Friday, December 30, 2016

The learning curve for lung ultrasound

From a recent paper:


Guidelines recommend teaching of lung ultrasound for critical care, though little information exists on how much training is required for independent practice, especially for non-physician trainees. We thus aimed to elucidate a threshold number of cases above which competency for independent practice may be attained for respiratory therapists (Rts)...


Eleven ultrasound-naïve RTs scanned an average of 15 patients each (170 patients in total)...

After trainees performed at least ten scans, less than 2 % of images required assistance with acquisition and less than 5 % were wrongly interpreted.


Our training method allowed RTs to independently perform lung ultrasound after at least ten directly supervised scans. Given that RTs are likely to have less ultrasound knowledge and less clinical know-how compared to physicians, we believe that the same threshold number of scans may be also safely applied to the latter.

Thursday, December 29, 2016

Long term antibiotics after a diagnosis of Lyme disease

Here is a report of a randomized trial of long term antibiotics for patients with persistent symptoms attributed to Lyme disease. From the report:


The treatment of persistent symptoms attributed to Lyme disease remains controversial. We assessed whether longer-term antibiotic treatment of persistent symptoms attributed to Lyme disease leads to better outcomes than does shorter-term treatment.


In a randomized, double-blind, placebo-controlled trial conducted in Europe, we assigned patients with persistent symptoms attributed to Lyme disease — either related temporally to proven Lyme disease or accompanied by a positive IgG or IgM immunoblot assay for Borrelia burgdorferi — to receive a 12-week oral course of doxycycline, clarithromycin plus hydroxychloroquine, or placebo. All study groups received open-label intravenous ceftriaxone for 2 weeks before initiating the randomized regimen. The primary outcome measure was health-related quality of life, as assessed by the physical-component summary score of the RAND-36 Health Status Inventory (RAND SF-36) (range, 15 to 61, with higher scores indicating better quality of life), at the end of the treatment period at week 14, after the 2-week course of ceftriaxone and the 12-week course of the randomized study drug or placebo had been completed.


Of the 281 patients who underwent randomization, 280 were included in the modified intention-to-treat analysis (86 patients in the doxycycline group, 96 in the clarithromycin–hydroxychloroquine group, and 98 in the placebo group). The SF-36 physical-component summary score did not differ significantly among the three study groups at the end of the treatment period, with mean scores of 35.0 (95% confidence interval [CI], 33.5 to 36.5) in the doxycycline group, 35.6 (95% CI, 34.2 to 37.1) in the clarithromycin–hydroxychloroquine group, and 34.8 (95% CI, 33.4 to 36.2) in the placebo group (P=0.69; a difference of 0.2 [95% CI, –2.4 to 2.8] in the doxycycline group vs. the placebo group and a difference of 0.9 [95% CI, –1.6 to 3.3] in the clarithromycin–hydroxychloroquine group vs. the placebo group); the score also did not differ significantly among the groups at subsequent study visits (P=0.35). In all study groups, the SF-36 physical-component summary score increased significantly from baseline to the end of the treatment period (P less than 0.001). The rates of adverse events were similar among the study groups. Four serious adverse events thought to be related to drug use occurred during the 2-week open-label ceftriaxone phase, and no serious drug-related adverse event occurred during the 12-week randomized phase.


In patients with persistent symptoms attributed to Lyme disease, longer-term antibiotic treatment did not have additional beneficial effects on health-related quality of life beyond those with shorter-term treatment.

Tuesday, December 27, 2016

Trends in the management of left main coronary artery disease

This review in JACC outlines the history of trends in the management of this condition and notes increasing acceptance of PCI in certain patients, and related guideline changes. The accompanying audio summary is available to non subscribers.

Monday, December 26, 2016

Potassium decline during heart failure hospitalization

---was associated with greater 6 month mortality in this study. I'm not sure why but would speculate that it is an indicator of more intense neurohumoral activation and might point to patients who would benefit most from more intense use of neurohumeral antagonists.

Friday, December 23, 2016

JAMA review on antimicrobial resistance

A nice review of the mechanisms of resistance, the impact of antibiotic stewardship programs and the current state of the problem.

Thursday, December 22, 2016

Incretin based drugs and gallbladder disease risk

Importance The use of dipeptidyl-peptidase–4 (DPP-4) inhibitors and glucagon-like peptide 1 (GLP-1) analogues—a group of drugs used in the management of type 2 diabetes mellitus—may be associated with an increased risk of bile duct and gallbladder disease. To date, no observational study has assessed this possible association.

Objective To determine whether the use of DPP-4 inhibitors and GLP-1 analogues is associated with an increased risk of incident bile duct and gallbladder disease in patients with type 2 diabetes.

Design, Setting, and Participants A population-based cohort study linked the United Kingdom Clinical Practice Research Datalink with the Hospital Episodes Statistics database, yielding a cohort of 71 369 patients, 18 years or older, initiating an antidiabetic drug (including oral and injectable agents) between January 1, 2007, and March 31, 2014.

Exposures Current use of DPP-4 inhibitors and GLP-1 analogues (alone or in combination therapy) compared with current use of at least 2 oral antidiabetic drugs.

Main Outcomes and Measures Time-dependent Cox proportional hazards models were used to estimate hazard ratios (HRs) with 95% CIs of incident bile duct or gallbladder events (cholelithiasis, cholecystitis, cholangitis) causing hospitalization, comparing current use of DPP-4 inhibitors and GLP-1 analogues with current use of at least 2 oral antidiabetic drugs.

Results During 227 994 person-years of follow-up, 853 of the 71 369 patients were hospitalized for bile duct and gallbladder disease (incidence rate per 1000 person-years, 3.7; 95% CI, 3.5-4.0). Current use of DPP-4 inhibitors was not associated with an increased risk of bile duct and gallbladder disease compared with current use of at least 2 oral antidiabetic drugs (3.6 vs 3.3 per 1000 person-years; adjusted HR, 0.99; 95% CI, 0.75-1.32). In contrast, the use of GLP-1 analogues was associated with an increased risk of bile duct and gallbladder disease compared with current use of at least 2 oral antidiabetic drugs (6.1 vs 3.3 per 1000 person-years; adjusted HR, 1.79; 95% CI, 1.21-2.67). In a secondary analysis, GLP-1 analogues were also associated with an increased risk of cholecystectomy (adjusted HR, 2.08; 95% CI, 1.08-4.02).

Conclusions and Relevance The use of GLP-1 analogues was associated with an increased risk of bile duct and gallbladder disease. Physicians should be aware of this potential adverse event when prescribing these drugs.

Wednesday, December 21, 2016

Identifying high frequency utilizers in the EMR with an airplane icon is unethical

---so say the authors of this JAMA piece.

Tuesday, December 20, 2016

Focused update incorporating ARNI and ivabradine into the heart failure guidelines

This was recently published in JACC. It applies to heart failure stage C class II and III. It calls for substitution of ARNI for the ACEI or ARB (class I recommendation) and adding on ivabradine in patients on optimal medical therapy but in whom maximal titration of the beta blocker (to blood pressure tolerance) still leaves them with a resting heart rate of 70 or greater (class IIa recommentation). The ARNI substitution has a mortality benefit over the use of ACEI or ARB alone. The ivabradine add on reduces hospitalizations. The recommendation for both applies only to systolic dysfunction heart failure (HFrEF). According to the wording of the guideline update ARNI substitution is an alternative. That is, it, the use of ACEI and the use of ARB all carry a class I recommendation.

Links below contain the prescribing information for the currently approved ARNI and ivabradine, respectively.

Monday, December 19, 2016

Autosomal dominant polycystic kidney disease

Here are some key points from a recent BMJ review:

What is it?

It is an inherited condition characterized by pathologic development of multiple renal cysts leading to enlargement and dysfunction.

What are the genetics?

Classic autosomal dominance. However, some patients will not have a family history, as 6-8% of cases represent de novo mutations. The mutation involves one of two identified genes.

The variable clinical spectrum is not fully explained.

This is in part due to there being two separate gene mutations. However, within a given mutation there is considerable variation in severity.

There is a wide array of renal manifestations.

Urinary concentrating impairment is an early manifestation. Episodic hematuria and cyst hemorrhage may occur and generally resolve in a matter of days. Cyst infection is complicated and requires prolonged antibiotic treatment with a lipid permeable agent. Hypertension is common and may be the initial presenting clinical feature. The median age of onset of ESRD is 55 but is quite variable.

What are the extrarenal manifestations?

Polycystic liver disease is seen in 80% of adults. Biliary tract compression, cholangitis, and cyst infection may occur but synthetic function generally remains unaffected. Cysts in other organs may occur but tend to be clinically insignificant. The prevalence of cerebral aneurysms is 8-12%.

Diagnostic criteria are based on family history and the number of cysts as a function of age.

Genetic testing may be indicated in limited circumstances.

What treatments are recommended to slow the progression?

Aggressive BP control with ACEIs and ARBs may help but tolvaptan is a recently emerging treatment which is supported by the best evidence.

Saturday, December 17, 2016

The gluten free lunacy

There's a great post at the Clinical Correlations blog on this topic. I can't do it justice by commenting here so visit the link and read the entire post. There's another great piece on this topic at Science Based Medicine from a while back.

Friday, December 16, 2016

Does folic acid protect the kidney?

Objective To test whether treatment with enalapril and folic acid is more effective in slowing renal function decline than enalapril alone across a spectrum of renal function…

Design, Setting, and Participants In this substudy of eligible China Stroke Primary Prevention Trial (CSPPT), 15 104 participants with an estimated glomerular filtration rate (eGFR) 30 mL/min/1.73 m2 or greater, including 1671 patients with CKD, were recruited from 20 communities in Jiangsu province in China.

Interventions Participants were randomized to receive a single tablet daily containing 10 mg enalapril and 0.8 mg folic acid (n = 7545) or 10 mg enalapril alone (n = 7559).

Main Outcomes and Measures The primary outcome was the progression of CKD, defined as a decrease in eGFR of 30% or more and to a level of less than 60 mL/min/1.73 m2 if the baseline eGFR was 60 mL/min/1.73 m2 or more, or a decrease in eGFR of 50% or more if the baseline eGFR was less than 60 mL/min/1.73 m2; or end-stage renal disease….

Results Overall, 15 104 Chinese adults with a mean (range) age of 60 (45-75) years were recruited; median follow-up was 4.4 years. There were 164 and 132 primary events in the enalapril group and the enalapril–folic acid group, respectively. Compared with the enalapril group, the enalapril–folic acid group had a 21% reduction in the odds of the primary event (odds ratio [OR], 0.79; 95% CI, 0.62-1.00) and a slower rate of eGFR decline (1.28% vs 1.42% per year; P = .02). Among the participants with CKD at baseline, folic acid therapy resulted in a significant reduction in the risks for the primary event (OR, 0.44; 95% CI, 0.26-0.75), rapid decline in renal function (OR, 0.67; 95% CI, 0.47-0.96) and the composite event (OR, 0.62; 95% CI, 0.43-0.90), and a 44% slower decline in renal function (0.96% vs 1.72% per year, P less than .001). Among those without CKD at baseline, there was no between-group difference in the primary end point.

Conclusions and Relevance Enalapril–folic acid therapy, compared with enalapril alone, can significantly delay the progression of CKD among patients with mild-to-moderate CKD.

Thursday, December 15, 2016

Acute kidney injury due to iodinated contrast

CI-AKI remains a concern for patients undergoing cardiac interventional procedures utilizing intravascular iodinated contrast. This form of renal injury appears to be amenable to volume expansion and to measures to increase urine flow and removal of highly water-soluble contrast. Minimizing contrast by use of ALARA principles and strategies to maximize the benefit of contrast exposure (i.e., revascularization) are reasonable. Although no adjunctive therapy is prophylactic or therapeutic for CI-AKI, statin use appears to reduce the incidence and severity of AKI, whereas continuation of RASi appears to increase the risk for CI-AKI. Further research is needed in the development of less toxic contrast agents, as well as therapies that can reduce cardiorenal complication of interventional cardiovascular procedures. Such agents hold the promise of improving long-term outcomes by minimizing the hazards of intercurrent events, such as ACS, and urgent and planned catheterization procedures.

The review focused on coronary angiography. Conspicuously absent were mention of ascorbic acid and ischemic preconditioning. An earlier review was posted here.

Wednesday, December 14, 2016

Cellulitis review

This is an excellent review, recently published in JAMA.

It needs to be read in the original but here are a few key points:

When is MRSA coverage needed?

From the article:

There has been increasing concern about antibiotic-resistant bacteria, such as community-acquired methicillin-resistant S aureus (MRSA), which is reflected in the increased use of anti-MRSA antibiotics (eg, vancomycin, trimethoprim-sulfamethoxazole, doxycycline, clindamycin) and broad-spectrum gram-negative antibiotics (eg, β-lactam/β-lactamase inhibitors, levofloxacin, ceftriaxone) during the past decade.40 However, most cases of cellulitis do not involve gram-negative organisms, and in cases of nonpurulent and uncomplicated cellulitis, the addition of antibiotics against community-acquired MRSA did not improve outcomes.41 As such, narrow-spectrum antibiotics against Streptococcus and methicillin-sensitive S aureus remain appropriate. In purulent cellulitis (presence of a pustule, abscess, or purulent drainage), S aureus infection is more likely, as demonstrated by a study of 422 patients who presented with “purulent skin and soft tissue infections” to 11 emergency departments throughout the United States, in which skin surface swab cultures revealed MRSA in 59% of patients, methicillin-sensitive S aureus in 17%, and β-hemolytic streptococci in 2.6%.42 Because methicillin-sensitive S aureus and MRSA can be difficult to differentiate according to clinical features alone,43 MRSA should be considered for purulent infections in known high-risk populations, such as athletes, children, men who have sex with men, prisoners, military recruits, residents of long-term care facilities, individuals with previous MRSA exposure, and intravenous drug users.44

The authors also recommend MRSA coverage for non purulent cellulitis in certain situations: severe systemic manifestations, rapid spread and immune compromise.

When should the spectrum be extended beyond staph and strep (eg anaerobes, gram negatives)?

Severe systemic manifestations, immune compromise, rapid spread.

What if purulent cellulitis is mild and can be treated with oral antibiotics?

Consider confining the coverage to strep and MSSA (but not MRSA). But if MRSA is deemed important to cover TMP/SMX, doxy or clinda may be acceptable (as well as, of course, linezolid).

What are some unusual organisms to consider in special situations?

Traditional (pharmacologic) immunosupression, HIV: strep pneumo, Mtb, gram negatives, crypto species.
Chronic liver disease, CKD: vibrio species ( including vulnificus), gram negatives (including pseudomonas).

When should nec fash (and other complications) be considered?

From the article:

In cases of suspected necrotizing fasciitis, early surgical assessment is recommended; however, laboratory testing may help differentiate cellulitis from early evolving necrotizing fasciitis. Wall et al75 found in a modeling study that a white blood cell count greater than 15 400 cells/mm3 or serum sodium level less than 135 mEq/L could suggest a diagnosis of necrotizing fasciitis with a sensitivity of 90%, specificity of 76%, positive likelihood ratio of 3.75, and negative likelihood ratio of 0.13. Similarly, Wong et al76 developed the Laboratory Risk Indicator for Necrotizing Fasciitis score according to white blood cell count and levels of C-reactive protein, hemoglobin, serum sodium, creatinine, and serum glucose, which had a sensitivity of 90%, specificity of 95%, positive likelihood ratio of 19.95, and negative likelihood ratio of 0.10. Finally, Murphy et al77 identified that for necrotizing fasciitis among cases in their series, a serum lactate level of 2.0 mmol/L had a sensitivity of 100%, specificity of 76%, positive likelihood ratio of 4.17, and negative likelihood ratio of 0. All of these tests are offered as adjunctive tools, along with history, physical examination, and surgical exploration, to guide diagnosis of necrotizing fasciitis.

Imaging studies are not diagnostic of cellulitis but can help distinguish it from more severe forms of infection and can identify drainable fluid collections, such as abscesses. Osteomyelitis can sometimes complicate cellulitis and when suspected can be best ruled out with magnetic resonance imaging or radiography, if chronic. Furthermore, magnetic resonance imaging or computed tomography can help differentiate cellulitis from necrotizing fasciitis or pyomyositis.78 The appearance of gas on computed tomography scan in the absence of soft tissue trauma or a rim-enhancing fluid collection, as would be found with an abscess, is considered pathognomonic of, but not requisite for, a diagnosis of necrotizing fasciitis.79- 81 A recent study evaluating the utility of modern-day computed tomography scanners demonstrated a positive predictive value of 76% and a negative predictive value of 100% and found that only 36% of cases of necrotizing fasciitis included gas.82

In cases of non response to treatment consider cellulitis mimics and possible derm consultation

Mimics include stasis dermatitis, calciphylaxis, erythema migrans and other conditions.

Tuesday, December 13, 2016

AL cardiac amyloidosis

This topic was recently reviewed in JACC. Although the focus is on cardiac AL amyloidosis it provides a nice overview of cardiac amyloidosis in general. For those who do not have access to the full text the freely available accompanying audio commentary provides an excellent summary.

Monday, December 12, 2016

GCA and PMR review

This review highlights the emerging role of imaging in the diagnosis of both diseases. In GCA it can be an adjunct, or even an alternative, to biopsy.

Duration of antibiotic therapy in community acquired pneumonia

This new study validates the IDSA guideline recommendation for shorter (around 5 days) antibiotic treatment in CAP.

Sunday, December 11, 2016

What's the best treatment strategy for stable CAD in DM 2?

Background There are scant outcomes data in patients with type 2 diabetes and stable coronary artery disease (CAD) stratified by detailed angiographic burden of CAD or left ventricular ejection fraction (LVEF).

Objectives This study determined the effect of optimal medical therapy (OMT), with or without percutaneous coronary intervention (PCI) or coronary artery bypass grafting (CABG), on long-term outcomes with respect to LVEF and number of diseased vessels, including proximal left anterior descending artery involvement.

Methods A patient-level pooled analysis was undertaken in 3 federally-funded trials. The primary endpoint was the composite of death, myocardial infarction (MI), or stroke, adjusted for trial and randomization strategy.

Results Among 5,034 subjects, 15% had LVEF less than 50%, 77% had multivessel CAD, and 28% had proximal left anterior descending artery involvement. During a median 4.5-year follow-up, CABG + OMT was superior to PCI + OMT for the primary endpoint (hazard ratio [HR]: 0.71; 95% confidence interval [CI]: 0.59 to 0.85; p = 0.0002), death (HR: 0.76; 95% CI: 0.60 to 0.96; p = 0.024), and MI (HR: 0.50; 95% CI: 0.38 to 0.67; p = 0.0001), but not stroke (HR: 1.54; 95% CI: 0.96 to 2.48; p = 0.074). CABG + OMT was also superior to OMT alone for prevention of the primary endpoint (HR: 0.79; 95% CI: 0.64 to 0.97; p = 0.022) and MI (HR: 0.55; 95% CI: 0.41 to 0.74; p = 0.0001), and was superior to PCI + OMT for the primary endpoint in patients with 3-vessel CAD (HR: 0.72; 95% CI: 0.58 to 0.89; p = 0.002) and normal LVEF (HR: 0.71; 95% CI: 0.58 to 0.87; p = 0.0012). There were no significant differences in OMT versus PCI + OMT.

Conclusions CABG + OMT reduced the primary endpoint during long-term follow-up in patients with type 2 diabetes and stable CAD, supporting this as the preferred management strategy.

Saturday, December 10, 2016

Assessment of volume responsiveness in critically ill patients

From JAMA’s Rational Clinical Examination series:

Objective To identify predictors of fluid responsiveness in hemodynamically unstable patients with signs of inadequate organ perfusion.

Data Sources and Study Selection Search of MEDLINE and EMBASE (1966 to June 2016) and reference lists from retrieved articles, previous reviews, and physical examination textbooks for studies that evaluated the diagnostic accuracy of tests to predict fluid responsiveness in hemodynamically unstable adult patients who were defined as having refractory hypotension, signs of organ hypoperfusion, or both. Fluid responsiveness was defined as an increase in cardiac output following intravenous fluid administration.

Data Extraction Two authors independently abstracted data (sensitivity, specificity, and likelihood ratios [LRs]) and assessed methodological quality. A bivariate mixed-effects binary regression model was used to pool the sensitivities, specificities, and LRs across studies.

Results A total of 50 studies (N = 2260 patients) were analyzed. In all studies, indices were measured before assessment of fluid responsiveness. The mean prevalence of fluid responsiveness was 50% (95% CI, 42%-56%). Findings on physical examination were not predictive of fluid responsiveness with LRs and 95% CIs for each finding crossing 1.0. A low central venous pressure (CVP) (mean threshold less than 8 mm Hg) was associated with fluid responsiveness (positive LR, 2.6 [95% CI, 1.4-4.6]; pooled specificity, 76%), but a CVP greater than the threshold made fluid responsiveness less likely (negative LR, 0.50 [95% CI, 0.39-0.65]; pooled sensitivity, 62%). Respiratory variation in vena cava diameter measured by ultrasound (distensibility index greater than 15%) predicted fluid responsiveness in a subgroup of patients without spontaneous respiratory efforts (positive LR, 5.3 [95% CI, 1.1-27]; pooled specificity, 85%). Patients with less vena cava distensibility were not as likely to be fluid responsive (negative LR, 0.27 [95% CI, 0.08-0.87]; pooled sensitivity, 77%). Augmentation of cardiac output or related parameters following passive leg raising predicted fluid responsiveness (positive LR, 11 [95% CI, 7.6-17]; pooled specificity, 92%). Conversely, the lack of an increase in cardiac output with passive leg raising identified patients unlikely to be fluid responsive (negative LR, 0.13 [95% CI, 0.07-0.22]; pooled sensitivity, 88%).

Conclusions and Relevance Passive leg raising followed by measurement of cardiac output or related parameters may be the most useful test for predicting fluid responsiveness in hemodynamically unstable adults. The usefulness of respiratory variation in the vena cava requires confirmatory studies.

Is simple pulse pressure measurement a reliable surrogate for CO? There is a relationship but it appears to be non linear as discussed here.

Of interest, CVP measurement had fair test characteristics. Ultrasound measurement of vena cava distensibility was of limited usefulness, and then only in mechanically ventilated patients with no spontaneous respiratory effort.

Friday, December 09, 2016

Antivirals added to steroids for treatment of Bell palsy

Clinical Question Compared with oral corticosteroids alone, are oral antiviral drugs associated with improved outcomes when combined with oral corticosteroids in patients presenting within 72 hours of the onset of Bell palsy?

Bottom Line Compared with oral corticosteroids alone, the addition of acyclovir, valacyclovir, or famcyclovir to oral corticosteroids for treatment of Bell palsy was associated with a higher proportion of people who recovered at 3- to 12-month follow-up. The quality of evidence is limited by heterogeneity, imprecision of the result estimates, and risk of bias.

AICD use in patients with non-ischemic dilated cardiomyopathy

The original use of the AICD for primary prevention of arrhythmic collapse (other than in patients with channelopathy) was in patients post MI with reduced ejection fraction as validated in the MADIT and MADIT II studies. The indications were expanded to patients with dilated cardiomyopathy of all causes after SCD-HeFT. In SCD-HeFT about half the patients had ischemic DCM and about half non-ischemic. But up to now no one had done this same study on a population composed purely of patients with non-ischemic DCM. That was the subject of this study recently published in NEJM. From the article:


The benefit of an implantable cardioverter–defibrillator (ICD) in patients with symptomatic systolic heart failure caused by coronary artery disease has been well documented. However, the evidence for a benefit of prophylactic ICDs in patients with systolic heart failure that is not due to coronary artery disease has been based primarily on subgroup analyses. The management of heart failure has improved since the landmark ICD trials, and many patients now receive cardiac resynchronization therapy (CRT).

In a randomized, controlled trial, 556 patients with symptomatic systolic heart failure (left ventricular ejection fraction, less than or equal to 35%) not caused by coronary artery disease were assigned to receive an ICD, and 560 patients were assigned to receive usual clinical care (control group). In both groups, 58% of the patients received CRT. The primary outcome of the trial was death from any cause. The secondary outcomes were sudden cardiac death and cardiovascular death.

After a median follow-up period of 67.6 months, the primary outcome had occurred in 120 patients (21.6%) in the ICD group and in 131 patients (23.4%) in the control group (hazard ratio, 0.87; 95% confidence interval [CI], 0.68 to 1.12; P=0.28). Sudden cardiac death occurred in 24 patients (4.3%) in the ICD group and in 46 patients (8.2%) in the control group (hazard ratio, 0.50; 95% CI, 0.31 to 0.82; P=0.005). Device infection occurred in 27 patients (4.9%) in the ICD group and in 20 patients (3.6%) in the control group (P=0.29).

In this trial, prophylactic ICD implantation in patients with symptomatic systolic heart failure not caused by coronary artery disease was not associated with a significantly lower long-term rate of death from any cause than was usual clinical care. (Funded by Medtronic and others; DANISH number, NCT00542945.)

But things are not as a superficial reading of the conclusion might indicate. First, if you had a device you were only half as likely to drop dead suddenly (NNT 25). Moreover, although it did not reach statistical significance the point estimate for all cause mortality in the device group was lower.

What are the implications for practice? First, before you exclude a patient with DCM from device therapy you would want to rule out coronary disease. We usually do that anyway but the guidelines give us some wiggle room. Second, for those in whom CAD is ruled out we will have to rethink device recommendations on each individual case. It can be expected, and considered appropriate, that individual clinician judgment and patient preferences will drive decision making and some degree of practice variation.

Wednesday, November 02, 2016

Skepticism about accountable care organizations

Here is a JAMA Viewpoint piece expressing a negative opinion about ACOs. (A companion article in the same issue was favorable). Key points:

The authors point out that any cost savings attributable to the ACOs appear to be nominal. Moreover they tend to be offset by the bonuses paid out to the participants. These bonuses cannot be considered optional because they are inherent to the core notion of the ACO: that “quality” will be rewarded.

The model creates incentives to integrate services. Thus smaller hospitals close or are merged, resulting in monopolies among health care delivery systems. This reduces competition and tends to drive costs up, not down.

Tuesday, November 01, 2016

Accountable care organizations: how are they working?

The authors of this JAMA Viewpoint article say the model has been a success, but the arguments are unconvincing. Here are some caveats:

The experiment is in its infancy.

Overall the results are mixed.

Cost savings have been modest and in some cases are diminishing and may prove to be transient. That's what we saw in the managed care experiment of a couple of decades ago.

Statements about quality improvement are suspect because real quality cannot be measured. Outcome data are very soft.

Monday, October 31, 2016

Multiple clinical manifestations of IgG4 related disease (IgG4-RD)

Here are some key issues addressed in a recent review.

What are some of the IgG4 related diseases?

These may coexist in the same patient:

Autoimmune pancreatitis type 1
Mikulicz disease (salivary gland infiltration)
Constrictive pericarditis
Coronary artery aneurysm
Inflammatory abdominal aortic aneurysm (and the related condition retroperitoneal fibrosis)
Sclerosing mediastinitis
Riedel's thyroiditis (and other forms of thyroid involvement)
Sclerosing mastitis
Pulmonary mass or interstitial disease
Lymphadenopathy (Castleman like and other forms)
Tubulointerstitial nephritis
Sclerosing cholangitis (which differs in some features from primary sclerosing cholangitis)

How is IgG4-RD diagnosed?

This has been in a state of some controversy and flux. From the article:

According to an international symposium held in 2011, the diagnosis of IgG4-RD requires both an appropriate histological appearance and increased numbers of IgG4-positive plasma cells (or an elevated IgG4:IgG ratio) in tissue...

In 2011, an “All Japan IgG4 Team,” with the aim to draft comprehensive diagnostic criteria for IgG4-RD 51 ( Table 3 ), proposed three major items 51 69 (1) single or multiple organs involved with diffuse or localized swelling, masses, nodules, and/or hypertrophic lesions; (2) elevated serum IgG4 levels (greater than or equal to 135 mg/dL); and (3) histopathologic features that include marked lymphocytic and plasma cell infiltration and fibrosis, with IgG4-positive plasma cell infiltration (IgG4/IgG-positive cell ratio of greater than or equal to 40% and IgG4-positive plasma cells exceeding 10/HPF). Based on these criteria, patients can be classified into the categories of definite, probable, or possible IgG4-RD.

How do autoimmune pancreatitis (AP) types 1 and 2 differ?

Age: older onset (6th decade) typical of type 1
Gender: male predominance in type 1, not 2
Relationship to IgG4: present in type 1, not clearly present in 2
Histology: lymphoplasmacytic sclerosing pancreatitis in type 1, idiopathic duct centric pancreatitis in 2
Abdominal pain: common in type 2, not in 1
Other organ involvement common in 1, not 2
Steroid responsiveness characterizes both types but type 1 is more prone to relapse.

Sunday, October 30, 2016

IgG-4 related disease overview

Here is an overview from Disease of the Month. IgG-4 diseases include one of the two types of autoimmune pancreatitis and several other conditions:

Immunoglobulin G4-related disease is a rare but increasingly recognized multisystem entity characterized by lymphoplasmacytic tissue infiltration...Related manifestations of this disease include Reidel’s thyroiditis, chronic sclerosing dacryoadenitis, autoimmune pancreatitis (type 1 AIP), retroperitoneal fibrosis, and tubulointerstitial nephritis. Usually occurring in older men, the diagnosis is primarily based upon finding of histopahtologic changes..

Saturday, October 29, 2016

High flow nasal cannula vs NIPPV post extubation

Question Is high-flow nasal cannula noninferior to noninvasive ventilation for preventing reintubation and postextubation respiratory failure?

Findings In this multicenter randomized noninferiority clinical trial that included 604 adults, the proportion requiring reintubation was 22.8% with high-flow therapy vs 19.1% with noninvasive ventilation, and postextubation respiratory failure was observed in 26.9% with high-flow therapy vs 39.8% with noninvasive ventilation, reaching the noninferiority threshold.

Meaning High-flow nasal cannula immediately after scheduled extubation was not inferior to noninvasive mechanical ventilation for risk of reintubation and postextubation respiratory failure in patients at high risk of reintubation.

Friday, October 28, 2016

Epilepsy driving laws by state

Here is the database from the epilepsy foundation.

Wednesday, October 26, 2016

Cystic lung disease as a manifestation of Sjogren Syndrome

From a recent paper in Chest:

Methods Eighty-four patients with primary or secondary SS and chest imaging, chest radiograph, or CT scan were retrospectively evaluated for CLD. Thirteen patients with cysts were found. Baseline characteristics of all patients were collected. A multivariate logistic regression model was used to look for predictors of CLD in patients with CT scan. Additional imaging, SS activity, and complications from CLD and SS were collected for the patients with cysts.

Results CLD had a frequency of 15.4% for all patients with chest imaging. Not all cysts were evident on radiography, and CLD frequency was 30.9% for the patients with chest CT scan. Six patients had cysts without other radiographic findings. CLD was associated with older age (OR, 1.1; 95% CI, 1.0-1.16), a diagnosis of secondary SS (OR, 12.1; 95% CI, 1.12-130.4), and seropositivity for anti-SS-related antigen A/Ro autoantibodies (OR, 26.9; 95% CI, 1.44-93.61). There was no radiologic progression of CLD for 12 patients after a 4-year median follow-up. Lung function did not exhibit temporal worsening. CLD did not correlate with a specific pattern in pulmonary function testing. Two patients had secondary infectious complications of the cysts.

And here is a nice general review of cystic lung disease and its various associations.

Monday, October 24, 2016

Viral infection in community acquired pneumonia

The advent of PCR has improved the identification of viruses in patients with community-acquired pneumonia (CAP). Several studies have used PCR to establish the importance of viruses in the aetiology of CAP.

We performed a systematic review and meta-analysis of the studies that reported the proportion of viral infection detected via PCR in patients with CAP. We excluded studies with paediatric populations. The primary outcome was the proportion of patients with viral infection. The secondary outcome was short-term mortality.

Our review included 31 studies. Most obtained PCR via nasopharyngeal or oropharyngeal swab. The pooled proportion of patients with viral infection was 24.5% (95% CI 21.5–27.5%). In studies that obtained lower respiratory samples in greater than 50% of patients, the proportion was 44.2% (95% CI 35.1–53.3%). The odds of death were higher in patients with dual bacterial and viral infection (OR 2.1, 95% CI 1.32–3.31).

Viral infection is present in a high proportion of patients with CAP. The true proportion of viral infection is probably underestimated because of negative test results from nasopharyngeal or oropharyngeal swab PCR. There is increased mortality in patients with dual bacterial and viral infection.