Dabigatran (Pradaxa)for Prevention of Stroke in Atrial Fibrillation

Dabigatran (Pradaxa)is an orally administered direct thrombin inhibitor labeledfor the prevention of stroke and systemic embolism in patients with nonvalvular atrial fibrillation. Unlikewarfarin (Coumadin), it does not induce anticoagulation through depletion of clotting factors, but through an immediate effect on thrombin, the last step in the coagulation cascade that causes clotformation.

Drug	Dosage	Doseform	Cost of full course [*]
Dabigatran (Pradaxa)	150 mg twice daily; 75 mg twice daily in patients with impaired renal function	75- and 150-mg capsules	$246for 60 150-mg capsules

<><><>

*	—Estimated retail price of one month's treatment based on information obtained at http://www.blogger.com/website/view?area=be&URL=http://www.drugstore.com (accessed October 25, 2010).

Safety Tolerability Effectiveness Price Simplicity

Dabigatran increases the risk of minor and major bleeding. In a randomized controlled trial ofdabigatran compared with dose-adjustedwarfarin (International Normalized Ratio of 2.0 to 3.0) in more than 18,000 patients with atrial fibrillation, life-threatening bleeding and intracranial hemorrhage occurred less often withdabigatran, with one fewer patient experiencing an intracranial hemorrhagefor every 117 patients treated withdabigatran instead ofwarfarin (number needed to treat [NNT] = 117; 95% confidence interval [CI], 82 to 201).^[1]Although gastrointestinal bleeding occurs more often withdabigatran, the incidence of minor bleedingis lower (NNT = 37; 95% CI, 23 to 99).^[1]Unlikewarfarin,dabigatran lacks significant drug interactions. However, the concurrent use of antiplatelet agents, heparin, or long-term nonsteroidal anti-inflammatory drugs may increase the risk of bleeding. Thereis no reversal agentfordabigatran. Itis renally eliminated, and the dosage must be reduced in patients with a creatinine clearance of less than 30 mL per minute per 1.73 m² (0.50 mL per second per m²).^[2]Dabigatran has not been studied in children or in pregnant or breastfeeding women. Itis a U.S Food and Drug Administration pregnancy category C drug.

In clinical trials, more patients receivingdabigatran withdrew because of adverse effects compared with those receivingwarfarin.Dabigatran causes dyspepsia and gastritis symptoms in about one-third of patients.

Dabigatran has been compared with enoxaparin (Lovenox) andwarfarin in randomized controlled trials. In a study of 18,000 patients with atrial fibrillation, those who receiveddabigatran had significantly fewerischemic strokes than those who receivedwarfarin for a median of two years (NNT = 91; 95% CI, 59 to 194).^[1]Dabigatran has been studiedfor surgery prophylaxis (versus enoxaparin) andfor the treatment of deep venous thrombosis and pulmonary embolism (versuswarfarin), but itis not labeledfor these uses

A one-month supply of 150-mgdabigatran capsules costs approximately $246; a one-month supply of genericwarfarin costs approximately $15.^[6]The lack of laboratory monitoring or office visitsfor dose titration may partially offset this difference.

Dabigatran produces an effect on coagulation in 30 to 90 minutes, has a predictable response, does not require routine laboratory monitoring, and does not have the drug and food interactions that can be problematic withwarfarin therapy. Patient compliance with twice-daily dosing must be stressed. The dose ofdabigatran is fixed and does not require titration when therapyis initiated or discontinued.

Bottom Line

Dabigatran is superior towarfarin for stroke prevention in patients with atrial fibrillation, with similar rates of major bleeding. Because it does not require laboratory monitoring,dabigatran therapyis less complicated thanwarfarin therapy, but it costs significantly more

this case i saw her in my clinic session,she is 9 year old girl with 3 days history of painful lesions over back
what do u think?
see the question upper right of the screen
 

What do u think?

This case i saw her last week ,she is 24 years old with 2 years history of nail disease
what do you think?

Hyperthyroidism

Common Etiology and Clinical Diagnosis of Hyperthyroidism

---

Cause	Pathophysiology	Gland size*	Nodularity	Tenderness
Toxic adenoma	Autonomous hormone production	Decreased	Single nodule	Nontender
Toxic multinodular goiter	Autonomous hormone production	Increased	Multiple nodules	Tender
Subacute thyroiditis	Leakage of hormone from gland	Increased	None	Tender
Lymphocytic thyroiditis, postpartum thyroiditis, medication-induced thyroiditis	Leakage of hormone from gland	Moderately increased	None	Nontender
Graves’ disease (thyroid-stimulating antibody)	Increased glandular stimulation (substance causing stimulation)	Increased	None	Nontender
Iodine-induced hyperfunctioning of thyroid gland (iodide ingestion, radiographic contrast, amiodarone [Cordarone])	Increased glandular stimulation (substance causing stimulation)	Increased	Multiple nodules or no nodules	Nontender
Functioning pituitary adenoma (thyroid-stimulating hormone); trophoplastic tumors (human chorionic gonadotropin)	Increased glandular stimulation (substance causing stimulation)	Increased	None	Nontender
Factitial hyperthyroidism	Exogenous hormone intake	Decreased	None	Nontender
Struma ovarii; metastatic thyroid cancer	Extraglandular production	Decreased	None	Nontender

Time course of changes in thyroid function tests in patients with thyroiditis. (T4= thyroxine; T3= triiodothyronine; TSH = thyroidstimulating hormone.)

Diagnosing Hyperthyroidism

Lung Function Decline in Smokers and Nonsmokers

The natural history of lung function decline. Smokers who are susceptible to lung injury experience an increase in the rate of age-related loss in FEV1 compared with nonsmokers (red, green, and blue lines). After lung function declines to threshold levels, clinical symptoms develop (black dotted lines). When a smoker stops smoking, the rate of FEV1 loss again approximates to that of a nonsmoker (blue dotted line). (FEV1 = forced expiratory volume in one second.)






GOLD Staging System for COPD Severity

---

Stage	Description	Findings*
0	At risk	Risk factors and chronic symptoms but normal spirometry
I	Mild	FEV1/FVC ratio less than 70 percentFEV1 at least 80 percent of predicted valueMay have symptoms
II	Moderate	FEV1/FVC ratio less than 70 percentFEV1 50 percent to less than 80 percent of predicted valueMay have chronic symptoms
III	Severe	FEV1/FVC ratio less than 70 percent FEV1 30 percent to less than 50 percent of predicted valueMay have chronic symptoms
IV	Very severe	FEV1/FVC ratio less than 70 percentFEV1 less than 30 percent of predicted value
			or
		FEV1 less than 50 percent of predicted value plus severe chronic symptoms

Treatment and Prevention of Kidney Stones: An Update

The incidence of nephrolithiasis (kidney stones) is rising worldwide, especially in women and with increasing age.

Kidney stones are associated with chronic kidney disease. Preventing recurrence is largely specific to the type of stone (e.g., calcium oxalate, calcium phosphate, cystine, struvite [magnesium ammonium phosphate]), and uric acid stones); however, even when the stone cannot be retrieved, urine pH and 24-hour urine assessment provide information about stone-forming factors that can guide prevention. Medications, such as protease inhibitors, antibiotics, and some diuretics, increase the risk of some types of kidney stones, and patients should be counseled about the risks of using these medications. Managing diet, medication use, and nutrient intake can help prevent the formation of kidney stones. Obesity increases the risk of kidney stones. However, weight loss could undermine prevention of kidney stones if associated with a high animal protein intake, laxative abuse, rapid loss of lean tissue, or poor hydration. For prevention of calcium oxalate, cystine, and uric acid stones, urine should be alkalinized by eating a diet high in fruits and vegetables, taking supplemental or prescription citrate, or drinking alkaline mineral waters. For prevention of calcium phosphate and struvite stones, urine should be acidified; cranberry juice or betaine can lower urine pH. Antispasmodic medications, ureteroscopy, and metabolic testing are increasingly being used to augment fluid and pain medications in the acute management of kidney stones

Are laxatives or methylnaltrexone (Relistor) helpful for the management of constipation in patients receiving palliative care?

Clinical Question

Are laxatives or methylnaltrexone (Relistor) helpful for the management of constipation in patients receiving palliative care?

Evidence-Based Answer

There is insufficient evidence to recommend one laxative over another for the treatment of constipation in patients receiving palliative care. Methylnaltrexone can increase the frequency of bowel movements at four hours (odds ratio = 7.0; 95% confidence interval, 3.8 to 12.6) and at 24 hours (odds ratio = 5.4; 95% confidence interval, 3.1 to 9.4). Methylnaltrexone also may increase the risk of flatulence and dizziness. (Strength of Recommendation: B, based on inconsistent or limited-quality patient-oriented evidence.)

Practice Pointers

Constipation affects up to 48 percent of all patients receiving palliative care,^[1] and up to 87 percent of patients receiving palliative care who also are taking opioids.^[2] For some patients, opioid-induced constipation may be so severe that they avoid opioid therapy and choose inadequate analgesia over constipation.^[3] Although constipation is difficult to define or quantify because normal bowel movements can range from one to three stools per day, three sets of factors can predispose patients to constipation: lifestyle-related factors, disease-related factors, and medications that predispose to constipation. Laxatives have long been recommended for prevention and treatment of palliative care-associated constipation, and methylnaltrexone is a peripherally acting opioid antagonist that is licensed for treatment of opioid-induced constipation when usual measures are ineffective.^[4]

To determine the effectiveness and safety of treating constipation in patients receiving palliative care, the authors searched for randomized controlled trials comparing laxatives or methylnaltrexone with another active treatment or with placebo. The authors found seven studies including 616 patients. Four trials of laxatives that included a variety of agents (i.e., senna, lactulose, misrakasneham, co-danthramer, and magnesium hydroxide with liquid paraffin) found no differences in stool frequency response. In all four trials, some patients experienced vomiting and colicky pain, and some required additional interventions for constipation. Three trials evaluated methylnaltrexone and found improved stool frequency at four and 24 hours. However, methylnaltrexone was associated with increased risk of flatulence and dizziness, and one patient had severe diarrhea, dehydration, and cardiovascular collapse.

Palliative care involves balancing symptom relief with avoidance of iatrogenic adverse effects from palliative treatments. For patients with constipation, especially those with opioid-induced constipation, there is insufficient evidence to recommend one laxative over another. The choice of laxatives should be based on past patient experience, tolerability, and adverse effects. Methylnaltrexone is a newer agent that may be useful especially for patients with opioid-induced constipation that has not responded to standard laxatives, but there is limited evidence of potential adverse effects. Therefore, judicious use preceded by a discussion with patients about known risks and benefits is warranted.

Prolotherapy for Chronic Musculoskeletal Pain

Prolotherapy is an injection-based complementary therapy for common chronic musculoskeletal conditions including tendinopathy, knee osteoarthritis, and low back pain.^[1] It involves the injection of irritant solutions into tender ligamentous and tendinous attachments and adjacent joint spaces. Central to the application of prolotherapy is the premise that chronic musculoskeletal pain and disability often result from degeneration associated with these structures, and that prolotherapy addresses this degeneration at the tissue level. Although the mechanism of action for prolotherapy is not clearly understood, recent animal model studies reported that prolotherapy is associated with local inflammation, which may lead to induction of tissue growth factors.^[2] Prolotherapy injections may also act as central pain modulators.^[1]

Although prolotherapy techniques and injected solutions vary by condition, clinical severity, and physician preferences, a core principle is that a small volume (0.2 to 0.5 mL) of solution is injected into tender ligamentous and tendinous attachments in a peppering fashion, and into adjacent joint spaces.^[1] The most common injectant is dextrose 15% (3 mL dextrose 50%, 5 mL saline 0.9%, and 2 mL lidocaine 2% [Xylocaine]); a similar volume of the sclerosant morrhuate sodium is also used.^[3] Treatment typically involves at least three injection sessions one month apart, but injection intervals vary from two to six weeks.^[1]

Since the mid-1980s, the quantity and quality of clinical prolotherapy research has increased, with a shift from case reports to randomized controlled trials (RCTs) for chronic tendinopathy, knee osteoarthritis, and low back pain. ^[1] , [4] The strongest data supporting the effectiveness of prolotherapy for any musculoskeletal condition, compared with saline control injections, are for severe refractory lateral epicondylosis. Participants treated with prolotherapy (n = 10) reported approximately a 90 percent reduction in resting elbow pain on a 10-point visual analog scale compared with a 22 percent reduction in the control group (n = 10) at baseline and 16 weeks (absolute effect size of 68 percent; P < .01). Participants in the prolotherapy group also demonstrated improved isometric strength (P < .05) at 16 and 52 weeks compared with the control group.^[3]

In limited studies, other overuse injuries have responded well to prolotherapy, including Achilles^[5] and adductor tendinopathies,^[6] and plantar fasciitis.^[7] Prolotherapy has also been used in multidisciplinary care plans. Participants in an Achilles tendinopathy study responded earlier and with less money spent on treatment when physical therapy and prolotherapy were combined compared with either treatment alone.^[5]

The data supporting prolotherapy for knee osteoarthritis are less clear. In one RCT, participants in the prolotherapy and sham injection groups reported substantial improvements in pain and functional measures compared with baseline measurements; however, there were no statistically significant differences between groups.^[8] A National Institutes of Health-sponsored pilot-level study (n = 36) assessing prolotherapy for patients with moderate to severe knee osteoarthritis at 52 weeks reported a 36 percent improvement in knee-related quality of life compared with baseline status on the validated Western Ontario and McMaster Universities Osteoarthritis Index.^[9]

The largest and most methodologically rigorous study compared prolotherapy with control (saline) injections in 110 participants with an average of 14 years of nonsurgical low back pain.^[10] Participants reported substantial and sustained reductions in pain (26 to 44 percent) and disability (30 to 44 percent) at 12 months. However, the reductions in pain and disability were not statistically significant between groups. These findings were contrary to two previous RCTs of lower quality that reported statistically significant positive findings. ^{[11] , [12]}

Following the contrasting, suggestive findings in low back pain studies, researchers have begun to assess prolotherapy in patients with more clearly diagnosed forms of low back pain in an effort to determine specific low back indications for which this treatment may be effective. Positive outcomes have been reported in prospective studies assessing prolotherapy for refractory coccygodynia,^[13] sacroiliac joint dysfunction,^[14] and leg pain caused by moderate to severe degenerative disk disease.^[15]

Prolotherapy performed by an experienced injector appears safe; no clinical trials report significant adverse events. Current data suggest that prolotherapy has a positive effect compared with baseline status, and in some cases compared with control therapy, in carefully selected patients for several indications ( Table 1 ^{[3] , [5] , [7] , [8] , [9] , [10] , [11] , [12] , [13] , [14] , [15]} ). However, a more complete understanding of its clinical application will require more research. Prolotherapy is the subject of ongoing federally funded RCTs in the United States ^{[16] , [17]} and Canada.^[18]

Table 1   -- Chronic Musculoskeletal Conditions for Which Prolotherapy Has Been Used as a Treatment

Condition	Reference	Type of study
Achilles tendinopathy	5	High-quality small RCT
Coccygodynia	13	Prospective single-arm study
Knee osteoarthritis	[8] , [9]	Moderately strong-quality RCT and prospective single-arm study
Lateral epicondylosis	3	Small RCT
Degenerative disk disease	15	Prospective single-arm study
Nonspecific low back pain	10[*]-12	RCTs
Plantar fasciitis	7	Prospective single-arm study
Sacroiliac joint dysfunction	14	Prospective single-arm study

RCT = randomized controlled trial.