct 13; 66:1669.
(http://dx.doi.org/10.1016/j.jacc.2015.08.041)
• Lloyd-Jones DM.Coronary artery calcium scoring: Are we there yet? J Am Coll Cardiol 2015 Oct 13; 66:1654.
(http://dx.doi.org/10.1016/j.jacc.2015.08.031)
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J Clin Psychiatry 2015 Sep; 76:1174
Medical Marijuana for Post-Traumatic Stress Disorder? No Way!
Outcomes are worse in patients continuing or initiating marijuana use after finishing a PTSD treatment program, compared with those not using or those who stopped use.
At least nine U.S. states consider post-traumatic stress disorder (PTSD) an indication for medical marijuana, based largely on preclinical data linking cannabidiol with enhanced fear extinction and anecdotal reports of improvement in PTSD with marijuana use. Researchers used Veterans Affairs (VA) data to examine effects of marijuana use in 2276 patients in PTSD treatment programs with no recent history of alcohol or drug use.
Patients reported marijuana use at program entry and 4 months after program discharge. Continuing users (n=296) and “starters” — those starting use after the program (n=831) — had worse PTSD symptoms and drug abuse problems, compared with never users (n=850) and those stopping after the program (n=299). “Starters” had more violent behavior and alcohol problems at follow-up than patients in the other three subgroups.
COMMENT: Findings from this observational study are consistent with those from smaller observational studies from VA inpatient PTSD programs suggesting that marijuana may worsen rather than improve PTSD. As the authors note, “starters” might be more severely ill patients who began use because the PTSD treatment they received was ineffective. Alternatively, use might have provided transient relief, but withdrawal worsened symptoms and overall outcome. Nonetheless, this analysis, the largest of its kind, does not indicate that marijuana use improves PTSD symptoms. Clinicians treating PTSD patients would be wise to share this information with them and to discourage their use of marijuana.
CITATION(S): Wilkinson ST et al. Marijuana use is associated with worse outcomes in symptom severity and violent behavior in patients with posttraumatic stress disorder. J Clin Psychiatry 2015 Sep; 76:1174.
(http://dx.doi.org/10.4088/JCP.14m09475)
http://www.ncbi.nlm.nih.gov/pubmed/26455669?access_num=26455669&link_
type=MED&dopt=Abstract
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J Clin Sleep Med 2015 Sep 15; 11:1029
Can Sleep Apnea Cause Depressive Symptoms in Some Patients?
Patients with obstructive sleep apnea had depression scores in the moderate range that fell to the normal range after treatment of the sleep apnea.
Sleep apnea is associated with multiple depressive symptoms, most notably insomnia and fatigue, and with an increased rate of major depression. A clinical study now provides further information about these diagnoses.
Of 426 patients presenting for apnea evaluation at a sleep clinic, 293 had mild-to-moderate apnea, and 228 were able to comply with continuous positive airway pressure (CPAP) treatment for 3 months. Before polysomnography, patients answered the nine-item Patient Health Questionnaire (PHQ-9).
The number of apnea episodes was directly correlated with PHQ-9 score in the entire sample and within CPAP-compliant patients. In these patients, mean PHQ-9 fell from 11.3 to 3.7 with CPAP, and the proportion of patients with PHQ-9 of ≥10 (a common cutoff for “depression”) fell from 74.6% to 3.9%. All individual symptoms were reduced, except for poor concentration; at baseline, 18% endorsed some suicidal ideation, which fell to 0% with treatment. Treatment was associated with similar decline in the 52% of patients taking antidepressants.
COMMENT: Practicing psychiatrists rarely think of sleep apnea as a possible cause of depression in their patients. Despite study limitations of lack of diagnostic instrument or clinical evaluation beyond a rating scale, the results are noteworthy, even if possibly inflated. An evaluation for sleep apnea is warranted in patients with obesity, daytime somnolence or even fatigue, a history of snoring or interrupted sleep, a large neck, or a short mandible. Although sleep apnea is unlikely to be a common cause of depression, I have personally seen a few patients with significant depression (despite antidepressant treatment) that disappeared entirely with sleep apnea treatment.
CITATION(S): Edwards C et al. Depressive symptoms before and after treatment of obstructive sleep apnea in men and women. J Clin Sleep Med 2015 Sep 15; 11:1029.
(http://dx.doi.org/10.5664/jcsm.5020)
http://www.ncbi.nlm.nih.gov/pubmed/25902824?access_num=25902824&link_
type=MED&dopt=Abstract
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