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Archive for January, 2015

Primary Care Corner with Geoffrey Modest MD: Low glycemic index diet

31 Jan, 15 | by EBM

By: Dr. Geoffrey Modest

A recent short-term study of overweight individuals did not show a benefit for a low glycemic index (low GI) diet (see JAMA. 2014;312(23):2531-2541​). In this randomized cross-over trial, overweight adults were given 4 different complete diets including all of their meals, snacks, and beverages, each for 5 weeks, with data below for those completing a minimum of 2 such diet rotations. Details:

–163 adults enrolled, mean age 53, 52% female, 51% black, 40% non-hispanic white, BMI 32 and waist circumference 104cm, 26% hypertensive, 16% smokers
–Diets (all based on DASH diet — high in whole grains, fruits, veges, and lower in low-fat dairy, lean meats/fish/poultry and nuts/seeds/legumes). all with similar amounts of potassium (4gm) , calcium (1 gm), sodium (2.3 gm), and all were 2000 kcal/day:
–High GI (65% on the glucose scale, high carbohydrate (58% of the energy)
–Low GI (<45% on glucose scale), high carbohydrate
–High GI, low carbohydrate (40% of the energy)
–Low GI, low carbohydrate
–Results (primary outcomes of insulin sensitivity, systolic BP, HDL, LDL, triglycerides):
–High carbohydrate diets: those on low GI vs high GI haddecreased insulin sensitivity (-20%, p=0.002), increased LDL from 139 to 147 (6%, p<0.001), no change in HDL, triglycerides, or blood pressure
–Low carbohydrate diets: those on low GI vs high GI had decreased triglycerides from 91 to 86 (-5%, p=0.02) and no change in other measures
​–Low GI low carb vs high GI high carb: decreased triglycerides from 111 to 86 (-23%, p<0.001). No change in other measures
–All of these diets, based on the DASH diet, led to decreases in LDL from baseline (from when people were eating their own diet) of 153 to 140 and systolic blood pressure from 132 to 123 mmHg.

Their conclusion is that the glycemic index of the foods “does not significantly improve cardiovascular risk factors or insulin resistance.” I am commenting on this very short-term study mostly because the last study published seems to have disproportionate weight in the minds of most of us… a few issues:

apple–This is a really short-term, though highly controlled study (done in research units of academic medical centers)
–Several, but not all studies of low GI diet, have found an increase in HDL and decrease in triglycerides (eg, see JAMA. 2007;297:2092-2102;​ or N Engl J Med 2008;359:229-41). this last study compared a calorie restricted low fat diet (1500 kcal/d for women, 1800 kcal/d for men) with calorie-restricted Mediterranean diet (same restrictions) vs. unrestricted low carb diet, finding the most weight loss over 2 years was in the calorie-unrestricted low carb diet. So, one interesting point is that those on low carb diets naturally eat less, perhaps related to the fact that, as opposed to carbs, fats do decrease appetite by their effect on the hypothalamic satiety center.
–A low carb vs low fat diet in 148 men and women at 12 months recently found a significant weight loss (3.5 kg), ratio of HDL/triglycerides, and increases in HDL (see Ann Intern Med. 2014;161:309-318)
–An interesting study found that low fat diets, as compared to very low carbohydrate and low GI diets (all isocaloric), led to decreases in resting and total energy expenditure – I.e., the low fat diet led to a compensatory decrease in energy expenditure, which could contribute to weight gain (see JAMA. 2012;307(24):2627-2634).

So, as a perspective on this study, there is reaffirmation that a DASH diet is healthier than the “usual diet”, with decreases in blood pressure and LDL.​ Although this very short-term study did not find additional value to the low GI diet, most other studies I’ve seen show lipid benefits even in nondiabetic patients. perhaps the issue with this study is having the underlying DASH diet (the first such study I have seen), though before making broad conclusions, it would be useful to have a confirmatory trial with longer diet durations. I also think that for many patients, eating a calorie-unrestricted low GI diet is easier than the comparable calorie-restricted low fat or Mediterranean diets, with at least as good results. This study, of note, does not deal with an important aspect of the low GI diet: in the prevention or treatment of diabetes.

Primary Care Corner with Geoffrey Modest MD: HIV transmission in serodiscordant couples

31 Jan, 15 | by EBM

By: Dr. Geoffrey Modest

One issue that comes up a lot is the transmissability of HIV in serodiscordant couples when the HIV-positive person has a suppressed viral load. A letter-to-the-editor was just published, reviewing 6 relevant studies (see doi.org/10.1097/QAI.0000000000000471). Lacking the best data, the researchers assumed that a surrogate for suppressed viral load was if the HIV-positive partner had been on combined antiretroviral treatment (cART) for >6 months (since usually the viral load is suppressed by then). They found:

–At most one transmission in 113,480 sex acts, of which 17% were not condom-protected.
–For that one transmission, data were not adequate to see if it happened before or after than 6-month mark
–So, their estimation varies as follows:
–Case 1: no transmission after 6 months — upper bound of risk-per-sex act was 8.7 per 100,000
–Case 2: 1 transmission after 6 months — upper bound of risk-per-sex act was 13 per 100,000

Then, they added the results of the PARTNER study presented at the CROI (conference on retroviruses and opportunistic infections) meeting in Boston in 2014 (see here), which looked at 767 HIV-discordant couples (40% gay) where there was condom-less sex and the HIV-infected partner had a viral load –NO transmissions so far!!! (the study will go on to 2017 — this is only an abstract of an interim report from the meeting)
–So, by adding this data to the above 6 studies, the estimates for case 1 above decreased to 5.2/100,000 sex acts and from case 2 to 7.9/100,000 sex acts

So, this is helpful. However, there needs to be more data on gay couples, since most of the above is on heterosexual couples. I do have some concern about reported discordance between suppressed viral load in blood and in semen. The studies I’ve seen are mostly in MSM (men who have sex with men), so I do have concern about the relative lack of data in the above studies about MSM. One recent article from Boston found that of 83 men with undetectable HIV in blood, 25% had HIV in their semen with HIV levels of 80 to 2560 copies/mL, with multivariate analysis showing sexually-transmitted infections/urethritis and unprotected insertive anal sex with an HIV-infected partner to be independent predictors of seminal fluid HIV detection (see AIDS 2012, 26:1535–1543​)​. Other studies have found detectable semen HIV levels in MSM with non-detectable plasma HIV levels in those with herpesvirus infections (eg CMV or EBV). But the study above is pretty reassuring, suggesting that transmission is still pretty rare (though likely non-zero). So, I think patients should still be warned that there is still a possibility of getting HIV infection if they don’t use condoms, as well as the variety of other potential sexually-transmitted infections.

Primary Care Corner with Geoffrey Modest MD: Interventions to prevent recurrent kidney stones

30 Jan, 15 | by EBM

By: Dr. Geoffrey Modest

The Am College of Physicians released a clinical practice guideline on interventions to prevent recurrent kidney stones (see doi:10.7326/M13-2908​).

Background:

–13% of men and 7% of women get kidney stones, and 35-50% have recurrence within 5 years without treatment
–80% are calcium oxalate or calcium phosphate or both
–Dietary efforts include increasing water intake, reducing dietary oxalate, reducing dietary animal protein and other purines, and maintaining normal calcium intake

Results of this systematic review:

–1 good quality and 28 fair-quality trials found insufficient evidence that assessing stone composition, or blood/urine chemistries reduces recurrences
–80 fair-quality trials of dietary interventions have found that:
–Increased fluid intake, reduced soft drink intake (esp. soda acidified by phosphoric acid, eg colas), and a high-calcium, low-protein, low-sodium diet reduce stone recurrences, though these studies were typically of low-quality and often with mixed results.
–One trial also found that low sodium intake (50 mmol/d) helped in patients with calcium oxalate stones.
–No trial specifically assessed low oxalate diet, though there was a trial finding benefit of high calcium (1200 mg/d) vs. low calcium diets (400 mg/d) — which has been attributed to dietary calcium binding oxalate in the gut and decreasing oxalate absorption.

Pharmacologic therapy:

–Thiazides — moderate-quality evidence from 6 fair-quality trials of 24.9% vs. 48.5% incidence of recurrent stones. no difference in type of thiazide. Though 8% vs. 1% withdrew for adverse reactions. ​ (In terms of dose — they note that these studies were done with higher dose thiazides. none with lower doses which have fewer adverse effects — it is evident that even low doses of thiazides increase serum calcium levels, though I could find no good data on dose-dependent calcium excretion. and I have prescribed lower dose thiazides with apparent good effect)
​–Citrates (which interfere with stone formation) — moderate-quality evidence in 5 trials of calcium stones with lower recurrence (11.1% vs. 52.3%). though 15% vs. 2% withdrew for adverse reactions.
–Allopurinol — moderate-quality evidence in 4 trials in patients with calcium oxalate stones of decreased recurrence (33.3% vs. 55.4%). no increase in adverse effects found.

So, their recommendations:

–Increase fluid intake spread throughout the day to achieve at least 2 L of urine/d (weak recommendation, low-quality evidence). They suggest avoiding colas (acidified by phosphoric acid) but not drinks acidified by citric acid (eg fruit-flavored sodas)
–Use drug monotherapy with thiazides, citrate or allopurinol in patients where increased fluid intake fails to reduce recurrent stones (weak recommendation, moderate-quality evidence)

So, a couple of comments:

1. Although I do give patients lists of high oxalate foods to avoid when they have calcium oxalate stones (and I do check stone chemistry analysis), my guess is that a more acceptable diet is the high calcium one, which I also recommend.
2. The issue of allopurinol. unclear what the mechanism is. 2 RCTs have found that patients who had hyperuricosuria put on allopurinol had fewer calcium oxalate stones, but an observational study found no difference in uric acid excretion in people with or without stones (observational study. controlled for some risk factors. but who knows?). Uric acid as nidus for stone formation (unclear). As most of you know by now, I am very concerned about food additives, and one of the obvious targets is high-fructose corn syrup, which is associated with dramatic increases in fructose consumption (currently about 25% of calories in the US, mostly from sodas, with increase from about 15 gm/d when fructose was consumed naturally from fruits to 73 gm/day now), has a different metabolism from glucose (which is converted into glycogen in the liver, vs. fructose, which is converted to fructose-1-phosphate and depletes the liver of phosphates, increases uric acid levels, increases small dense and more atherogenic LDL particles, and may increase insulin resistance). I have had some patients completely stop soda intake and have found pretty dramatic decreases in uric acid levels. So, this is now one of my dietary recommendations for those with kidney stones.

Primary Care Corner with Geoffrey Modest MD: Dabagratan, again

30 Jan, 15 | by EBM

By: Dr. Geoffrey Modest 

There have been a slew of articles recently promoting dabigatran and the direct acting thrombin inhibitors, and a remarkable number of articles in the on-line throw-away journals (delete-away??), like MedPage, interviewing leading researchers (many on the pharma dole) extolling the virtues of these medications. Recent articles include:

1. A meta-analysis noting that dabigatran, rivaroxaban, apixaban and edoxaban are non-inferior to vitamin K antagonists in stroke prevention for patients with atrial fibrillation, assessed the endpoints of all-cause and vascular mortality along with safety issues (see DOI:10.1111/jth.12651).

–71,683 patients with nonvalvular atrial fibrillation (from 4 RCTs , with follow-up of 1.8-2.8 years) found significant declines in all-cause mortality by 11% with NNT=132 (p<0.0001) and vascular mortality by 12%, NNT =189 (p<0.0001)​, with a striking decrease in mortality from bleeding (RR 0.54, p<0.0001, esp. intracranial bleeding with RR 0.42, p<0.00001)

2. A meta-analysis were done of the efficacy and treatment of acute venous thromboembolism — VTE (see doi:10.1001/jama.2014.10538). they assessed 8 strategies, though this was a “network meta-analysis”, mathematically combining different studies, since there were no direct comparisons of them. Strategies included: unfractionated heparin (UFH), low-molecular weight heparin (LMWH) in combo with vitamin K antagonists (VKA), LMWH with dabigatran or edoxaban, rivaroxaban, apixaban, and LMWH alone.

–45 studies with 45K patients, 22 comparing UFH-VKA with LMWH-VKA. only 6 studies looked at the new agents (2 with rivaroxaban, 2 with dabigatran, one each with edoxaban and apixaban), median follow-up of 3 months.
–Compared with LMWH-VKA, UFH-VKA associated with increased risk of recurrent VTE (HR 1.42), with proportion of patients with recurrent VTE over the 3 months: UFH-VKA 1.84%, LMWH-VKA 1.30%. so, no statistically signif diff for efficacy in any of these strategies, except UFH-VKA (which did badly)
–Risk of major bleeding event: rivaroxaban with 0.49%, apixaban 0.28%, LMWH-VKA 0.89%, with apixaban being the only one with statistically significant decrease in bleeding

BUT, a study released by JAMA Internal Medicine assessed retrospectively the Medicare pharmacy and medical claims for 1302 people on dabigatran used in atrial fibrillation vs. 8102 on warfarin (see doi:10.1001/jamainternmed.2014.5398). This was a real-world post-marketing study, assessing major and minor bleeding events (major= intracranial hemorrhage, hemoperitoneum, hosp visits/admits for hematuria, GI or other hemorrhage).

–Dabigatran associated with higher risk of bleeding than warfarin– 32.7% vs. 26.5%, with HR 1.30 (CI 1.20-1.41) for any bleeding event, major bleeding 9.0% vs. 5.9%, with HR 1.58. GI bleeding​ 17.4% vs. 10.0%, with HR 1.58 (CI 1.36-1.83), though risk of intracranial bleeding lower with dabigatran, 0.6% vs. 1.8%, with HR 0.32 (CI 0.20-0.50)​
–The risk of major bleeding with dabigatran was especially high in certain subgroups: African Americans had more bleeding with dabigratan with HR 2.12, and patients with chronic kidney disease had an increase with HR 2.07. the increased rate of intracranial bleeds was only higher in warfarin in white patients older than 75 (no diff in those

So, what does this all mean? I posted several blogs on dabigatran, some showing drug company malfeasance in promoting it, both withholding data and their own sense that levels should be monitored (the big push for this drug was that you didn’t need to do INRs, so it was easy for patients and providers). Also an article on increase in MI and ACS. and one on post marketing surveillance and increased bleeding with dabigatran. the current article on the Medicare population confirms (at least to me) the importance of post-marketing surveillance. All-too-often, there are serious adverse effects of meds (eg COX-2 inhibitors such as vioxx….) that are not found on initial studies, either legitimately through the gaps of statistical analysis or drug company malfeasance (or both). Some may be due to study design or to the cloistered setting of the academic medical center and selection biases. In any event, post-marketing analysis provides larger numbers of real-world patients on the med. As noted below, one of the big issues with direct thrombin inhibitor bleeding, unlike warfarin, is that there is no antidote/ability to reverse the effect.

Primary Care Corner with Geoffrey Modest MD: WHO opioid overdose recommendations

30 Jan, 15 | by EBM

By: Dr. Geoffrey Modest

The World Health Organization published their “community management of opioid overdose“,​ which basically makes the following recommendations:

1) People likely to witness an opioid overdose should have access to naloxone and be instructed in its administration to enable them to use it for the emergency management of suspected opioid overdose. strong recommendation, very low quality of evidence [basis of this recommendation is that most overdoses happen in private homes and most are witnessed — eg close friends, partner, family members]
2) Naloxone is effective when delivered by intravenous, intramuscular, subcutaneous and intranasal routes of administration. Persons using naloxone should select a route of administration based on the formulation available, their skills in administration, the setting and local context. conditional recommendation, very low quality of evidence

3) In suspected opioid overdose, first responders should focus on airway management, assisting ventilation and administering naloxone. strong recommendation, very low quality of evidence

4) After successful resuscitation following the administration of naloxone, the level of consciousness and breathing of the affected person should be closely observed until full recovery has been achieved. Strong recommendation, very low quality of evidence of note there have been approx. 69K world-wide deaths from opioid overdose each year (with 16651 in the US from prescription opioids in 2010). these guidelines acknowledge upfront that these recommendations, though important and should reduce opioid deaths, do not address the underlying issues (monitoring opioid prescribing practices, curbing inappropriate prescribing, increasing the rate of treatment for opioid dependence including prescription opioids). Unfortunately, the guidelines do not comment on the bigger social issues underlying opioid abuse: the importance of societies that value people/spur on motivation, empowerment and self-esteem; provide the necessary social framework for that, including good quality education, access to healthy diets/lifestyle, housing, etc.; and in general create real hope for the future and not increase income disparities, as is happening in many societies, industrialized and nonindustrialized.

Primary Care Corner with Geoffrey Modest MD: More tolerable fecal transplant for resistant c diff infections

30 Jan, 15 | by EBM

By: Dr. Geoffrey Modest

So, yet another positive but small fecal transplant study for relapsing c diff infection, this time using (more tolerable/acceptable) oral capsules. On the ever recurrent microbiome theme, the point of these fecal transplants is to re-establish a healthy microbiome directly, as opposed to decimating the diseased microbiome with aggressive antibiotics (vanco, metronidazole). In this open-labeled study, 20 patients (median age 64.5, range 11-89) with at least 3 episodes of mild-to-moderate c diff infections who had failed 6-8 week tapers with vanco (with or without other antibiotic, including metronidazole or the very expensive fidaxomicin) or at least 2 severe episodes of c diff requiring hospitalization were given 15 capsules of frozen fecal microbiota transplant (FMT) from an unrelated donor for 2 consecutive days and followed up to 6 months (see doi:10.1001/jama.2014.13875​). Stool was harvested (if that is the correct term) from 4 healthy volunteers. Mean capsule storage was 113 days at -80 C. Results:

–Resolution of diarrhea in 14 of the 20 (70%, with CI 47-85%) after a single treatment with FMT
–The 6 nonresponders were retreated: 4 had resolution (i.e., total of 90%). nonresponders were defined as no change in diarrhea after 72 hours, retested and found positive for c diff.
–Effect pretty quick: daily number of bowel movements decreased from 5 the day prior to FMT, to 2 at day 3 and 1 at 8 weeks, with attendant increases in self-ranked health status
–Interesting that 9 of the patients (who all failed antibiotic therapy) had received the new and likely more powerful fidaxomicin​, and 6 resolved after only 1 treatment with FMT
–No serious adverse effects, no vomiting and only mild abdominal cramping and bloating in 6 patients.

So, FMT seems to work in this difficult, non-responsive group of patients with relapsing c diff infections. Although we need confirmation from both larger studies and studies done at different institutions, it all seems pretty promising and reflects a significant ideological shift: we should certainly do everything we can to decrease microbiome destruction (in this case, largely by avoiding unnecessary antibiotics and using as narrow-spectrum as possible — for example, using trimethoprim/sulfa instead of cipro for simple UTIs), and once the microbiome is disrupted, restore it with a healthy one instead of hitting it with more antibiotics (in fact, the antibiotics used seem to have increasing failure rates, now 30% for first occurrences and 60% for treatment failures!!). one advantage of this study is that FMT is scalable: does not require fresh stool from healthy donors which has to be screened (and is only good for 6 hours), limited availability, etc., and it uses stool from unrelated donors/healthy volunteers (some prior studies used related donors, which might even be worse, as we learned with blood donations: the chance of transmitting infection was actually higher with related donors, who were likely reticent to mention their own exposures).

Primary Care Corner with Geoffrey Modest MD: Radiation exposure

29 Jan, 15 | by EBM

By: Dr. Geoffrey Modest 

As many of you know from being exposed to my rantings, I am very concerned about excessive iatrogenic radiation exposure. (I believe exposure to my rantings are less toxic than the radiation).

An article in JAMA looks at 6 integrated health care delivery systems with 1-2 millions people over 15 years. Effective doubling of radiation exposure in this period , esp with CT scans (increased 3-fold). Calculated anticipated 2% increased risk of cancer from this increased exposure (this may be an argument to dissuade some patients who seek a CT scan unnecessarily).

Primary Care Corner with Geoffrey Modest MD: CT scanning in kids and radiation exposure

29 Jan, 15 | by EBM

By: Dr. Geoffrey Modest

I will post an old blog:

The use of CT scans is increasing dramatically in kids. Data collected from 7 large HMOs in the US over 10 years (2001-2011) in kids <15yo, with 4.9M child-years of observation. One advance in this study is that they collected the actual technical parameters (radiation dose) used in diverse facilities.

Major findings:

— a doubling of CT scans done in kids –large variability of radiation dose per scan at different sites. highest dosages overall with abd/pelvic CTs (40% done for pain, 11% for r/o appendicitis, 6% for infection)
–Head CT was the most commonly done CT and increased 50%, though the % increase was highest in abd CT for children 5-14yo.
–using risk models (some based on the Japanese atomic bomb survivors, with those numbers of cancers being similar in a recent CT study), they calculated that:
–in kids under 5yo, those getting head scans (the most common) assoc with one solid cancer developing per 570 CTs in girls and 1350 CTs in boys, and one case of leukemia in 5000 scans (less in older kids);
–for abd/pelvic CT: 300 scans in girls and 670 scans in boys assoc with likely development of one solid tumor (not much difference by age)

So, not huge increased risk for an individual getting a scan (i.e., get one if really necessary), but in population overall, the annual pedi CT scan rate of about 4-9 million CTs/year leads to a large projected increase in cancer, on the order of 5000 cancers/yr. Some studies suggest that 1/3 of CT scans in kids are unnecessary, though changing this is sometimes difficult (we recently had a kid where we suggested doing an ultrasound as initial w/u for possible appendicitis, but the ER/surgeon insisted on CT scan). Also, the great variability in radiation dosage per test (which seems in part due to radiology techs not scaling down radiation exposure sufficiently in kids) needs to be reduced. the potential reduction in cancer by eliminating the unnecessary CTs and decreasing the radiation dosage per CT could decrease the cancer rate by more than 60%. Behavior change for us guys ain’t easy, but the good news is that after repeated battering, we are really doing better at not prescribing antibiotics for likely viral bronchitis, etc.

Primary Care Corner with Geoffrey Modest MD: Meds for diabetic neuropathy

29 Jan, 15 | by EBM

By: Dr. Geoffrey Modest

The Annals of Internal Medicine had a meta-analysis of medications for painful diabetic neuropathy (see doi:10.7326/M14-0511). As most of us know, this is a very common clinical issue (30-50% of diabetics get it, predominantly distal symmetric sensorimotor polyneuropathy). The first approach is to optimize glycemic control (data are clear that nerve conduction improves, less clear that symptoms improve), but patients typically need meds to control the burning, painful discomfort. many classes of agents have been used, including tricyclics (TCAs, most often studied is amitriptyline), anticonvulsants (gabapentin, pregabalin, carbamazepine), serotonic-norepinephrine reuptake inhibitors (SNRIs, eg duloxetine or venlafaxine), opioids, opioid-like substances, and topicals (eg capsaicin cream).

Results:

–65 RCTs analyzed, with 12632 patients and 27 pharmacologic interventions. though 1/2 of studies with high or unclear risk of bias. Network meta-analysis done (which combines effect sizes for all possible pairwise comparisons)
–9 head-to-head trials showed greater pain relief with SNRIs than anticonvulsants; also greater improvement with TCAs than with topical capsaicin 0.075%
–SNRIs, capsaicin, TCAs and anticonvulsants were better than placebo for short-term pain control; in assessing individual drugs, carbamazepine, venlafaxine, duloxetine, and amitriptyline are better than placebo
–Adverse effects common: somnolence and dizziness with TCAs, SNRIs, and anticonvulsants; xerostomia with TCAs, and peripheral edema and burning sensation with pregabalin and capsaicin
–Of note, when looking at pain score reductions of drugs vs. placebo, from highest to lowest, were SNRIs, topical capsaicin, anticonvulants (though notably carbamazepine was the best), TCAs, and last (by a fair margin) opioids.

It is hard with these types of complex analyses to be sure about the relative effectiveness of meds, since head-to-head trials were limited. My personal bias is to use TCAs as first-line, with really very impressive results in the vast majority of patients, even long-term. Because of the really common adverse effects of amitriptyline, especially in the elderly (which is the majority of patients with diabetic neuropathy), I have been using desipramine (in the 25-75mg range) and nortriptyline (in the 10-50mg range) pretty much exclusively, with desipramine having the fewest adverse reactions of any TCA and nortriptyline being useful in those who have trouble sleeping. the reason I chose these is from a New England J Med article in 1992 — dating myself again — (see NEJM 1992; 326:1250-6), which found that desipramine was as good as amitriptyline, and fluoxetine actually was as good but only in those with depression. I mentioned this article to a really phenomenal neurologist I knew then, and he said that he almost exclusively used desipramine for all neurologic indications where amitriptyline had been used in studies (eg migraine)​ and had great results. My guess is that desipramine may even be better than amitriptyline since many patients have adverse effects with amitriptyline and drop out of treatment. My experience with gabapentin and duloxetine are limited, but in the few instances I’ve used them I have had few patients who tolerate the adverse effects. I’ve had very good results with carbamazepine or oxcarbazepine, but only with trigeminal neuralgia (I have not used with diabetic neuropathy, but they may well be useful, from the above study).

Primary Care Corner with Geoffrey Modest MD: Community-acquired pneumonia

29 Jan, 15 | by EBM

By: Dr. Geoffrey Modest

A review article in NEJM on community acquired pneumonia (see DOI: 10.1056/NEJMra1312885). Some points:

–Pneumococcal pneumonia (from staph pneumoniae) was 95% of cases of pneumonia in pre-antibiotic era, now 10-15% [though the studies cited were predominantly for patients hospitalized with community-acquired pneumonia (CAP). I suspect that for the vast majority, we just don’t know — partly because we do not get cultures or even gram stains of people coming in with “walking pneumonia” and not hospitalized, partly because the etiology may be different in those with non-hospitalized cases, and partly because the etiology may vary dramatically from one area to another]

–Changes in ecology likely related to use of pneumococcal vaccine in adults, near universal use of conjugate vaccine in kids, and decreased smoking (vs. in Europe and other places, where less widespread use of vaccine and higher rates of smoking, pneumococcus assoc with more CAP).

–Other CAP causes in US include H flu, staph, moraxella catarrhalis, psuedomonas aeruginosa and gram negatives; mycoplasma and chlymydophila pneumoniae vary widely, in part depending on diagnostic testing used. For COPD, P. aeruginosa and gram negatives more common, esp. in those on steroids.

–During influenza, more viral pneumonia but also more bacterial super infections [including staph]

–Other viruses important (RSV, parainfluenza, metapneumovirus, adeno, corona, rhinoviruses), causing both pneumonia and secondary bacterial infections

–In terms of presentation, important to remember that some (esp. elderly) do not cough, produce sputum, or have elevated white count, and 30% (esp. elderly) are afebrile when hospitalized [?? even more in those seen in outpatient settings]

–Workup: authors favor gram stain (but need good specimen, with >10 inflammatory cells for each epithelial cell), culture, blood cultures, urine testing for legionella and pneumococcal antigens, PCR for mycoplasma and chlamydophila, and serum procalcitonin (since if –??outpatient vs. inpatient treatment: there are an array of validated instruments to help determine if patient should be hospitalized (see here for the Pneumonia Severity Index. But can also use the CURB-65 and the IDSA/ATS guidelines)

–Empiric therapy: IDSA/ATS guidelines — for those without coexisting disease (eg chronic heart, lung, liver, or renal disease; diabetes; alcoholism; cancer or immunosuppressing conditions; or use of antibiotics in past 3 months), use a macrolide (if <25% of pneumococcal in community have high-level resistance) or doxycycline. For those with coexisting disease, use levofloxacin/moxifloxacin alone or a beta-lactam (eg amoxacillin-clavulanate) plus a macrolide (this regimen works 90% of the time). The authors favor a bata-lactam, since most clinicians do not know the prevalent resistance patterns, pneumococcus is more susceptible to penicillins than macrolides, and if not prompt response, can always substitute macrolide or doxy. And they would choose a beta-lactam, since 1/3 of h. flu and majority of Mor. catarrhalis are resistant to penicillins. For IDSA/ATS guidelines, see here.

–Duration of therapy: 5 days are as good as 10 (though it seems that clinicians have increased duration from 10 to 14 days!!). So they recommend 5-7 days

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