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OBJECTIVE: Existing studies present conflicting evidence for the role of cigarette smoking as a risk factor in the development of systemic lupus erythematosus (SLE). We performed an extensive search of the medical literature for all studies examining this relationship, and performed a meta-analysis to arrive at a more precise estimate of effect. METHODS: We performed a computerized literature search for all studies (in all languages), using Medline and EMBASE (1966 to present) and the Cochrane Collaboration database, and completed hand searches of relevant bibliographies and abstracts of conference proceedings. Several investigators systematically extracted data from the relevant studies. Unpublished data were obtained from the author of one abstract. Studies were examined in aggregate for heterogeneity and publication bias. The relationships of current smoking and past smoking (prior to the onset of SLE) to development of SLE were analyzed separately. RESULTS: Fifty-two studies were identified and chosen for detailed review. Of these, 9 (7 case-control and 2 cohort studies) were appropriate for inclusion in our meta-analyses. For current smokers compared with nonsmokers, the odds ratio (OR) for development of SLE was significantly elevated (OR 1.50, 95% confidence interval [95% CI] 1.09-2.08). Former smokers, compared with nonsmokers, did not demonstrate an increased risk of SLE (OR 0.98, 95% CI 0.75-1.27). Several subgroups were also analyzed. CONCLUSION: Our meta-analysis of the 7 existing case-control and 2 cohort studies revealed a small but statistically significant association between current smoking and development of SLE. However, no association between past smoking and development of SLE was observed.
BACKGROUND: Death from infected necrosis in acute pancreatitis is common and prevention has focused on prophylactic antibiotics. This study assesses whether intravenous prophylactic antibiotic use reduces infected necrosis and death in acute necrotizing pancreatitis. METHODS: A meta-analysis of randomized controlled trials was carried out. Medline, Web of Science, the Cochrane controlled trials register and international conference proceedings were searched, with a citation review of relevant primary and review articles. RESULTS: Six of 328 studies assessed were included in data extraction. Primary outcome measures were infected necrosis and death. Secondary outcome measures were non-pancreatic infections, surgical intervention and length of hospital stay. Prophylactic antibiotic use was not associated with a statistically significant reduction in infected necrosis (relative risk (RR) 0.77 (95 per cent confidence interval (c.i.) 0.54 to 1.12); P = 0.173), mortality (RR 0.78 (95 per cent c.i. 0.44 to 1.39); P = 0.404), non-pancreatic infections (RR 0.71 (95 per cent c.i. 0.32 to 1.58); P = 0.402) and surgical intervention (RR 0.78 (95 per cent c.i. 0.55 to 1.11); P = 0.167). It was, however, associated with a statistically significant reduction in hospital stay (P = 0.040). CONCLUSION: Prophylactic antibiotics do not prevent infected necrosis or death in acute necrotizing pancreatitis.
BACKGROUND: Recent advances in the treatment of nasopharyngeal carcinoma (NPC) have transpired into better treatment outcomes for patients with locoregionally advanced NPC, and have broadened the chemotherapeutic options for patients with metastatic disease. METHODS: Data for this review were identified through searches of articles published in PubMed, MEDLINE, and abstracts from selected conference proceedings up to 2004. RESULTS: The results of two meta-analyses and at least six randomized trials supported a survival benefit with the use of concurrent chemotherapy (e.g., platinum, tegafur-uracil [UFT)] and standard fractionated radiotherapy (with or without adjuvant chemotherapy) in the management of patients with locoregionally advanced NPC (nonmetastatic Stage III/IV disease, according to the staging system of the International Union Against Cancer). For those patients with metastatic NPC, platinum-based doublets using newer agents such as gemcitabine and the taxanes are reported to be better tolerated and can yield response rates comparable to those obtained with older, multidrug regimens. CONCLUSIONS: The current study reviewed the latest literature and pertinent issues concerning the role of chemotherapy in the treatment of patients with metastatic and locoregionally advanced NPC.
The clinical heterogeneity of intermediate-risk prostate carcinoma presents a challenge to urologic oncology in terms of prognosis and management. There is controversy regarding whether patients with intermediate-risk prostate carcinoma should be treated with dose-escalated external beam radiotherapy (EBRT) (e.g., doses > 74 gray [Gy]), or conventional-dose EBRT (e.g., doses < 74 Gy) combined with androgen deprivation (AD). Data for this review were identified through searches for articles in MEDLINE and in conference proceedings, indexed from 1966 to 2004. Currently, the intermediate-risk prostate carcinoma grouping is defined on the basis of prostate-specific antigen (PSA), tumor classification (T classification), and Gleason score. Emerging evidence suggests that additional prognostic information may be derived from the percentage of positive core needle biopsies at the time of diagnosis and/or from the pretreatment PSA doubling time. Novel prognostic biomarkers include protein expression relating to cell cycle control, cell death, DNA repair, and intracellular signal transduction. Preclinical data support dose escalation or combined AD with radiation as a means to increase prostate carcinoma cell kill. There is Level I evidence that patients with intermediate-risk prostate carcinoma benefit from dose-escalated EBRT or AD plus conventional-dose EBRT. However, clinical evidence is lacking to support the uniform use of AD plus dose-escalated EBRT. Patients in the intermediate-risk group should be entered into well designed, randomized clinical trials of dose-escalated EBRT and AD with sufficient power to address biochemical failure and cause-specific survival endpoints. These studies should be stratified by novel prognostic markers and accompanied by strong translational endpoints to address clinical heterogeneity and to allow for individualized treatment.
Endoscopic treatment (ET) is frequently used to prevent variceal rebleeding but this still occurs in about 50% of patients. Recently, transjugular intrahepatic portosystemic shunt (TIPS) has been compared with ET in several trials. Using a meta-analysis, we evaluated randomized trials comparing TIPS to ET assessing prevention of rebleeding, survival, and the effects on resource use and the quality of patients' lives. Medical databases were searched between January 1988 and January 1999 as well as published citations and conference proceedings. Sensitivity analyses for type of publication, methodological quality score, mean duration of follow-up, type of ET, etiology, and severity of liver disease were performed. Eleven randomized trials involving 811 patients fulfilled the selection criteria. The median follow-up ranged from 10 to 32 months. Variceal rebleeding was significantly more frequent with ET (47%) compared with TIPS (19%) (odds ratio [OR], 3.8; 95% confidence interval [CI], 2.8-5.2; P <.001), but there was no difference in mortality (OR, 0.97; 95% CI, 0.71-1.34). Post-treatment encephalopathy occurred significantly less often after ET (19%) than after TIPS (34%) (OR, 0.43; 95% CI, 0.30-0.60; P <.001). In the studies showing resource use this was more extensive for TIPS. The sensitivity analyses did not alter the main conclusion, and sole comparison with endoscopic ligation did not alter these results. In conclusion, in patients with variceal bleeding, TIPS compared with ET reduces the rebleeding rate, but does not improve survival, and increases the incidence of encephalopathy in a period of 1 to 2.5 years. Thus, TIPS cannot be recommended as the first choice treatment for prevention of variceal rebleeding.
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AIMS: The use of electrotherapeutics to improve filling and emptying dysfunction of the adult bladder has been well established, however the practice in children is less well known. The purpose of this review is to summarize the rationale behind the use of electro neuromodulation in children, examine the reported efficacy of the intervention for different presentations of dysfunction, and establish the current limitations to knowledge and practice. MATERIALS AND METHODS: A modified systematic review was carried out on all Medline studies identified as considering the use of electrotherapy or neuromodulation in children with bladder problems. Literature relating to use of this approach in adults was also searched in order to present current understanding of the treatment rationale and modes of application. RESULTS: A Medline search and handsearch of relevant conference proceedings revealed six studies of neuromodulation in children with non-neurogenic bladder dysfunction. There were no reports of the intervention in children with isolated pelvic floor dyssynergia, irritative symptoms, structural changes predisposing the pelvic floor to weakness, or monosymptomatic nocturnal enuresis. One report of the favorable effect of neuromodulation on gut dysmotility was identified. Study design and quality generated level 4 evidence. Positive post-intervention changes reported included: increased bladder capacity, decreased severity of urge, improved continence, and decrease frequency of urinary tract infection. Significant improvement in the urodynamic parameters of bladder compliance, number of uninhibited contractions, and bladder volume at first detrusor contraction were also reported. CONCLUSIONS: There are clear benefits from the use of electroneuromodulation in children with differing forms of voiding dysfunction. The treatment approach is independent of cognitive and pharmacological therapy, is minimally invasive, and free of side effects. To date, there are no clinical variables that reliably predict efficacy of electrotherapy in the various presentations of over and under active detrusor, sphincter dyssynergia, or irritative symptoms.
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OBJECTIVE: The objective was to locate, appraise, and summarize evidence from scientific studies on intestinal obstruction due to advanced gynecological and gastrointestinal cancer in order to assess the efficacy of surgery. MATERIALS AND METHODS DATA SOURCES: A comprehensive list of studies was provided by an extensive search of electronic databases, relevant journals, bibliographic databases, conference proceedings, reference lists, the gray literature, personal contact, and the worldwide web. DATA SYNTHESIS: Two researchers extracted the data independently. Due to the methodological quality of the studies, only a qualitative assessment was possible. RESULTS: The role of surgery in malignant bowel obstruction remains controversial, and no firm conclusions from the many retrospective case series can be made. Control of symptoms varies from 42% to over 80%, although it is often unclear how symptoms were measured and whether the symptom scores used are validated. There is a large range in the rates of reobstruction, from 10 to 50%, although time to reobstruction was often not included. There is a wide range of postoperative morbidity and mortality, although again the definition of both of these surgical outcomes varied among many of the papers. CONCLUSION: The role of surgery in malignant bowel obstruction needs careful evaluation, using validated outcome measures on symptom control and quality of life scores. Further information would include reobstruction rates together with the morbidity associated with the various surgical procedures. Currently, bowel obstruction is managed empirically, and there are marked variations in clinical practice by different units. There needs to be a greater standardization of management so that comparisons between different series can be made.
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PURPOSE: Postdural puncture headache (PDPH) is an iatrogenic complication of neuraxial blockade. We systematically reviewed the literature on parturients to determine the frequency, onset, and duration of PDPH. METHODS: Citations on PDPH in the obstetrical population were identified by computerized searches, citation review, and hand searches of abstracts and conference proceedings. Citations were included if they contained extractable data on frequency, onset, or duration of PDPH. Using meta-analysis, we calculated pooled estimates of the frequency of accidental dural puncture for epidural needles and pooled estimates of the frequencies of PDPH for epidural and spinal needles. RESULTS: Parturients have approximately a 1.5% [95% confidence interval (CI) 1.5% to 1.5%) risk of accidental dural puncture with epidural insertion. Of these, approximately half (52.1%; 95% CI, 51.4% to 52.8%) will result in PDPH. The risk of PDPH from spinal needles diminishes with small diameter, atraumatic needles, but is still appreciable (Whitacre 27-gauge needle 1.7%; 95% CI, 1.6% to 1.8%). PDPH occurs as early as one day and as late as seven days after dural puncture and lasts 12 hr to seven days. CONCLUSION: PDPH is a common complication for parturients undergoing neuraxial blockade.
PURPOSE: To summarize the evidence comparing noninvasive positive pressure ventilation (NPPV) and invasive positive pressure ventilation (IPPV) weaning on mortality, ventilator associated pneumonia and the total duration of mechanical ventilation among invasively ventilated adults with respiratory failure. SOURCE: Meta-analysis of randomized and quasi-randomized studies comparing early extubation with immediate application of NPPV to IPPV weaning. We selected randomized studies that 1) included adults, with respiratory failure, invasively ventilated for at least 24 hr; 2) compared extubation with immediate application of NPPV to weaning using IPPV; and 3) reported at least one clinically important outcome. PRINCIPAL FINDINGS: We searched MEDLINE (1966 to 2003), EMBASE (1980 to 2003) and the Cochrane Central Register of Controlled Trials (The Cochrane Library, Issue 2, 2003) for randomized controlled trials comparing NPPV and IPPV weaning. Additional data sources included personal files, conference proceedings and author contact. Two reviewers independently assessed trial quality and abstracted data. Five studies enrolling 171 patients demonstrated that compared to IPPV, noninvasive weaning decreased mortality (relative risk, 0.41 [95% confidence interval [CI] 0.22-0.76]), ventilator associated pneumonia (relative risk, 0.28 [95% CI 0.09-0.85]) and the total duration of mechanical ventilation (weighted mean difference, -7.33 days [95% CI -11.45 to -3.22 days]). CONCLUSIONS: In the absence of a large randomized controlled trial, this meta-analysis demonstrated a consistent positive effect of noninvasive weaning on mortality. Notwithstanding, the use of NPPV to facilitate weaning, in mechanically ventilated patients, with predominantly chronic obstructive pulmonary disease, is associated with promising, but insufficient, evidence of net clinical benefit at present.
PURPOSE: To review multiple organ dysfunction syndrome with respect to: 1) clinical measurement systems; 2) molecular mechanisms; and 3) therapeutic directions based upon molecular mechanisms. METHODS: The Medline, Cochrane, and Best Evidence databases (1996 to 2000), conference proceedings, bibliographies of review articles were searched for relevant articles. Key index words were multiple organ failure, multiple system organ dysfunction, sepsis, septic shock, shock, systemic inflammatory response syndrome. Outcomes prospectively defined were death and physiological reversal of end organ failure. RESULTS: Multiple organ dysfunction/failure (MODS) is the most common cause for death in intensive care units. The recognition of this syndrome in the last 30 yr may be due to advances in early resuscitation unmasking these delayed sequelae in those that would have died previously. Multiple organ dysfunction occurs after shock of varied etiologies and may be the result of unbridled systemic inflammation. As yet, therapy directed to prevent or improve MODS has not dramatically altered outcomes. CONCLUSION: Multiple organ dysfunction may serve as useful measure of disease severity for risk adjustment and outcome marker for quality of care and therapy provided. Anesthesiologists treating shock patients will note the subsequent development of MODS in the critical care unit and may be required to provide anesthetic support to these patients.
OBJECTIVE: To determine the impact of the antifungal component of selective decontamination of the digestive tract on fungal carriage, infection and fungaemia. DESIGN: Meta-analysis of randomized controlled trials of selective decontamination of the digestive tract. STUDY SELECTION: Data sources included Medline, Embase, Cochrane Register of Controlled Trials, previous meta-analyses, personal communications and conference proceedings, without restriction of language or publication status. All randomized trials were selected that compared oropharyngeal and/or intestinal administration of antifungals amphotericin B or nystatin, as part of selective decontamination protocol, with no treatment in the controls. There were 42 randomized controlled trials with a total of 6,075 critically ill patients. METHODS: Three reviewers independently applied selection criteria, performed quality assessment and extracted the data. The main outcome measures were patients with fungal carriage, patients with fungal infections and patients with fungaemia. Odds ratios were pooled with the random effect model. MEASUREMENTS AND RESULTS: Enteral antifungals significantly reduced fungal carriage (odds ratio 0.32, 95% confidence interval 0.19-0.53) and overall fungal infections (0.30, 0.17-0.53). Fungaemia was not significantly reduced in the treatment group (0.89, 0.16-4.95). CONCLUSIONS: Antifungals, as part of selective decontamination of the digestive tract, reduce fungal carriage and infection but not fungaemia in critically ill patients and may justify the inclusion of an antifungal component in the decontamination protocol.
The aim of this review is to summarize the available literature on gynecological management of posterior vaginal wall prolapse. A MEDLINE search and a hand search of conference proceedings of the International Continence Society and International Urogynecological Association was performed. Two randomized trials demonstrated that the transvaginal approach to rectocele is superior to the transanal repair in terms of recurrent prolapse. The traditional posterior colporrhaphy with levator ani plication was largely superceded by fascial repairs with similar anatomic success rates but favorable functional outcome. The midline fascial plication may offer a superior anatomic and functional outcome compared to the discrete site-specific fascial repair. Controlled studies are necessary to evaluate whether a sacrocolpopexy combined with posterior mesh interposition is an effective alternative to the transvaginal repair. There is currently no evidence to recommend the routine use of any graft and complications such as mesh erosion, infection, and rejection have to be considered.
The aim of this review is to summarize the available literature on surgical management of anterior vaginal wall prolapse. A Medline search from 1966 to 2004 and a hand-search of conference proceedings of the International Continence Society and International Urogynecological Association from 2001 to 2004 were performed. The success rates for the anterior colporrhaphy vary widely between 37 and 100%. Augmentation with absorbable mesh (polyglactin) significantly increases the success rate for anterior vaginal wall prolapse. Abdominal sacrocolpopexy combined with paravaginal repair significantly reduced the risk for further cystocele surgery compared to anterior colporrhaphy and sacrospinous colpopexy. The abdominal and vaginal paravaginal repair have success rates between 76 and 100%, however, no randomized trials have been performed. There is currently no evidence to recommend the routine use of any graft in primary repairs, and possible improved anatomical out-comes have to be tempered againstcomplications including mesh erosions, infections and dyspareunia.
Vertebral collapse is one of the most common fractures associated with osteoporosis. The subsequent back pain is severe and often requires medications, bed rest and hospitalization to control pain and improve mobilization. The purpose of this systematic review was to assess the effects of calcitonin versus placebo for the treatment of acute pain in patients sustaining stable, recent, osteoporotic vertebral compression fractures. MEDLINE (1966-2003), EMBASE (1980-2003), Cochrane Controlled Trial Registry (2003, volume 3), other databases, and conference proceedings were searched for relevant research. Primary study authors and the pharmaceutical manufacturer were contacted, and bibliographies of relevant papers were hand-searched. Randomized, double-blind, placebo-controlled trials comparing calcitonin versus placebo for the acute pain of recent osteoporotic vertebral compression fractures were included. Two reviewers extracted data, performed numeric calculations and extrapolated graphical data independently. The combined results from five randomized controlled trials, involving 246 patients, determined that calcitonin significantly reduced the severity of pain using a visual analogue scale following diagnosis. Pain at rest was reduced as early as 1 week into treatment (weighted mean difference [WMD] =3.08; 95% confidence interval [CI]: 2.64, 3.52) and this effect continued weekly to 4 weeks (WMD =4.03; 95% CI: 3.70, 4.35). A similar pattern was seen for pain scores associated with sitting, standing, and walking. Side effects were gastrointestinal, minor and often self-limited. Calcitonin appears to be effective in the management of acute pain associated with acute osteoporotic vertebral compression fractures by shortening time to mobilization.