After hearing and assimilating this program, the listener will be better able to: ( 1 ) Increase his/her basic knowledge of important advances in medicine; ( 2 ) Identify a broad range of clinical research reported in the medical literature; ( 3 ) Synthesize research findings through one-on-one interviews with authors and editorialists; ( 4 ) Integrate new treatments reviewed in the summaries into current practice; ( 5 ) Challenge oneself with thoughtful, clinically relevant questions. Disclosure In adherence to the ACCME Standards for Commercial Support, Audio-Digest requires all faculty and members of the planning committee to disclose relevant financial relationships within the past 12 months that might create any personal conflicts of interest. Any identified conflicts were resolved to ensure that this educational activity promotes quality in health care and not a proprietary business or commercial interest. For this program, Dr. Jeffrey Curtis reported receiving research grants and consulting fees from Roche/Genentech, UCB, Janssen, CORRONA, Amgen, Pfizer, Bristol-Myers Squibb, Crescendo, and AbbVie. Dr. Mary Vaughan Sarrazin and the planning committee members reported that they had nothing to disclose. GI BLEEDING ASSOCIATED WITH DABIGATRAN OR RIVAROXABAN IS SIMILAR TO THAT ASSOCIATED WITH WARFARIN Last year, several studies explored the risk for gastrointestinal bleeding with the novel oral anticoagulants, dabigatran (trade name: Pradaxa) and rivaroxaban (trade name: Xarelto). In a trial of treatment for atrial fibrillation, dabigatran and rivaroxaban were associated with a slightly higher risk for GI bleeding than was warfarin ( www.jwatch.org /na33185 ); in trials of treatment for thromboembolism, GI bleeding risks with the novel anticoagulants and warfarin were similar ( www.jwatch.org /na35816 ). But how is this playing out in real-world use? Two studies on the website of The BMJ provide some answers. In the first study ( http:// dx.doi.org /10.1136/bm j. h1585 ), researchers used a large administrative database of commercially insured patients and retrospectively compared the risk for GI bleeding among 50,000 new users of dabigatran, rivaroxaban, and warfarin. After adjusting for multiple potential confounders, the researchers found no statistically significant differences in the risks for GI bleeding between either dabigatran or rivaroxaban use and the use of warfarin. In the second study ( http:// dx.doi.org /10.1136/bm j. h1857 ), researchers used propensity matching to compare the risk for GI bleeding among 90,000 new users of these anticoagulants. The risks for GI bleeding associated with dabigatran and rivaroxaban were similar to that associated with warfarin in both patients with atrial fibrillation and in patients without it. Notably, the risk for GI bleeding increased at a faster rate with increasing age among the users of the novel anticoagulants than among the users of warfarin, especially among the patients older than 75. These two real-world retrospective studies suggest that, in general, the risk for gastrointestinal bleeding thats associated with dabigatran or rivaroxaban is similar to that associated with warfarin. Even so, clinicians should be cautious when prescribing novel anticoagulants to elders and to patients with renal impairment and should use the lowest available effective dose. For example, an editorialist notes that ( http:// dx.doi.org /10.1136/bm j. h1679 ), in most studies from the United States, researchers have evaluated a 150-mg dose of dabigatran. Yet, evidence suggests that the 110-mg dose (which isnt available in the U.S.) is not only effective, but is also associated with lower GI bleeding risk for patients with atrial fibrillation. Similar evidence exists for rivaroxaban dosing. EARLY CPR IS ASSOCIATED WITH IMPROVED SURVIVAL During the past 30years, some 3 million people in Sweden have been trained to perform cardiopulmonary resuscitation thats nearly a third of the countrys population. To see whether starting CPR before the arrival of emergency medical services affects 30-day survival in patients with out-of-hospital cardiac arrest, researchers reviewed the data from 1990 to 2011 in a Swedish registry. Details appear in the June11 New England Journal of Medicine ( http:// dx.doi.org /10.1056/NEJMoa1405796 ). The analysis included more than 30,000 cases of bystander-witnessed, emergency medical services-treated cardiac arrest; half of the patients got CPR before emergency medical services arrived. Thirty-day survival was significantly higher in the patients who got early CPR than in those who didnt. After propensity-score adjustment for various potentially confounding factors, the difference in 30-day survival remained significant. Early and effective bystander cardiopulmonary resuscitation should be the goal for all witnessed out-of-hospital cardiac arrests if we want to maximize positive outcomes. Potential next steps to improving survival from out-of-hospital cardiac arrest include shorter and more focused CPR training ( www.jwatch.org /na33511 ), mandatory CPR training in high schools, improved public education about the benefits of CPR, and a better understanding of why bystander CPR isnt performed more routinely ( http:// dx.doi.org /10.1056/NEJMe1504659 ). CT ANGIOGRAPHY OR MYOCARDIALPERFUSION IMAGING IN ACUTE CHEST PAIN? Clinicians have long used stress myocardial perfusion imaging to risk-stratify patients with acute chest pain, but computed tomography angiography is an increasingly popular alternative. In a single-center study on the website of the Annals of Internal Medicine ( http:// dx.doi.org /10.7326/M14-2948 ), researchers randomized 400 patients with acute chest pain who needed further imaging to either CT angiography or myocardial perfusion imaging. During the subsequent year, 15% of the patients in both of the groups underwent invasive angiography. Of those who underwent invasive angiography, roughly half of the patients in each group didnt undergo revascularization after their angiograms (which was the primary endpoint for the study). Adverse effects (like death or nonfatal cardiovascular events) and healthcare use were similar in the two groups during a median follow-up of longer than 3years. But the median radiation exposure from both initial and downstream testing was lower in the CT angiography group, and measures of patient experience also favored CT angiography. In this study, clinical outcomes after computed tomography angiography and myocardial perfusion imaging were similar. CT angiography was associated with lower radiation exposure, but it didnt lower the rate of invasive angiography not resulting in revascularization. In the recently published and larger PROMISE study of outpatients with suspected coronary artery disease, where the comparator group for CT angiography included various forms of functional testing, CT angiography resulted in a significantly lower percentage of invasive angiograms that didnt show substantial obstructive epicardial coronary disease ( www.jwatch.org /na37279 ). One wonders how stress echocardiography would fare in a head-to-head comparison, when the advantage of CT angiography in radiation exposure would presumably be lost or minimized. In the meantime, both CT angiography and myocardial perfusion imaging remain viable options for further work-ups of patients with chest pain, depending on individual patient factors, local expertise, and cost or insurance coverage issues. CARDIOVASCULAR EFFECT OF SITAGLIPTIN IN TYPE 2 DIABETES Two years ago, it was shown that the diabetes drug saxagliptin (trade name: Onglyza) was associated with a modest, but statistically significant, increase in hospital admissions for heart failure ( www.jwatch.org /na32162 ). Saxagliptin is a dipeptidyl peptidase-4 inhibitor. Now, in a study on the website of the New England Journal of Medicine ( http:// dx.doi.org /10.1056/NEJMoa1501352 ), researchers have examined the cardiovascular safety of sitagliptin (trade name: Januvia), which is another DPP-4 inhibitor. They enrolled nearly 15,000 patients with type2 diabetes and established cardiovascular disease; the patients had hemoglobin A 1c levels between 6.5% and 8% while taking one or two glucose-lowering agents. The patients were randomized to add either sitagliptin or placebo to their diabetes regimens, and treating clinicians were encouraged to adjust the regimens to achieve individually appropriate hemoglobin A 1c targets. During a median follow-up of 3years, hemoglobin A 1c levels averaged 0.3% lower with sitagliptin than with placebo. The primary composite outcome (namely, cardiovascular-related death; nonfatal myocardial infarction or stroke; or hospitalization for unstable angina) was seen in about 12% of the patients in both of the groups; sitagliptin was statistically noninferior, but not superior, to placebo. The rates of hospitalization for heart failure were 3% in both of the groups. Although this study didnt focus on microvascular outcomes, the incidences of diabetic eye conditions, neuropathy, microalbuminuria, and renal failure were similar in the groups. Back in April, it was already announced that this trial achieved its primary goal showing that sitagliptin is safe from the cardiovascular perspective. But showing that a drug for treating patients with type2 diabetes isnt worse than placebo (with respect to cardiovascular outcomes) isnt enough to support its use. The ultimate goal here is to improve important clinical outcomes, and this trial showed no lower incidence of either macrovascular or microvascular outcomes with sitagliptin. So the role of sitagliptin which costs about US$5000 /year for patients who have to pay out of pocket isnt clear. This study was industry-supported. DULAGLUTIDE AS A SUBSTITUTE FOR LONG-ACTING INSULIN IN A BASAL-BOLUS REGIMEN? Often, when type2 diabetes is difficult to control, clinicians resort to basal-bolus insulin regimens. Could the long-acting basal insulin in this kind of a regimen be replaced by a long-acting glucagon-like peptide-1 inhibitor, maybe conferring a lower risk for hypoglycemia? Last year, a glucagon-like peptide-1 inhibitor called dulaglutide (trade name: Trulicity) was approved by the Food and Drug Administration for once-weekly injection. In a manufacturer-conducted study in the May23 issue of The Lancet ( http:// dx.doi.org /10.1016/ S0140-6736(15)60936-9 ), researchers randomized 900 adults with hemoglobin A 1c levels of 7% or greater, despite fixed insulin doses once/ or twice /day , to either weekly dulaglutide (at doses of 0.75 or 1.5mg) or daily bedtime insulin glargine (trade name: Lantus). All of the patients got prandial insulin lispro (trade name: Humalog) three times /day . The patients were allowed to take metformin, but no other oral diabetes medications. The doses of glargine and lispro were titrated by algorithm to achieve fasting and preprandial blood glucose levels of 71 to 99 mg/ dL. Treatment assignments werent concealed, except for the dose of dulaglutide. After 6months, the adjusted average declines in hemoglobin A 1c were significantly greater with high- and low-dose dulaglutide than with glargine, and significantly more dulaglutide patients than glargine patients reached the hemoglobin A 1c target of less than 7%. Gastrointestinal side effects were significantly more common with dulaglutide than with glargine, and the incidence of symptomatic hypoglycemia was about 80% in all of the groups. Substituting a long-acting glucagon-like peptide-1 inhibitor for long-acting insulin in a regimen that also includes aggressively titrated prandial insulin boluses might improve overall glycemic control slightly, but the incidence of hypoglycemia remains high, and gastrointestinal side effects are common. WEIGHT LOSS IS ASSOCIATED WITH IMPROVED AIRWAY HYPERRESPONSIVENESS AND ASTHMA CONTROL In a prospective parallel-group study in the Juneissue of Chest ( http:// dx.doi.org /10.1378/chest.14-3105 ), researchers in Canada followed 20 adult patients with obesity and asthma for 3months to examine the effect of weight loss on airway hyperresponsiveness. The intervention group was enrolled in a yearlong behavioral weight-loss program, whereas the patients in the control group were awaiting bariatric surgery. All of the patients had asthma diagnosed by methacholine challenge and a body-mass index greater than 32.5kg/m 2 . The intervention group got liquid meal replacements and behavioral and exercise counseling. During the study, the intervention patients lost an average of 17kg, whereas the controls gained 0.6kg. The intervention groups PC 20 (which is the provocative concentration of methacholine causing a 20% fall in forced expiratory volume in 1 second) improved significantly from 5 to 10 mg/ mL (a higher number indicates less airway hyperresponsiveness); the control group showed no improvement. FEV 1 and forced vital capacity increased by 5% (the FEV 1 /FVC ratio didnt change), and asthma symptoms and asthmaspecific quality of life improved in the intervention group only. In this small study, weight loss was associated with somewhat improved airway hyperresponsiveness, lung function, and asthma symptoms. Although the improvements could be attributed to the patients increased exercise and participation in social-support groups, patients with obesity and asthma should be counseled on healthy lifestyle measures and the potential benefit of improved asthma control. SHOULD MACROLIDES BE USED FOR PATIENTS WITH COMMUNITY-ACQUIRED PNEUMONIA? Streptococcus pneumoniae is implicated in up to 60% of the cases of community-acquired pneumonia that require hospitalization. Macrolide antibiotics are recommended alone or in combination for patients with pneumonia. But the prevalence of macrolide resistance in S. pneumoniae is currently 35%. To examine the clinical outcomes of patients with pneumonia caused by macrolide-resistant S.pneumoniae , researchers performed an observational study using data from a hospital in Barcelona, Spain. Details appear in the June1 American Journal of Respiratory and Critical Care Medicine ( http:// dx.doi.org /10.1164/rccm.201502-0212OC ). From 2000 through 2013, 640 nonimmunocompromised hospitalized adults with community-acquired pneumonia had cultures positive for S. pneumoniae ; 80% were macrolide susceptible, and 20% were resistant. The patients with macrolide-resistant pneumococci were less likely to exhibit fever, bacteremia, pulmonary complications, or shock; they didnt have worse clinical outcomes than patients with macrolide-susceptible organisms. Of the 100 patients with macrolide-resistant pneumococci who were treated using combination therapy, two-thirds got regimens that included a macrolide. Those taking a macrolide were significantly less likely to be admitted to an intensive care unit or to have multilobar pulmonary infiltrates. Only 3 of the patients with macrolide-resistant S. pneumoniae got macrolide monotherapy. An editorialist notes ( http:// dx.doi.org /10.1164/rccm.201504-0701ED ) that the clinical relevance of macrolide resistance remains unclear. This might be because, in addition to antibacterial activity, macrolides have immunomodulatory effects that can improve clinical outcomes. So these agents seem to still have a role in treating patients (particularly hospitalized patients) with community-acquired pneumonia when theyre used in combination with other antibiotics. ANTIBIOTICS INSTEAD OF SURGERYFOR APPENDICITIS? Research of antibiotics vs . surgery for appendicitis has yielded conflicting results ( www.jwatch.org /na34545 , www.jwatch.org /na34606 , and www.jwatch.org /em201106030000002 ). In a multicenter study in the June16 issue of JAMA ( http:// dx.doi.org /10.1001/jama.2015.6154 ), researchers in Finland randomized 530 patients between the ages of 18 and 60 with uncomplicated acute appendicitis confirmed by computed tomography to either surgery or antibiotic treatment. The antibiotic group got intravenous ertapenem (1 g /day ) for 3days followed by oral levofloxacin (500 mg/ day) plus metronidazole (500mg three times /day ) for a week. The patients were followed for a year. Successful appendectomy (which was the main outcome in the surgery group), was realized in all but one patient. That patients symptoms resolved, obviating the need for surgery. In the antibiotic group, treatment efficacy was defined as the resolution of appendicitis with no need for appendectomy and no recurrence within a year. Of the patients randomized to antibiotics, 30% underwent appendectomy within a year. No patient died from appendicitis. Complications, like surgical site infections and possible adhesion-related gastrointestinal symptoms, were significantly more common with surgery than with antibiotics. Antibiotic treatment for uncomplicated acute appendicitis as an alternative to appendectomy is controversial. This study shows that more than a quarter of patients treated with antibiotics instead of surgery have recurrences within a year. The take-away message here is that, for some patients with appendicitis confirmed by computed tomography, antibiotic treatment can be a reasonable option based on patient preferences, individualized surgical risk, and other factors so long as everyone understands that the chance of recurrence is quite high ( http:// dx.doi.org /10.1001/jama.2015.6266 ). PREDICTING RETAINED COMMONBILEDUCT STONES IN GALLSTONEPANCREATITIS In patients with gallstone pancreatitis, the presence or the absence of retained common bile duct stones affects clinical management strategy. Several years ago, five variables were identified that predicted the presence of common bile duct stones, namely: A duct size of 9mm or larger A γ-glutamyl transferase level of 350 U/ L or higher An alkaline phosphatase level of 250 U/ L or higher A total bilirubin level of 3 mg/ dL or higher A direct bilirubin level of 2 mg/ dL or higher ( http:// dx.doi.org /10.1007/s11605-009-1041-1 ) Now, in a prospective single-center study in the Juneissue of Surgery ( http:// dx.doi.org /10.1016/ j. surg.2015.01.005 ), researchers sought to validate these criteria by enrolling 80 patients hospitalized with gallstone pancreatitis; patients with cholangitis were excluded. Sixteen patients were found to have common bile duct stones: Of the patients with none of the five criteria (meaning a score of 0), none had common bile duct stones. Of the patients with scores of 1 or 2, 18% had common bile duct stones. Of the patients with scores of 3 or 4, more than half had common bile duct stones. Of the patients with a score of 5, all had common bile duct stones. In this study, having either 0 or 5 criteria perfectly predicted the absence or the presence of common bile duct stones. Although the application of these criteria will vary according to local institutional preferences, the researchers propose that: Patients with scores of 0 should undergo cholecystectomy without intraoperative cholangiography. Patients with scores of 1 or 2 should undergo cholecystectomy with intraoperative cholangiography. Patients with scores of 3 or 4 should undergo magnetic resonance cholangiopancreatography to select those who need endoscopic retrograde cholangiopancreatography or intraoperative common bile duct exploration. Patients with scores of 5 should directly undergo endoscopic retrograde cholangiopancreatography. A larger multicenter study of these criteria would be welcome. DO CAUSES OF EARLY AND LATEREADMISSIONS WITHIN 30 DAYS OF DISCHARGE DIFFER? Although the Centers for Medicare and Medicaid Services use 30-day readmission rates as a quality metric, we dont know whether early and late readmissions during this window have the same causal factors. If the causes differ, strategies to prevent these readmissions will also differ. In a retrospective, single-center cohort study in the June2 Annals of Internal Medicine ( http:// dx.doi.org /10.7326/M14-2159 ), researchers reviewed 14,000 admissions to a large urban teaching hospital during 2years. The primary outcomes were divided into early readmissions (within a week after discharge) and late readmissions (between 8days and a month after discharge). The overall 30-day readmission rate was 20% (of these, 40% were early and 60% were late). The patients with higher comorbidity index scores had greater odds of both early and late readmissions. The researchers spotted some correlation between early readmission and acute illness burden (necessitating a longer length of stay and the occurrence of a rapid response call), but when other acute illness criteria (like a longer length of intensive care stay and more consultants) were evaluated, an excess risk for early readmission wasnt seen. Counterintuitively, shared access to electronic medical records between the hospital and the patients primary care providers was associated with a greater chance of early readmission. The researchers speculate that risk factors for readmission change during the month after hospital discharge, but the findings of this study dont strongly support that conclusion. Although understanding which variables put patients at an excess risk for readmission (and at what point those readmissions are likely to happen) is worthy of further study, editorialists rightfully note ( http:// dx.doi.org /10.7326/M15-0878 ) that tailoring interventions to a patients underlying vulnerabilities is preferable to basing interventions solely on a particular time in the discharge period. STILL A ROLE FOR α -FETOPROTEIN IN HEPATOCELLULAR CARCINOMA SURVEILLANCE? Measuring serum α-fetoprotein for the surveillance of hepatocellular carcinoma is controversial due to high rates of false-positives and false-negatives. To evaluate the accuracy of α-fetoprotein levels, abdominal ultrasound, and both combined in diagnosing hepatocellular carcinoma in patients with cirrhosis, researchers in Taiwan conducted a retrospective analysis of 1600 patients who underwent both α-fetoprotein measurement and ultrasound between 2002 and 2010 at a single tertiary care center. The patients were followed until 2013. Findings appear in the June American Journal of Gastroenterology ( http:// dx.doi.org /10.1038/ajg.2015.100 ). During a median follow-up of 5years, a quarter of the patients developed liver cancer. Using the traditional cutoff level of 20 ng/ mL, the sensitivity of α-fetoprotein was 50% and its specificity was 90%. Ultrasound alone had a sensitivity of 90% and a specificity of 74%. Using both modalities combined yielded a higher sensitivity (99%), but a lower specificity (70%). Better sensitivity with the combination of α-fetoprotein and ultrasound compared with ultrasound alone wasnt seen in patients with nonviral hepatitis etiologies. Should α-fetoprotein be completely abandoned in the surveillance of hepatocellular carcinoma, or should it be used in a more directed fashion? This studys capacity to answer this question is limited by its retrospective design and focus on sensitivity and specificity alone as opposed to actual clinical outcomes like mortality related to liver cancer. But the data do suggest that, especially in viral hepatitisrelated cirrhosis, adding α-fetoprotein to imaging might increase sensitivity without a large decrease in specificity. We need more definitive studies to end the ongoing debate. TIME TO BENEFIT FOR SCREENINGFLEXIBLE SIGMOIDOSCOPY Screening for colorectal cancer should be limited to patients whose life expectancies exceed the time to benefit. In a survival meta-analysis on the website of The BMJ ( http:// dx.doi.org /10.1136/bm j. h1662 ), researchers examined four randomized, controlled trials (with nearly 500,000 patients ranging in age from 50 to 74) in which screening flexible sigmoidoscopy was compared with no screening to determine the time to benefit for screening sigmoidoscopy. Average follow-up was about 12years. The sigmoidoscopy group experienced an up to 30% lower risk for colorectal cancerrelated death than the no-screening group. It took 9.4years to prevent 1 colorectal cancerrelated death among every 1000 patients who underwent screening flexible sigmoidoscopy thats slightly shorter than the 10.3-year benefit time seen with fecal occult blood testing. Because 1 out of every 1000 patients who undergo flexible sigmoidoscopy experiences serious complications (caused by the procedure itself or by follow-up procedures), the researchers assume that preventing 1 colorectal cancer death for every 1000 patients screened is a reasonable threshold at which the benefits of screening outweigh the risks. The researchers conclude that screening flexible sigmoidoscopy is most appropriate for older adults whose life expectancy is longer than 10years. The United States Preventive Services Task Force recommends against routine screening in people older than 75 because life expectancy at age 75 is 10.5 [years] for men and 12.5years for women, respectively ( www.jwatch.org /jw200810280000003 ). Trial data about the time to benefit for screening colonoscopy are forthcoming. PERSONALIZED MEDICINE FOR ADVANCED PROSTATE CANCER: ENCOURAGING RESULTS We have all heard the term personalized medicine ; its defined as studying an individuals genome to help with the selection of proper therapies. In a multicenter study in the May21 issue of Cell ( http:// dx.doi.org /10.1016/ j. cell.2015.05.001 ), researchers systematically collected metastatic tumor tissue (from lymph nodes, bone, liver, and other sources) from 150 patients with castration-resistant prostate cancer and compared this tissues genetic makeup with that of tumor tissue from 440 primary prostate cancers. The researchers determined the nucleic acid sequences of all exons (these are gene sequences that encode proteins) and of all genes that were being transcribed into mRNA. The goal was to identify sequence variants seen in metastatic tumors, but not in the primary tumors variations that might explain metastasis and resistance to androgen-deprivation treatments. The researchers discovered a large group of sequence differences in the metastases, most often involving the gene for the androgen receptor and the TP53 gene. Some of the sequence aberrations involved genes known to be important in other malignancies, including BRAF , BRCA2 , and BRCA1 . The researchers determined that 90% of the patients had so-called clinically actionable aberrations meaning, changes in genes that are already the targets of approved drugs or of drugs in late development stages. This study shows that advanced castration-resistant prostate tumors have different underlying genetic changes than primary prostate tumors. The identification of an individuals mutations could help prioritize treatment options. The study also indicates that already approved medications might help in this type of prostate cancer. If treatment trials bear this out, the day of personalized medicine will have arrived for prostate cancer. NEW HYPOTHESIS ON WHAT ALLOWS METASTATIC DEPOSITS TO GROW Many cancers shed malignant cells, but these micrometastases usually fail to grow in their new locations. What encourages a micrometastasis to become a clinically apparent macrometastasis? In an article in the Juneissue of Nature Cell Biology ( http:// dx.doi.org /10.1038/ncb3169 ), researchers studied pancreatic cancer in mice to investigate an interesting hypothesis: Exosomes (which are membrane vesicles of endocytic origin that contain lipids, DNA, RNA, and proteins) are released by malignant cells, travel to the liver, and prepare it to foster the growth of metastatic cells. The researchers showed that exosomes released by pancreatic ductal adenocarcinoma cells traveled to the liver and were ingested by Kupffer cells. The contents of the exosomes caused the Kupffer cells to elaborate various factors that supported the growth of micrometastases. In particular, exosomes that were rich in macrophage migration inhibitory factor were the most likely to foster growth. Blocking this factor abolished the growth of micrometastases. The researchers then determined that people with pancreatic cancers who make exosomes rich in macrophage migration inhibitory factor are much more likely to have liver macrometastases than similar patients whose exosomes arent rich in the factor. This finding suggests that these mouse studies could be relevant to humans. Exosomes are emerging as important mechanisms for intercellular communication. This report might have identified a biological mechanism exosomes shed by malignant cells that encourages the growth of micrometastases into macrometastases. If this finding proves robust, it could lead to new treatments for metastatic disease. CT SCREENING FOR LUNG CANCER: HERE COME THE EUROPEAN TRIALS The United States National Lung Screening Trial was the first randomized trial to show an effect of computed tomography screening on lung cancer mortality: At 6.5years, there was 1 fewer lung cancerspecific death per 320 smokers screened ( www.jwatch.org /jw201107140000001 ). Now, in the May15 American Journal of Respiratory and Critical Care Medicine ( http:// dx.doi.org /10.1164/rccm.201408-1475OC ), the results of another screening study the DANTE trial, from Italy have been published. DANTE included about 2500 men between the ages of 60 and 74 with smoking histories of 20 or more pack-years; all were current smokers or had quit within 10years. The patients were randomized to either five rounds of annual low-dose CT screening or to no screening. During a median follow-up of 8.4years, 100 of the screened patients and 70 of the controls were diagnosed with lung cancer. Lung cancerspecific mortality was identical in the two groups at about 5 deaths per 1000 person-years. During the screening phase, nearly 40% of the screened patients had at least one abnormal CT scan. Additional CT scans, invasive diagnostic procedures, and surgeries were all significantly more common in the screening group than in the control group. Although the failure of computed tomography screening for lung cancer to yield even a trend toward lower mortality is notable in this study, its obvious limitations are its small size (only 2500 men) and low statistical power; by contrast, 50,000 patients were enrolled in the National Lung Screening Trial from the United States. Its important to mention that six similar trials from Europe (including nearly 40,000 patients) are ongoing, and the researchers are planning to pool their results ( http:// dx.doi.org /10.1002/jso.23383 ). Their final mortality data testing is expected sometime this year. PATIENT-REPORTED RISK FACTORS ACCURATELY PREDICTED 5-YEARMORTALITY RISK When researchers study predictors of mortality, they usually consider only elders, a few risk factors, or small populations. Now, analyzing data from almost 500,000 patients in the United Kingdom between the ages of 37 and 73 in a biobank, researchers determined sex-specific associations of 650 baseline demographic, health, and lifestyle variables with 5-year all-cause mortality and with six categories of cause-specific mortality. Details appear on the website of The Lancet ( http:// dx.doi.org /10.1016/ S0140-6736(15)60175-1 ). Self-reported health was the strongest predictor of 5-year all-cause mortality in men and a past cancer diagnosis was the strongest predictor in women. Among the patients without major diseases at baseline, smoking behaviors predicted mortality most strongly in both of the sexes. Self-reported measures of health and medical history were the strongest predictors of cause-specific mortality in all disease-related categories, and psychosocial factors were the strongest predictors of death from external causes (like accidents and suicide). A mortality prediction model based on age and 13 patient-reported risk factors for men and 11 for women was a stronger predictor of mortality than was age alone or age plus the Charlson comorbidity index; the Charlson score added no predictive power to age plus the prediction model. The prediction model was validated in a subpopulation in Scotland. An interactive website called Ubble ( www.ubble.co.uk ) allows users to explore the power of any of 650 baseline variables to predict all-cause or cause-specific mortality by age and sex. Using the mortality-prediction model, the website also allows patients to enter their own risk factors and calculate their 5-year mortality risk. Further analyses of this huge, detailed dataset will likely provide many additional insights of value to patients, clinicians, and public health officials. YEARS OF LIFE LOST DUE TO CURRENTSMOKING AND YEARSGAINED BY QUITTING The risk-advancement period is the average time by which a risk factor (like current smoking) advances an adverse clinical event (like cardiovascular-related death); estimates of the risk-advancement period can be meaningful to affected patients. In a meta-analysis on the website of TheBMJ ( http:// dx.doi.org /10.1136/bm j. h1551 ), researchers reviewed the data from 25 prospective cohort studies (with 500,000 patients 60 or older) to determine the effect of smoking and smoking cessation on risk-advancement periods for cardiovascular-related adverse outcomes. Average follow-up ranged from 2 to 13years. Not surprisingly, current smokers had a significantly higher risk for cardiovascular-related death than did never smokers and former smokers; the corresponding risk-advancement periods for current smokers were nearly 6 adversely affected years, when compared with never smokers, and 2 adversely affected years, when compared with former smokers. The highest risk was seen in current smokers who smoked more than 20 cigarettes /day ; their risk-advancement period was 7 adversely affected years. In former smokers, the risk for cardiovascular-related death and corresponding risk-advancement periods decreased continuously with time since smoking cessation. For example, compared with current smokers, former smokers who quit 20 or more years before baseline had a lower risk for cardiovascular-related death, which translates into a corresponding risk-reduction period of 4years. The results were similar for acute adverse coronary events and stroke. This meta-analysis not only affirms that older patients who are current and former smokers are at an excess risk for cardiovascular-related adverse events, it also translates these risks into potential years of life lost or that are adversely affected (which is the risk-advancement period); clearly, these calculations can be significant, in very real terms, to patients. The analysis affirms the benefits of smoking cessation in similar terms. ADDING DENOSUMAB TO A BIOLOGICMIGHT NOT INCREASERISKFOR INFECTION Often, treating patients with rheumatoid arthritis and osteoporosis is difficult because of comorbid conditions (like renal insufficiency), inconvenience, and expense. Bisphosphonates have become the mainstay for managing osteoporosis, but potential side effects, like osteonecrosis of the jaw, esophageal carcinoma, and atypical fractures, must be considered. Teriparatide (trade name: Forteo) is expensive and has to be injected every day. The biologic agent denosumab (trade name: Prolia) is another option, but its been associated with a possible excess risk for cellulitis, and patients with rheumatoid arthritis might be more prone to infections when two biologics are used together. In a study in the Juneissue of Arthritis & Rheumatology ( http:// dx.doi.org /10.1002/art.39075 ), researchers used a Medicare database to identify 6000 patients with rheumatoid arthritis who got any rheumatoid arthritis biologic therapy for a year and who then were administered denosumab or the bisphosphonate zoledronic acid concomitantly with their biologic medication. In a subgroup analysis, 500 denosumab patients were matched with 500 zoledronic acid patients by age, infection risk score, specific rheumatoid arthritis biologic medication, and time since the start of biologic therapy. In both overall and matched analyses, the rates of infection requiring hospitalization were similar in the two groups (in the matched analysis, there were about 10 hospitalizations for infection per 100 person-years). Although follow-up of these patients was short (an average of 6months), this study is helpful, because it expands therapeutic options for patients with rheumatoid arthritis and osteoporosis who are taking biologic therapies. Denosumab is injected every 6months and out-of-pocket costs are about US$1000 per injection. MONTHLY PROPHYLAXIS TO PREVENTVAGINAL INFECTIONS Even though common vaginal infections (namely, vulvovaginal candidiasis, trichomoniasis, and bacterial vaginosis) tend to recur, we havent determined the optimal regimens for their suppression. In a study in the June15 Journal of Infectious Diseases ( http:// dx.doi.org /10.1093/infdis/jiu818 ), researchers randomized 230 women from one clinic in the United States and three clinics in Africa to an intravaginal suppository containing either placebo or 750mg of metronidazole plus 200mg of miconazole; the suppository was used for 5 consecutive nights every month for a year. At study entry, all of the patients had 1 or more of the common vaginal infections, but none reported more than 3 of these infections during the past year, and none was HIV-positive. During follow-up, smears were collected every 2months, and symptomatic recurrences were treated. At a year, the women who got the active drugs were about a third less likely to have been diagnosed with bacterial vaginosis than were the placebo patients. The rates of candidiasis and trichomoniasis were similar in the two groups, and there were no serious side effects associated with treatment. Past studies of metronidazole for suppressing recurrent bacterial vaginosis have been beleaguered by an excess risk for candidiasis, so the flat rate seen in this study can be considered progress. Although a 35% reduction in relative risk isnt dramatic, this regimen seems safe enough to suggest to women who are plagued by moderately frequent recurrences of bacterial vaginosis. DONT FALL FOR THAT: PREVENTINGINPATIENT FALLS THROUGH EDUCATION When patients fall in hospitals and rehabilitation facilities, the event often results in physical injury and additional healthcare costs. Most studies of single interventions (like bed alarms) have shown no benefit in preventing falls. In a study on the website of The Lancet ( http:// dx.doi.org /10.1016/ S0140-6736(14)61945-0 ), researchers in Australia instituted a quality-improvement program ( www.jwatch.org /hm201101310000001 ) in eight inpatient rehabilitation wards with 3600 cognitively intact patients who were an average of 81years old; most of the patients were community dwellers before their index admissions. The patients got an educational intervention, including fall prevention strategies and training about personal fall risks, administered by a trained physical therapist. The researchers compared the fall rates before and after the intervention was offered to each unit. The overall fall rate significantly declined from a baseline of 14 falls per 1000 patient-days before the intervention to 6 per 1000 patient-days after the intervention was implemented. The overall fall rate was reduced by 40% and the rate of injurious falls decreased by 35%. The total percent of elderly patients who fell declined from 13% to 8%. The number needed to treat to prevent 1 fall was 20. This education program effectively prevented falls in the inpatient setting. Patients with cognitive impairment, who are 60% more likely to fall in the hospital than are patients without cognitive impairment, were excluded from this study; this exclusion might limit the general applicability of these findings. Even so, as hospitals struggle to assure patient safety, investment in this type of intervention could improve outcomes.
Ratings and Reviews
To review this course, please login.Login