7-1 THE NEW DEFINITION OF MYOCARDIAL INFARCTION
      In 2000, the European and American Cardiology Societies published a new definition of AMI which for the first time included troponins. According to the definition, 1) elevated levels of enzymes (CK-MB or troponin I or T), with 2) either symptoms or ECG changes suggestive of ischemia constitute an AMI.
      Application of new criteria for diagnosis of AMI resulted in a substantial increase in the number of patients diagnosed with AMI.

7-2 MRC/BHF HEART PROTECTION STUDY OF CHOLESTEROL LOWERING WITH SIMVASTATIN IN 20 536 HIGH-RISK INDIVIDUALS.
      Lowering LDL with simvastatin produced substantial benefits in reduction of cardiovascular events in a wide range of high-risk patients, irrespective of their initial cholesterol levels.
      Benefits appeared to be largely independent of, and hence additional to, those of all other treatments being used by participants.
      The benefits in reducing risk of stroke should resolve any uncertainty about the effects of statins on the risk of stroke.
      It has been suggested that there might be a threshold of LDL below which lowering would not further reduce risk. This study demonstrated unequivocally that there is no threshold. Lowering LDL from 116 to 78 reduced vascular events over 5 years, similar to the reduction in events following lowering from 134 to 96. “If a threshold exists it is a LDL lower than 77 mg/dL and a total cholesterol below 135.”

7-3 RISKS AND BENEFITS OF ESTROGEN PLUS PROGESTIN IN HEALTHY POSTMENOPAUSAL WOMEN
      Among a large cohort of healthy postmenopausal women, overall health risks slightly exceeded benefits from use of combined estrogen/progestin for an average of 5 years. (Overall, 19 more adverse effects per 10 000 persons per year.)
      Combined HRT should not be used for primary prevention of chronic diseases.

7-4 CARDIOVASCULAR DISEASE OUTCOMES DURING 6.8 YEARS OF HORMONE THERAPY (Heart and Estrogen/progestin Replacement Study Follow-up (HERS II)
      HRT did not reduce risk of cardiovascular events in a group of women with established coronary heart disease. Neither was there an increase in risk

7-5 NON-CARDIAC OUTCOMES DURING 6.8 YEARS OF HORMONE THERAPY
(The HERS II Follow-up Study)
      Treatment with estrogen plus progestin in older women with coronary disease was associated with an increase in rates of venous thromboembolism and biliary tract surgery.

7-6 ASSOCIATION OF HEALTH LITERACY WITH DIABETES OUTCOMES
      Two thirds of patients in this sample who had a high school education or less, had inadequate health literacy.
      Among primary care patients with type 2 diabetes, inadequate health literacy was independently associated with poorer glycemic control and higher rates of retinopathy. Inadequate health literacy contributes to the disproportionate burden of diabetes-related problems among disadvantaged populations. (This large subset of patients is not included in randomized, controlled trials. Therefore primary care clinicians must treat these individuals empirically. RTJ)

7-7 METFORMIN: AN UPDATE
      In treatment of type 2 diabetes, metformin has an excellent safety profile. It is effective as monotherapy and in combination with other drugs. It does not promote weight gain and may even cause weight reduction. It appears to have substantial benefit on lipid metabolism, clotting factors, and platelet function. It improves vascular relaxation and probably reduces BP. These cardio-protective benefits are in addition to its anti-hyperglycemic effect

7-8 RAPID MEASUREMENT OF B-TYPE NATRIURETIC PEPTIDE IN THE EMERGENCY DIAGNOSIS OF HEART FAILURE.
      B-TNP is included in the European guidelines for diagnosis of chronic HF. It offers valuable predictive information and assessment of severity of the disease. It will improve the ability of clinicians to differentiate patients with dyspnea due the HF from dyspnea due to other causes in the acute care setting. The diagnostic information can be immediately available.

7-9 B-TYPE NATRIURETIC PEPTIDE – A Window to the Heart
      Measurement of B-type natriuretic peptide is valuable in the diagnosis of congestive heart failure. It parallels the severity of the congestive heart failure. It can be measured rapidly and accurately at the point of care. It can be used to confirm the diagnosis of congestive heart failure; to measure the severity of left ventricular compromise; to quantify the functional class; to estimate the prognosis and predict future cardiac events, including sudden death in patients with cardiomyopathy; and to evaluate efficacy of treatment.

7-10 PRESCRIBED EXERCISE IN PEOPLE WITH FIBROMYALGIA
      Prescribed, graded aerobic exercise was effective in improving symptoms of fibromyalgia. It is simple, cheap, and potentially widely available. Compliance with the protocol was poor.

7-11 DEBRIDEMENT AND LAVAGE FOR OSTEOARTHRITIS OF THE KNEE
      “Numerous uncontrolled, retrospective case series have reported substantial pain relief after arthroscopic lavage or arthroscopic debridement for osteoarthritis of the knee.” “This study provides strong evidence that arthroscopic lavage with and without debridement is not better than, and appears to be equivalent to a placebo procedure in improving knee pain and self-reported function.” The study has also shown the great potential for a placebo effect of surgery.

7-12 IS PLACEBO SURGERY UNETHICAL?
      The editorialist states that we should not confound the ethics of clinical research with the ethics of clinical care. The randomized, controlled trial is not a form of individualized medical therapy. It is a scientific tool for evaluating treatments in groups of research participants with the aim of improving the care of patients in the future. Clinical trials are not designed to promote the medical best interests of enrolled patients. Indeed, they often expose them to risks that are not outweighed by known potential medical benefits. “The use of placebo surgery must be evaluated in terms of the ethical principles appropriate to clinical research, which are not identical to the ethical principles of clinical practice.”

7-13 ”POLYMYALGIA RHEUMATICA AND GIANT-CELL ARTERITIS”
      Recognizable and treatable. Devastating if neglected. A review of points of interest, both old and new.

7-14 BETA-BLOCKER THERAPY AND SYMPTOMS OF DEPRESSION, FATIGUE, AND SEXUAL DYSFUNCTION
      Beta-blocker therapy, compared with placebo, was not associated with substantial risk of depression, fatigue and sexual dysfunction. These small risks should be put in the context of the documented benefits of beta-blockers.

7-15 THE VALUE OF INFLAMMATION FOR PREDICTING UNSTABLE ANGINA
      Morphologically, atherosclerosis is an inflammatory disease.
      “Active” coronary disease is clearly associated with evidence of inflammation, both systemically and at the level of the arterial wall. Elevated levels of fibrinogen (an acute-phase reactant) were independently associated with future coronary events. Increased levels of markers of inflammation (eg, cytokines, adhesion molecules, and C-reactive protein ) predict future cardiovascular events.
      Statin drugs, which reduce risk of coronary events, also reduce circulating inflammatory markers independently of their cholesterol-lowering effect.
      Coronary angiography is not particularly useful in identifying the inflamed atherosclerotic plaques that are prone to produce clinical events. Acute myocardial infarction is often a consequence of coronary stenosis which is mild on angiography. Persons with an increased risk of acute coronary events are likely to have many vulnerable plaques throughout the coronary circulation. Plaque modification may be best modulated by systemic means (eg, statins; diet).
      “The current challenge remains the identification of persons with vulnerable atherosclerotic plaques”

7-16 CONTACTS WITH VARICELLA OR WITH CHILDREN AND PROTECTION AGAINST HERPES ZOSTER IN ADULTS
      Re-exposure to varicella-zoster virus via contact with children seemed to protect latently infected adults against HZ.
      This suggests that vaccination of the elderly might protect against HZ.

7-17 COMPARATIVE EFFICACY OF INSECT REPELLENTS AGAINST MOSQUITO BITES
      Only DEET products offered long-lasting protection after a single application. Currently available non-DEET repellants cannot be relied on to provide prolonged protection in environments where mosquito-borne diseases are a substantial threat. DEET has a remarkable safety record

1. Followed over 450 consecutive patients (mean age 65) admitted with suspected AMI.
2. Patients with suggestive symptoms and elevated cardiac enzymes were divided into 2 groups:

   1) Group A: symptoms of ischemia, and/or new ECG changes (ST-elevation or left bundle branch block), and elevated peak CK-MB, and
   2) Group B: symptoms of ischemia, and an elevated troponin with a normal peak CK-MB, and without ECG changes. Group B would not have been diagnosed as AMI by the old criteria. They constitute additionally diagnosed patients.

1. Fifty one additional patients were diagnosed as AMI by the new criteria. (Additional 11%)
2. Patients in group B were older women with increased co-morbidities.
3. In-hospital events (reinfarction, heart failure, shock, and mortality) were similar between groups.
4. At 6 months, mortality was higher in group B (16.3% vs 5.9%).

1. The new criteria detected about 10% additional patients with AMI. The old criteria would have missed 51 of 450 individuals who had an AMI. The new criteria can identify patients with AMI who are likely to be missed by the previous diagnostic criteria or, at best, were labeled as unstable angina.
2. The new criteria did not miss the diagnosis of any patient who was diagnosed as AMI by the old criteria.
3. The new criteria identified patients with more co-morbid conditions leading to a higher 6-month mortality.
4. The new criteria will allow physicians to tailor specific treatments that may decrease mortality. It is likely that the new criteria will lead to more aggressive therapy

1. Followed over 20 000 adults (age 40-80).
2. All had non-fasting total cholesterols of over 135 mg/dL. All were considered to be at substantial 5-year risk of death from coronary disease because of past history of CHD, occlusive disease of non-coronary arteries, or diabetes. Males over age 65 with treated hypertension were also included. (Ie, a secondary prevention trial.) "
3. Randomized to 1) 40 mg simvastatin daily, or 2) placebo.
4. Primary outcomes = overall mortality, and fatal or non-fatal cardiovascular events.
5. Follow-up = mean of 5 years.

1. L Total cholesterol levels fell by 46 mg/dL and LDL-cholesterol fell by 38 mg/dL compared with placebo.
2.  

   Outcomes at 5 years:	Simvastatin	Placebo	Absolute difference	NNT(over 5 y to benefit 1)
   All cause mortality	12.9%	14.7%	1.8%	55
   Coronary deaths	5.7%	6.9%	1.2%	83
   Non-fatal MI or coronary death	8.7%	11.8%	3.1%	32
   Stroke	4.3%	5.7%	1.4%	71
   First occurrence of any event	19.8%	25.2%	5.4%	18

3. Proportional reductions in risk did not appear to be materially influenced by the pretreatment lipid levels:
       First major vascular event associated with presenting lipid levels:
   
   

   	Absolute reduction in events	NNT(over 5 years to benefit 1)
   Total cholesterol (mg/dL)
   Presenting level 230
   Treatment level 184	5.2%	19
   Presenting level 192
   Treatment level 146	5.4%	18
   (This assumes a 46 mg/dL reduction.)
   LDL-cholesterol
   Presenting level 134
   Treatment level 96	5.2%	19
   Presenting level 116
   Treatment level 78	4.6%	21

   (This assumes a 38 mg/dL reduction.) (Ie, simvastatin just as beneficial when it lowered total cholesterol from 192 to 146 as when it was lowered from 230 to 184. Reducing LDL-cholesterol was just as beneficial when lowered from 134 to 96 as when lowered from 116 to 78. Ie, benefit was similar regardless of the initial cholesterol levels. This surprised me. I would have believed that there would be greater benefit when the levels were initially high, simply because the risks are higher at the higher levels. RTJ )
4. Benefits were evident in smokers, those with hypertension, and in those not taking aspirin, beta-blockers or ACE inhibitors. Benefits were also evident in older persons and women.
5. Benefits of simvastatin were additional to other cardioprotective treatments.
6. During the first year the reduction in major vascular events was not significant. Subsequently, it was highly significant. (Ie, the lag period has been reported in several studies. RTJ)
7. Adverse effects: Levels of alanine aminotransferases were measured at each follow-up. Few were found elevated. Those allocated to simvastatin showing no significant risk of liver enzyme elevations compared with placebo patients. Annual excess risk of myopathy was about 1 in 10 000. (Simvastatin was very safe. RTJ)

1. Lowering LDL-cholesterol with a statin produced a substantial reduction in the incidence of major vascular events in a much wider range of high-risk individuals than previously shown.
2. Benefits appeared to be largely independent of, and hence additional to, those of all other treatments being used by participants.
3. The benefits in reducing risk of stroke should resolve any uncertainty about the effects of statins on the risk of stroke.
4. It has been suggested that there might be a threshold of LDL below which lowering would not further reduce risk. This study demonstrated unequivocally that there is no threshold, Lowering LDL from 116 to 77 reduced vascular events by about one quarter, similar to the reduction in events following lowering from 134 to 96. If a threshold exists it is a LDL lower than 77 mg/dL and a total cholesterol below 135.
5. Present guidelines may mislead by suggesting target levels which are too high.
6. Benefits extend to prevention of ischemic stroke and peripheral revascularizations as well as coronary revascularizations.
7. The substantial benefits were not much influenced by the initial concentrations of lipids.
8. Lowering cholesterol to these levels by simvastatin was safe.
9. Given the large numbers of subjects, it was inevitable that some in the active treatment group discontinued the drug, and some in the placebo group began taking the drug. This would dilute the reported benefits. (Ie, statins likely produce greater benefits than reported by the study.)
10. Statin treatment would, over a 5-year period, prevent up to 100 major vascular events per 1000 individuals. More prolonged treatment would likely produce additional benefits.

1. Randomized over 16 500 postmenopausal women, age 50-79 (mean = 63) at baseline, to:

   A.	Conjugated equine estrogen (Premarin; 0.625 mg) + medroxyprogesterone (Provera; 2.5 mg) or
   B.	Placebo

2. All had an intact uterus. The great majority was healthy and free of cardiovascular disease; only 8% reported prior CVD. (Ie, this was essentially a primary prevention trial. )
3. Primary outcome = coronary heart disease (CHD death and non-fatal myocardial infarct), invasive breast cancer, stroke, pulmonary embolism, endometrial cancer, colorectal cancer, hip fracture, or death due to other causes.

1. The trial was terminated early (at 5 years) because risks of invasive breast cancer exceeded the stopping boundary.
2. Outcomes (harm annualized):

   	E + P (%)	Placebo (%)	Absolute difference	NNT
   	(n = 8506)	(n = 8102)	%	(harm one over 1 year)
   CHD death	33 (0.07)	26 (0.06)	0.01	10 000
   Non-fatal MI	133 (0.30)	96 (0.23)	0.07	1428
   Stroke	127 (0.29)	85 (0.21)	0.08	1250
   Venous thromboembolic disease	151 (0.34)	67 (0.16)	0.18	555
   Invasive breast cancer	166 (0.38)	124 (0.30)	0.08	1250

3. Outcomes (benefit annualized)

   				NNT (benefit one over 1 year)
   Fractures	650 (1.47)	788 (1.91)	+0.44	227
   Colorectal cancer	45 (0.10)	67 (0.16)	+0.06	1616
   Death due to other causes	165	166	--	--

4.  

   Global index considering both benefits and harms

   751 (1.70)

   623 (1.51)

   -0.19

   526 (harm one over 1 year)

   (I calculated these NNT from the table on page 326. I do not believe many clinicians would consider these high NNTs to be clinically significant. RTJ)
5. No difference between groups in risk of all-cause mortality.
6. The investigators presented the absolute risks and benefits as number of events for ten thousand women per year:

   CHD events	+7 (harm)
   Stroke	+8 (harm)
   Pulmonary embolism	+8 (harm)
   Invasive breast cancer	+8 (harm)
   Colorectal cancer	-6 (benefit)
   Hip fractures	-5 (benefit)
   Global index	+19 (harm)

1. This study addressed the question as to whether HRT with estrogen/progestin prevents chronic disease in a large cohort of healthy postmenopausal women. It does not.
2. The number of harms exceeded benefits.
3. The authors caution that the study does not relate to women taking only estrogen. The progestin content of the present study may be the factor leading to increased risk of breast cancer and CHD and stroke. A study considering only estrogen continues.
4. “The risk-benefit is not consistent with the requirements for a viable intervention for the primary prevention of chronic diseases.”
5. The trial did not address the short-term risks and the significant benefits of hormones given for treatment of menopausal symptoms.

1. Randomized placebo-controlled trial of 4.1 years (HERS I) was followed by 2.7 years of open-label observation. (HERS II)
2. Over 2700 postmenopausal women had coronary disease at baseline. Average age = 67.
3. Randomized to: 1) 0.625 mg conjugated estrogen plus 2.5 mg medroxyprogesterone, or 2) placebo during the first 4.1 years. This was followed by open-label hormone therapy prescribed by personal physicians. By the end of the study, adherence to HRT declined from about 80% to about 45% in the HRT group, and use of HRT increased to about 8% in the placebo group.
4. Main outcome measures – thromboembolic events, biliary tract surgery, cancer, fracture, and total mortality.

1.  

   Events per 1000 persons per year	HRT	Placebo	Absolute difference	NNT(over 1y to harm 1)
   Venous thromboembolism	4.5	2.2	0.23 %	434
   Pulmonary embolism	2.0	0.7	0.13 %	767
   Total thromboembolic events	5.9	2.8	0.31 %	322
   Biliary tract surgery	19.1	12.9	0.62 %	161
   Breast cancer	5.9	4.7	0.12 %	833
   Any cancer	19.7	16.5	0.32 %	312
   Any fracture	29.7	28.4	0.13 %	769

   (I calculated these NNT from table 2 p 61. All indicate small harms for HRT, even for cancer and fractures. The NNT indicate the number of patients needed to treat for one year to harm one patient. I believe the numbers needed to treat are so large as to be clinically irrelevant. RTJ )
2. Deaths were more common in the HRT groups – 22.5% vs 20.5%.

1. Over 6 years, treatment with combined HRT was associated with a statistically significant increase in venous thromboembolism and biliary tract surgery.
2. That hormone therapy increases risk of venous thromboembolism is well documented. Estrogen is the likely cause since estrogen without progestin is associated with venous thromboembolism, and selective estrogen receptor modulators also increase risk. Use of aspirin or statins appears to be protective.
3. This study represents a population with a relatively high absolute risk of deep vein thrombosis and pulmonary embolism.
4. The higher rate of fracture (including hip fracture) and the higher rate of colon cancer in the HRT group was surprising, given past reports of increase in bone mass density and fewer fractures in HRT-treated women.. The finding may be due to chance.¹

1. Cross-sectional study of over 400 English- and Spanish-speaking patients (mean age =58) with type-2 diabetes. All attended primary care health clinics.
2. Patients completed questionnaires assessing literacy by a short-form test of functional health literacy in adults in English and Spanish.
3. Main outcome measure = most recent HbA1c related to health literacy. Classified patients as having good glycemic control if their HbA1c was in the lowest quartile; poor control if in the highest quartile.

1. 66% of patients in this sample who had a high school education or less, had inadequate health literacy.
2. After adjusting for multiple possible confounding factors, for each 1-point decrement in test score, the HbA1c value increased by 0.02.
3. Patients with inadequate health literacy were less likely than patients with adequate health literacy to achieve tight glycemic control (HbA1c < 7.2%); and were more likely to have poor control (HbA1c. > 9.5%).
4. More in the poor health literacy group reported retinopathy.

1. “Our study demonstrates that, among patients who have type 2 diabetes and access to primary care physicians in public hospital clinics, health literacy was independently associated with glycemic control.
2. Poor health literacy was an independent predictor of poor glycemic control and was associated with a lower likelihood of achieving tight control and a higher rate of retinopathy.
3. It is possible that patients with inadequate health literacy are less likely to recognize signs and symptoms of diabetes and present to care late.
4. Poor health literacy probably impedes successful communication across many levels.

1. Prospectively followed over 1500 patients (mean age 64) presenting to the ED with acute dyspnea.
2. Performed rapid B-TNP in the ED. (A rapid quantitative assay is available by a kit using a fluorescent immunoassay method.)
3. Two cardiologists determined the actual diagnosis of HF or no-HF independently using clinical criteria.
4. Correlated levels of B-TNP with the clinical diagnosis confirmed by other tests.

1. Final diagnosis: HF confirmed (47%); dyspnea due to non-cardiac causes in persons with a history of left ventricular dysfunction (5%); no HF (49%).
2. B-TNP by itself was more accurate than any historical or physical finding or other laboratory finding in identifying HF as a cause of the dyspnea.
3. Mean B-TNP in patients with acute HF = 675 pg/mL; in those without HF = 110 pg/mL. In the 72 patients with baseline left ventricular dysfunction without an acute exacerbation of HF mean B-TNP = 346 pg/mL.
4. Diagnostic accuracy at a cutoff point of 100 pg/mL was 83%. Predictive value of a negative test (< 50 pg/mL) was 96%.1
5. Median B-TNP levels increased as severity of HF increased.
6. B-TNP added independent predictive power to other clinical variables assessing HF.
7. The authors judged the optimal cutoff point for making the diagnosis was 100 pg/mL

1. B-TNP levels by themselves were more accurate than any other finding in the history, physical examination, or laboratory value in delineating the cause of dyspnea.
2. The B-TNP levels correspond with the severity of the HF.
3. B-TNP is included in the European guidelines for diagnosis of chronic HF. It offers valuable predictive information and assessment of severity of the disease. It will improve the ability of clinicians to differentiate dyspnea due the HF from dyspnea due to other causes in the acute care setting. The diagnostic information can be immediately available.

1. Followed 132 patients with fibromyalgia. (median age = 45.) Participants had low self-rated scores indicating high levels of disability. Most were unemployed and came from ethnic minorities.
2. Randomized to: 1) community-based graded, aerobic exercise, or 2) relaxation and flexibility therapy.
3. Therapy comprised individualized aerobic exercise, mostly walking on treadmills and cycling on exercise bicycles. Participants were encouraged to increase the amount of exercise steadily from 6 minutes twice weekly to 25 minutes as tolerated at an intensity that made them sweat slightly.
4. Patients self-assessed any degree of improvement, tender point counts, and impact on condition.
5. Primary outcome measure = change in self rated global impression. Follow-up = 12 weeks.

1. Compared with relaxation, exercise led to significantly more participants rating themselves as much or very much better at 3 months [35% vs 18%; NNT(benefit one person over 3 months) = 6.]
2. Tender point counts were reduced from 4.2 to 2.0.
3. Benefits were maintained or improved at one year at which time fewer in the exercise group fulfilled the criteria for fibromyalgia. (45% vs 66%; NNT = 5)
4. But compliance was poor. Only slightly over half attended 1/3 or more of the classes. Twelve in each group (18%) withdrew.

1. A three month program of prescribed, graded exercise significantly benefited patients’ global self rating of fibromyalgia.
2. Tender point counts were reduced and scores on fibromyalgia impact also improved.
3. Prescribed exercise can be undertaken effectively in the community by personal trainers previously inexperienced in management of ill persons.
4. Compliance with a program may be a problem. Patients may experience initial increases in pain and stiffness immediately after exercise, and believe that exercise worsens their condition.

Age 50 or older
Bilateral aching and stiffness for one month or more involving two of 3 areas (neck, shoulders, pelvic girdle (most commonly in the shoulders).
Rapid response to prednisone 20 mg/d or less.
Sedimentation rate over 40 mm/hour
Exclusion of all diagnoses other than giant cell arteritis.

Age of onset 50 or over
New headache
Temporal artery abnormality (tenderness, decreased pulsation)
Elevated sedimentation rate. (Over 50 mm/h)
Abnormal biopsy of temporal artery. (At least 3 of the criteria must be met)

1. Search for randomized trials testing beta-blockers in treatment of myocardial infarction, heart failure, and hypertension found 15 studies (over 35 000 subjects) meeting authors’ inclusion criteria. All reported on depressive symptoms, fatigue, or sexual dysfunction in beta-blocker groups compared with placebo.
2. All had a follow-up of at least 6 months.

1.  

   Adverse effects (compared with placebo)	per 1000 patients/y	NNT (harm one patient/y)
   Depressive symptoms	6	166
   Fatigue	18	57
   Sexual dysfunction	5	199

   (Symptoms were compared with frequency in placebo groups. Symptoms of fatigue, depression and sexual dysfunction were common among the placebo groups.)
2. Adverse effects did not result in an increased number of patients withdrawing from therapy. (13 patients withdrew from both active treatment and placebo groups; 4 per 1000/y for fatigue and 2 per 1000/y for sexual dysfunction.
3. None of the risks of adverse effects differed significantly by degree of beta-blocker lipid solubility. Reported risk of fatigue was less for late-generation beta-blockers than for the early-generation (eg, propanolol; timolol).

1. This quantitative review combined all available data from randomized trials concerning symptoms of fatigue, depression and sexual dysfunction related to beta-blocker therapy.
2. The study found no increased risk of depression, and only small risks for fatigue and sexual dysfunction.
3. Patients rarely withdrew from therapy due to these adverse effects.
4. Concerns about these adverse effects may have contributed to the relatively slow adoption of beta-blocker therapy. “Our findings should alleviate concerns that long-term treatment with beta-blockers causes substantial increases in these symptoms that may compromise quality-of-life, and should encourage the implementation of this life-saving therapy. “
5. Symptoms of fatigue, depression and sexual dysfunction were common among the placebo groups.

1. Case-control study selected 244 adult patients with HZ; and 485 matched controls who had no history of HZ. Median age =57.
2. Asked participants about contacts over the past 10 years with people who had active varicella or zoster. And also with social and occupational contacts with children as proxies for varicella contacts.

1. Social contacts by adults with many children outside the household and occupational contact with ill children were associated with graded protection against HZ. Compared with the group least exposed to children, the group most heavily exposed experienced 80% less risk of developing HZ.
2. Protection increased with longer duration of occupational exposure to many ill children, and exposure to children not living in the household.
3. Contact with persons with HZ was not associated with protection.

1. The findings suggest that continuous exogenous exposure to varicella protects against HZ in latently infected adults.
2. Dose-response effects were associated with a range of occupational and social exposures to children and exposures to varicella.
3. Living with children seems to protect against HZ by increasing access to a range of other children outside the household.
4. Protection against HZ was strongest when contacts were in groups of changing membership in occupational or social settings (increasing the likelihood of contacting a case of varicella).
5. Contact with HZ patients was not protective.
6. Children who are vaccinated against varicella might be at a lower risk of later developing HZ. Widespread varicella vaccination programs might eventually decrease the incidence of HZ. However, this may lead to a temporary increase in HX in latently infected adults because they will be less exposed to children carrying the virus, and thus not re-immunized by contacts.
7. We should consider whether varicella vaccination in adults will protect against HZ. Studies are underway.

1. Recruited 15 volunteers to test relative efficacy of 7 different insect repellants. Four contained DEET (N,N diethyl-3methylbenxamide). Others included repellant-impregnated wristbands and a moisturizer commonly claimed to have repellant effects. (See text)
2. Tested them in a controlled environment in which the species of the mosquitoes, their age and degree of hunger were kept constant; and the humidity, temperature and the light-dark cycle of a cage were kept constant.
3. Volunteers covered their forearm and hand with the products or wore the wristband while inserting their forearm into a cage containing the mosquitoes.

1. DEET-based products provided complete protection for the longest duration. Higher concentrations of DEET provided longer-lasting protection. A product containing 24% DEET had a mean complete-protection of 5 hours.
2. A soy bean-oil-based product protected for 1 ½ hours; others protected for less than ½ hour.
3. Repellant-impregnated wrist bands (impregnated with either DEET or citronella) offered no protection.

1. After the study was completed, two new repellants were introduced into the USA – 1) Repel Lemon Eucalyptus Insect Repellant, and 2) Fite Bite Plant-Based Insect Repellant. In one study a localized cutaneous reaction occurred after the first test and the subject discontinued the study. All others completed 3 tests. The mean complete protection time was 2 hours.
2. A commonly used preparation of DEET is termed “OFF”. “OFF Deep Woods” contains 24% DEET.
3. DEET has been used worldwide since 1957. It has is a broad spectrum of activity -- effective against chiggers, biting flies, fleas, and ticks, as well as many species of mosquitoes.
4. No oral compound (including garlic and thiamine) has been found capable of repelling biting arthropods.
5. DEET is not a perfect repellant. It may be washed off by perspiration. Its efficacy decreases dramatically with rising outdoor temperatures. It is also a plasticizer and can dissolve watch crystals, frames of glasses, and some synthetic fabrics.
6. DEET has a remarkable safety record. After millions of users, fewer than 50 cases of serious toxicity have been reported, and most resolved without sequelae. “Normal use of DEET does not present a health concern to the general US population. DEET remains the gold standard.”