COMPARISON OF THE ANALGESIC EFFECT OF TEN NONSTEROIDAL ANTI-INFLAMMATORY DRUGS

The analgesic effect of 10 anti-inflammatory drugs was comparedusing a single-blind method in 90 patients with rheumatoid arthritis.Each patient received two different drugs, for three days eachand each drug was evaluated in 18 patients. After the trial,the patients considered which of the drugs they preferred. The greatest relief from pain was achieved by diclofenac, indomethacin,naproxen and tolfenamic acid, each of these being preferredby the majority of patients and being significantly (p>0.01)better than the least effective drugs ketoprofen and proquazone.Acetylsalicylic acid, azapropazone, carprofen and ibuprofenwere considered intermediate in efficacy. KEY WORDS: Rheumatoid arthritis, Nonsteroidal drugs     

Preference for nonsteroidal antiinflammatory drugs over acetaminophen by rheumatic disease patients: a survey of 1,799 patients with osteoarthritis, rheumatoid arthritis, and fibromyalgia

OBJECTIVE: Because there is controversy regarding the efficacy of acetaminophen in rheumatic diseases and because apparently safer nonsteroidal antiinflammatory drugs (NSAIDs) are being produced, we surveyed rheumatic disease patients about their preferences for these agents to determine the degree to which one type of therapeutic agent is preferred over the other. METHODS: In 1998, we surveyed by mailed questionnaire 1,799 patients with osteoarthritis (OA), rheumatoid arthritis, or fibromyalgia who were participating in a long-term outcome study. Patients who had taken acetaminophen rated the effectiveness of acetaminophen, compared its effectiveness with that of NSAIDs, and then rated their overall satisfaction with acetaminophen compared with NSAIDs when both effectiveness and side effects were considered. RESULTS: Two-thirds of study participants had taken acetaminophen. About 37% of patients who had taken acetaminophen found it to be moderately or very effective and about 63% indicated that it was not effective or was only slightly effective. One-fourth of the patients found acetaminophen and NSAIDs to be equally effective, but >60% found acetaminophen to be much less effective or somewhat less effective. About 12% preferred acetaminophen to NSAIDs. When both effectiveness and side effects were considered together, 25% of the patients had no preference, 60% preferred NSAIDs, and 14% preferred acetaminophen. CONCLUSION: There was a considerable and statistically significant preference for NSAIDs compared with acetaminophen among the 3 groups of rheumatic disease patients. Although this preference decreased slightly with age and was less pronounced in OA patients, the preference was noted among all categories of patients and was not altered by disease severity. If safety and cost are not issues, there would hardly ever be a reason to recommend acetaminophen over NSAIDs, since patients generally preferred NSAIDs and fewer than 14% preferred acetaminophen. If safety and costs are issues, then the recommendation of the American College Rheumatology that acetaminophen be tried first seems correct, since 38.2% found acetaminophen to be as effective or more effective than NSAIDs.     

Patient preferences for treatment of rheumatoid arthritis

OBJECTIVE: To elicit treatment preferences of patients with rheumatoid arthritis (RA) for disease modifying antirheumatic drugs (DMARDs) with varying risk profiles. METHODS: Patient values for 16 DMARD characteristics were ascertained using published data about side effects, effectiveness, and cost. Patient preferences were determined by Adaptive Conjoint Analysis, an interactive computer program that predicts preferences by asking patients to make trade-offs between specific treatment characteristics. Simulations were run to derive preferences for four drugs: methotrexate, gold, leflunomide, and etanercept, under different risk-benefit scenarios. Infliximab was not included because it is given with methotrexate, and we did not include preferences for combination therapy. Based on each patient's expressed preferences, and the characteristics of the treatments available at the time of the study, the option that best fitted each patient's perspective was identified. RESULTS: 120 patients (mean age 70 years) were interviewed. For the base case scenario (which assumed the maximum benefits reported in the literature, a low probability of adverse effects, and low equal monthly "co-pays" (out of pocket costs)), 95% of the respondents preferred etanercept over the other treatment options. When all four options were described as being equally effective, 88% continued to prefer etanercept owing to its safer short term adverse effect profile. Increasing etanercept's co-pay to $30.00 decreased the percentage of patients preferring this option to 80%. CONCLUSIONS: In this study, older patients with RA, when asked to consider trade-offs between specific risk and benefits, preferred etanercept over other treatment options. Preference for etanercept is explained by older patients' risk aversion for drug toxicity.     

Capturing the paradigm shift in HIV treatment: changing attitudes in the choice of combination antiretroviral drugs by high HIV caseload Australian GPs (1996-1997)

The use of combination antiretroviral therapy for HIV infection is a rapidly changing field. To assess the impact of recent studies on prescribing patterns, two surveys of 21 high HIV caseload Australian GPs were undertaken in June 1996 and June 1997 to plot changes in the choice of combination antiviral therapy. Of the 17 GPs who responded to the survey in each year, the number of HIV-infected patients seen at their practices were estimated to be 5,061 in 1996 and 5,912 in 1997. In 1996, 40% of their patients were estimated to be on antiretroviral therapy compared to 60% in 1997 (p < 0.05). In 1996, most GPs preferred using dual combination therapy (59%); whereas in 1997, triple combination therapy was preferred (82%). Between 1996 and 1997, there was a significant change by high caseload Australian GPs in the choice of antiretroviral drugs with many combinations being preferred prior to presentation of efficacy data for those combinations, or recommendation through national guidelines.     

Stent for palliation of advanced colorectal cancer

In palliation of advanced colorectal cancer, self-expanding metal stent (SEMS) can be an alternative to surgical resection for malignant obstruction proximal to the splenic flexure. SEMS is recommended as the preferred treatment for palliation of left-sided advanced malignant colonic obstruction with a high quality of evidence, except in patients (1) with a presumed long life expectancy (>1 year) and (2) treated or considered for treatment with antiangiogenic drugs (ie, bevacizumab). The validity of the recommendation that palliative stenting is contraindicated in patients with a presumed long life expectancy (>1 year) because of late stent-related complications is debatable and might be an erroneous conclusion. It is recommended that each institution should decide a clear strategy for this palliative group of long-term survivors. Understanding the risks of surgery is important for both patients and surgeons in the shared decision-making process, and it is recommended to implement a surgical risk prediction system. Patients who have undergone palliative stenting can be safely treated with chemotherapy without antiangiogenic agents. Given the high risk of colonic perforation, it is not recommended to use SEMS as palliative decompression of obstructions if a patient is being treated or considered to be treated with antiangiogenic therapy (ie, bevacizumab).     

Current status of treatment of paroxysmal atrial tachycardia

The various technics and drugs useful in the management of paroxysmal atrial tachycardia have been reviewed from the pertinent literature with an appraisal added based upon personal experiences. Accurate diagnosis of the tachycardia by electrocardiographic technies in every patient is emphasized. The majority of attacks are recurrent, brief, annoying but not serions and need little or no therapy beyond rest. sedation. carotid sinus stimulation and preventive measures. For persistent episodes, phenylephrine is preferred in the young, while Lanatoside C is the choice drug for the older patient and those in whom hypertension or heart disease is a complication. Procaine amide and quinidine are preferred to magnesium sulfate, prostigmine and methacholine. Potassium offers practically specific therapy for atrial tachycardia with block secondary to digitalis intoxication. In difficult situations, each drug must be tried in maximally tolerated doses before sympathectomy as a last resort is considered. Newer and more effective drugs for therapy will be enthusiastically welcomed.     

Dual platelet inhibition in ACS—The Styrian consensus

Dual antiplatelet therapy facilitated treatment of acute coronary syndromes and enabled the wide use of stents after clopidogrel emerged on the market about twenty years ago. Although this was a milestone in cardiology, clopidogrel inherits several disadvantages which are likely to reduce clinical benefit of its use and a new generation of drugs including prasugrel and ticagrelor is now available. One megatrial was done for each substance and various publications regarding subgroups have been published. Since these broad data is difficult to overview, especially for clinicians not focused on cardiology patients, the invasive centers of Styria aimed to design an easy-to use algorithm for dual antiplatelet therapy in ACS. The algorithm divides patients with acute coronary syndromes into STEMI patients with preferred use of prasugrel and NSTEMI patients being preferentially treated with ticagrelor. Only two subgroups were included to facilitate the use of the algorithm. Recommended treatment in diabetic patients is the use of prasugrel and ticagrelor is recommended in small and old patients.     

Algorithms useful in the treatment of atrial fibrillation.

Atrial fibrillation (AF) is a heterogeneous disorder; its management must be individualized depending upon the mode of presentation, underlying substrate, and need for either rate or rhythm control. In hemodynamically unstable patients with new onset AF, conversion by electrical cardioversion is the preferred approach; however, in stable patients pharmacological options may be considered. Recurrence rate after conversion is high in the majority of patients, necessitating the use of antiarrhythmic agents. Because of modest efficacy and potential for untoward effects, various nonpharmacologic approaches are being explored. Some of these modalities are considered curative in the short-term but techniques are still being refined.     

Questionnaire survey evaluating disease-related knowledge for 149 primary gout patients and 184 doctors in South China

This study aims to investigate the disease-related knowledge of gout patients and doctors in south China and to identify the important targets of education for patients and doctors. A cross-section survey of 154 primary gout patients and 185 doctors who may see gout patients was conducted with a modified questionnaire with ten items of gout-related knowledge. The participants were considered to have gout-related knowledge if he or she correctly answered seven or more items. One hundred and forty-nine valid questionnaires from patients, 33 from rheumatology physicians, and 151 from non-rheumatology doctors were collected for statistical analysis. The mean correctly answered items of three groups were 6.6?±?2.2, 9.6?±?0.53, and 8.0?±?1.4, with rate of being considered to have knowledge about gout 51.7, 100, and 90.1 %, respectively (P?<?0.05). The correct answer rate for each particular item was over 80 % in the rheumatology physician group. Patients or non-rheumatology doctors knew the optimal serum uric acid (sUA) level (48.3 vs 55.6 %), the need to take lifelong urate-lowering drugs (29.5 vs 43.6 %), that allopurinol is a urate-lowering drug (55.7 vs 76.0 %), and how to prevent attacks induced by urate-lowering therapy (ULT) (60.4 vs 74.0 %). Logistic regression showed that higher education predicted which patients had gout-related knowledge. Both the gout patients and non-rheumatology doctors in south China had poor knowledge on ULT. Since many gout patients do not see rheumatologists, our data suggest that further education should focus on patients and non-rheumatologists and emphasize the use of urate-lowering drugs, treatment duration, the target sUA level, and prophylaxis against acute attacks.     

Timing of ileocolonic resection for symptomatic Crohn's disease--the patient's view.

Eighty patients were asked if they would have preferred their ileocolonic resection and anastomosis for Crohn's disease, to have been carried out sooner, later or at the same time as it was done. Seventy of the patients replied (88%). No patient would have preferred their operation to have been later, while 74% thought it should have been earlier. A preferred operation time was given for 69 resections, between 0 months--that is, at the same time--and 15 years earlier. The median preferred operation time was 12 months earlier (95% confidence intervals 18 months earlier to 7 months earlier). The remaining 18 patients were satisfied with the timing of their operation. Reasons given for earlier surgery in 58 resections included the severity of Crohn's symptoms preoperatively (97%), the ability to eat normally after resection (86%), feeling of well being after the resection (62%), and abolishing the need for drugs (43%). Patients preferring an earlier operation time were less likely to have had a previous resection (13/58) than patients in the 'same time' group (10/21, chi 2 = 4.746; p < 0.05).     

The reasoning behind decisions not to take up antiretroviral therapy in Australians infected with HIV

A substantial minority of HIV-infected Australians are not taking antiretroviral drugs. This study investigated the reasons behind their decision not to do so. Anyone who was HIV-infected but not taking antiretroviral drugs could participate. A self-administered, anonymous questionnaire was used, the principal recruitment method being through insertion of the questionnaire into gay community newspapers in Sydney and Melbourne. All respondents were asked questions covering demographics, previous AIDS-defining illnesses, T-cell and viral load monitoring, and previous use of antiretroviral drugs. In addition, respondents who had considered going on antiretroviral treatment, but then decided not to do so, were given a list of possible reasons for their decision and asked to indicate how much each played a role in their thinking. Of the 270 respondents, the great majority were gay men. One-eighth had experienced AIDS-defining illnesses. Two-thirds had recently had T-cell and viral load tests. One-third had taken antiretroviral drugs previously. Over two-thirds had considered antiretroviral therapy, most having given the matter quite some thought. Reasons for not taking up therapy did not differ greatly at different stages of HIV disease. The most common individual reason was fear of side effects. Important themes that emerged from factor analysis of the reasons data included distrust of conventional medical approaches to treatment, practical problems associated with taking antiretroviral drugs, unpleasant thoughts that being on therapy would evoke, and acceptance of the idea of dying. The findings can be used by doctors and counsellors to help patients clarify and evaluate their concerns about antiretroviral therapy.     

Short-course chemotherapy of pulmonary tuberculosis: a new approach to drug dosage in the initial intensive phase

An analysis carried out on the dosage schemes adopted in several controlled clinical trials in tuberculosis has indicated that preestablishing the daily doses of isoniazid, rifampicin, and pyrazinamide in the initial intensive phase results in large deviations of the doses administered from those considered appropriate in mg/kg body weight. This is due partly to the variations in the patients' body weight and partly to the restrictions in terms of fine adjustments of dosage imposed by the unitary content of active principle in the available individual preparations of the drugs. The availability of a fixed-triple combination of the same 3 drugs where the content of each component is established multiplying the mg/kg requirement of each drug by 10, allows a complete coincidence between the appropriate and the administered dose simply administering 1 tablet every 10 kg of body weight. The implications of the large overdosing in light patients if the conventional approach is followed are discussed in terms of toxicity and drug purchasing cost, both being of great relevance for Third World countries where the majority of patients are of low body weight.     

Geoepidemiology and changing mortality in primary biliary cholangitis

Primary biliary cholangitis (PBC), formerly called primary biliary cirrhosis, is a chronic cholestatic disease characterized by an autoimmune-mediated destruction of small and medium-sized intrahepatic bile ducts. Originally PBC was considered to be rare and almost invariably fatal, mainly because the diagnosis was made in patients presenting with advanced symptomatic disease (jaundice and decompensated cirrhosis). However, the development of a reproducible indirect immunofluorescence assay for antimitochondrial antibody made it possible to diagnose the disease at an earlier stage, and introduction of ursodeoxycholic acid therapy as the first-line therapy for PBC drastically changed PBC-related mortality. At present, patients with an early histological stage have survival rates similar to those of an age- and sex-matched control population. Although 30% of patients treated with ursodeoxycholic acid may exhibit incomplete responses, obeticholic acid and drugs currently in development are expected to be effective for these patients and improve outcomes. Meanwhile, more etiology and immunopathology studies using new technologies and novel animal models are needed to dissect variances of clinical course, treatment response, and outcome in each patient with PBC. Precision medicine that is individualized for each patient on the basis of the cause identified is eagerly awaited.     

Survey on treatment of hypertension and implementation of World Health Organization/International Society of Hypertension risk stratification in primary care in Belgium

OBJECTIVE : To gain insight into the prevalence, treatment and control of hypertension and into the implementation of the 1999 World Health Organization/International Society of Hypertension guidelines for the management of hypertension in general practice in Belgium. DESIGN : A prospective cross-sectional survey. SETTING : Primary care. METHODS : Participating physicians enrolled the first 15 men, at least 55 years old, who visited the surgery, measured their blood pressure with a validated automatic device and recorded data on age, medical history, drug utilization, cardiovascular risk factors and target organ damage. Patients were considered to have hypertension when systolic blood pressure was >or= 140 mmHg, diastolic blood pressure was >or= 90 mmHg or when they were under antihypertensive therapy. RESULTS : Among 3761 evaluable patients, 74% were considered to be hypertensive, 80% of whom were treated with antihypertensive drugs. Blood pressure was under control in 38% of the treated patients and in 31% of all hypertensives. Among the 1316 hypertensive patients in whom risk stratification was possible, 47, 56 and 86% of the patients in, respectively, the medium, high and very high risk groups were treated with antihypertensive drugs. Among the treated patients, 46, 37 and 31%, respectively, had reached goal pressure. Within each risk category, patients were treated more frequently when baseline blood pressure was higher. Logistic regression analysis revealed that hypertension grade and level of risk contributed independently to the odds of being treated. CONCLUSIONS : The results indicate that a large number of older hypertensive men are treated with antihypertensive drugs in primary care, but that the goal blood pressure is not reached in a substantial number of patients due to undertreatment. Furthermore, whereas patients at higher risk are treated more frequently than patients at lower risk, blood pressure itself remains an important factor for the initiation of antihypertensive drug therapy within each risk category.     

Anti-inflammatory drugs in experimental atherosclerosis. Part 4. Inhibition of atherosclerosis in vivo and thromboxane synthesis and platelet aggregation in vitro.

Groups of New Zealand white male rabbits were fed atherogenic diets containing 1% cholesterol. The diets of experimental groups were supplemented additionally with either aspirin, phenylbutazone, mefenamic acid, flufenamic acid, oxyphenylbutazone or aminopyrine. Blood cholesterol and phospholipids were measured at 3--4 week intervals. After 12 weeks the animals were sacrificed and the severity of atherosclerosis in the thoracic aorta was measured. In separate experiments, rabbit platelets were incubated with each of the drugs individually and conversion of [14C]arachidonic acid to thromboxanes and related compounds was assayed. Inhibition of collagen and arachidonic acid-induced platelet aggregation by each drug was also measured. All drugs inhibited thromboxane synthesis and platelet aggregation in varying degrees with flufenamate and aspirin being most and aminopyrine least effective. The pattern of metabolite formation from [14C]arachidonate was consistent with a block in the cyclooxygenase reaction. Phenylbutazone, flufenamic acid and oxyphenylbutazone produced significant reductions in atherosclerotic plaque formation without major changes in blood cholesterol levels or blood cholesterol--phospholipid ratios. Aspirin and aminopyrine were ineffective. The results indicate that the effectiveness of anti-inflammatory drugs as inhibitors of thromboxane synthesis and platelet aggregation in vitro does not afford a sufficient predictive index of their anti-atherogenicity in vivo. The significance of these findings is discussed in terms of the possible involvement of cyclooxygenase derivatives in atherogenesis.     

Prostaglandin synthetase activity from human rheumatoid synovial microsomes. Effect of ''aspirin-like'' drug therapy.

Using a radiometric technique, prostaglandin synthetase activity was measured in vitro in the microsomal fraction of 19 synovial tissues taken from 17 rheumatoid arthritis patients. The enzyme was inhibited in vitro by low concentrations of several 'aspirin-like' drugs, though paracetamol and salicylic acid were virtually inactive. While the synthetase preparations from patients receiving indomethacin, ibuprofen, or naproxen therapy exhibited considerable activity in vitro, we were unable to show any activity in preparations from patients taking aspirin, even in low doses. These findings suggest that in vivo aspirin may be unique in being an irreversible inhibitor of the enzyme, compared with other 'aspirin-like' drugs.     

Drug-testing in patients with pulmonary hypertension of unknown cause.

The acute haemodynamic effects of seven different drugs were serially evaluated in eight patients suffering from pulmonary hypertension of unknown cause. The following drugs were tested in randomized order: nifedipine, amrinone, isoproterenol, captopril, prostacyclin, dihydralazine and nitroglycerin. Only a reduction in pulmonary vascular resistance (PVR) of more than 30% of baseline was considered a satisfactory response. Overall, the decrease in PVR ranged from 9 +/- 12% (nitroglycerin) to 38 +/- 23% (prostacyclin). However, marked inter- and intra-individual variability in the efficacy of all drugs was observed, making cross reactivity totally unpredictable. The number of responders for each drug varied between five (prostacyclin) and zero (dihydralazine, nitroglycerin). Conversely, a maximum of three drugs was capable of eliciting a response in an individual patient, with only two out of eight patients being total non-responders. A reduction in PVR of more than 30% (n = 16) was associated with a significant decrease in mean pulmonary artery pressure (49.1 +/- 8.2 versus 39.4 +/- 6.4 mmHg) and a significant increase in cardiac index (2.5 +/- 0.6 versus 3.4 +/- 0.8l.min-1.m-2). Overall, none of the drugs tested proved to be clearly superior. However, because of marked inter- and intra-individual variability, the therapeutic approach must be based on trial and error and the evaluation of all drugs is indicated if one fails.     

Chlorthalidone reduces cardiovascular events compared with hydrochlorothiazide: a retrospective cohort analysis

There is significant controversy around whether chlorthalidone (CTD) is superior to hydrochlorothiazide (HCTZ) in hypertension management. The objective of this analysis was to evaluate the effects of CTD compared with HCTZ on cardiovascular event (CVE) rates. We performed a retrospective observational cohort study from the Multiple Risk Factor Intervention Trial data set from the National Heart, Lung, and Blood Institute. The Multiple Risk Factor Intervention Trial was a cardiovascular primary prevention trial where participants were men 35 to 57 years of age enrolled and followed beginning in 1973. CVEs were measured yearly, and time to event was assessed by Cox regression. Systolic blood pressure, total cholesterol, low-density lipoprotein cholesterol, high-density lipoprotein cholesterol, triglyceride, potassium, glucose, and uric acid were measured yearly. The difference between groups was evaluated by repeated-measures mixed modeling, and each model was adjusted for predictors of each variable. CVEs were significantly lower in those on CTD (adjusted hazard ratio: 0.51 [95% CI: 0.43 to 0.61]; P<0.0001) and on HCTZ (adjusted hazard ratio: 0.65 [95% CI: 0.55 to 0.75]; P<0.0001) compared with those who took neither drug. When comparing the 2 drugs, CTD had significantly fewer CVEs compared with HCTZ (P=0.0016). CTD displayed significantly lower SBP (P<0.0001), lower total cholesterol (P<0.0001), lower low-density lipoprotein cholesterol (P=0.0009), lower potassium (P=0.0003), and higher uric acid (P<0.0001) over time compared with HCTZ. In conclusion, both HCTZ and CTD reduce CVEs compared with neither drug. When comparing both drugs, CTD reduces CVEs more than HCTZ, suggesting that CTD may be the preferred thiazide-type diuretic for hypertension in patients at high risk of CVEs.