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Content 7

 

The Doctor and the Pharmacist

Radio Show Articles:
March 19, 2016

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Lyme Disease in the Southeastern United States
Which Drugs are best for Osteoarthritis Pain?
Ice the Pain
Opioid Prescribing after Nonfatal Overdose
Aerobic Exercise, but not Resistance Training, Promotes Neurogenesis in Rat Brains
Antihypertensive Benefits in Diabetic Patients are Limited to those with
   Systolic BP ≥140 mm Hg
PPIs Associated with Increased Risk for Chronic Kidney Disease
Melatonin for Childhood Atopic Dermatitis and Sleep Disturbance
Metronidazole vs. Ivermectin
Increase Fitness to Improve Health in Patients with Schizophrenia

Open Forum Infect Dis 2015 Sep 27
Lyme Disease in the Southeastern United States
The progressive increase of Lyme disease cases, particularly in southwestern Virginia, over a 15-year period is striking and suggests southward expansion of the disease.
Lyme disease (LD) has been endemic to limited areas of the U.S., including the northeast coastal states and the upper Midwest. In response to an increasing number of cases reported in Virginia, including from the southern border of Virginia (which is shared by North Carolina) — i.e., outside of previously identified endemic areas — researchers conducted a detailed evaluation, including spatial and spatiotemporal cluster analyses. Investigators included both probable and confirmed cases, based on CDC surveillance definitions, reported to the respective state health departments between 2000 and 2014. In addition, they included residential zip codes for each case and used a geographic information system to geographically show pertinent data.
More than 11,000 LD cases were included for subsequent analysis, 89% and 11% of which were registered by the Virginia and North Carolina health departments, respectively. A trend toward an increase in the number of cases was apparent only for Virginia; the most marked annual increase was in southwestern Virginia. New disease clusters were identified along the Appalachian chain between Charlottesville and the North Carolina border and along the southeastern border of older clusters in northern Virginia.
COMMENT: The findings of this survey are critically important. Clinicians in the newer areas of expansion of LD may not be familiar with the varied presentations of the disease and its potential complications, which could result in misdiagnoses or delays in diagnosis, which could affect patient outcomes.
CITATION(S):Lantos PM et al. Geographic expansion of Lyme disease in the southeastern United States, 2000–2014. Open Forum Infect Dis 2015 Sep 27; [e-pub]. (http://dx.doi.org/10.1093/ofid/ofv143)
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Which Drugs are best for Osteoarthritis Pain?
By Kelly Young, Edited by André Sofair, MD, MPH, and William E. Chavey, MD, MS
Diclofenac, etoricoxib, and rofecoxib were associated with the greatest pain reduction for patients with knee or hip osteoarthritis, while acetaminophen was not superior to placebo, in a network meta-analysis in the Lancet. (Etoricoxib is not available in the U.S.; rofecoxib was withdrawn worldwide in 2004.)
Researchers assessed 74 randomized, controlled trials of nearly 60,000 patients with knee or hip osteoarthritis that compared NSAIDs (rofecoxib, lumiracoxib, etoricoxib, diclofenac, celecoxib, ibuprofen, naproxen), acetaminophen, and placebo.
The following regimens appeared to be the most effective in pain reduction: diclofenac (150 mg/day), etoricoxib (60 mg/day), and rofecoxib (25 mg/day). Meanwhile, acetaminophen did not have a consistent, clinically meaningful benefit up to doses of 4000 mg per day.
Commentators write: "The most remarkable result is that [acetaminophen] does not seem to confer any demonstrable effect or benefit in osteoarthritis, at any dose. ... [Acetaminophen] has been on the market for as long as most of us remember. Its efficacy has never been properly established or quantified in chronic diseases, and is probably not as great as many would believe."
http://www.thelancet.com/journals/lancet/article/PIIS0140-6736(16)30002-2/abstract
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J Invest Dermatol 2015 Nov; 135:2623
Ice the Pain
Skin cooling induced month-long diminution of mechanical and thermal pain sensation but did not affect perception of itch.
Cryolipolysis uses skin cooling to reduce fat. Hypoesthesia over the treated area is a usual side effect. Cooling causes crystallization of cytoplasmic lipids, selectively injuring fat cells, and apparently nerve cells as well. Perhaps cryolipolysis could be used to treat chronic cutaneous pain or itch?
To study this hypothesis, investigators prospectively evaluated nociception by quantitative sensory testing to a range of stimuli in 11 healthy subjects with visible adiposity of the thighs. Skin on one leg was cooled with cold metal plates for 60 minutes, and the other leg served as a control. Hyposensitivity to mechanical pain was observed at each time point for 56 days. The mechanical pain threshold was raised compared to baseline and control sites. Control sites saw no change. The cold pain threshold also increased. This effect began 48 to 72 hours after treatment and persisted for at least 35 days. The heat pain threshold was less affected. Thresholds for detection of vibration, warmth, and coolness significantly increased after cryolipolysis treatment. Response to itch provocation was evaluated by testing after histamine iontophoresis. The peak itch and general intensity of itch seemed unaffected. Skin biopsy specimens at baseline and 21 and 56 days after treatment showed reduced densities of dermal myelinated nerves (P<0.001). Unmyelinated nerves were also reduced, but not as much.
COMMENT: Cryolipolysis induced specific loss of mechanical and thermal pain sensation but did not change perception of peak or mean itch intensity or duration compared to untreated control sites. This is a bit surprising, but the effect may be useful in research if itch-specific fibers remain unaltered. Even though cryolipolysis generally produces reversible hypoesthesia and physically damages nerves, cryolipolysis probably cannot be used to treat local spots of itching.
CITATION(S):Garibyan L et al. Transient alterations of cutaneous sensory nerve function by noninvasive cryolipolysis. J Invest Dermatol 2015 Nov; 135:2623. (http://dx.doi.org/10.1038/jid.2015.233)
  
http://www.ncbi.nlm.nih.gov/pubmed/26099028?access_num=26099028&link_
type=med&dopt=abstract

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Ann Intern Med 2016 Jan 5; 164:1
Opioid Prescribing after Nonfatal Overdose
More than 90% of overdose survivors continued to be prescribed opioids; for most, the prescribing clinician didn't change.
Opioid misuse and overdose have risen dramatically in recent years. In this study, researchers used data from a large U.S. health insurer to examine opioid use after hospitalization or emergency room presentation for nonfatal opioid overdose in 2848 patients (mean age, 44) who were receiving long-term opioid therapy (duration, ≥12 weeks) for noncancer pain. During the 60 days prior to overdose, opioids were prescribed at an average daily morphine-equivalent dosage of ≥100 mg, 50–100 mg, and <50 mg in 46%, 22%, and 33% of patients, respectively.
During median follow-up of about 300 days, 91% of patients received one or more opioid dispensings; only 7% did not receive opioids during the postoverdose period. Among patients who continued to be prescribed opioids, about one third continued to receive high daily dosages (i.e., ≥100 mg). Among patients for whom pre- and postoverdose prescribers could be identified, only 30% received their prescriptions from entirely new clinicians.
COMMENT: In this study, nearly all patients who experienced nonfatal opioid overdoses continued to receive opioid prescriptions; for most, the same clinician issued both the pre- and postoverdose prescriptions. Although no single process can be expected to resolve this complex issue, an editorialist discusses several potential interventions including: (1) building on state prescription monitoring programs to ensure that prescribing clinicians are informed when their patients overdose; (2) increasing clinicians' knowledge on managing chronic opioid use and dependency; (3) ensuring that hospitals and emergency departments have systems to identify patients who present with problems related to substance abuse; and (4) ensuring availability of programs for addiction treatment. One final issue is worth mentioning: Many clinicians feel that they are being scrutinized not only for overprescribing opioids but also for undertreating pain.
CITATION(S): Larochelle MR et al. Opioid prescribing after nonfatal overdose and association with repeated overdose: A cohort study. Ann Intern Med 2016 Jan 5; 164:1. (http://dx.doi.org/10.7326/M15-0038)
  
http://www.ncbi.nlm.nih.gov/pubmed/26720742?access_num=26720742&link_
type=MED&dopt=Abstract

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J Physiol 2016 Feb 4
Aerobic Exercise, but not Resistance Training, Promotes Neurogenesis in Rat Brains
Whether these results from rat studies apply to humans is unclear.
Both animal and human studies have shown that regular aerobic exercise is healthy for the brain. Finnish investigators asked whether the type of exercise matters.
These researchers developed strains of rats that responded either robustly or poorly to aerobic exercise. Individual rats of both strains were trained in one of four exercise programs: sustained aerobic exercise, high-intensity interval training (HIT; defined as short-duration, intense anaerobic exercise), resistance training, or sedentary. Upon completion of the assigned programs, hippocampal neurogenesis was significantly greater in rats that performed sustained aerobic exercise — but not HIT or resistance training — than in sedentary rats. These results were noted in both strains of rats (robust responders and poor responders).
COMMENT: Given the growing popularity of HIT and resistance training for humans, these studies in rats are of interest. The obvious question is whether these findings apply to humans. Determining the answer will require improved noninvasive techniques for estimating hippocampal neurogenesis in humans. In the meantime, we and our patients should decide if we want to emphasize sustained aerobic exercise over HIT and resistance training in our weekly exercise programs.
CITATION(S): Nokia MS et al. Physical exercise increases adult hippocampal neurogenesis in male rats provided it is aerobic and sustained. J Physiol 2016 Feb 4; [e-pub].
(http://dx.doi.org/10.1113/JP271552)
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BMJ 2016; 352:i717
Antihypertensive Benefits in Diabetic Patients are Limited to those with Systolic BP ≥140 mm Hg
Treatment provided no benefit — and caused harm — in patients with systolic blood pressure <140 mm Hg.
Although lowering blood pressure (BP) in patients with diabetes can lower risk for adverse cardiovascular (CV) events, the BP level at which antihypertensive treatment should be initiated is unclear. In this meta-analysis of 49 randomized, controlled trials (12 unpublished), researchers assessed the effects of antihypertensive treatment at different baseline systolic BPs on death and adverse CV outcomes in people with diabetes. The trials involved 74,000 diabetic participants (predominantly with type 2 diabetes) who were treated for ≥12 months. Comparisons included antihypertensive drug versus placebo, two drugs versus one drug, or different BP targets.
If baseline systolic BP was ≥150 mm Hg, antihypertensive treatment significantly lowered risks for all-cause death (by 11%), CV-related death (by 25%), myocardial infarction (by 26%), stroke (by 23%), and end-stage kidney disease (by 18%). If baseline systolic BP was 140 mm Hg to 150 mm Hg, antihypertensive treatment significantly lowered risks for all-cause death (by 13%), myocardial infarction (by 16%), and heart failure (by 20%). However, if baseline systolic BP was <140 mm Hg, antihypertensive treatment provided no benefit — and raised risk for CV death (by 15%).
COMMENT: These results substantiate that, for patients with diabetes, clinicians should focus antihypertensive treatment on those whose systolic blood pressure is ≥140 mm Hg. Notably, the American Diabetes Association Standards of Care recommend antihypertensive treatment for diabetic patients whose systolic blood pressure is ≥140 mmHg, with a treatment goal of <140 mmHg.
CITATION(S):Brunström M and Carlberg B.Effect of antihypertensive treatment at different blood pressure levels in patients with diabetes mellitus: Systematic review and meta-analyses. BMJ 2016; 352:i717.
(http://dx.doi.org/10.1136/bmj.i717)
  
http://www.bmj.com/content/352/bmj.i717?ijkey=a096f8d5a050580616a59fc
69636b66a22527843&keytype2=tf_ipsecsha

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PPIs Associated with Increased Risk for Chronic Kidney Disease
By Kelly Young
Use of proton-pump inhibitors (PPIs) is associated with a 20% to 50% increased risk for developing chronic kidney disease (CKD), suggests an observational study in JAMA Internal Medicine.
In the main, population-based cohort, researchers followed over 10,000 people without CKD at baseline. Over roughly 14 years, nearly 14% developed CKD. Rates of CKD were higher among patients using PPIs at baseline, compared with nonusers (14.2 vs. 10.7 events per 1000 person-years). PPI users also had higher rates of acute kidney injury than did nonusers. Similar associations were observed in a larger replication cohort.
Dr. Thomas Schwenk, deputy editor of NEJM Journal Watch General Medicine, notes that the findings "add to increasing concerns about PPI use, including excess risks for Clostridium difficile infections, pneumonia, and fractures, and less platelet inhibition when PPIs are used concomitantly with clopidogrel." Editorialists recommend monitoring renal function and magnesium levels in patients taking PPIs, switching to H2 receptor antagonists when feasible, and not using PPIs for vague complaints of "heartburn."
http://archinte.jamanetwork.com/article.aspx?articleid=2481157
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JAMA Pediatr 2016 Jan 1; 170:35
Melatonin for Childhood Atopic Dermatitis and Sleep Disturbance
A well-conducted randomized, double-blind trial suggests that melatonin may improve both.
Sleep disturbance is common in patients with atopic dermatitis (AD), but effective management is lacking. Reduced nocturnal melatonin has been found to be associated with sleep disturbance and greater AD severity.
Investigators in a Taiwanese tertiary care hospital performed a randomized, double-blind, placebo-controlled, crossover study in children with AD (age, 1–18 years, with AD on >5% body surface area), and sleep problems >3 days/week over 3 months. Children with sleep disorders or taking insomnia or antidepressant medications were excluded. All underwent a 2-week preparation using a sleep diary, a fixed sleep schedule, and caffeine avoidance. Children were then randomized to either 30-mg melatonin or placebo tablets orally once daily, for 4 weeks. After a 2-week washout, the groups switched treatments. AD skin-care regimens were unchanged. On the first and last day of each treatment, blood/urine samples were collected, questionnaires given, and the scoring atopic dermatitis (SCORAD) index was assessed by the same blinded physician. Sleep was assessed by actigraphy in all, and polysomnography in a subgroup of patients.
Compared to placebo, melatonin decreased the SCORAD index from a mean of 49 to 40 (P< 0.001), and sleep onset latency shortened by 21 minutes. More patients reported AD and sleep improvement with melatonin than with placebo. There was no significant difference in sleep stages and limb movement with melatonin versus placebo. No adverse event was reported during the study.
COMMENT: Sleep disturbance has far-reaching consequences for children and families. This small but carefully conducted study suggests that melatonin may improve not only sleep, but also AD severity. Further studies are needed to establish safety, efficacy, and optimum dosing.
CITATION(S): Chang Y-S et al. Melatonin supplementation for children with atopic dermatitis and sleep disturbance: A randomized clinical trial. JAMA Pediatr 2016 Jan 1; 170:35. (http://dx.doi.org/10.1001/jamapediatrics.2015.3092)
  
http://www.ncbi.nlm.nih.gov/pubmed/26569624?access_num=26569624&link_
type=MED&dopt=Abstract

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J Eur Acad Dermatol Venereol 2015 Dec 21
Metronidazole vs. Ivermectin
Which drug for remission of rosacea?
Topical metronidazole 0.75% cream (MET) twice daily and ivermectin 1% cream daily (IVER) both effectively treat the papulopustular component of rosacea. Is one better at producing remissions? Investigators conducted a 36-week, randomized, parallel group phase III study to find out.
They enrolled 399 patients who had been judged clear or almost clear (Investigators Global Assessment [IGA] score, 0 or 1) after 16 weeks of treatment in an earlier, phase III, investigator-blinded, randomized, parallel group study showing superiority of IVER for reducing papule and pustule counts (P<0.001). These patients now stopped treatment. If recurring papules and pustules warranted an IGA score of ≤2, patients resumed their original topical treatment until remission was again obtained. Primary endpoints were relapse rate and days to first relapse.
The median number of days to first relapse was higher in IVER recipients (median, 115 days; 95% confidence interval, 113–165 days) than in MET recipients (median, 85 days; 95% CI, 85–113 days). The relapse rate by study end at 36 weeks was lower for IVER recipients (62.7%) than MET recipients (68.4%). No serious adverse treatment-related events were recorded.
COMMENT:As in other rosacea remission studies, remissions were maintained after treatment with both drugs. Some remissions proved quite durable. At the start of the remission study, more IVER recipients than MET recipients had IGA scores of 0, so the IVER group was winning at the start. The number of subjects was large (n=762), but even so, the between-group difference in remission rates was small (P =0.037). In my opinion, topical IVER can successfully and safely treat the papulopustular elements of rosacea and produce durable remissions. This places topical IVER treatment among other first-tier treatments.
successful treatment of papulopustular rosacea with ivermectin 1% cream vs. metronidazole 0.75% cream: 36-week extension of the ATTRACT randomized study. J Eur Acad Dermatol Venereol 2015 Dec 21; [e-pub].
(http://dx.doi.org/10.1111/jdv.13537)
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Schizophr Res 2016 Feb; 170:336
Increase Fitness to Improve Health in Patients with Schizophrenia
Jonathan Silver, MD reviewing Vancampfort D et al. Schizophr Res 2016 Feb. Lalande D et al. Schizophr Res 2016 Mar. Kimhy D et al. Schizophr Res 2016 Feb 3. Ho RTH et al. Schizophr Res 2016 Mar.
Being more fit is associated with improved physical health, cognition, and psychiatric symptoms.
Patients with schizophrenia are at heightened risk for obesity and metabolic disorders. Several reports have highlighted the importance of physical assessment and prescription of activity in patients with schizophrenia.
Assessment of whether someone engages in sufficient physical activity can be straightforward. Vancampfort and colleagues used the “Physical Activity Vital Sign” exercise assessment, asking 100 outpatients how many average days per week they engaged in moderate-to-vigorous activity (e.g., brisk walking) and, on those days, how many minutes they were active at this level. Patients who did not exercise the recommended 150 minutes weekly were older and more likely to be women. Low exercisers performed worse on a 6-minute walking test and faced greater risk for abdominal obesity, hypertension, and metabolic syndrome.
In Lalande and colleagues' study of eight patients, 8 weeks of biweekly 75-minute sessions of strength training and cardiovascular fitness improved sleep quality and waking state, muscular fitness, and strength.
Kimhy and coworkers examined how intensive aerobic exercise (1-hour session/week for 12 weeks in a single-blind, randomized trial) affected cognition in 13 patients. At baseline, VO2max and maximal heart rate were measured. Intensity of exercise was increased over 3 weeks. Fidelity with the target training intensity (75% maximum), not compliance with the number of sessions, was correlated with significant improvements in cognition.
In a 12-week study, Ho and colleagues randomized 153 chronically ill patients to tai chi, aerobic exercise (with stretching and mild weight training; 50%–60% maximal heart rate), or waitlist. Active interventions involved 60 minutes/week, plus twice-weekly 45-minute practice sessions. Motor coordination, memory, daily functioning, and stress improved similarly after exercise and tai chi; the exercise group had fewer negative and depressive symptoms. In both active groups, cortisol levels increased.
COMMENT: These studies' unified message: Assessment of physical activity is easy and important in patients with schizophrenia, and sufficiently vigorous exercise is beneficial in many ways. We need to actively encourage exercise in all patients, not just those with schizophrenia.
CITATION(S):Vancampfort D et al. Physical activity as a vital sign in patients with schizophrenia: Evidence and clinical recommendations. Schizophr Res 2016 Feb; 170:336. (http://dx.doi.org/10.1016/j.schres.2016.01.001)
http://www.ncbi.nlm.nih.gov/pubmed/26782636?access_num=26782636&link_type=
MED&dopt=Abstract

  Lalande D et al. The effect of exercise on sleep quality and psychological, physiological, and biological correlates in patients with schizophrenia: A pilot study. Schizophr Res 2016 Mar; 171:235.
(
http://dx.doi.org/10.1016/j.schres.2016.01.042)

PubMed abstract (Free)
  Kimhy D et al. Aerobic exercise for cognitive deficits in schizophrenia: The impact of frequency, duration, and fidelity with target training intensity. Schizophr Res 2016 Feb 3; [e-pub].
(
http://dx.doi.org/10.1016/j.schres.2016.01.055)

  Ho RTH et al. A randomized controlled trial on the psychophysiological effects of physical exercise and Tai-chi in patients with chronic schizophrenia. Schizophr Res 2016 Mar; 171:42.
(
http://dx.doi.org/10.1016/j.schres.2016.01.038)

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