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Source: Alper BS, et al. J Fam Pract. 2002;51:121-128.
Best management of postherpetic neuralgia (PHN) remains problematic, since a variety of reports suggest modest favorable effects of a diversity of interventions, with little confirmation of relative efficacy through head-to-head comparative trials. This systematic literature review included 27 randomized controlled trials felt to be methodologically sound to assess outcomes of pain and quality of life as impacted by topical (eg, lidocaine patch, capsaicin cream), oral (eg, amitriptyline, gabapentin, opioid analgesia), and other (eg, acupuncture, TENS) therapies.
Literature analysis indicated that tricyclic antidepressants (TCA) provide the best evidence for efficacy, though conclusions are limited by the short duration of trials (none > 8 weeks). Topical capsaicin, gabapentin, and opioid analgesia were also found effective. For refractory patients, methylprednisolone and bupivacaine sympathetic blocks merit consideration. Tools for which insufficient evidence to establish efficacy was found include lidocaine patch, benzydamine cream, tramadol, vincristine, and iontophoresis. Treatments deemed unlikely to be of benefit included benzodiazepines, dextromethorphan, acyclovir, and acupuncture.
Among the demonstrated effective agents, side effect profile, cost, and ease of administration ultimately determine which agent will be preferred for an individual patient.
Source: Seshadri S, et al. N Engl J Med. 2002;346:476-483.
Elevated homocysteine (hcys) levels have been correlated with vascular toxicity, in particular, coronary heart disease. Conflicting reports on the relationship between HCYS and cognitive function have left the issue unresolved. Data from the Framingham Study, which details the relationship between dementia (DEM), Alzheimer’s disease (ALZ) and HCYS, is presented in this study by Seshadri and colleagues.
The population studied (n = 1092) had undergone measurement of HCYS in 1986-1990, and almost all of them (86%) had had measurements obtained in the 1979-1982 time period also. Only subjects who were free of dementia at inception of the trial were included.
Over 8 years’ observation, 111 subjects developed dementia (83 = ALZ); for every 5 mcmol/L increase in HCYS, the risk of ALZ increased 40%. This progressive increase in risk was not altered by adjustment for gender or age. Interestingly, since it is well known that supplementation with folate, B12, and pyridoxine may have a favorable effect upon HCYS, adjustment for plasma levels of these vitamins did not alter the relationship between HCYS and subsequent development of DEM/ALZ. It remains to be shown by interventional trials whether reductions in HCYS can translate into reduced risk for dementia.
Source: Addolorato G, et al. Am J Med. 2002;112:226-229.
For persons with chronic alcohol abuse habits, alcohol withdrawal is both psychologically and physically difficult, and not without risk. The distressing symptoms of withdrawal often begin 6-24 hours after initiation of abstinence, and animal studies have suggested that baclofen suppresses alcohol withdrawal syndrome symptoms. Since baclofen has also been shown to favorably effect alcohol craving and intake in persons suffering alcohol dependency, a trial to assess its use in severe alcohol withdrawal syndrome was undertaken.
Addolorato and colleagues studied 5 patients who scored higher than 20 on the Clinical Institute Withdrawal Assessment for Alcohol scale, indicative of severe alcohol withdrawal syndrome. Subjects received 10 mg baclofen orally initially, and then 10 mg orally every 8 hours for 30 days, with measurement of the Withdrawal Assessment for Alcohol scale daily for 1 week, and then weekly for the remaining 3 weeks of the treatment course.
All 5 of the patients reported rapid (within 2 hours) alcohol withdrawal symptom resolution after administration of 10 mg baclofen. Similarly, all patients were able to remain abstinent and asymptomatic using baclofen 10 mg q.8.h. The remarkably favorable outcome of this small study suggests need for a larger scale trial of this method.
Source: Cummings SR, et al. Am J Med. 2002;112:281-289.
There is an inverse and linear relationship between bone mineral density (BMD) and fracture risk in women. Investigators have queried whether BMD fully explains the fracture reduction benefits seen with osteoporosis therapies, since it appears that fracture reduction benefits are substantial with small incremental improvements in BMD. It is unclear whether other factors, such as improved bone integrity or architecture, might also be responsible for reduced fracture risk.
By meta-analysis of 12 osteoporosis treatment trials that used antiresorptive therapies, Cummings and colleagues measured the relationship between incremental change in BMD and incident vertebral fractures. This relationship was compared with data from the placebo arm of the Fracture Intervention trial, which demonstrated a 1.5-fold increase in vertebral fracture risk for each 0.10 decline in BMD, which establishes a baseline for the relationship between "natural" changes in BMD and subsequent fracture.
Based on this analysis, Cummings et al calculate that increases in BMD by antiresorptive treatments explain only a small portion of the reduced fracture risk. For instance, the 4% improvement in BMD seen in 1 3-year trial of alendronate would only explain 16% of the reduction in fractures. Although the improvements in BMD induced by antiresorptive treatment are important, other mechanisms not apparent on BMD must play a role in fracture reduction.
Source: Katz DA, McHorney CA. J Fam Pract. 2002;51:229-235.
In persons who suffer compelling chronic health conditions such as congestive heart failure, diabetes mellitus, and depression, it is easy for complaints like insomnia to be misperceived as modest in affecting overall quality of life (QOL). Indeed, comorbidities may complicate sleep quality, and worsen primary sleep disturbances. In this study, Katz and McHorney sought to discern whether, in patients suffering other chronic conditions, insomnia is independently detrimental to health-related QOL, and to quantify the effect of insomnia upon QOL in comparison with the effect of other chronic conditions.
The study population was comprised of patients from outpatient settings who were administered a depression scale, and the SF-36 QOL assessment tool. Inclusion criteria required the patient to also have either hypertension, diabetes, congestive heart failure, recent MI, or depression.
Sixteen percent of study subjects had severe insomnia, and 34% had mild. As severity of insomnia increased, so did decrements in QOL. Insomnia was independently associated with impaired QOL, even after adjustment for competing conditions (including depression). Although insomnia had diverse effect across the SF-36 parameters, certain select categories showed prominent impact. For instance, in persons with severe insomnia, the decline in physical function score was of comparable magnitude to the effect of congestive heart failure. Addressing insomnia as an independent morbidity, even in persons with major competing chronic medical conditions, may have a valuable effect on QOL.
Source: Reid IR, et al. Am J Med. 2002;112:343-347.
Calcium supplementation (CAS) is generally recommended for adult women based on the fact that osteoporosis (OSPS) may be prevented or ameliorated by enhanced dietary calcium. Previously, some data have shown that oral CAS tends to bind intestinal fatty acids and bile acids, resulting in reduced fat absorption, and subsequent favorable effect on HDL and LDL, but other studies have failed to confirm this phenomenon. Reid and colleagues report on the first randomized controlled trial to study the issue in normal postmenopausal women.
Women (n = 223) had to be free of OSPS at entry, postmenopausal for > 5 years, older than age 55, and not long-term users of HRT or other treatments for OSPS. Women were randomly assigned to placebo or 400 mg CAS QAM and 600 mg QPM (before meals) for 1 year. Calcium was administered as calcium citrate. Outcomes measured were changes in fasting HDL, triglycerides, and LDL (calculated), measured at baseline, 2, 6, and 12 months.
At 1 year, the most substantial effect of CAS upon lipids was a 7% increase in HDL compared with baseline. There was a trend toward reduced LDL, and a statistically significant improvement in HDL/LDL ratio. It remains to be explored whether men might enjoy similar benefits from CAS.