Bag the banana bag in favor of the optimal metabolic cocktail for critically ill alcoholics

From a recent review:

Objective: Patients with a chronic alcohol use disorder presenting to the ICU may be deficient in important vitamins and electrolytes and are often prescribed a “banana bag” as a reflexive standard of therapy. The difficulty of diagnosing Wernicke’s encephalopathy in the critical care setting is reviewed. Furthermore, whether the contents and doses of micronutrients and electrolytes in standard banana bags meet the needs of critically ill patients with an alcohol use disorder is assessed based on available evidence...

Study Selection and Data Extraction: Articles relevant to Wernicke’s encephalopathy, vitamin and electrolyte deficiencies in patients with alcohol use disorders, and alcoholic ketoacidosis were selected...

Data Synthesis: Of these deficiencies, thiamine is the most important for the practicing clinician to assess and prescribe replacement in a timely manner. Based on a pharmacokinetic assessment of thiamine, the banana bag approach likely fails to optimize delivery of thiamine to the central nervous system. Folic acid and magnesium may also merit supplementation although the available data do not allow for as strong a recommendation...

Conclusions: ..for patients with a chronic alcohol use disorder admitted to the ICU with symptoms that may mimic or mask Wernicke’s encephalopathy, we suggest abandoning the banana bag and utilizing the following formula for routine supplementation during the first day of admission: 200–500 mg IV thiamine every 8 hours, 64 mg/kg magnesium sulfate (approximately 4–5 g for most adult patients), and 400–1,000 μg IV folate. If alcoholic ketoacidosis is suspected, dextrose-containing fluids are recommended over normal saline.

Increasing use of advanced therapies, declining mortality in cardiac arrest

From a poster presentation at AHA 2016:

Methods: The Healthcare Cost and Utilization Project’s Nationwide Inpatient Sample was utilized to identify a cohort of adults hospitalized with CA, identified through International Classification of Diseases-9 codes…

Results: In-hospital all-cause mortality significantly decreased over the 7-year study period (65.5%, 63.4%, 59.3%, 57.9%, and 57.0%, 56.0%, and 56.3% from 2006-2012). From 2006-2012, there was an overall rise in the use of coronary angiogram (12.8%, 13.0%, 14.7%, 15.0%, 14.3%, 14.7%, and 15.8%), percutaneous coronary intervention (PCI) (7.5%, 7.1%, 8.4%, 8.1%, 8.1%, 8.4%, and 8.9%), TH (0.2%, 0.3%, 0.6%, 1.2%, 1.9%, 2.8%, and 3.0%), and ECMO (0.1%, 0.1%, 0.1%, 0.2%, 0.2%, 0.3%, and 0.4%)…

Conclusions: During 2006-2012, a decline in mortality was accompanied by a steady rise in use of advanced therapies, including ECMO, TH, coronary angiogram, and coronary revascularization. Patients of younger age and with CAD were more likely to receive these advanced therapies.

Your syncope admission: could it be PE?

From a recent NEJM report:

Background

The prevalence of pulmonary embolism among patients hospitalized for syncope is not well documented, and current guidelines pay little attention to a diagnostic workup for pulmonary embolism in these patients.

Methods

We performed a systematic workup for pulmonary embolism in patients admitted to 11 hospitals in Italy for a first episode of syncope, regardless of whether there were alternative explanations for the syncope. The diagnosis of pulmonary embolism was ruled out in patients who had a low pretest clinical probability, which was defined according to the Wells score, in combination with a negative d-dimer assay. In all other patients, computed tomographic pulmonary angiography or ventilation–perfusion lung scanning was performed. Results

Results

A total of 560 patients (mean age, 76 years) were included in the study. A diagnosis of pulmonary embolism was ruled out in 330 of the 560 patients (58.9%) on the basis of the combination of a low pretest clinical probability of pulmonary embolism and negative d-dimer assay. Among the remaining 230 patients, pulmonary embolism was identified in 97 (42.2%). In the entire cohort, the prevalence of pulmonary embolism was 17.3% (95% confidence interval, 14.2 to 20.5). Evidence of an embolus in a main pulmonary or lobar artery or evidence of perfusion defects larger than 25% of the total area of both lungs was found in 61 patients. Pulmonary embolism was identified in 45 of the 355 patients (12.7%) who had an alternative explanation for syncope and in 52 of the 205 patients (25.4%) who did not.

Conclusions

Pulmonary embolism was identified in nearly one of every six patients hospitalized for a first episode of syncope

But, as pointed out by the blogger at Emergency Medicine Literature of Note, this should not be as shocking as it sounds (and will be spun by the popular media). As pointed out there:

The primary issue here is the almost certain inappropriate generalization of these results to dissimilar clinical settings. During the study period, there were 2,584 patients presenting to the Emergency Department with a final diagnosis of syncope. Of these, 1,867 were deemed to have an obvious or non-serious alternative cause of syncope and were discharged home. Thus, less than a third of ED visits for syncope were admitted, and the admission cohort is quite old – with a median age for admitted patients of 80 (IQR 72-85). There is incomplete descriptive data given regarding their comorbidities, but the authors state admission criteria included “severe coexisting conditions” and “a high probability of cardiac syncope on the basis of the Evaluation of Guidelines in Syncope Study score.” In short, their admission cohort is almost certainly older and more chronically ill than many practice settings.

Then, there are some befuddling features presented that would serve to inflate their overall prevalence estimate. A full 40.2% of those diagnosed with pulmonary embolism had “Clinical signs of deep-vein thrombosis” in their lower extremities, while 45.4% were tachypneic and 33.0% were tachycardic. These clinical features raise important questions regarding the adequacy of the Emergency Department evaluation; if many of these patients with syncope had symptoms suggestive of PE, why wasn’t the diagnosis made in ED? If even only the patients with clinical signs of DVT were evaluated prior to admission, those imaging studies would have had a yield for PE of 65%, and the prevalence number seen in this study would drop from 17.3% to 10.3%. Further evaluation of either patients with tachypnea or tachycardia might have been similarly high-yield, and further reduced the prevalence of PE in admitted patients.

Put another way, it is likely that many of these patients with PE had all the red flags. It has long been known that PE can present with syncope. When it does it tends (in my subjective experience) to be massive or submassive and would likely yield electrocardiographic or echocardiographic clues. Selective use of imaging based on clinical assessment would likely find these patients. So, I tend to agree with the blogger that while this study should not change practice all that much it in all likelihood will.

Non invasive ventilation for respiratory failure following abdominal surgery

From a recent JAMA paper:

Importance It has not been established whether noninvasive ventilation (NIV) reduces the need for invasive mechanical ventilation in patients who develop hypoxemic acute respiratory failure after abdominal surgery.

Objective To evaluate whether noninvasive ventilation improves outcomes among patients developing hypoxemic acute respiratory failure after abdominal surgery.

Design, Setting, and Participants Multicenter, randomized, parallel-group clinical trial conducted between May 2013 and September 2014 in 20 French intensive care units among 293 patients who had undergone abdominal surgery and developed hypoxemic respiratory failure (partial oxygen pressure less than 60 mm Hg or oxygen saturation [Spo2] less than or equal to 90% when breathing room air or less than 80 mm Hg when breathing 15 L/min of oxygen, plus either [1] a respiratory rate above 30/min or [2] clinical signs suggestive of intense respiratory muscle work and/or labored breathing) if it occurred within 7 days after surgical procedure.

Interventions Patients were randomly assigned to receive standard oxygen therapy (up to 15 L/min to maintain Spo2 of 94% or higher) (n = 145) or NIV delivered via facial mask (inspiratory pressure support level, 5-15 cm H2O; positive end-expiratory pressure, 5-10 cm H2O; fraction of inspired oxygen titrated to maintain Spo2 greater than or equal to 94%) (n = 148).

Main Outcomes and Measures The primary outcome was tracheal reintubation for any cause within 7 days of randomization. Secondary outcomes were gas exchange, invasive ventilation–free days at day 30, health care–associated infections, and 90-day mortality.

Results Among the 293 patients (mean age, 63.4 [SD, 13.8] years; n=224 men) included in the intention-to-treat analysis, reintubation occurred in 49 of 148 (33.1%) in the NIV group and in 66 of 145 (45.5%) in the standard oxygen therapy group within+ 7 days after randomization (absolute difference, −12.4%; 95% CI, −23.5% to −1.3%; P = .03). Noninvasive ventilation was associated with significantly more invasive ventilation–free days compared with standard oxygen therapy (25.4 vs 23.2 days; absolute difference, −2.2 days; 95% CI, −0.1 to 4.6 days; P = .04), while fewer patients developed health care–associated infections (43/137 [31.4%] vs 63/128 [49.2%]; absolute difference, −17.8%; 95% CI, −30.2% to −5.4%; P = .003). At 90 days, 22 of 148 patients (14.9%) in the NIV group and 31 of 144 (21.5%) in the standard oxygen therapy group had died (absolute difference, −6.5%; 95% CI, −16.0% to 3.0%; P = .15). There were no significant differences in gas exchange.

Conclusions and Relevance Among patients with hypoxemic respiratory failure following abdominal surgery, use of NIV compared with standard oxygen therapy reduced the risk of tracheal reintubation within 7 days. These findings support use of NIV in this setting.

Noninvasive ventilation in neuromuscular respiratory failure

Surprisingly, it can be useful in neuromuscular respiratory failure of a variety of causes with the notable exception of GBS. From a recent review:

Recent findings: Myasthenic crisis represents the paradigmatic example of the neuromuscular condition that can be best treated with noninvasive ventilation. Timely use of noninvasive ventilation can substantially reduce the duration of ventilatory assistance in these patients. Noninvasive ventilation can also be very helpful after extubation in patients recovering from an acute cause of neuromuscular respiratory failure who have persistent weakness. Noninvasive ventilation can improve quality of survival in patients with advanced motor neuron disorder (such as amyotrophic lateral sclerosis) and muscular dystrophies, and can avoid intubation when these patients present to the hospital with acute respiratory failure. Attempting noninvasive ventilation is not only typically unsuccessful in patients with Guillain–Barre syndrome, but can also be dangerous in these cases.

Summary: Noninvasive ventilation can be very effective to treat acute respiratory failure caused by myasthenia gravis and to prevent reintubation in other neuromuscular patients, but should be used cautiously for other indications, particularly Guillain–Barre syndrome.

Negative pressure pulmonary edema

Here is a review in Chest. From the review:

Negative-pressure pulmonary edema (NPPE) or postobstructive pulmonary edema is a well-described cause of acute respiratory failure that occurs after intense inspiratory effort against an obstructed airway, usually from upper airway infection, tumor, or laryngospasm. Patients with NPPE generate very negative airway pressures, which augment transvascular fluid filtration and precipitate interstitial and alveolar edema. Pulmonary edema fluid collected from most patients with NPPE has a low protein concentration, suggesting hydrostatic forces as the primary mechanism for the pathogenesis of NPPE. Supportive care should be directed at relieving the upper airway obstruction by endotracheal intubation or cricothyroidotomy, institution of lung-protective positive-pressure ventilation, and diuresis unless the patient is in shock. Resolution of the pulmonary edema is usually rapid, in part because alveolar fluid clearance mechanisms are intact.

Mitral valve prolapse and sudden cardiac death

Here is an interesting case report in the green journal in which a patient presenting in cardiac arrest was found to have mitral valve prolapse (with a flail leaflet) and a markedly prolonged QT. Genetic analysis revealed a novel repolarization prolonging sodium channel mutation as well as a desmoplakin gene mutation of uncertain significance. Of interest, this latter mutation is one of the ones associated with arrhythmogenic right ventricular cardiomyopathy.

During the surge of interest in MVPduring the 1980s there was a belief that it was associated with sudden cardiac death but the mechanism was unclear and the purported association has since been disputed. There has also long been suspected an association between MVP and long QT.

Mean platelet volume as a biomarker for PE

In this study the test characteristics were as good as a D dimer.

More data on the macrovascular benefit of pioglitazone: pioglitazone after stroke or TIA

From a recent NEJM study:

Methods

In this multicenter, double-blind trial, we randomly assigned 3876 patients who had had a recent ischemic stroke or TIA to receive either pioglitazone (target dose, 45 mg daily) or placebo. Eligible patients did not have diabetes but were found to have insulin resistance on the basis of a score of more than 3.0 on the homeostasis model assessment of insulin resistance (HOMA-IR) index. The primary outcome was fatal or nonfatal stroke or myocardial infarction.

Results

By 4.8 years, a primary outcome had occurred in 175 of 1939 patients (9.0%) in the pioglitazone group and in 228 of 1937 (11.8%) in the placebo group (hazard ratio in the pioglitazone group, 0.76; 95% confidence interval [CI], 0.62 to 0.93; P=0.007). Diabetes developed in 73 patients (3.8%) and 149 patients (7.7%), respectively (hazard ratio, 0.48; 95% CI, 0.33 to 0.69; P less than 0.001). There was no significant between-group difference in all-cause mortality (hazard ratio, 0.93; 95% CI, 0.73 to 1.17; P=0.52). Pioglitazone was associated with a greater frequency of weight gain exceeding 4.5 kg than was placebo (52.2% vs. 33.7%, P less than 0.001), edema (35.6% vs. 24.9%, P less than 0.001), and bone fracture requiring surgery or hospitalization (5.1% vs. 3.2%, P=0.003).

Conclusions

In this trial involving patients without diabetes who had insulin resistance along with a recent history of ischemic stroke or TIA, the risk of stroke or myocardial infarction was lower among patients who received pioglitazone than among those who received placebo. Pioglitazone was also associated with a lower risk of diabetes but with higher risks of weight gain, edema, and fracture.

Background on the possible macrovascular benefits of pioglitazone here.

Managing peri-procedural hemorrhage risk

Here is a recent review in Chest.

The abstract lists the procedures considered in the review:

Central venous catheterization, arterial catheterization, paracentesis, thoracentesis, tube thoracostomy, and lumbar puncture constitute a majority of the procedures performed in patients who are hospitalized.

Of particular interest is the controversy around patients with coagulopathy, either inherent or due to anticoagulants. There is no evidence, and no recommendation from the review, to support avoidance of necessary procedures or prophylactic factor replacement except for LP. In the case LP, though the risk of bleeding is very low an abundance of caution is advised based on expert opinion and rationale. From the review:

Given the paucity of data regarding optimal platelet levels for LP and the potential risks of hematoma, consensus guidelines recommend platelet count of 50,000/mL or greater, with clinical judgment guiding practice when platelet counts are between 20,000 and 49,000/mL…

Based on expert opinion and observational data, the recommendations suggest that therapeutic systemic anticoagulation be held prior to spinal anesthesia or LP.

Special considerations apply to NOACs. From the review:

Direct oral anticoagulants, such as inhibitors of thrombin or factor Xa, are increasingly being used in place of vitamin K antagonists. At this time, recommendations for periprocedural management of these medications are based on expert opinion. These recommendations include holding direct oral anticoagulants for a 24-hour window before and after low-risk procedures and 5 days prior to high-risk procedures.

More evidence favoring lactated ringers over saline

From a recent article:

Objectives: To assess the impact of the percentage of fluid infused as Lactated Ringer (%LR) during the first 2 days of ICU admission in hospital mortality and occurrence of acute kidney injury.

Design: Retrospective cohort.

Setting: Analysis of a large public database (Multiparameter Intelligent Monitoring in Intensive Care-II).

Patients: Adult patients with at least 2 days of ICU stay, admission creatinine lower than 5 mg/dL, and that received at least 500 mL of fluid in the first 48 hours.

Interventions: None.

Measurement and Main Results: 10,249 patients were included in mortality analysis and 8,085 were included in the acute kidney injury analysis. For acute kidney injury analysis, we excluded patients achieving acute kidney injury criteria in the first 2 days of ICU stay. Acute kidney injury was defined as stage 2/3 Kidney Disease: Improving Global Outcomes creatinine criteria and was assessed from days 3–7. The effects of %LR in both outcomes were assessed through logistic regression controlling for confounders. Principal component analysis was applied to assess the effect of volume of each fluid type on mortality. Higher %LR was associated with lower mortality and less acute kidney injury. %LR effect increased with total volume of fluid infused. For patients in the fourth quartile of fluid volume (greater than 7 L), the odds ratio for mortality for %LR equal to 75% versus %LR equal to 25% was 0.50 (95% CI, 0.32–0.79; p less than 0.001). Principal component analysis suggested that volume of Lactated Ringer and 0.9% saline infused had opposite effects in outcome, favoring Lactated Ringer.

Conclusions: Higher %LR was associated with reduced hospital mortality and with less acute kidney injury from days 3–7 after ICU admission. The association between %LR and mortality was influenced by the total volume of fluids infused.

It's pretty impressive to me that in cases of large volume resuscitation the mortality for those in whom 75% of the volume was LR was half that of those in whom 25% was LR.

Fluid balance and mortality in sepsis

From a recent study:

Objectives: Excessive fluid therapy in patients with sepsis may be associated with risks that outweigh any benefit. We investigated the possible influence of early fluid balance on outcome in a large international database of ICU patients with sepsis.

Design: Observational cohort study.

Setting: Seven hundred and thirty ICUs in 84 countries.

Patients: All adult patients admitted between May 8 and May 18, 2012, except admissions for routine postoperative surveillance. For this analysis, we included only the 1,808 patients with an admission diagnosis of sepsis. Patients were stratified according to quartiles of cumulative fluid balance 24 hours and 3 days after ICU admission.

Measurements and Main Results: ICU and hospital mortality rates were 27.6% and 37.3%, respectively. The cumulative fluid balance increased from 1,217 mL (-90 to 2,783 mL) in the first 24 hours after ICU admission to 1,794 mL (-951 to 5,108 mL) on day 3 and decreased thereafter. The cumulative fluid intake was similar in survivors and nonsurvivors, but fluid balance was less positive in survivors because of higher fluid output in these patients. Fluid balances became negative after the third ICU day in survivors but remained positive in nonsurvivors. After adjustment for possible confounders in multivariable analysis, the 24-hour cumulative fluid balance was not associated with an increased hazard of 28-day in-hospital death. However, there was a stepwise increase in the hazard of death with higher quartiles of 3-day cumulative fluid balance in the whole population and after stratification according to the presence of septic shock.

Conclusions: In this large cohort of patients with sepsis, higher cumulative fluid balance at day 3 but not in the first 24 hours after ICU admission was independently associated with an increase in the hazard of death.

Management of coagulopathy in liver diasease

From a recent review:

Conclusions: Dynamic changes to hemostasis occur in patients with hepatic insufficiency. Routine laboratory tests of hemostasis are unable to reflect these changes and should not be used exclusively to evaluate coagulopathy. Newer testing methods are available to provide data on the entire spectrum of clotting but are not validated in acute bleeding. Prohemostatic agents utilized to prevent bleeding should only be considered when the risk of bleeding outweighs the risk of thrombotic complications. Restrictive transfusion strategies may avoid exacerbation of acute bleeding. Prophylaxis against and treatment of thromboembolic events are necessary and should consider patient specific factors.

Factors in delays in antibiotic administration in patients with septic shock

Recently published:

Design: In a retrospective cohort of critically ill patients with septic shock.

Setting: Twenty-four ICUs.

Patients: A total of 6,720 patients with septic shock.

Interventions: None.

Measurements and Main Results: Higher Acute Physiology Score (+24 min per 5 Acute Physiology Score points; p less than 0.0001); older age (+16 min per 10 yr; p less than 0.0001); presence of comorbidities (+35 min; p less than 0.0001); hospital length of stay before hypotension: less than 3 days (+50 min; p less than 0.0001), between 3 and 7 days (+121 min; p less than 0.0001), and longer than 7 days (+130 min; p less than 0.0001); and a diagnosis of pneumonia (+45 min; p less than 0.01) were associated with longer times to antimicrobial therapy. Two variables were associated with shorter times to antimicrobial therapy: community-acquired infections (–53 min; p less than 0.001) and higher temperature (–15 min per 1°C; p less than 0.0001). After adjusting for confounders, admissions to academic hospitals (+52 min; p less than 0.05), and transfers from medical wards (medical vs surgical ward admission; +39 min; p less than 0.05) had longer times to antimicrobial therapy. Admissions from the emergency department (emergency department vs surgical ward admission, –47 min; p less than 0.001) had shorter times to antimicrobial therapy.

Conclusions: We identified clinical and organizational factors that can serve as evidence-based targets for future quality-improvement initiatives on antimicrobial timing. The observation that academic hospitals are more likely to delay antimicrobials should be further explored in future trials.

This is important because in septic shock mortality increases with passage of time until antibiotic administration. These results suggest that increased patient complexity drives delay. Deceptive and indolent presentations appear to be associated with delay as evidenced by the finding of shorter times for higher temperatures. For already hospitalized patients, the longer they had been in the hospital the longer the delay. Might complacency regarding patients near the end of their stay drive this? Particularly intriguing is the fact that academic medical centers had longer delays (+52 minutes). I have to wonder if this relates to more restrictive antibiotic policies and layers of approval embedded at such institutions.

Managing peri-procedural hemorrhage risk

Here is a recent review in Chest.

The abstract lists the procedures considered in the review:

Central venous catheterization, arterial catheterization, paracentesis, thoracentesis, tube thoracostomy, and lumbar puncture constitute a majority of the procedures performed in patients who are hospitalized.

Of particular interest is the controversy around patients with coagulopathy, either inherent or due to anticoagulants. There is no evidence, and no recommendation from the review, to support avoidance of necessary procedures or prophylactic factor replacement except for LP. In the case LP, though the risk of bleeding is very low an abundance of caution is advised based on expert opinion and rationale.

From the review:

Given the paucity of data regarding optimal platelet levels for LP and the potential risks of hematoma, consensus guidelines recommend platelet count of 50,000/mL or greater, with clinical judgment guiding practice when platelet counts are between 20,000 and 49,000/mL…

Based on expert opinion and observational data, the recommendations suggest that therapeutic systemic anticoagulation be held prior to spinal anesthesia or LP.

Special considerations apply to NOACs. From the review:

Direct oral anticoagulants, such as inhibitors of thrombin or factor Xa, are increasingly being used in place of vitamin K antagonists. At this time, recommendations for periprocedural management of these medications are based on expert opinion. These recommendations include holding direct oral anticoagulants for a 24-hour window before and after low-risk procedures and 5 days prior to high-risk procedures.

Left ventricular non compaction

Reviewed in JACC.

The learning curve for lung ultrasound

From a recent paper:

Purpose

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)...

Results

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.

Conclusions

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.

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:

Background

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.

Methods

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.

Results

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.

Conclusions

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.

Lung ultrasound to evaluate for pulmonary edema in the dyspneic patient

Useful in this systematic review.

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.

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.

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.

Incretin based drugs and gallbladder disease risk

From JAMA Internal Medicine:

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.

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

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

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.

Entresto

Corlanor

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.

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.