Here are the last 20 additions to the PBrain (total entries as of now = 3659)


What Family Physicians Can Do to Combat Bullying (3640)
McClowry et al JFP 66:82 02-01-2017

Full article


Recurrent UTIs in Women: How You Can Refine Your Care (3641)
Quinlan et al JFP 66:94 02-01-2017

There is apparently no data supporting voiding after intercourse to reduce the risk of recurrent UTI. Other myths are bubble baths, non-cotton underwear, and douching. Their threshold for prophylactic antibiotics is 2 events in 6 months, or 3 in a year. Continuous prophyalaxis (daily, or MWF) and post-coital prophylaxis are discussed, with suggestions regarding medication choices.

Full article


Thyroid hormone therapy for older adults with subclinical hypothyroidism (3642)
Stott DJ et al NEJM 04-03-2017

Subclinical hypothyroidism (i.e., elevated thyroid-stimulating hormone [TSH] and normal free thyroxine levels) is common, but the value of treatment remains controversial. In this U.K. randomized trial, investigators identified 737 older patients (age, ≥65) who had laboratory evidence of subclinical hypothyroidism within the previous 3 years (TSH levels, 4.6 to 19.99 mIU/L) and were not treated. Patients received either supplemental levothyroxine or placebo; initial levothyroxine dose was either 25 μg or 50 μg daily, depending on body weight and cardiac history, and dosing was titrated to achieve a normal TSH level (0.4 to 4.6 mIU/L). At baseline, mean TSH level was 6.4 mIU/L, and mean free thyroxine level was 1.03 ng/dL.

During 1 year of follow-up, standardized thyroid symptom scores and fatigue scores (the primary outcomes) and numerous secondary outcomes - including quality of life, grip strength, and body-mass index - were similar in the two groups. No adverse effects from supplemental levothyroxine were noted.

Comment: One year of treatment for older patients with subclinical hypothyroidism has no obvious clinical value; whether longer duration of treatment confers benefit (or harm) remains unclear. An additional observation is notable: Of patients who initially were eligible for this trial based on past test results, about 60% had normal TSH levels when they were retested prior to randomization (such patients were excluded from enrollment). Frequent spontaneous normalization of mildly elevated TSH levels has been described previously.


Validating the HERDOO2 rule to guide treatment duration for women with unprovoked venous thrombosis: Multinational prospective cohort management study (3643)
Rodger MA et al BMJ 356:j1065 03-17-2017

As many as 10% of patients with unprovoked venous thromboembolism (VTE) develop recurrent VTE within 1 year after stopping anticoagulation therapy. To identify a subgroup of patients with unprovoked VTE who were at low risk for recurrence, researchers previously derived the HERDOO2 rule (Hyperpigmentation, Edema, or Redness in either leg; d-dimer level ≥250 mcg/L; Obesity [body-mass index ≥ 30 kg/m2]; and Older [age, ≥65]). In the original derivation study, women with ≤ 1 HERDOO2 criterion had a low recurrence rate (1.6% annually), but the rule was unable to identify a low-risk male group (NEJM JW Gen Med Oct 1 2008 and CMAJ 2008; 179:417).

Now, the researchers have validated this rule prospectively in 2785 patients with unprovoked VTE who had completed 5 to 12 months of anticoagulation. During additional average follow-up of 1 year, results were as follows:

Comment: In this study, 3% of women with unprovoked VTE and zero or one HERDOO2 criterion developed recurrent VTE by 1 year. The authors conclude that this rate is low enough to justify stopping anticoagulation therapy after a standard course. Given that about half of women with unprovoked VTEs met low-risk criteria, this recommendation would apply to a substantial number of patients. Notably, the HERDOO2 decision rule should not be used in men.


The USPSTF Draft Guideline on Prostate Cancer Screening (3644)
Brett JW 37:79 05-15-2017

On April 12, 2017, the U.S. Preventive Services Task Force (USPSTF) issued a "draft recommendation" on prostate cancer screening using prostate-specific antigen (PSA) testing. These preliminary releases are made available briefly for public comment, which the USPSTF considers before publishing a final, formal statement. Because the draft recommendation received such widespread media publicity, it's worth a brief review.

In 2012, the USPSTF recommended against prostate cancer screening, giving it a "D" recommendation (NEJM JW Gen Med Jul 1 2012 and Ann Intern Med 2012; 157:120). Although the new draft statement retains the D grade for older men (age, ≥70), the recommendation for younger men (age range, 55- 69) has been upgraded to C"." A C grade is defined generally as: "The USPSTF recommends selectively offering or providing this service to individual patients based on professional judgment and patient preferences." Specifically, the new recommendation asks clinicians to "inform men ages 55 to 69 years about the potential benefits and harms of prostate-specific antigen (PSA)-based screening for prostate cancer."

What changed between 2012 and now? The USPSTF offers two main reasons. First, in the original report from the European screening trial published in 2009 after average follow-up of 9 years, screening prevented less than 1 prostate cancer-related death per 1000 screened men. In 2014, after 13 years of follow-up, this figure had improved to slightly more than 1 per 1000 (NEJM JW Gen Med Sep 15 2014 and Lancet 2014; 384:2027). Second, for men with low-risk, PSA-detected, localized prostate cancer, active surveillance - i.e., periodic monitoring with PSA testing and prostate biopsy, proceeding to treatment only if progression appears to occur - has become more prevalent in recent years. In a recent randomized trial, active surveillance compared favorably with immediate surgery or radiotherapy (NEJM JW Gen Med Nov 1 2016 and N Engl J Med 2016; 375:1415). For the USPSTF, these two developments tipped the balance slightly more toward screening, but not enough to justify an A or B recommendation in favor of generalized screening. Notably, the USPSTF did not find sufficient evidence to make stronger recommendations for groups with above-average risk (blacks or men with positive family history).

To its credit, the USPSTF continues to emphasize that the balance between benefits and harms remains a close call. Although the new statement is only a "draft," the new C recommendation almost certainly will persist in the final version. For now, my concerns are twofold: First, some media portrayals exaggerated the new recommendation and implied that all men now should be screened. And second, although the recommendation's heavy emphasis on elaborate individualized decision making is laudable, pulling that off in daily practice is extremely difficult, as I wrote in 2012 (NEJM JW Gen Med Jul 1 2012). The USPSTF provides a well-intentioned patient information flow diagram that might help somewhat with the process of shared decision making, and some members of the Task Force have written an editorial that defines their goals (JAMA 2017 Apr 11; [e-pub]). However, conveying the probabilities and combinations and permutations of all the downstream events that happen when one initiates PSA screening - and somehow assimilating all those probabilities into the patient's "values and preferences" (the USPSTF's language) - is a daunting, if not impossible, task during primary care office visits.


Determinants of reflux-induced chronic cough (3645)
Herregods TVK et al Gut 03-15-2017

Although cough is a well-recognized "extraesophageal manifestation" of gastroesophageal reflux disease (GERD), it does not respond well to acid suppression with proton-pump inhibitors (PPIs), especially in patients who do not have typical GERD symptoms of heartburn or regurgitation. To identify determinants of cough in GERD, researchers in Europe evaluated 24-hour esophageal pH impedance pressure monitoring results (off PPIs) in 49 patients identified with reflux-induced cough. They compared characteristics of reflux episodes with and without an accompanying cough burst (≥2 rapid simultaneous pressure peaks within 3 seconds). A reflux episode was defined as an orally progressing sequential drop in impedance to <50% of baseline value and was considered acidic if pH was <4 for at least 4 seconds.

Of 2270 reflux episodes identified, 395 included cough bursts. Factors significantly associated with cough burst were a higher proximal extent of the refluxate and longer volume clearance time, but not pH drop or acid clearance time. The percentage of reflux episodes that were acidic was similar with or without cough. Among the 49 patients, 19 had no typical GERD symptoms (heartburn, regurgitation, or both).

Comment: Although acid is an extremely important contributing factor in GERD, this study indicates its lack of causal importance in GERD-related cough. The fact that some reflux episodes reaching only the distal esophagus included cough events suggests a neurogenic esophagobronchial reflex in some, rather than frank aspiration. Clearly, impedance pH monitoring in patients with GERD-related cough is helpful to guide therapies and expectations for successful response.


Top 20 Research Studies of 2016 for Primary Care Physicians (3646)
Ebell et al AFP 95:573 05-01-2017

Full article


Achieved blood pressure and cardiovascular outcomes in high-risk patients: Results from ONTARGET and TRANSCEND trials (3647)
Bohm et al Lancet 04-05-2017

Optimal target blood pressure (BP) for patients who are receiving antihypertensive therapy remains controversial; numerous studies have suggested that excessive BP lowering can increase risk for some adverse cardiovascular (CV) events. However, in the SPRINT trial, targeting a systolic BP of <120 mm Hg lowered the incidence of adverse CV events more than did less-aggressive treatment, although average achieved systolic BP actually remained slightly higher than 120 mm Hg (NEJM JW Gen Med Dec 15 2015 and N Engl J Med 2015; 373:2174). To elucidate further the relation between BP and adverse CV outcomes, researchers analyzed pooled data from 31,000 high-risk patients (age, ≥55; history of CV disease or diabetes with organ damage; 70% with hypertension) who were assigned to take ramipril, telmisartan, both, or neither for a median 56 months in two trials funded by the manufacturer of telmisartan. Outcomes included a composite endpoint (CV-related death, myocardial infarction, stroke, or hospitalization for heart failure), individual CV endpoints, and all-cause death.

Mean BP achieved on treatment was a stronger predictor of CV outcomes than was baseline BP or last recorded BP before an adverse CV event. For most outcomes, risk was lowest at mean achieved systolic and diastolic BPs of 120 to 140 mm Hg and 70 to 80 mm Hg, respectively. The composite outcome, CV-related death, heart failure hospitalization, and all-cause death all occurred significantly more commonly at lower systolic BPs, and all outcomes except stroke were more frequent at lower diastolic BPs.

Comment: Statistical adjustments could not completely eliminate the possibility of reverse causality in this observational study. Optimal BP targets might vary for preventing specific adverse CV outcomes, but, for most patients at high CV risk, targets of 120/70 to 140/80 mm Hg probably are safest and most effective.


Serum creatinine elevation after renin-angiotensin system blockade and long term cardiorenal risks: Cohort study (3648)
Schmidt M et al BMJ 356:j791 03-09-2017

National Kidney Foundation guidelines recommend stopping angiotensin-converting-enzyme (ACE) inhibitors or angiotensin-receptor blockers (ARBs) if serum creatinine increases by ≥30% after starting treatment. However, the rationale for this 30% threshold is unclear. In this cohort study of 122,000 U.K. adults, researchers assessed outcomes associated with rises in serum creatinine concentrations during the first 2 months after beginning ACE inhibitor or ARB treatment.

About 2100 patients (1.7%) had serum creatinine increases of ≥30% after starting treatment. Compared with patients in whom creatinine increased by <30%, those with larger increases were more likely to die (adjusted incident rate ratio, 1.84) or to develop end-stage kidney disease (IRR, 3.43), heart failure (IRR, 1.37), or myocardial infarction (IRR, 1.46) during about 10 years of follow-up. Moreover, dose-response relations between serum creatinine and these outcomes were observed even when creatinine rose by 10% to 19% or 20% to 29% following ACE inhibitor or ARB initiation.

Comment: In this real-world study, which was subject to residual confounding, any increase in serum creatinine after starting ACE inhibitor or ARB treatment was associated with higher risks for death, end-stage kidney disease, heart failure, and myocardial infarction - with no distinct cutoff at 30%. Whether ACE inhibitors or ARBs directly cause adverse outcomes or just unmask underlying pathophysiology are unknown. Nonetheless, patients with increases in serum creatinine after starting these drugs should be recognized as a high-risk group and monitored closely.


Association between clinically recorded alcohol consumption and initial presentation of 12 cardiovascular diseases: Population based cohort study using linked health records (3649)
Bell S et al BMJ 356:j909 03-22-2017

Prior studies have shown that both drinking no alcohol and heavy alcohol consumption are associated with higher risk for cardiovascular (CV) morbidity and mortality compared with moderate drinking a "U-shaped" association. However, some of these studies categorized both never drinkers and former drinkers as nondrinkers - a methodological flaw that could have biased results, because former drinkers might have excess risk for CV disease. In this population-based U.K. cohort study, researchers assessed associations between specific categories of alcohol consumption and multiple adverse CV outcomes in almost 2 million adults without known CV disease at baseline.

During a median follow-up of 6 years, 115,000 participants received incident CV diagnoses. The following associations were noted in analyses adjusted for possible confounders (e.g., smoking):

Comment: This study supports the U-shaped relation between alcohol intake and CV disease. Both teetotalers and heavy drinkers had higher risks for various adverse CV outcomes than did moderate drinkers. Whether clinicians should endorse alcohol intake in the generally accepted moderate range (i.e., 1-2 drinks daily for men, and 1 drink daily for women) for carefully selected patients remains controversial.


Effect of oral dexamethasone without immediate antibiotics vs placebo on acute sore throat in adults: A randomized clinical trial (3650)
Hayward GN et al JAMA 317:1535 04-18-2017

Oral corticosteroids have been studied in patients with sore throats, but not in the absence of antibiotics. In this U.K. general practice study, investigators recruited 576 adults with acute sore throat judged by their physicians not to require immediate antibiotics. Participants' throats were swabbed, but rapid streptococcal antigen test results were not made available to clinicians. Patients were randomized to receive oral dexamethasone (10 mg in a single dose) or placebo. Physicians could prescribe antibiotics to be taken 48 hours later if symptoms had not improved.

About 40% of patients in both groups were offered delayed antibiotic prescriptions. At 48 hours (but not at 24 hours), dexamethasone patients were significantly more likely than placebo patients to have complete symptom resolution (35% vs. 27%); given the 8% absolute difference in risk, 12 patients would need to be treated with dexamethasone for 1 to have symptom resolution at 48 hours. However, groups did not differ in average time to symptom resolution or in average number of days with "moderately bad" symptoms. Results were similar among those who did and did not receive delayed antibiotics. Throat swab results showed that 17% of patients had streptococcus; of these, about half had received delayed antibiotics.

Comment: These results should be assessed in light of patient selection: Participants had sore throats that did not require initial antibiotics. It does not seem prudent to expose 12 patients to even a single corticosteroid dose in order to shorten 1 patient's course of a relatively mild, self-limited sore throat by a few hours. However, some patients will see this study and ask for a prescription.


Short term use of oral corticosteroids and related harms among adults in the United States: Population based cohort study (3651)
Waljee AK et al BMJ 357:j1415 04-12-2017

Although the adverse effects of long-term corticosteroids are clear, relatively little is known about short-term use. In this retrospective U.S. study, researchers used a nationwide commercial insurance claims dataset to determine the incidence of three adverse effects (sepsis, venous thromboembolism, and fracture) associated with oral corticosteroid use for <30 days by >1.5 million adults (age range, 18-64; mean age, 45) continuously enrolled from 2012 through 2014.

In all, 21% of participants received at least one short-term prescription for an oral corticosteroid (median duration, 6 days; median prednisone equivalent dose, 20 mg daily). Nearly half (47%) of patients received a 6-day "dosepack" of methylprednisolone. Respiratory tract infections and disorders, spinal conditions, and allergies accounted for 56% of prescriptions. In users compared with nonusers, incidence rates for sepsis (1.8 vs. 1.0 per 1000 person-years), venous thromboembolism (VTE; 4.6 vs. 2.4), and fracture (21.4 vs. 14.3) were significantly higher regardless of age. In a self-controlled case series, risks for sepsis (incidence rate ratio, 5.3), VTE (IRR, 3.3), and fracture (IRR, 1.9) were significantly higher during the 5 to 30 days after the prescription date than the 5 to 180 days before the prescription date.

Comment: An astonishing one in five commercially insured adults received a short course of oral corticosteroid therapy during this 3-year study period. Although the absolute excess risk for sepsis, VTE, and fracture associated with short-term corticosteroid use was low, the cumulative number of affected people was not trivial; widespread use of short-term oral corticosteroids thus has substantial public health implications. Clinicians should not administer short-term oral corticosteroids for conditions in which such agents are ineffective. For conditions in which corticosteroids might provide transient symptom relief but are not essential, clinicians should think twice before prescribing these drugs.


Cost-effectiveness of common diagnostic approaches for evaluation of asymptomatic microscopic hematuria (3652)
Halpern JA et al JAMA Intern Med 04-17-2017

Asymptomatic microscopic hematuria (AMH; defined by red blood cells on urine microscopy, not dipstick testing) raises concerns about occult genitourinary cancer. In this decision analysis, investigators used standard research sources and evidence-based assumptions to assess the cost-effectiveness of detecting genitourinary cancer with each of four strategies:

Neither ultrasound alone nor voided-urine cytology were evaluated, due to their relatively poor sensitivity.

Combination renal ultrasound and cystoscopy was the most cost-effective, with an incremental cost per cancer detected of about US$53,000. Substituting CT urography for ultrasound detected only one additional cancer, at markedly higher incremental cost per cancer detected (≈$6.5 million) and greater clinical risk (e.g., radiation, contrast exposure). Analyses in high-risk patients (i.e., men, smokers, and older patients [age, ≥50]) yielded similar results, although at a lower incremental cost per cancer detected. Results were the same in multiple sensitivity analyses.

Comment: These results challenge the recommendations of some U.S. professional organizations, and confirm those of some international groups. This was not a cost-utility analysis, in which length and quality of life are taken into account. However, the stability of these results across multiple analyses suggests that renal ultrasound and cystoscopy is the preferred approach to evaluation of asymptomatic microscopic hematuria.


A Man with Pain and Swelling of the Left Calf and a Purpuric Rash (3653)
Miloslavsky et al NEJM 376:1868 05-11-2017

A very interesting and clear discussion of vasculitis. First, try to determine if it is secondary to cancer, infection (RMSF, meningococcal infection, SBE), drug use (cocaine/levamisole), other inflammatory conditions (SLR, Sjogrens). If it is a primary vasculitis, check ANCA, look for eosinophils on a CBC, look for renal/lung/sinus involvement, check for hepatitis B/C - in this case, the cause was IgA vasculitis (formerly known as Henoch-Schonlien purpura).

Full article


Management of Depression in Older Adults: A Review (3654)
Kok et al JAMA 317: 2114 05-23-2017

Observations: Depression presents with the same symptoms in older adults as it does in younger populations. In contrast to younger patients, older adults with depression more commonly have several concurrent medical disorders and cognitive impairment. Depression occurring in older patients is often undetected or inadequately treated. Antidepressants are the best-studied treatment option, but psychotherapy, exercise therapy, and electroconvulsive therapy may also be effective. Psychotherapy is recommended for patients with mild to moderate severity depression. Many older patients need the same doses of antidepressant medication that are used for younger adult patients. Although antidepressants may effectively treat depression in older adults, they tend to pose greater risk for adverse events because of multiple medical comorbidities and drug-drug interactions in case of polypharmacy. High-quality evidence does not support the use of pharmacologic treatment of depression in patients with dementia. Polypharmacy in older patients can be minimized by using the Screening Tool of Older Persons Prescriptions and Screening Tool to Alert doctors to Right Treatment (STOPP/START) criteria, a valid and reliable screening tool that enables physicians to avoid potentially inappropriate medications, undertreatment, or errors of omissions in older people. Antidepressants can be gradually tapered over a period of several weeks, but discontinuation of antidepressants may be associated with relapse or recurrence of depression, so the patient should be closely observed.

Conclusions and Relevance: Major depression in older adults is common and can be effectively treated with antidepressants and electroconvulsive therapy. Psychological therapies and exercise may also be effective for mild-moderate depression, for patients who prefer nonpharmacological treatment, or for patients who are too frail for drug treatments.

STOPP-START

Full article


Antithrombotic Therapy for Venous Thromboembolic Disease (3655)
Jain et al JAMA 317:2008 05-16-2017

Major recommendations:

Full article


Thiazide treatment in primary hyperparathyroidism - a new indication for an old medication? (3656)
Tsvetov G et al J Clin Endocrinol Metab 102 04-01-2017

A recent study suggested that primary hyperparathyroidism often is present in patients with thiazide-associated hypercalcemia and that the hypercalcemia usually is mild and nonprogressive in these cases (NEJM JW Gen Med Apr 15 2016 and J Clin Endocrinol Metab 2016; 101:1166). In this new retrospective study, researchers analyzed data on 72 patients with known primary hyperparathyroidism who had serum and urine calcium measurements both before initiation of hydrochlorothiazide (HCTZ) and during an average of 3 years of HCTZ therapy.

Mean serum calcium level was 10.7 mg/dL before HCTZ exposure and did not change significantly during HCTZ therapy. Eleven patients had pre-HCTZ serum calcium levels ≥11.5 mg/dL; after HCTZ was initiated, serum calcium levels declined in 9 of these patients and increased to >12.0 mg/dL in 2 patients. HCTZ was associated with decreases in mean urine calcium level (from 427 mg/day to 251 mg/day) and mean parathyroid hormone level (from 115 pg/day to 74 pg/dL).

Comment: This study suggests that thiazide diuretics can be given safely to patients with primary hyperparathyroidism. In fact, thiazide-induced reduction in hypercalciuria might benefit patients by lowering risk for calcium kidney stone formation. However, serum calcium levels still should be monitored periodically, because they occasionally will increase further when patients with primary hyperparathyroidism receive thiazide diuretics.


Global strategy for the diagnosis, management, and prevention of chronic obstructive lung disease 2017 report: GOLD executive summary (3657)
Vogelmeier CF et al Am J Respir Crit Care Med 195:557 03-01-2017

The World Health Organization (WHO) and NIH convened the original GOLD expert panel in 1998 to make recommendations for managing COPD. Since the release of its first guidelines in 2001, GOLD has published several revisions, most recently in 2014.

Key Points:

COMMENT: Although not a lot is new in these guidelines, big "take homes" include less emphasis on inhaled steroids, shorter duration of systemic steroids for exacerbations, and more emphasis on symptoms and exacerbation history in guiding therapy choices. A 37-page "pocket guide" to the 2017 GOLD guidelines is available online.


Spiraling Out of Control (3658)
Mixter et al NEJM 376:2183 06-01-2017

A 22-year-old man presented to the emergency department on Christmas Day with a 5-day history of myalgias, cough, dyspnea, nonbilious emesis, and nonbloody diarrhea. Although he had been ill for several days, he ultimately sought treatment because of intractable vomiting. He reported feeling feverish, although he had not measured his temperature, and noted one episode of hemoptysis.

Full case report.


A Boy with Acute Fear of Choking while Swallowing (3659)
Carroll et al NEJM 376:2266 06-08-2017

A 14-year-old boy was seen in the emergency department of this hospital because of fear of choking while swallowing.

The patient had been well until 2 days before admission, when he choked while eating a piece of chicken during dinner. He became fearful of swallowing and was unable to finish the meal despite cutting his food into small pieces. The next day, he vomited after trying to eat ice cream, and his daily fluid intake decreased to only 710 ml (24 oz) of water. He reportedly needed his mother near him throughout the day and had an "irrational fear" of choking. He had not had recent fevers, rhinorrhea, cough, or sore throat. Nine days earlier, during a routine annual examination at the clinic of the patient’s primary care pediatrician, the patient's mother reported that he had had several episodes of inspiratory stridor while he was sleeping during the past few weeks; the patient was referred to an otolaryngologist, but this visit had not yet occurred. On the day of this presentation, the patient consumed only small sips of water, reported feeling hungry, and slept most of the day. His mother noted that, in addition to the inspiratory stridor during sleep, the patient had some gasping for air that was associated with deep involuntary burping. She contacted a physician at this hospital and was advised to bring the patient to the emergency department for evaluation.

Full case report


Here are the last 10 additions to the PBrain by date


A Boy with Acute Fear of Choking while Swallowing (3659)
Carroll et al NEJM 376:2266 06-08-2017

A 14-year-old boy was seen in the emergency department of this hospital because of fear of choking while swallowing.

The patient had been well until 2 days before admission, when he choked while eating a piece of chicken during dinner. He became fearful of swallowing and was unable to finish the meal despite cutting his food into small pieces. The next day, he vomited after trying to eat ice cream, and his daily fluid intake decreased to only 710 ml (24 oz) of water. He reportedly needed his mother near him throughout the day and had an "irrational fear" of choking. He had not had recent fevers, rhinorrhea, cough, or sore throat. Nine days earlier, during a routine annual examination at the clinic of the patient’s primary care pediatrician, the patient's mother reported that he had had several episodes of inspiratory stridor while he was sleeping during the past few weeks; the patient was referred to an otolaryngologist, but this visit had not yet occurred. On the day of this presentation, the patient consumed only small sips of water, reported feeling hungry, and slept most of the day. His mother noted that, in addition to the inspiratory stridor during sleep, the patient had some gasping for air that was associated with deep involuntary burping. She contacted a physician at this hospital and was advised to bring the patient to the emergency department for evaluation.

Full case report


Spiraling Out of Control (3658)
Mixter et al NEJM 376:2183 06-01-2017

A 22-year-old man presented to the emergency department on Christmas Day with a 5-day history of myalgias, cough, dyspnea, nonbilious emesis, and nonbloody diarrhea. Although he had been ill for several days, he ultimately sought treatment because of intractable vomiting. He reported feeling feverish, although he had not measured his temperature, and noted one episode of hemoptysis.

Full case report.


Management of Depression in Older Adults: A Review (3654)
Kok et al JAMA 317: 2114 05-23-2017

Observations: Depression presents with the same symptoms in older adults as it does in younger populations. In contrast to younger patients, older adults with depression more commonly have several concurrent medical disorders and cognitive impairment. Depression occurring in older patients is often undetected or inadequately treated. Antidepressants are the best-studied treatment option, but psychotherapy, exercise therapy, and electroconvulsive therapy may also be effective. Psychotherapy is recommended for patients with mild to moderate severity depression. Many older patients need the same doses of antidepressant medication that are used for younger adult patients. Although antidepressants may effectively treat depression in older adults, they tend to pose greater risk for adverse events because of multiple medical comorbidities and drug-drug interactions in case of polypharmacy. High-quality evidence does not support the use of pharmacologic treatment of depression in patients with dementia. Polypharmacy in older patients can be minimized by using the Screening Tool of Older Persons Prescriptions and Screening Tool to Alert doctors to Right Treatment (STOPP/START) criteria, a valid and reliable screening tool that enables physicians to avoid potentially inappropriate medications, undertreatment, or errors of omissions in older people. Antidepressants can be gradually tapered over a period of several weeks, but discontinuation of antidepressants may be associated with relapse or recurrence of depression, so the patient should be closely observed.

Conclusions and Relevance: Major depression in older adults is common and can be effectively treated with antidepressants and electroconvulsive therapy. Psychological therapies and exercise may also be effective for mild-moderate depression, for patients who prefer nonpharmacological treatment, or for patients who are too frail for drug treatments.

STOPP-START

Full article


Antithrombotic Therapy for Venous Thromboembolic Disease (3655)
Jain et al JAMA 317:2008 05-16-2017

Major recommendations:

Full article


The USPSTF Draft Guideline on Prostate Cancer Screening (3644)
Brett JW 37:79 05-15-2017

On April 12, 2017, the U.S. Preventive Services Task Force (USPSTF) issued a "draft recommendation" on prostate cancer screening using prostate-specific antigen (PSA) testing. These preliminary releases are made available briefly for public comment, which the USPSTF considers before publishing a final, formal statement. Because the draft recommendation received such widespread media publicity, it's worth a brief review.

In 2012, the USPSTF recommended against prostate cancer screening, giving it a "D" recommendation (NEJM JW Gen Med Jul 1 2012 and Ann Intern Med 2012; 157:120). Although the new draft statement retains the D grade for older men (age, ≥70), the recommendation for younger men (age range, 55- 69) has been upgraded to C"." A C grade is defined generally as: "The USPSTF recommends selectively offering or providing this service to individual patients based on professional judgment and patient preferences." Specifically, the new recommendation asks clinicians to "inform men ages 55 to 69 years about the potential benefits and harms of prostate-specific antigen (PSA)-based screening for prostate cancer."

What changed between 2012 and now? The USPSTF offers two main reasons. First, in the original report from the European screening trial published in 2009 after average follow-up of 9 years, screening prevented less than 1 prostate cancer-related death per 1000 screened men. In 2014, after 13 years of follow-up, this figure had improved to slightly more than 1 per 1000 (NEJM JW Gen Med Sep 15 2014 and Lancet 2014; 384:2027). Second, for men with low-risk, PSA-detected, localized prostate cancer, active surveillance - i.e., periodic monitoring with PSA testing and prostate biopsy, proceeding to treatment only if progression appears to occur - has become more prevalent in recent years. In a recent randomized trial, active surveillance compared favorably with immediate surgery or radiotherapy (NEJM JW Gen Med Nov 1 2016 and N Engl J Med 2016; 375:1415). For the USPSTF, these two developments tipped the balance slightly more toward screening, but not enough to justify an A or B recommendation in favor of generalized screening. Notably, the USPSTF did not find sufficient evidence to make stronger recommendations for groups with above-average risk (blacks or men with positive family history).

To its credit, the USPSTF continues to emphasize that the balance between benefits and harms remains a close call. Although the new statement is only a "draft," the new C recommendation almost certainly will persist in the final version. For now, my concerns are twofold: First, some media portrayals exaggerated the new recommendation and implied that all men now should be screened. And second, although the recommendation's heavy emphasis on elaborate individualized decision making is laudable, pulling that off in daily practice is extremely difficult, as I wrote in 2012 (NEJM JW Gen Med Jul 1 2012). The USPSTF provides a well-intentioned patient information flow diagram that might help somewhat with the process of shared decision making, and some members of the Task Force have written an editorial that defines their goals (JAMA 2017 Apr 11; [e-pub]). However, conveying the probabilities and combinations and permutations of all the downstream events that happen when one initiates PSA screening - and somehow assimilating all those probabilities into the patient's "values and preferences" (the USPSTF's language) - is a daunting, if not impossible, task during primary care office visits.


A Man with Pain and Swelling of the Left Calf and a Purpuric Rash (3653)
Miloslavsky et al NEJM 376:1868 05-11-2017

A very interesting and clear discussion of vasculitis. First, try to determine if it is secondary to cancer, infection (RMSF, meningococcal infection, SBE), drug use (cocaine/levamisole), other inflammatory conditions (SLR, Sjogrens). If it is a primary vasculitis, check ANCA, look for eosinophils on a CBC, look for renal/lung/sinus involvement, check for hepatitis B/C - in this case, the cause was IgA vasculitis (formerly known as Henoch-Schonlien purpura).

Full article


Top 20 Research Studies of 2016 for Primary Care Physicians (3646)
Ebell et al AFP 95:573 05-01-2017

Full article


Bariatric Surgery Summary (3630)
Kney Various 04-21-2017

Zinc supplements: If level is < 60 (normal 60-130 mcg/dl) - supplement with 1-2 mg/kg of elemental zinc. One common form is zinc sulfate 220 mg - containing 50 mg of elemental zinc.

Labs for following bariatric patients with malabsorptive surgery: CBC, CMP, iron/TIBC/ferritin, B12, lipid, vitamin D, PTH, thiamine, folate.


Effect of oral dexamethasone without immediate antibiotics vs placebo on acute sore throat in adults: A randomized clinical trial (3650)
Hayward GN et al JAMA 317:1535 04-18-2017

Oral corticosteroids have been studied in patients with sore throats, but not in the absence of antibiotics. In this U.K. general practice study, investigators recruited 576 adults with acute sore throat judged by their physicians not to require immediate antibiotics. Participants' throats were swabbed, but rapid streptococcal antigen test results were not made available to clinicians. Patients were randomized to receive oral dexamethasone (10 mg in a single dose) or placebo. Physicians could prescribe antibiotics to be taken 48 hours later if symptoms had not improved.

About 40% of patients in both groups were offered delayed antibiotic prescriptions. At 48 hours (but not at 24 hours), dexamethasone patients were significantly more likely than placebo patients to have complete symptom resolution (35% vs. 27%); given the 8% absolute difference in risk, 12 patients would need to be treated with dexamethasone for 1 to have symptom resolution at 48 hours. However, groups did not differ in average time to symptom resolution or in average number of days with "moderately bad" symptoms. Results were similar among those who did and did not receive delayed antibiotics. Throat swab results showed that 17% of patients had streptococcus; of these, about half had received delayed antibiotics.

Comment: These results should be assessed in light of patient selection: Participants had sore throats that did not require initial antibiotics. It does not seem prudent to expose 12 patients to even a single corticosteroid dose in order to shorten 1 patient's course of a relatively mild, self-limited sore throat by a few hours. However, some patients will see this study and ask for a prescription.


Cost-effectiveness of common diagnostic approaches for evaluation of asymptomatic microscopic hematuria (3652)
Halpern JA et al JAMA Intern Med 04-17-2017

Asymptomatic microscopic hematuria (AMH; defined by red blood cells on urine microscopy, not dipstick testing) raises concerns about occult genitourinary cancer. In this decision analysis, investigators used standard research sources and evidence-based assumptions to assess the cost-effectiveness of detecting genitourinary cancer with each of four strategies:

Neither ultrasound alone nor voided-urine cytology were evaluated, due to their relatively poor sensitivity.

Combination renal ultrasound and cystoscopy was the most cost-effective, with an incremental cost per cancer detected of about US$53,000. Substituting CT urography for ultrasound detected only one additional cancer, at markedly higher incremental cost per cancer detected (≈$6.5 million) and greater clinical risk (e.g., radiation, contrast exposure). Analyses in high-risk patients (i.e., men, smokers, and older patients [age, ≥50]) yielded similar results, although at a lower incremental cost per cancer detected. Results were the same in multiple sensitivity analyses.

Comment: These results challenge the recommendations of some U.S. professional organizations, and confirm those of some international groups. This was not a cost-utility analysis, in which length and quality of life are taken into account. However, the stability of these results across multiple analyses suggests that renal ultrasound and cystoscopy is the preferred approach to evaluation of asymptomatic microscopic hematuria.