You don't need to be signed in to read BMJ Blogs, but you can register here to receive updates about other BMJ products and services via our site.

Archive for March, 2014

Primary Care Corner with Geoffrey Modest MD: Radical prostatectomy for prostate cancer

28 Mar, 14 | by EBM

the Scandinavian prostate cancer group study published their 18 year followup of radical prostatectomy vs watchful waiting in men with localized prostate cancer (study prior to PSA testing, and was largely of men with palpable nodules). see DOI: 10.1056/NEJMoa1311593. this follows their 15 year followup published a couple of years ago. in brief,
–695 men with early prostate cancer randomized to surgery vs watchful waiting, followed up to 23.2 years, though overall analysis at 18 year mark: 
63 deaths from prostate cancer in surgery group and 99 in watchful waiting (18% vs 29%, RR 0.56), absolute diff of 11% and NNT to prevent one death = 8
–200 deaths from all causes in the surgery group and 247 in the watchful waiting group (56.1% vs 68.9%, RR 0.71, abs diff 12.8%)
–androgen-deprivation therapy in fewer pts in surgery group vs watchful waiting, (42.5 vs 67.4%, abs diff 25%)
–benefit of surgery largest in men younger than 65 and those with intermediate-risk prostate cancer (eg gleason score <8), though also reduced risk of metastases in older men.
–both death from any cause and death from prostate cancer were significantly lower in those <65yo (RR 0.50, abs risk reduction ARR 25.5% for death from any cause; and RR 0.45, ARR 15.8% for prostate ca deaths. both NS for those >=65yo).  distant mets with RR 0.49 and ARR 15.8% in <65yo and RR 0.75 and ARR 6.6% if >=65yo.
–no evidence that effect diminished over time
so, my general assessment of this update is not really different from the last one. will append my blog from 7/26/2012 below on the PIVOT study with comments on Scandanavian one. of course, one major concern with the scandanavian study is that about 90% of the men were randomized after prostate cancer detected on rectal exam (which has worse prognosis than picking up with PSA), so current applicability a bit murky).

Primary Care Corner with Geoffrey Modest MD: Change to vaginal swabs does NOT lead to decreased screening

26 Mar, 14 | by EBM

new guidelines came out from the CDC on screening for chlamydia and gonorrhea, with a few significant changes (see here).  although there is no clear gold standard test for either Chlamydia or gonorrhea, nucleic acid amplification tests (NAATs) are considered the most reliable.  Recommendations:

–Sexually active women less than 26yo as well as those older with risk factors (e.g., new sex partner, multiple partners) should be screened annually for chlamydial infection
–For gonorrhea, there is wide difference in local epidemiology, and testing strategies should be adaptable.  In general targeted screening is indicated in women at high risk, since infections are so frequently asymptomatic.
For screening in women, the vaginal swab is the preferred specimen type.  These are as sensitive as cervical swabs and there is no difference in specificity.  Self-collected vaginal swabs are of equal sensitivity and specificity.  Cervical swabs are acceptable, though vaginal swabs are considered to be the appropriate sample type, even when full pelvic exams are being done (no data presented as to why vaginal swabs preferred….).  First catch urines, “while acceptable for screening, might detect up to 10% fewer infections when compared with vaginal and endocervical swab samples”.
–For men, the consensus on testing is less clear.  The USPSTF suggest testing sexually active heterosexual man in clinical settings with a high prevalence of Chlamydia.  For gonorrhea, again, the prevalence varies in different communities.  It is not appropriate to check men at low risk for infection.  And in general for men first catch urine samples are highly acceptable for both gonorrhea and chlamydia, and probably better than urethral swabs.
–For men and women with a positive NAAT for gonorrhea, treatment should be offered.  A repeat NAAT should be done at least 7 days after treatment, and if positive, a swab specimen should be sent for culture (endocervical for women and urethral for men), assuming that the person did not engage in sexual activity in this interim period.
–NAATs are the preferred test for rectal and oropharyngeal specimens as well (though not cleared for this indication by the FDA).  There may be some false positives in the oropharyngeal specimens, since other, commensal neisseria species may be present.  Again, if positive, and a repeat NAAT is positive more than 7 days after treatment, a culture should be sent for antibiotic susceptibility.

so, this brings up a few issues. the Massachusetts State Lab has taken the strong position that any testing is better than no testing: so, a streamlined system where medical assistants regularly get urines for routine chlam/gonorrhea screening is superior to one which gets the slightly better test of vaginal swabs but is less consistent in getting specimens. also, for the assays we use (Becton-Dickenson at the state lab, Aptima at boston medical center), you need a special vaginal swab kit for the vaginal secretion collection (ie, though counterintuitive, you cannot use the endocervical swab to collect the vaginal sample). boston medical center can provide these special swab kits, to be used in facilities where either the clinician does the sampling or the patients have “procedural supervision” and support to explain how the woman collects their own samples, and the women are not pregnant and at least 16 years old. so, bottom line: vaginal swabs are better for detection of chlamydia in women, but should only be implemented if there are systems to support this process, and a change to vaginal swabs does NOT lead to decreased screening.


Primary Care Corner with Geoffrey Modest MD: Skin Abscesses Treatment

25 Mar, 14 | by EBM

review article in new england journal last week on management of skin abscesses in era of methicillin-resistant staph aureaus MRSA (see DOI: 10.1056/NEJMra1212788). both the incidence of skin abscesses overall and the % of MRSA have increased over time. a few comments:

–diagnostic accuracy is not great: eg, a study of 126 adults with cellulitis where ER MD felt abscess not evident, ultrasound found abscess in 50%
–treatment of abscess is primarily I&D
–there may be more rapid healing if the I&D incision is closed vs leaving it open (studies mostly in the anogenital area, showing half the healing time and no diff in recurrences). should consider primary closure if incision >2cm. [goes against conventional wisdom that needs to be open to continue draining]
–no data as to whether to irrigate the wound, and data on whether packing helps is unclear (a couple of very small studies done, one in adults showing more pain but no outcome difference, one in kids found more frequent subsequent drainage and antibiotic treatment in those not packed)
–antibiotics. in 2008, 63% of abscesses were from community-associated MRSA. 15% in MSSA, 2% b-hemolytic strep, 20% other. but cure rates for just I&D alone are in the 85% range. a study in kids found no diff if give tmp/smx vs placebo after I&D, though some decrease in new lesion development. so, Infectious Diseases Society of America recommends systemic antibiotics for patients with extensive disease (multiple sites), rapidly progressive dz, signs/symptoms of systemic illness, immunosuppression, very young or old, abscess in difficult area to drain, associated septic phlebitis, or drained abscess not responding just to I&D.
–empirical antibiotic therapy when chosen should cover MRSA, ie first choice of tmp/smx 1-2 DS tabs bid. some resistance to clinda and tetras, but can do clindamycin 300-450 tid, doxycylcine 100 bid or minocycline 200, then 100 q12h.
–if cellulitis alone, more likely to be strep (difficult to really know the organism if just cellulitis, though), and TMP/SMX and tetracyclines less active. clinda may be better choice. and my experience is that TMP/SMX, which has limited activity against strep, typically works well with cellulitis (though i never do ultrasound to rule-out small abscess…). if severe cellulitis, might cover with TMP/SMX plus cephalexin. there are no great data for these suggestions from clinical trials, and some trials are currently ongoing.

so, this brings up a few issues. even though it is commonly incorrect to conclude that an abscess is not present without the aid of an ultrasound, those of us in the community cannot typically get an ultrasound easily. unless the patient has severe infection needing hospitalization, we treat them by I&D if there is an evident abscess present, will occasionally needle it if not sure (though sometimes purulent collections can be quite viscous and can be missed with a needle), and (probably more often than is necessary) prescribe antibiotics. my experience is that small abscesses/collections often resorb with heat and antibiotics without I&D.


Primary Care Corner with Geoffrey Modest MD: Antibiotics for URI

21 Mar, 14 | by EBM

BMJ online recently published an article showing utility of delaying antibiotics, or giving no antibiotics, in patients with upper resp infection (see doi: 10.1136/bmj.g1606 ). in brief,

–889 pts over age 3 (median age 30) in 25 practices in UK were given advice about symptom control (antipyretics, +/- vaporizer) and then either immediate antibiotics in 333 (37%) (the group felt to have more severe sx and felt more likely to have lower resp tract infection), and in 556 (63%) randomized to the following different strategies:

–having the patient subsequently recontact the clinic to request a prescription if needed — pts told that symptoms typically worst on days 2-4
–post-dating the prescription
–having the patient come back to the clinic just for a prescription if needed
–given a prescription but asking the patient to wait to fill it
–no antibiotic prescribed


 –mean symptom severity at 3-4 days no diff between getting no prescription vs any of the delayed methods.
–no diff in duration of sx rated moderately bad or worse (median 3-4 days), whether in the immediate script, delayed script, or no script groups
–nonsignif difference in patient satisfaction in the different groups, belief in antibiotics, or antibiotic use, though no benefit in symptom severity or duration of symptoms. no diff in patient revisits to the clinic.
–with the no prescription or delayed prescription policies, the median day that antibiotics were started was day 4, and <40% of patients actually took antibiotics (approx 25% of the no prescription group ultimately got antibiotics)

 the background here is that, per the NICE guidelines (natl institute for health and care excellence in the UK), it is suggested to give an antibiotic prescription advising the patient to wait for at least the expected natural history of the illness (the study found that delayed scripts only have a slightly higher fill rate than giving no antibiotics). the advantage of the delayed script over none is that the former decreases the likelihood of patients coming back for another visit. also didn’t seem to matter which method used for delayed scripts. and, in this study, only a minority of patients actually filled the prescriptions, even if they were given them with the advice to wait a few days to see how they were.  also, of note, no difference in disease response in the group given immediate antibiotics vs those in delayed or no antibiotics (not an RCT, however). my experience is that, at least in our clinic and perhaps through reiteration over the years of the lack of utility of antibiotics, most patients are happy to be reassured that “it is just a virus” and not insist on getting antibiotics. and, perhaps in some patients, it is a good idea to see them in a few days if they are not getting better/getting worse.


Primary Care Corner with Geoffrey Modest MD: Hepatitis C treatment cost

19 Mar, 14 | by EBM

editorial in NY times last week about the cost of sofosbuvir, new highly effective oral medication for hepatitis c (see here). a few points:

–150 million people infected worldwide
–typical 12-week course costs $84K ( that is, $1000/pill). this translates to $18 billion for one year treatment in  california alone
–pricing is based not on costs (R&D), but Gilead’s assessment of costs of other therapies (which they seem to overstate) and expected savings since the drug is so great (also questionable)
–prices in the US are much higher than in Europe or other countries.

it is a great drug. but the cost may make it inaccessible to lots of people (some insurors not cover), or increase overall costs of health care (which is passed on to the govt and all of us), or limiting access to particular groups with perhaps more advanced disease (may be assoc with increased morbidity/mortality in waiting too long).


Primary Care Corner with Geoffrey Modest MD: HPV screening alone recommended by FDA subcommittee

18 Mar, 14 | by EBM

NY times reports unanimous vote by FDA subcommittee to replace pap smears with HPV testing alone. prior to this being a new policy, has to be approved by FDA (which almost always happens), though many providers may not use this test alone unless approved by professional societies. the initial test would be done at age 25. for full article, click here

of note,

–approx cost (in houstin texas): $50 for pap, $150 for HPV
–only one of the hpv tests, the one by roche (not the most common one done), is approved
–the current guidelines (pap age 21-30 q3yrs, then combo pap/HPV after age 30 q5yrs), have consciously postponed hpv screening til age 30 because in younger sexually active women, these infections most often regress spontaneously and, if picked up by screening, could lead unnecessarily to more invasive followup procedures (eg culposcopy and maybe more).

see prior blog posted last year here.



Primary Care Corner with Geoffrey Modest MD: HPV vaccine and decrease in cervical abnormalities. Maybe.

11 Mar, 14 | by EBM

article last week in BMJ from Australia finding that HPV vaccination in females led to decrease in high grade cervical abnormalities (see doi: 10.1136/bmj.g1458). not an RCT, but a case-control study “real-world” study to see if effect of prior vaccination on first cervical screen. results:

–females offered free quadrivalent HPV vaccine aged 12-26.
–at time of first pap smear, high grade cases in 1062 women, “other cases” (any other abnormality) in 10,887, and normal cytology (controls) of 96,404
–odds ratio for exposure to 3 doses of HPV vaccine vs no vaccine 0.54 for high grade cases and 0.66 for “other cases”, vs controls (ie vaccine effectiveness of 46% and 34%, with number needed to vaccinate being 125 and 22 respectively)
–if got only 2 of the 3 shots for vaccination, odds ratios of 0.79 for both high grade as well as for “other cases” (ie, vaccine effectiveness of 21% for each)
–on further analysis of their data,

–effectiveness of vaccination was not even close to being significant in the oldest age stratum (age 23-27)
–standard pap smears done at that time (2007-2011) first done between age 18-20 in sexually active women, or 1-2 years after first sexual intercourse, whichever is later
–of the 1062 high grade abnormalities, 7 were invasive squamous cell ca, 944 CIN 3, 84 CIN 2, 1 adenoca microinvasive, and 11 adenoca in situ
–1/3 of paps done age 15-18, 1/3 age 19-22 and 1/3 age 23-27

so, i bring this up mostly because of the strong title of the article and that it seems to be getting some play in the press. not sure how really useful it is, given that most of the patients were under 22 (and we stopped doing pap smears before age 21 given the very high number of HPV-related abnormalities, the vast majority of which spontaneously regress), and perhaps as confirmation of that, there was no difference in effectiveness of vaccine for high grade cases in those 23-27 years old. there are some similar data from the US finding 50% decrease in HPV types 16,18,6,11 in young women aged 14-19 (again, younger than we are testing with paps) and even in young women for oral HPV 16/18 infection. though it is concerning that there were several cancers (but very low %) in this young group…..


Primary Care Corner with Geoffrey Modest MD: Exenatide and pancreatitis FDA/EMA assessment

3 Mar, 14 | by EBM

of all of the new diabetes meds, the one i am most impressed with is exenatide. mostly because the long-acting preparation is injected only once a week, has studies showing it is at least as good an effect as lantus in patients without endstage diabetes, and is pretty physiologic (stimulates postprandial insulin release and decreases appetite, so unusual to be hypoglycemic and tend to lose weight). that being said, none of the new meds have real clinical outcome data, just surrogate marker of A1C improvement (as does rosiglitazone, which we know is associated with increased heart disease). one concern with GLP-1 agonists such as exenitide is that a couple of studies suggested increased risk of pancreatitis, and even some concern about pancreatic cancer. in this light, the FDA and EMA (european medicines agency) independently investigated and came out with a safety assessment (see DOI: 10.1056/NEJMp1314078).  their conclusions after reviewing all of the human and animal data so far, including postmarketing info:

–animal toxicology studies (healthy animals, those with diabetes, and those with pancreatitis) — no evidence of any exenitide-induced pancreatitis
–human studies — “may” be slight increase in amylase/lipase, but within normal range. asymptomatic. the incidence of pancreatic cancer was actually lower in patients on a DPP-4 antagonist (which decreases the degradation of endogenous GLP-1). both FDA and EMA found the observational data suggesting a relation with pancreatitis to have methodologic shortcomings (limited power, inadequate outcome verification, inadequate confounding control)

so, although the FDA and EMA “have not reached a final conclusion at this time regarding a causal relationship”, both agencies feel that the current data do not support a real association, though both agencies will continue to consider pancreatitis  “a risk associated with these drugs until more data are available”.  i have used the exenitide on a few patients so far. some GI intolerance, but generally impressive results.


Primary Care Corner with Geoffrey Modest MD: Intensifying platelet inhibition in patients with lacunar stroke does not help

2 Mar, 14 | by EBM

so, just after i posted about the neurology association recommendations on anticoagulation for nonvalvular atrial fibrillation, i found this article — which looked at patients who had lacunar strokes while already on aspirin to see if adding clopidogrel helped (see  DOI 10.1212/WNL.0000000000000076).  this is a post-hoc analysis of patients with aspirin failure and recent lacunar stroke in the larger SPS3 study (secondary prevention of small subcortical strokes trial).

–SPS3 involved 3000 patients with recent (<180d) symptomatic lacunar stroke with ipsilateral carotid artery disease not amenable to surgery, then all received aspirin 325mg/d and were randomly assigned to get additional clopidogrel vs placebo. this present study looked at the group (secondary analysis) of 838 patients who had been on aspirin prior to the lacunar stroke (the aspirin failure group) to see if those put on aspirin plus clopidogrel did better than those continued on aspirin alone. followup 3.5 years
–results: no diff in recurrent stroke if on aspirin or both drugs, each with 3% annual stroke rates. all-cause mortality in combo group was higher than in aspirin alone group (HR 2.13), along with doubling of hemorrhagic risk of GI bleeding
–this lack of protective effect of adding on clopidogrel was evident even in this subgroup of “aspirin failure”, which had a 30% higher risk profile for ischemic stroke.

so, i think this study does add to clinical management, though the results were a post-hoc analysis.  the not-so-uncommon clinical conundrum is the patient already on aspirin who has a stroke: what should we do? an appealing option was to intensify the anti-platelet attack, but this study suggests otherwise.  studies have found that the combo aspirin/dipyridamole or using clopidogrel alone seems to be somewhat more effective in secondary prevention of stroke than aspirin by itself, but to my knowledge, no one has looked at the cohort of “aspirin failures” with these meds (though probably best choice in patient who would not benefit from surgical intervention would be switching aspirin to one of these 2 therapies).


Primary Care Corner with Geoffrey Modest MD: New pediatric preventative health recs

2 Mar, 14 | by EBM

the am acad of pediatrics just came out with new pediatric preventive care guidelines (see the guidelines are basically a chart of either things to do on all kids, or targeted assessments — risk assessment with appropriate action to follow if positive. the basic changes are: 


–depression screen yearly from ages 11 through 21, esp using PHQ-2

–alcohol and drug screen yearly from ages 11 through 21, esp using CRAFFT (this is to do targeted assessment, with appropriate action if positive)


–lipid screening: targeted at age 24 mo, 2 y, 4 y, 6 y, 8 y, then once for all kids aged 9-11 y (this is the new recommendation), then targeted annually from 12-17 y, then again once for all kids aged 18-21 y

–hematocrit/hgb: targeted by risk assessment at 4 mo, all kids at 12 mo, then targeted at every well-child visit thereafter (added 15 and 30 month targeted screen)
–STI/HIV screen: targeted annually age 11-15, then once in all kids aged 16-18, then targeted annually thereafter (HIV screen was added in the 16-18 year range)

–cervical screen/pap: age 21, all girls. not before age 21 (consistent with other recommendations)

so, all seems reasonable to me, except i have concerns about over-testing for lipids. the real goal for the 9-11 yo screen i think is to pick up kids with severe familial dyslipidemia. i agree that many kids should be retested in late adol/early adulthood (when they are at an age to be more responsible in dietary and other lifestyle changes), though kids who actually have pristine lipids at age 9-11 and eat well/are not obese/are athletic (yes, there are some…) probably do not need a repeat lipid test 9 or 10 years later, esp girls who, even with awful diet, are pretty well protected from atherosclerotic disease until middle adulthood.


Latest from Evidence-Based Medicine

Latest from EBM