Management of patients with hypertensive urgencies and emergencies: a systematic review of the literature

BACKGROUND: Hypertensive urgencies and emergencies are common clinical occurrences in hypertensive patients. Treatment practices vary considerably to because of the lack of evidence supporting the use of one therapeutic agent over another. This paper was designed to review the evidence for various pharmacotherapeutic regimens in the management of hypertensive urgencies and emergencies, in terms of the agents' abilities to reach predetermined "safe" goal blood pressures (BPs), and to prevent adverse events. METHODS: medline was searched from 1966 to 2001, and the reference lists of all the articles were retrieved and searched for relevant references, and experts in the field were contacted to identify other relevant studies. The Cochrane Library was also searched. Studies that were eligible for inclusion in this review were systematic reviews of randomized control trials (RCTs) and individual RCTs, all-or-none studies, systematic reviews of cohort studies and individual cohort studies, and outcomes research. No language restrictions were used. RESULTS: None of the trials included in this review identified an optimal rate of BP lowering in hypertensive emergencies and urgencies. The definitions of hypertensive emergencies and urgencies were not consistent, but emergencies always involved target end-organ damage, and urgencies were without such damage. Measures of outcome were not uniform between studies. The 4 hypertensive emergency and 15 hypertensive urgency studies represented 236 and 1,074 patients, respectively. The evidence indicated a nonsignificant trend toward increased efficacy with urapidil compared to nitroprusside for hypertensive emergencies (number needed to treat [NNT] for urapidil to achieve target BP, 12; 95% confidence interval [95% CI], number of patients needed to harm [NNH], 5 to NNT, 40 compared to nitroprusside). Several medications were efficacious in treating hypertensive urgencies, including: nicardipine (NNT for nicardipine compared to plabebo, 2 in one study [95% CI, 1 to 5] and 1 in another [95% CI, 1 to 1]); lacidipine (NNT, 2; 95% CI, 1 to 8 for lacidipine vs nifedipine) or urapidil (NNT for urapidil compared to enalaprilat and nifedipine, 4; 95% CI, 3 to 6); and nitroprusside and fenoldopam (all patients reached target BP in 2 studies). The studies reported 2 cases of cerebral ischemia secondary to nifedipine. CONCLUSIONS: Many effective agents exist for the treatment of hypertensive crises. Because of the lack of large randomized controlled trials, many questions remain unanswered, such as follow-up times and whether any of the studied agents have mortality benefit.     

Assessment of unmet needs and the lack of generalizability in the design of randomized controlled trials for scleroderma treatment

OBJECTIVE: To determine the generalizability of randomized controlled trials (RCTs) in the treatment of systemic sclerosis (SSc) using the Canadian Scleroderma Research Group (CSRG) database. METHODS: We identified articles related to SSc published from 1958 to 2006. Key points on trial design were recorded. The inclusion/exclusion criteria were used in conjunction with the CSRG database to determine the proportion of patients with SSc who would theoretically be eligible for these trials. Articles were classified into subcategories according to the target system. The CSRG database contains 438 patients with SSc from 14 Canadian centers. Results were in median (%) and mean (%) with 95% confidence intervals (95% CIs). RESULTS: In total, 210 articles were evaluated and 73 were selected for inclusion in this study. The mean percentage of eligible patients with SSc associated with other conditions was 35% (95% CI 17-53) for Raynaud's phenomenon, 24% (95% CI 1-47) for digital ulcers, 48% (95% CI 27-68) for gastrointestinal (GI) involvement, 32% (95% CI 20-43) for overall disease modification, 6% (95% CI 4-8) for pulmonary arterial hypertension, 2% (95% CI 0-4) for interstitial lung disease, and 38% (95% CI 12-64) for other categories. CONCLUSION: Except for GI trials, <38% of the identified patients with SSc would have been suitable to enter the RCTs. Although some patients would be ineligible because they lack certain organ involvement, RCTs designed to include appropriate patients with SSc are needed; there are few proven treatments and trials typically do not include the majority of those who could potentially benefit from the intervention.     

A systematic review of the effectiveness of smoking relapse prevention interventions for abstinent smokers

Aims To carry out a systematic review of the effectiveness of relapse prevention interventions (RPIs) among abstinent smokers who had completed an initial course of treatment or who had abstained unassisted, pooling only outcome data from similar follow‐up time points. Methods We used the same search strategy as was used in Cochrane reviews of RPIs to identify randomized trials of behavioural and pharmacological studies of smoking RPIs published up to July 2008. Abstinence from smoking was defined as either continuous abstinence or point prevalence abstinence, measured at three follow‐up time points: short term (1–3 months post randomization), medium term (6–9 months) and long term (12–18 months). Abstinence among pregnant/postpartum women was also measured at delivery or the last follow‐up prior to delivery. Random effect meta‐analysis was used to estimate pooled odds ratios (OR) with 95% confidence intervals (CI). Results Thirty‐six studies randomizing abstainers were included. Self‐help materials appeared to be effective in preventing relapse at long‐term follow up in initially unaided quitters (pooled OR 1.52; 95% CI 1.15 to 2.01, I2 = 0%, NNT = 11, 3 studies). Other behavioural interventions for relapse prevention appeared effective in the short term only. There were positive results for the use of pharmacotherapies for relapse prevention. Bupropion was effective at long‐term follow‐up (pooled OR 1.49; 95% CI 1.10 to 2.01; I2 = 0%; NNT = 11; 4 studies). Nicotine replacement therapy (NRT) was effective at medium‐term (pooled OR 1.56; 95% CI 1.16 to 2.11; I2 = 37%; NNT = 14; 4 trials) and long‐term follow‐ups (pooled OR 1.33; 95% CI 1.08 to 1.63; I2 = 0%; NNT = 20; 4 trials). Single trials of extended treatment of Varenicline and rimonabant were also found to be effective at short‐term and medium‐term follow‐ups. Conclusions Self‐help materials appear to prevent relapse in initially unaided quitters. Use of NRT, bupropion and varenicline appears to be effective in preventing relapse following an initial period of abstinence or an acute treatment episode. There is currently no good evidence that behavioural support prevents relapse after initial unaided abstinence or following an acute treatment period.     

Efficacy of brief interventions for hazardous drinkers in primary care: systematic review and meta-analyses

BACKGROUND: Because recent research in primary care has challenged the findings of previous reviews on the efficacy of brief interventions (BIs) on hazardous drinkers, we conducted a systematic review and meta-analysis to update the evidence of BIs as applied in the primary care setting. METHODS: We obtained source material by searching electronic databases and reference lists and hand-searching journals. We selected randomized trials providing frequency data that allowed assessment of the efficacy of BIs on an intention-to-treat basis. Results were summarized by the odds ratio (OR) of response. When appropriate, risk difference (RD) and its inverse (number needed to treat [NNT] to achieve a positive result) were also computed. Fixed and/or random effect models were fitted according to heterogeneity estimates. RESULTS: Thirteen studies provided data for a dose-effect analysis, 12 for comparison of BIs with reference categories. No clear evidence of a dose-effect relationship was found. BIs outperformed minimal interventions and usual care (random effects model OR = 1.55, 95% confidence interval [CI] = 1.27-1.90; RD = 0.11, 95% CI = 0.06-0.16; NNT = 10, 95% CI = 7-17). Similar results were obtained when two influential studies were removed (fixed effect model OR = 1.57, 95% CI = 1.32-1.87; RD = 0.11, 95% CI = 0.07-0.15; NNT = 9, 95% CI = 7-15). The heterogeneity between individual estimates was accounted for by the type of hazardous drinkers (heavy versus moderate) and by the characteristics of the included individuals (treatment seekers versus nontreatment seekers). The funnel plot did not show evidence of publication bias. CONCLUSION: Our results, although indicating smaller effect sizes than previous meta-analyses, do support the moderate efficacy of BIs. Further research is outlined.     

Non-invasive assessment of digital vascular reactivity in patients with primary Raynaud's phenonenon and systemic sclerosis

OBJECTIVE: To examine digital microvascular responses in patients with primary Raynaud's phenomenon (PRP) and systemic sclerosis (SSc), and compare these to the responses in healthy control subjects. METHODS: Digital microvascular responses to repeated episodes of iontophoresis of acetylcholine chloride (endothelial-dependent), sodium nitroprusside (endothelial-independant) and adrenaline were measured using dual-channel laser Doppler in 8 healthy control subjects, 8 patients with PRP and 8 patients with SSc. RESULTS: There were no significant differences in responses between groups. For each chemical the greatest response was generally seen in period 7 of the protocol (after the third episode of iontophoresis). For acetylcholine chloride in period 7, the age and baseline adjusted ratio of the maximum response of PRP to control was 0.93, 95% CI (0.26, 3.38) and for SSc to control it was 0.60, 95% CI (0.13, 2.81). For sodium nitroprusside in period 7, this age and baseline adjusted ratio of the maximum response of PRP to control was 1.31, 95% CI (0.74, 2.32) and for SSc to control it was 1.35, 95% CI (0.68, 2.67). For adrenaline in period 7, the age and baseline adjusted ratio of PRP to control was 1.51, 95% CI (0.79, 2.89) and for SSc to control it was 2.18, 95% CI (1.01, 4.69). CONCLUSION: This study demonstrates the usefulness of iontophoresis of vasoactive chemicals, combined with laser Doppler blood flowmetry, in the non-invasive assessment of dermal microvascular responses. One possible explanation for the lack of difference in responses between groups is that vasoactive chemicals other than those discussed are important in the pathophysiology of primary and secondary Raynaud's phenomenon.     

Erectile dysfunction associated with scleroderma: a case-control study of men with scleroderma and rheumatoid arthritis

OBJECTIVE: To determine if men with systemic sclerosis (SSc) are at increased risk of developing erectile dysfunction (ED) compared to men with rheumatoid arthritis (RA), and to investigate the temporal relationship of ED related to rheumatologic disease. METHODS: Men with SSc identified from the practices of 2 rheumatologists were age matched to men with RA and were sent a standardized, validated questionnaire (SHIM IIEF-5) to assess ED and related factors. The questionnaire also addressed information on the subject's overall health and rheumatic disease status. RESULTS: The response rate was 50% (48% in SSc and 55% in RA), thus 43 with SSc and 23 with RA were included. The mean age of respondents was 53 yrs +/- 1.34 (SEM), (range 34 to 83). No statistical differences were found for marital status, alcohol or drug use, or past/present smoking. Men with scleroderma weighed less than men with RA (p < 0.004) and were more likely to have Raynaud's phenomenon (p < 0.0001), and to have fewer biological children (2.0 +/- 0.2 vs 2.7 +/- 0.2, p < 0.01). The prevalence of erectile dysfunction was 81% (SSc) and 48% (RA), (relative risk for SSc vs RA: 4.77; 95% CI: 1.55, 14.66; p < 0.005). In subjects who had ED, 78% (both SSc and RA) reported it occurring after disease onset. Men with SSc noted their ED began 2.7 +/- 1.2 (mean +/- SEM) years after their disease was diagnosed, and similarly, men with RA noted their ED began 3.3 +/- 2.2 years after disease diagnosis, p = 0.82. Eighty-six percent of patients with SSc had Raynaud's phenomenon (RP) compared to 19% RA, p < 0.0001. Eighty percent of subjects with RP (SSc + RA) had ED versus 50% of men without RP, p < 0.01. In RA subjects with RP (n = 4), 75% had experienced ED, versus 39% of RA without RP, p = 0.18. Possible confounding factors for ED were examined including smoking, hypertension, diabetes, and steroid use; all except self-reported history of nerve damage (p < 0.0005) and diabetes (p < 0.02) were insignificant for predicting the likelihood of increased ED. Patients with SSc were not more likely than RA to have experienced nerve damage (p = 0.25), or diabetes (p = 0.19). CONCLUSION: ED occurs frequently in SSc, is more common than in RA, and occurs on average 3 years after disease onset. RP appears to be associated with ED in both SSc and RA, but is not necessarily an independent risk factor for ED in SSc alone.     

Risk factors associated with pulmonary arterial hypertension in Colombian patients with systemic sclerosis: review of the literature

OBJECTIVE: Considering the significant morbidity and mortality of pulmonary arterial hypertension (PAH) in patients with systemic sclerosis (SSc) and the lack of precise information on disease in Latin America, we investigated the clinical and laboratory characteristics associated with PAH in Colombian patients with SSc and review the literature. METHODS: This multicenter study included patients followed at 5 rheumatology units that were systematically assessed using a pretested questionnaire on clinical and immunological variables, focusing on PAH. Conditional logistic regression was employed to assess association between PAH and specific clinical characteristics. A systematic review of the literature was performed through electronic databases. RESULTS: Of a total of 349 patients with SSc, 61 (17%) met the criteria for PAH. Pulmonary fibrosis [adjusted odds ratio (AOR) 7.37, 95% CI 3.67-14.81, p < 0.0001], microstomia (AOR 3.3, 95% CI 1.70-6.28, p < 0.0001), gastroesophageal reflux (AOR 2.41, 95% CI 1.31-4.43, p = 0.005), dysphagia (AOR 2.7, 95% CI 1.49-4.77, p = 0.001), hyperpigmentation (AOR 2.15, 95% CI 1.11-4.16, p = 0.02), and hypopigmentation (AOR 2.4, 95% CI 1.26-4.64, p = 0.008) were the most prevalent clinical characteristics associated with PAH, while anemia (AOR 5.4, 95% CI 1.98-14.93, p = 0.001) was observed as the unique laboratory risk factor. Association between subtypes of SSc and PAH was not observed. Significant differences in both clinical and laboratory data were observed among different series. CONCLUSION: PAH may be a frequent complication of SSc in the Colombian population regardless of disease subtype. The identified clinical and laboratory risk factors might assist earlier diagnosis and guide decisions on therapeutic interventions on this critical complication of SSc. The reasons underlying the reported divergences among patients from different ethnicities are not fully understood, but it is most likely that both genetic and environmental factors are responsible for them.     

Low level laser therapy for osteoarthritis and rheumatoid arthritis: a metaanalysis

OBJECTIVE: Osteoarthritis (OA) and rheumatoid arthritis (RA) affect a large proportion of the population. Low level laser therapy (LLLT) was introduced as an alternative noninvasive treatment for RA and OA about 10 years ago, but its effectiveness is still controversial. We assessed the effectiveness of LLLT in the treatment of RA and OA. METHODS: A systematic review was conducted, following an a priori protocol, according to the methods recommended by the Cochrane Collaboration. Trials were identified by a literature search of Medline, Embase, and the Cochrane Controlled Trials Register. Only randomized controlled trials of LLLT for the treatment of patients with a clinical diagnosis of RA or OA were eligible. Thirteen trials were included, with 212 patients randomized to laser and 174 patients to placebo laser, and 68 patients received active laser on one hand and placebo on the opposite hand. Treatment duration ranged from 4 to 10 weeks. Followup was reported by only 2 trials for up to 3 months. RESULTS: In patients with RA, relative to a separate control group, LLLT reduced pain by 70% relative to placebo and reduced morning stiffness by 27.5 min (95% CI -52.0 to -2.9), and increased tip to palm flexibility by 1.3 cm (95% CI -1.7 to -0.8). Other outcomes such as functional assessment, range of motion, and local swelling were not different between groups. There were no significant differences between subgroups based on LLLT dosage, wavelength, site of application, or treatment length. In RA, relative to a control group using the opposite hand, there was no difference between control and treatment hand, but all hands were improved in terms of pain relief and disease activity. For OA, a total of 197 patients were randomized. Pain was assessed by 3 trials. The pooled estimate (random effects) showed no effect on pain (standardized mean difference -0.2, 95% CI -1.0 to +0.6), but there was statistically significant heterogeneity (p > 0.05). Other outcomes of joint tenderness, joint mobility, and strength were not significant. CONCLUSION: LLLT should be considered for short term relief of pain and morning stiffness in RA, particularly since it has few side effects. For OA, the results are conflicting in different studies and may depend on the method of application and other features of the LLLT. Clinicians and researchers should consistently report the characteristics of the LLLT device and the application techniques. New trials on LLLT should make use of standardized, validated outcomes. Despite some positive findings, this metaanalysis lacked data on how effectiveness of LLLT is affected by 4 factors: wavelength, treatment duration of LLLT, dosage, and site of application over nerves instead of joints. There is a need to investigate the effects of these factors on effectiveness of LLLT for RA and OA in randomized controlled clinical trials.     

Comparison of clinical and self reported diagnosis for rheumatology outpatients.

OBJECTIVE--To examine the sensitivity of patient self reported diagnoses compared with physician diagnoses in a rheumatology outpatient population. METHODS--A mailed survey to 472 rheumatology outpatients (81% response rate) asked about joint symptoms, disabilities, and underlying rheumatic conditions. The self-reported diagnoses were linked with physician diagnoses in the rheumatology clinic computer based diagnostic registry. RESULT--Overall there was an 87% sensitivity for self reported compared with physician diagnoses when the matching criteria included compatible yet different diagnoses such as rheumatoid arthritis (RA) and osteoarthritis (OA). The sensitivity for exact match was 65%, and it varied with the underlying clinical diagnosis, and was greatest for RA (90%) and ankylosing spondylitis (AS) (100%), and intermediate for OA (52%) and psoriatic arthritis (50%). The sensitivity of self report was primarily related to the type of diagnosis (RA or AS v other rheumatic conditions; odds ratio = 16.3, 95% confidence interval (CI) 9.0 to 29.5), and also to difficulty in activities of daily living (odds ratio = 2.3, 95% CI 1.1 to 4.6) but not age, gender, duration of disease, or clinic attendance, as shown by multivariate analysis. CONCLUSIONS--This study in a rheumatology outpatient population indicated that most patients report a diagnosis which is compatible with the clinical diagnosis. These findings give an upper limit to the sensitivity of self reported diagnoses, though further research is needed to assess the extent to which our results may be generalised to other settings.     

Calcium-channel blockers for Raynaud's phenomenon in systemic sclerosis

OBJECTIVE: Most patients with systemic sclerosis (SSc) have Raynaud's phenomenon (RP), which is often more severe than idiopathic RP. This study was a meta-analysis to determine the efficacy of calcium-channel blockers for the treatment of RP in SSc. The primary outcome measures were frequency and severity of ischemic attacks, digital skin temperature, patient and physician global assessments, and digital ulcers. METHODS: The Cochrane search strategy was used to ascertain all trials in all languages. Primary data sources included Medline, Current Contents, and the Cochrane Controlled Trials Register. Studies that met the inclusion criteria were randomized controlled trials of >2 days' duration with a dropout rate of <35%. Twenty-nine studies were found, of which 8 randomized controlled trials were eligible for inclusion. The total number of patients included was small (n = 109). Most trials included primary and secondary RP, and the main reasons for trial exclusion were inability to extract subset data on SSc patients (18 trials), data published previously (2 trials), and lack of a control group (1 trial). Data were abstracted independently by 2 reviewers, and either a weighted mean difference (WMD) or a standardized mean difference (SMD) was calculated for all continuous outcomes; however, information was not available for all outcomes within trials. RESULTS: The WMD of all calcium-channel blockers versus placebo (6 trials) and of nifedipine alone versus placebo (5 trials) for the reduction in the frequency of ischemic attacks over a 2-week period was -8.31 (95% confidence interval [95% CI] -15.71, -0.91) and -10.21 (95% CI -20.09, -0.34), respectively. The SMD of all calcium-channel blockers versus placebo (3 trials) and of nifedipine alone versus placebo (2 trials) for the reduction in the severity of ischemic attacks was -0.69 (95% CI -1.21, -0.17) and -0.99 (95% CI -1.74, -0.24), respectively. CONCLUSION: Calcium-channel blockers for RP in SSc have been tested in several small clinical trials and appear to lead to significant clinical improvement in both the frequency and the severity of ischemic attacks. Most trials were crossover trials in which order effect was not studied. This could have introduced bias. The results of this study suggest that the efficacy of calcium-channel blockers in reducing the severity and frequency of ischemic attacks in RP secondary to SSc is moderate at best (mean reduction of 8.3 attacks in 2 weeks and 35% less severity), and a further large, randomized controlled trial needs to be conducted.     

Pharmacological therapies for the prevention of acute kidney injury following cardiac surgery: a systematic review

Post-cardiac surgery acute kidney injury (AKI) is common and is associated with a significant increase in morbidity and mortality. We aimed to systematically review randomised trials that assessed the renoprotective utility of pharmacological agents in patients undergoing cardiac surgery. We searched PubMed, Embase and the Cochrane Central Register of Controlled Trials for randomised controlled trials comparing renoprotective pharmacological interventions with control in adult patients undergoing cardiac surgery with cardiopulmonary bypass. We extracted data for mortality, need for renal replacement therapy (RRT), incidence of AKI, and creatinine clearance at 24–48 h. About 49 randomised controlled trials involving 4605 patients were included. Pharmacological interventions included dopamine, fenoldopam, calcium channel antagonists, natriuretic peptides, diuretics, and N-acetylcysteine. Most trials were of poor quality, with small sample sizes, under-reporting of randomisation procedure, allocation concealment and method of blinding. No pharmacological intervention significantly reduced mortality. Fenoldopam and Atrial Natriuretic Peptide (ANP) reduced the need for renal replacement therapy by 5% (NNT 20, 95% CI 11.3, 83.0) and 3.5% (NNT 29, 95% CI 17.1, 84.4), respectively. Brain Natriuretic Peptide resulted in a 10% reduction in the incidence of AKI (NNT 11, 95% CI 6.2, 32.0). Dopamine caused a significant reduction in creatinine clearance (−4.26 ml/min, 95% CI −7.14, −1.39). The quality of studies that have assessed pharmacological renoprotective agents in cardiac surgery is generally poor. Fenoldopam, ANP and BNP show evidence of renoprotection. Randomised studies evaluating the effect of novel renoprotective agents that are powered to detect clinically relevant differences in outcomes are required.     

RAYNAUD'S PHENOMENON IN RHEUMATOID ARTHRITIS

The prevalence of Raynaud's phenomenon in RA was retrospectivelyreviewed in 411 consecutive RA patients and in a control groupof 919 consecutive outpatients with OA. Raynaud's phenomenonwas found in 19 (4.6%) of 411 RA patients and in 52 (5.6%) of919 patients with OA: its prevalence was 4.3% (13 cases) inRA inpatients and 5.4% (six cases) in RA outpatients. Amongthe RA patients, the prevalence of Raynaud's phenomenon was7.5% in men (7% of inpatients, 8.8% of outpatients) and 3.2%in women (3% of inpatients, 3.9% of outpatients) (P = N.S.).Conversely, the prevalence of Raynaud's phenomenon in patientswith OA was higher in women (6.5%) than in men (2.9%) (P = 0.045).Our study indicates that the reported association between Raynaud'sphenomenon and RA cannot be confirmed on the basis of a retrospectiveassessment of its prevalence. KEY WORDS: Raynaud's phenomenon, Rheumatoid arthritis, Osteoarthritis     

Number needed to treat in cardiac rehabilitation

Clinicians, patients, and health policy-makers must judge whether healthcare interventions are worth the side effects, inconvenience, and costs. The number needed to treat (NNT) provides an estimate of the number of patients who need to be treated to attain an additional favorable outcome, or to prevent an additional adverse outcome, and is the reciprocal of the absolute risk reduction. The closer the NNT is to 1.0-meaning that every patient who is treated achieves a benefit-the more effective the treatment. Traditionally, mortality has been considered a primary outcome measure of the effectiveness of cardiac rehabilitation and, if the event rates in two groups (ie, rehabilitation and usual care) are known, the absolute risk reduction can be calculated and the NNT estimated. Mortality data were derived from three meta-analyses of cardiac rehabilitation trials: one published in 1988 (n = 3614), one in 1989 (n = 4247), and one in 2001 (n = 7683). The respective estimated NNT for mortality in the meta-analyses were 32, 46, and 72 (95% confidence intervals [95% CI] 19, 1403).Improved exercise tolerance and patient-perceived health-related quality of life (HRQL) are also considered important and attainable outcomes of cardiac rehabilitation but are continuous, not dichotomous, variables. If the minimal important difference for a continuous outcome is known, then the proportions of patients who improve, remain the same, or deteriorate can be determined and the NNT estimated. Exercise tolerance and HRQL data from two randomized controlled trials of 8 weeks of rehabilitation after myocardial infarction, the Cardiac Rehabilitation in Advanced Age trial (CR-AGE; n = 270) and the McMaster Early Rehabilitation Study (MERS; n = 201) were used to estimate the NNT. In CR-AGE, the improvement in exercise tolerance was significantly greater in the rehabilitation than usual care group and the estimated NNT was 5 (95% CI 3, 13). The generic global HRQL score increased significantly in CR-AGE with rehabilitation with an estimated NNT of 12 (95% CI 5, 26) but, as the subscale group differences were not significant, the NNT was not estimated. The NNT for exercise tolerance was not estimated in MERS, as the group difference was not significant. On the other hand, specific HRQL scores in MERS increased significantly with rehabilitation giving an estimated NNT for global HRQL of 6 (95% CI 3, 21) and 6 to 10 for the HRQL sub-scales.The data and the estimated NNT from the meta-analyses of cardiac rehabilitation in large numbers of patients suggest a limited mortality effect, probably reflecting current cardiology practice. The estimated NNT from the two trials with relatively small numbers of patients suggest inconsistent exercise tolerance effects and a relatively short duration for improved HRQL. Along with the classic reporting scales, information about clinical and laboratory variables, and patient preferences, the NNT is a useful additional measure of effectiveness that provides both clinicians and patients with information about the impact of cardiac rehabilitation as secondary prevention therapy.     

Patient education interventions in osteoarthritis and rheumatoid arthritis: A meta-analytic comparison with nonsteroidal antiinflammatory drug treatment

Objective. To compare the effects of education interventions and nonsteroidal antiinflammatory drug (NSAID) treatment on pain and functional disability in patients with osteoarthritis (OA), and on pain, functional disability, and tender joint counts in patients with rheumatoid arthritis (RA). Methods. Two meta-analyses were performed: one of controlled trials of patient education interventions and one of placebo-controlled trials of NSAID treatments. Results. Nineteen patient education trials comprised of 32 treatment arms and 28 NSAID trials comprised of 46 treatment arms were included. The weighted average effect size for pain was 0.17 in the education trials and 0.66 in the NSAID trials. The average effect size for functional disability was 0.03 in the education trials and 0.34 in the NSAID trials; effects of education were much larger in RA studies than in OA studies. In RA studies, the average effect size for the tender joint count was 0.34 in the education trials and 0.43 in the NSAID trials. Because most patients in the education trials were being treated with medications, the effect sizes of these trials represent the additional, or marginal, effects of patient education interventions beyond those achieved by medication. Conclusions. Based on this meta-analysis, patient education interventions provide additional benefits that are 20–30% as great as the effects of NSAID treatment for pain relief in OA and RA, 40% as great as NSAID treatment for improvement in functional ability in RA, and 60–80% as great as NSAID treatment in reduction in tender joint counts in RA.     

Upper gastrointestinal tolerability of celecoxib compared with diclofenac in the treatment of osteoarthritis and rheumatoid arthritis

OBJECTIVE: To compare the upper gastrointestinal (UGI) tolerability of celecoxib (a cyclooxygenase-2 specific inhibitor) and diclofenac using data from three randomised, double-blind clinical trials in osteoarthritis (OA) and rheumatoid arthritis (RA). METHODS: Patients in two OA studies received either celecoxib 100 mg BID (n = 545), diclofenac 50 mg BID or TID (n = 540), or placebo (n = 200) for 6 weeks. In the RA study, patients received celecoxib 200 mg BID (n = 326) or diclofenac 75 mg BID (n = 329) for 24 weeks. The cumulative incidence of abdominal pain, dyspepsia, nausea or any of these events (UGI tolerability composite endpoint) after the first 6 weeks was estimated using time-to-event analysis. RESULTS: In the pooled OA trials, the cumulative incidence of the composite endpoint was significantly higher with diclofenac (17.6%; 95% CI: 14.4-20.9%) than celecoxib (11.1%; 95% CI: 8.4-13.8%; p = 0.002) and comparable with placebo (13.3%; 95% CI: 8.1-18.4%; p = 0.157). In the PA trial, the cumulative incidence of the UGI tolerability composite endpoint was also significantly higher with diclofenac (20.7%; 95% CI: 16.3-25.1%) than celecoxib (15.9%; 95% CI: 11.9-20.0%; p = 0.013). Celecoxib was also better tolerated than diclofenac in this trial in terms of the cumulative incidences of abdominal pain (p = 0.031) and dyspepsia (p = 0.062). The results of the UGI tolerability composite endpoint analysis were confirmed using the Cox proportional hazards model to controlfor other predictors of UGI adverse events. CONCLUSION: The UGI tolerability of therapeutic dosages of celecoxib was significantly better than diclofenac in patients with RA or OA.     

Sensitivity and positive predictive value of medicare part B physician claims for rheumatologic diagnoses and procedures

Objective. To examine the sensitivity and positive predictive value of Medicare physician claims for select rheumatic conditions managed in rheumatology specialty practices. Methods. Eight rheumatologists in 3 states abstracted 378 patient office records to obtain information on diagnosis and office procedures. The Medicare Part B physician claims for these patient visits were obtained from the Health Care Financing Administration. The sensitivity of the claims data for a specific diagnosis was calculated as the proportion of all patients whose office records for a particular visit documented that diagnosis and who also had physician claims for that visit which identified that diagnosis. The positive predictive value was evaluated in a separate sample of 331 patient visits identified in Medicare physician claims. The positive predictive value of the claims data for a specific diagnosis was calculated as the proportion of patients with that diagnosis coded in the claims for a particular visit who also had the diagnosis documented in the medical record for that visit. Results. Ninety percent of abstracted office medical records were matched successfully with Medicare physician claims. The sensitivity of the Medicare physician claims was 0.90 (95% confidence interval [CI] 0.85–0.95) for rheumatoid arthritis (RA), 0.85 (95% CI 0.73–0.97) for systemic lupus erythematosus (SLE), and 0.85 (95% CI 0.78–1.0) for aspiration or injection procedures. The sensitivity for osteoarthritis (OA) of the hip or knee was ≤0.50 if 5-digit codes specifying anatomic site were required. The sensitivity for fibromyalgia (FM) was 0.48 (95% Cl 0.28–0.68). The positive predictive values were at least 0.90 for RA, SLE, and aspiration or injection procedures. Positive predictive values for FM and the 5-digit site-specific codes for OA of the knee were 0.83 (95% CI 0.66–1.0) and 0.88 (95% CI 0.75–1.0), respectively, while the positive predictive value of the 5-digit site-specific codes for OA of the hip was zero (95% CI 0–0.26). The positive predictive value of OA at any site was 0.83 (95% CI 0.76–0.90). Conclusion. In specialty practice, Medicare physician claims had high sensitivity and positive predictive value for RA, SLE, OA without specification of anatomic site, and injection or aspiration procedures. The claims had lower sensitivity and predictive value for FM and for OA of the hip. The accuracy of Medicare physician claims for other conditions and in the primary care setting requires further investigation.     

Efficacy of treating hypertension in women

OBJECTIVE: To assess whether the relative and absolute benefit of hypertension treatment in women varies with age or race. DESIGN: Systematic review of studies from 1966 to 1998 using MEDLINE, reviews, and consultation with experts. Eleven randomized controlled trials of pharmacologic treatment of prJgiary hypertension with cardiovascular morbidity and mortality outcomes were selected, with a pooled population of 23,000 women. Relative risks were combined for each end point to form a summary risk ratio using meta-analytic techniques based on a random-effects model. Summary risk ratios were converted to numbers needed to treat (NNTs). Data were dichotomized by age to approxJgiate menopausal status (30 to 54 years, and 55 years and older), and by race (white and African American). MAIN RESULTS: In women aged 55 years or older (90% white), hypertension treatment resulted in a 38% risk reduction in fatal and nonfatal cerebrovascular events (95% confidence interval [CI] 27%, 47%; 5-year NNT 78), a 25% reduction in fatal and nonfatal cardiovascular events (95% CI 17%, 33%; 5-year NNT 58), and a 17% reduction in cardiovascular mortality (95% CI 3%, 29%; 5-year NNT 282). In women aged 30 to 54 years (79% white), hypertension treatment resulted in a 41% risk reduction in fatal and nonfatal cerebrovascular events (95% CI 8%, 63%; 5-year NNT 264), and a 27% risk reduction in fatal and nonfatal cardiovascular events (95% CI 4%, 44%; 5-year NNT 259). Hypertension treatment in African-American women (mean age, 52 years) reduced the risk of fatal and nonfatal cerebrovascular events by 53% (95% CI 29%, 69%; 5-year NNT 39), fatal and nonfatal cardiovascular events by 45% (95% CI 18%, 63%; 5-year NNT 21), fatal and nonfatal coronary events by 33% (95% CI 6%, 52%; 5-year NNT 48), and all-cause mortality by 34% (95% CI 14%, 49%; 5-year NNT 32). Analyses in white women aged 30 to 54 years did not show any statistically significant treatment benefit or harm. CONCLUSIONS: Hypertension treatment lowers the relative and absolute risk of cardiovascular morbidity and mortality in women aged 55 years and older and in African-American women of all ages. A greater effort should be made to increase awareness and treatment in these groups of women. Although relative risk reductions for cerebrovascular and cardiovascular events are sJgiilar for younger and older women, the NNT of younger women is at least 4 tJgies higher. Decisions about treatment of hypertension in younger white women should be influenced by the individual patient's absolute risk of cardiovascular disease.     

Respiratory physiotherapy to prevent pulmonary complications after abdominal surgery: a systematic review

OBJECTIVES: To examine the efficacy of respiratory physiotherapy for prevention of pulmonary complications after abdominal surgery. METHODS: We searched in databases and bibliographies for articles in all languages through November 2005. Randomized trials were included if they investigated prophylactic respiratory physiotherapy and pulmonary outcomes, and if the follow-up was at least 2 days. Efficacy data were expressed as risk differences (RDs) and number needed to treat (NNT), with 95% confidence intervals (CIs). RESULTS: Thirty-five trials tested respiratory physiotherapy treatments. Of 13 trials with a "no intervention" control group, 9 studies (n = 883) did not report on significant differences, and 4 studies (n = 528) did: in 1 study, the incidence of pneumonia was decreased from 37.3 to 13.7% with deep breathing, directed cough, and postural drainage (RD, 23.6%; 95% CI, 7 to 40%; NNT, 4.3; 95% CI, 2.5 to 14); in 1 study, the incidence of atelectasis was decreased from 39 to 15% with deep breathing and directed cough (RD, 24%; 95% CI, 5 to 43%; NNT, 4.2; 95% CI, 2.4 to 18); in 1 study, the incidence of atelectasis was decreased from 77 to 59% with deep breathing, directed cough, and postural drainage (RD, 18%; 95% CI, 5 to 31%; NNT, 5.6; 95% CI, 3.3 to 19); in 1 study, the incidence of unspecified pulmonary complications was decreased from 47.7% to 21.4 to 22.2% with intermittent positive pressure breathing, or incentive spirometry, or deep breathing with directed cough (RD, 25.5 to 26.3%; NNT, 3.8 to 3.9). Twenty-two trials (n = 2,734) compared physiotherapy treatments without no intervention control subjects; no conclusions could be drawn. CONCLUSIONS: There are only a few trials that support the usefulness of prophylactic respiratory physiotherapy. The routine use of respiratory physiotherapy after abdominal surgery does not seem to be justified.     

IL13RA2 gene polymorphisms are associated with systemic sclerosis

OBJECTIVE: To investigate the influence of genetic variability on the phenotypic expression of systemic sclerosis (SSc), by testing possible associations between single nucleotide polymorphisms (SNP) in IL13RA1 and IL13RA2 genes and SSc in a Caucasian population. METHODS: As IL13RA1 and IL13RA2 are located on the X chromosome and SSc occurs far more frequently in women than in men, only women were genotyped. The study group comprised 97 women with SSc, 36 with diffuse (dcSSc) and 61 with limited (lcSSc) cutaneous forms of disease, and 109 healthy controls. Patients and controls were Caucasian. We investigated 4 SNP in IL13RA1 and 3 in IL13RA2 by polymerase chain reaction amplifications and enzymatic digestion or primer extension reactions and denaturing high-performance liquid chromatography. RESULTS: We detected an association between IL13RA2 rs638376 and patients with SSc [p = 0.004, odds ratio (OR) = 1.85, confidence interval (CI) 1.22-2.74, p corr = 0.02], as well as with dcSSc in that subgroup of patients (p = 0.01, OR 2.22, 95% CI 1.27-3.89, p corr = 0.05). The IL13RA2 rs638376G allele frequency was higher in patients with SSc (51.6%) than in controls (36.4%, p = 0.003, OR 1.86, 95% CI 1.24-2.79, p corr = 0.015) and in the subgroup with dcSSc (57.6%) than in controls (36.4%, p = 0.003, OR 2.37, 95% CI 1.35-4.15, p corr = 0.015). One other IL13RA2 SNP was only associated with the dcSSc subgroup: the IL13RA2 rs5946040G allele was more common in patients with dcSSc (33.8%) than in controls (17%, p = 0.004, OR 2.5, 95% CI 1.36-4.60, p corr = 0.02). CONCLUSION: Our data suggest that IL13RA2 gene polymorphisms may be involved in susceptibility to SSc. Further studies are under way to show that they contribute to disease.