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1.

Background

The number of births attended by individual family physicians who practice intrapartum care varies. We wanted to determine if the practice–volume relations that have been shown in other fields of medical practice also exist in maternity care practice by family doctors.

Methods

For the period April 1997 to August 1998, we analyzed all singleton births at a major maternity teaching hospital for which the family physician was the responsible physician. Physicians were grouped into 3 categories on the basis of the number of births they attended each year: fewer than 12, 12 to 24, and 25 or more. Physicians with a low volume of deliveries (72 physicians, 549 births), those with a medium volume of deliveries (34 physicians, 871 births) and those with a high volume of deliveries (46 physicians, 3024 births) were compared in terms of maternal and newborn outcomes. The main outcome measures were maternal morbidity, 5-minute Apgar score and admission of the baby to the neonatal intensive care unit or special care unit. Secondary outcomes were obstetric procedures and consultation patterns.

Results

There was no difference among the 3 volume cohorts in terms of rates of maternal complications of delivery, 5-minute Apgar scores of less than 7 or admissions to the neonatal intensive care unit or the special care unit, either before or after adjustment for parity, pregnancy-induced hypertension, diabetes, ethnicity, lone parent status, maternal age, gestational age, newborn birth weight and newborn head circumference at birth. High- and medium-volume family physicians consulted with obstetricians less often than low-volume family physicians (adjusted odds ratio [OR] 0.586 [95% confidence interval, CI, 0.479–0.718] and 0.739 [95% CI 0.583–0.935] respectively). High- and medium-volume family physicians transferred the delivery to an obstetrician less often than low-volume family physicians (adjusted OR 0.668 [95% CI 0.542–0.823] and 0.776 [95% CI 0.607–0.992] respectively). Inductions were performed by medium-volume family physicians more often than by low-volume family physicians (adjusted OR 1.437 [95% CI 1.036–1.992].

Interpretation

Family physicians'' delivery volumes were not associated with adverse outcomes for mothers or newborns. Low-volume family physicians referred patients and transferred deliveries to obstetricians more frequently than high- or medium-volume family physicians. Further research is needed to validate these findings in smaller facilities, both urban and rural.More than 20 years ago, Luft and associates1 conducted one of the earliest volume–outcome studies. Since then, many studies addressing the relation between volume of procedures and patient outcomes have been published.2,3 In some of these studies, either the hospital size or the physician procedural volume was used as a surrogate for physician expertise. Among studies analyzing hospital volumes and outcomes, better outcomes have been associated with higher patient volumes in some instances4,5,6,7 but not others.3,8,9 Some studies of individual provider volume have shown a positive relation between volume and outcomes,10,11 whereas others have shown no relation or inconsistent results.3,12 Finally, a few studies analyzing both hospital volume and provider volume have reported a positive volume–outcome relation.13,14Criticism levelled at the methods used in volume–outcome studies have addressed the lack of adjustment for case mix, different cutoff points for volume categories and retrospective design.3 Other factors that have an effect on patient outcomes but that have not been included in previous volume analyses include health maintenance organization status, physician certification and years since graduation, and patient socioeconomic status, age and ethnicity. Furthermore, most of the studies on volume have covered surgical or oncology specialities.The few studies that have been done on volume and outcome in maternity care have shown variable effects. Rural health care is often associated with lower volumes of obstetric procedures. However, no differences in maternal or newborn outcomes have been shown in some comparisons of births in urban and rural locations.15,16,17,18 Other studies have shown poorer maternal and newborn outcomes in low-volume hospitals, neonatal intensive care units (NICUs) and rural locations.19,20,21,22 Conversely, higher volume (hospitals with more than 1000 deliveries per year) has been associated with more maternal lacerations or complications.23When the health care provider has been the unit of analysis, a relation between volume and maternal or newborn outcome has been demonstrated in at least one study24 but not in others.25,26 Low volume has been defined as 20 to 24 deliveries per year.24,26 Hass and colleagues24 reported an adjusted odds ratio (OR) of 1.4 for low birth weight for infants delivered by low-volume non-board-certified physicians relative to high-volume non-board-certified physicians; the adjusted OR was 1.56 for low-volume board-certified physicians relative to high-volume board-certified physicians (98.7% of whom were obstetricians).Possible explanations for the differences among studies include differences in health care delivery systems, insurance coverage, experience and training of providers, maternal risk factors, triage or transfer of high-risk cases, choice of outcome measures, and changes over time in access to care, quality assurance and standard of living. Relations have been reported between maternal or newborn outcomes and smoking, maternal history of low birth weight (for previous pregnancies), pregnancy–induced hypertension, diabetes, prepregnancy weight, gestational weight gain, maternal height and age, multiple gestation, previous vaginal birth after cesarean section, history of previous delivery problems, parity, large-for-date fetus, ethnicity and fetal sex.25,27,28,29 Few studies of the relation between volume of births and obstetric outcome have been able to control for these potentially confounding variables and adjust for maternal risk factors.Our database of detailed accounts of births in one hospital setting allowed us to examine this issue more rigorously. We posed 2 research questions: Is there a relation between the volume of deliveries attended by individual family physicians and maternal and newborn outcomes? If there are differences in outcomes, are they related to different physician practice styles and consultation patterns?  相似文献   

2.

Background

Measurement of bone mineral density is the most common method of diagnosing and assessing osteoporosis. We sought to estimate the average rate of change in bone mineral density as a function of age among Canadians aged 25–85, stratified by sex and use of antiresorptive agents.

Methods

We examined a longitudinal cohort of 9423 participants. We measured the bone mineral density in the lumbar spine, total hip and femoral neck at baseline in 1995–1997, and at 3-year (participants aged 40–60 years only) and 5-year follow-up visits. We used the measurements to compute individual rates of change.

Results

Bone loss in all 3 skeletal sites began among women at age 40–44. Bone loss was particularly rapid in the total hip and was greatest among women aged 50–54 who were transitioning from premenopause to postmenopause, with a change from baseline of –6.8% (95% confidence interval [CI] –7.5% to –4.9%) over 5 years. The rate of decline, particularly in the total hip, increased again among women older than 70 years. Bone loss in all 3 skeletal sites began at an earlier age (25–39) among men than among women. The rate of decline of bone density in the total hip was nearly constant among men 35 and older and then increased among men older than 65. Use of antiresorptive agents was associated with attenuated bone loss in both sexes among participants aged 50–79.

Interpretation

The period of accelerated loss of bone mineral density in the hip bones occurring among women and men older than 65 may be an important contributor to the increased incidence of hip fracture among patients in that age group. The extent of bone loss that we observed in both sexes indicates that, in the absence of additional risk factors or therapy, repeat testing of bone mineral density to diagnose osteoporosis could be delayed to every 5 years.Low bone mineral density is one of the most important risk factors for fracture.1,2,3–7 Treatment with antiresorptive agents has been widely used for several decades, and the results of randomized controlled trials have shown that at least part of their efficacy is associated with their capacity to increase or stabilize bone density.4 Although clinical guidelines recommend measurement of bone density, among other important risk factors, when assessing a patient''s risk for fracture,3,8,9 there is no international consensus on the optimal age at which to begin measurement, or on the frequency of measurement.10 The Canadian guidelines recommend it for patients aged 65 and older, even in the absence of risk factors or treatment, and suggest a frequency of every 2–3 years.8 Furthermore, it has been suggested that the rate of decline rather than a single measurement of bone density may better identify patients with an elevated risk for fracture.11 Consequently, determining changes in bone density over time may provide clues on the pathophysiology of fractures and provide more accurate estimates of the optimal timing for repeat measurement.Previous studies of change in bone mineral density as a function of age have had a number of limitations. Many were cross-sectional; had small samples, limited age ranges or differing inclusion and exclusion criteria; and most excluded men.12–20 The third National Health and Nutrition Examination Survey,21 a large cross-sectional study based in the United States included women and men aged 20 years and older but excluded only those who were pregnant or who had a fracture in both hips. It reported that, based on a single measurement of bone density in the hip, age-dependent bone loss in the hips begins early (20–40 years) and continues in both sexes throughout life. Cross-sectional data from the ongoing Canadian Multicentre Osteoporosis Study suggested that, although this finding may hold true for the femoral neck, which consists of both cortical and trabecular bone, it is not true for the largely trabecular lumbar spine.22 Furthermore, the use of cross-sectional data to estimate changes over time has fundamental limitations: the effect of age cannot be separated from the effect of birth cohort and survivorship, and estimates are based on between-group differences rather than changes in an individual participant.The use of longitudinal data would allow examination of the rate of change of bone mineral density over time with and without antiresorptive therapy. We sought to assess the average rate of change in bone density as a function of age among Canadians aged 25–85, stratified by sex and use of antiresorptive agents.  相似文献   

3.

Background

Rosiglitazone and pioglitazone may increase the incidence of fractures. We aimed to determine systematically the risk of fractures associated with thiazolidinedione therapy and to evaluate the effect of the therapy on bone density.

Methods

We searched MEDLINE, EMBASE, the Cochrane Central Register of Controlled Trials (CENTRAL), other trial registries and product information sheets through June 2008. We selected long-term (≥ 1 year) randomized controlled trials involving patients with type 2 diabetes and controlled observational studies that described the risk of fractures or changes in bone density with thiazolidinediones. We calculated pooled odds ratios (ORs) for fractures and the weighted mean difference in bone density.

Results

We analyzed data from 10 randomized controlled trials involving 13 715 participants and from 2 observational studies involving 31 679 participants. Rosiglitazone and pioglitazone were associated with a significantly increased risk of fractures overall in the 10 randomized controlled trials (OR 1.45, 95% confidence interval [CI] 1.18–1.79; p < 0.001). Five randomized controlled trials showed a significantly increased risk of fractures among women (OR 2.23, 95% CI 1.65–3.01; p < 0.001) but not among men (OR 1.00, 95% CI 0.73–1.39; p = 0.98). The 2 observational studies demonstrated an increased risk of fractures associated with rosiglitazone and pioglitazone. Bone mineral density in women exposed to thiazolidinediones was significantly reduced at the lumbar spine (weighted mean difference –1.11%, 95% CI –2.08% to –0.14%; p = 0.02) and hip (weighted mean difference –1.24%, 95%CI –2.34% to –0.67%; p < 0.001) in 2 randomized controlled trials.

Interpretation

Long-term thiazolidinedione use doubles the risk of fractures among women with type 2 diabetes, without a significant increase in risk of fractures among men with type 2 diabetes.Recent systematic reviews have focused on the adverse cardiovascular effects of the thiazolidinediones rosiglitazone and pioglitazone.1–5 In late 2006, the risk of fractures with the use of rosiglitazone was raised in a footnote of the report of the A Diabetes Outcome and Progression Trial (ADOPT).6 The manufacturers of rosiglitazone7 and pioglitazone followed this up by issuing warning letters about the risk of fractures.7–9Women with type 2 diabetes are at an increased risk of nonvertebral fractures,10 with a near doubling in the risk of hip fractures.11 Any additional risk from thiazolidinedione therapy could have a considerable impact. Our primary objective was to determine systematically the relative and absolute risks of fractures with long-term thiazolidinedione therapy for type 2 diabetes. We also reviewed the effect of thiazolidinedione therapy on bone mineral density to ascertain its biological plausibility.  相似文献   

4.

Background

Up to 50% of adverse events that occur in hospitals are preventable. Language barriers and disabilities that affect communication have been shown to decrease quality of care. We sought to assess whether communication problems are associated with an increased risk of preventable adverse events.

Methods

We randomly selected 20 general hospitals in the province of Quebec with at least 1500 annual admissions. Of the 145 672 admissions to the selected hospitals in 2000/01, we randomly selected and reviewed 2355 charts of patients aged 18 years or older. Reviewers abstracted patient characteristics, including communication problems, and details of hospital admission, and assessed the cause and preventability of identified adverse events. The primary outcome was adverse events.

Results

Of 217 adverse events, 63 (29%) were judged to be preventable, for an overall population rate of 2.7% (95% confidence interval [CI] 2.1%–3.4%). We found that patients with preventable adverse events were significantly more likely than those without such events to have a communication problem (odds ratio [OR] 3.00; 95% CI 1.43–6.27) or a psychiatric disorder (OR 2.35; 95% CI 1.09–5.05). Patients who were admitted urgently were significantly more likely than patients whose admissions were elective to experience an event (OR 1.64, 95% CI 1.07–2.52). Preventable adverse events were mainly due to drug errors (40%) or poor clinical management (32%). We found that patients with communication problems were more likely than patients without these problems to experience multiple preventable adverse events (46% v. 20%; p = 0.05).

Interpretation

Patients with communication problems appeared to be at highest risk for preventable adverse events. Interventions to reduce the risk for these patients need to be developed and evaluated.Patient safety is a priority in modern health care systems. From 3% to 17% of hospital admissions result in an adverse event,1–8 and almost 50% of these events are considered to be preventable.3,9–12 An adverse event is an unintended injury or complication caused by delivery of clinical care rather than by the patient''s condition. The occurrence of adverse events has been well documented; however, identifying modifiable risk factors that contribute to the occurrence of preventable adverse events is critical. Studies of preventable adverse events have focused on many factors, but researchers have only recently begun to evaluate the role of patient characteristics.2,9,12,13 Older patients and those with a greater number of health problems have been shown to be at increased risk for preventable adverse events.10,11 However, previous studies have repeatedly suggested the need to investigate more diverse, modifiable risk factors.3,6,7,10,11,14–16Language barriers and disabilities that affect communication have been shown to decrease quality of care;16–20 however, their impact on preventable adverse events needs to be investigated. Patients with physical and sensory disabilities, such as deafness and blindness, have been shown to face considerable barriers when communicating with health care professionals.20–24 Communication disorders are estimated to affect 5%–10% of the general population,25 and in one study more than 15% of admissions to university hospitals involved patients with 1 or more disabilities severe enough to prevent almost any form of communication.26 In addition, patients with communication disabilities are already at increased risk for depression and other comorbidities.27–29 Determining whether they are at increased risk for preventable adverse events would permit risk stratification at the time of admission and targeted preventive strategies.We sought to estimate the extent to which preventable adverse events that occurred in hospital could be predicted by conditions that affect a patient''s ability to communicate.  相似文献   

5.

Background

The use of proton pump inhibitors has been associated with an increased risk of hip fracture. We sought to further explore the relation between duration of exposure to proton pump inhibitors and osteoporosis-related fractures.

Methods

We used administrative claims data to identify patients with a fracture of the hip, vertebra or wrist between April 1996 and March 2004. Cases were each matched with 3 controls based on age, sex and comorbidities. We calculated adjusted odds ratios (OR) for the risk of hip fracture and all osteoporosis-related fractures for durations of proton pump inhibitor exposure ranging from 1 or more years to more than 7 years.

Results

We matched 15 792 cases of osteoporosis-related fractures with 47 289 controls. We did not detect a significant association between the overall risk of an osteoportic fracture and the use of proton pump inhibitors for durations of 6 years or less. However, exposure of 7 or more years was associated with increased risk of an osteoporosis-related fracture (adjusted OR 1.92, 95% confidence interval [CI] 1.16–3.18, p = 0.011). We also found an increased risk of hip fracture after 5 or more years of exposure (adjusted OR 1.62, 95% CI 1.02–2.58, p = 0.04), with even higher risk after 7 or more years exposure (adjusted OR 4.55, 95% CI 1.68–12.29, p = 0.002).

Interpretation

Use of proton pump inhibitors for 7 or more years is associated with a significantly increased risk of an osteoporosis-related fracture. There is an increased risk of hip fracture after 5 or more years exposure. Further study is required to determine the clinical importance of this finding and to determine the value of osteoprotective medications for patients with long-term use of proton pump inhibitors.Osteoporosis is a common condition throughout the developed world, affecting up to 16% of women and 7% of men aged 50 years and older.1 The presence of underlying osteoporosis is a major risk factor for the development of fractures of the hip, proximal femur, spinal vertebra and forearm. In 2000, the estimated number of people with fractures worldwide was 56 million, and about 9 million new osteoporotic fractures occur each year.2 In 1993/94, the number of hip fractures in Canada was 23 375.3 This number is predicted to increase to 88 124 by the year 2041, with a parallel increase in the number of days in hospital (465 000 patient-days in 1993/94 to 1.8 million in 2041).3 Moreover, the case-fatality rate for hip fractures can exceed 20%,4 and all osteoporosis-related fractures can lead to substantial long-term disability and decreased quality of life.5Many risk factors for the development of osteoporosis-related fracture have been identified, including white ethnic background, low body mass index, physical inactivity and female sex.6–8 There are also a number of medication classes, including corticosteroids and serotonin selective reuptake inhibitors, whose use has been linked to higher rates of osteoporosis.9–11 Furthermore, any condition or drug that increases the risk of falls and injury also increases the risk of an osteoporosis-related fracture.12,13One medication class that may affect bone mineral metabolism is proton pump inhibitors. This class of drugs inhibits the production and intragastric secretion of hydrochloric acid, which is believed to be an important mediator of calcium absorption in the small intestine.14 Recent studies have suggested that the use of proton pump inhibitors for 1 or more years is associated with hip fracture and other osteoporotic fractures; however, there is limited data on additional risk beyond 4 years exposure.15,16Because proton pump inhibitors are commonly prescribed to control and prevent symptoms of chronic unrelenting conditions, it is likely that many patients will use these medications for more than 4 years. Therefore, we used an adminstrative database to examine the effects of longer durations of proton pump inhibitor use on the development of osteoporosis-related fractures.  相似文献   

6.

Background

Patients taking oral anticoagulant therapy balance the risks of hemorrhage and thromboembolism. We sought to determine the association between anticoagulation intensity and the risk of hemorrhagic and thromboembolic events. We also sought to determine how under-or overanticoagulation would influence patient outcomes.

Methods

We reviewed the MEDLINE, EMBASE, Cochrane Central Register of Controlled Trials and CINAHL databases to identify studies involving patients taking anticoagulants that reported person-years of observation and the number of hemorrhages or thromboemboli in 3 or more discrete ranges of international normalized ratios. We estimated the overall relative and absolute risks of events specific to anticoagulation intensity.

Results

We included 19 studies. The risk of hemorrhage increased significantly at high international normalized ratios. Compared with the therapeutic ratio of 2–3, the relative risk (RR) of hemorrhage (and 95% confidence intervals [CIs]) were 2.7 (1.8–3.9; p < 0.01) at a ratio of 3–5 and 21.8 (12.1–39.4; p < 0.01) at a ratio greater than 5. The risk of thromboemboli increased significantly at ratios less than 2, with a relative risk of 3.5 (95% CI 2.8–4.4; p < 0.01). The risk of hemorrhagic or thromboembolic events was lower at ratios of 3–5 (RR 1.8, 95% CI 1.2–2.6) than at ratios of less than 2 (RR 2.4, 95% CI 1.9–3.1; p = 0.10). We found that a ratio of 2–3 had the lowest absolute risk (AR) of events (AR 4.3%/yr, 95% CI 3.0%–6.3%).

Conclusions

The risks of hemorrhage and thromboemboli are minimized at international normalized ratios of 2–3. Ratios that are moderately higher than this therapeutic range appear safe and more effective than subtherapeutic ratios.Oral anticoagulant therapy is essential for the treatment and prevention of many thromboembolic disorders. Since anticoagulants can cause serious adverse events,1–3 physicians monitor the international normalized ratios of patients taking these drugs to ensure that their ratios fall within a target range.An international normalized ratio of 2–3 is the most common target range. Results of previous studies revealed an increased risk of bleeding among patients whose ratios exceeded 4, an increased risk of stroke among patients whose ratios were 1.5–2 and a decreased risk of stroke at a ratio of 2.4.4,5 However, the evidence supporting the range of 2–3 has some deficiencies. We sought to determine whether the risk of hemorrhagic and thromboembolic events is minimized at an international normalized ratio of 2–3 among patients taking anticoagulants. In addition, it has been observed that patients spend more time with a ratio below 2 than above 3.6,7 The impact of such systematic underanticoagulation on patient outcomes is unknown. We sought to determine the effect of under-or overanticoagulation on the risk of thromboemboli and hemorrhage.  相似文献   

7.

Background

Peripherally inserted central catheters (PICC) in children and adolescents are being used with increasing frequency. We sought to determine the incidence and characterize risk factors of deep vein thrombosis associated with peripherally inserted central catheters in a pediatric population.

Methods

We conducted a prospective study involving consecutive patients referred to the radiology department of a tertiary care university-affiliated hospital for insertion of a peripherally inserted central catheter. We included patients aged 18 years or less who weighed more than 2.5 kg and had a peripherally inserted central catheter successfully inserted in his or her arm between June 2004 and November 2005. The primary outcome was the occurrence of partial or complete deep vein thrombosis evaluated by clinical examination, ultrasonography and venous angiography.

Results

A total of 214 patients (101 girls, 113 boys) were included in the study. Partial or complete deep vein thrombosis occurred in 20 patients, for an incidence of 93.5 per 1000 patients and 3.85 per 1000 catheter-days. Only 1 of the cases was symptomatic. In the univariable analyses, the only variable significantly associated with deep vein thrombosis was the presence of factor II mutation G20210A (odds ratio 7.08, 95% confidence interval 1.11–45.15, p = 0.04), a genetic mutation that increases the risk of a blood clot and that was present in 5 (2.3%) of the 214 patients.

Interpretation

The incidence of deep vein thrombosis related to peripherally inserted central catheters in our study was lower than the incidence related to centrally inserted venous catheters described in the pediatric literature (11%–50%).Most data available in the adult and pediatric literature on the incidence of deep vein thrombosis concern centrally inserted venous catheters, which are inserted directly in a central vein (jugular, subclavian or femoral). Typical symptoms of deep vein thrombosis are frequently absent in children and adolescents. Although the diagnosis of deep vein thrombosis is more reliable when based on Doppler ultrasonography or venous angiography,1–10 in most studies these diagnostic tests were performed only when patients presented clinical symptoms of deep vein thrombosis or catheter dysfunction. In studies focused on the pediatric population, the frequency of deep vein thrombosis related to centrally inserted venous catheters has varied from 11% to 50%.1,5,6,8,11In the past 10 years, peripherally inserted central catheters (PICC) have been used with increasing frequency in children and adolescents. The catheter is inserted percutaneously via a peripheral vein, with its tip residing in the superior vena cava. The main indications for this type of catheter insertion are difficult venous access, home intravenous antibiotic therapy, administration of chemotherapy or other hyperosmolar solution and long-term parenteral nutrition. The risk of deep vein thrombosis related to peripherally inserted central catheters could be greater among children and adolescents than among adults, given the size of the veins. Several studies have published complications related to peripherally inserted central catheters,12–20 but few focused on the pediatric population.13–21 Furthermore, in all of these studies, screening for deep vein thrombosis was not systematic. The real incidence of deep vein thrombosis related to peripherally inserted central catheters and their complications in the pediatric population are therefore unknown. We conducted this study to determine the incidence and characterize the risk factors of deep vein thrombosis related to peripherally inserted central catheters in children and adolescents in our institution.  相似文献   

8.

Background

Survivors of out-of-hospital cardiac arrest are at high risk of recurrent arrests, many of which could be prevented with implantable cardioverter defibrillators (ICDs). We sought to determine the ICD insertion rate among survivors of out-of-hospital cardiac arrest and to determine factors associated with ICD implantation.

Methods

The Ontario Prehospital Advanced Life Support (OPALS) study is a prospective, multiphase, before–after study assessing the effectiveness of prehospital interventions for people experiencing cardiac arrest, trauma or respiratory arrest in 19 Ontario communities. We linked OPALS data describing survivors of cardiac arrest with data from all defibrillator implantation centres in Ontario.

Results

From January 1997 to April 2002, 454 patients in the OPALS study survived to hospital discharge after experiencing an out-of-hospital cardiac arrest. The mean age was 65 (standard deviation 14) years, 122 (26.9%) were women, 398 (87.7%) had a witnessed arrest, 372 (81.9%) had an initial rhythm of ventricular tachycardia or ventricular fibrillation (VT/VF), and 76 (16.7%) had asystole or another arrhythmia. The median cerebral performance category at discharge (range 1–5, 1 = normal) was 1. Only 58 (12.8%) of the 454 patients received an ICD. Patients with an initial rhythm of VT/VF were more likely than those with an initial rhythm of asystole or another rhythm to undergo device insertion (adjusted odds ratio [OR] 9.63, 95% confidence interval [CI] 1.31–71.50). Similarly, patients with a normal cerebral performance score were more likely than those with abnormal scores to undergo ICD insertion (adjusted OR 12.52, 95% CI 1.74–92.12).

Interpretation

A minority of patients who survived cardiac arrest underwent ICD insertion. It is unclear whether this low usage rate reflects referral bias, selection bias by electrophysiologists, supply constraint or patient preference.People who survive out-of-hospital cardiac arrest have an increased risk of recurrent arrest of 18%–20% in the first year.1,2 Three large randomized studies evaluated the use of implantable cardioverter defibrillators (ICDs) versus antiarrhythmic drugs in survivors of out-of-hospital cardiac arrest.3,4,5 The largest of the 3 studies involved 1016 patients and found a 39% relative risk reduction in mortality in the ICD group.3 The 2 smaller studies both reported nonsignificant reductions in mortality in the ICD group.4,5 Two recent meta-analyses showed that the use of ICDs was associated with significant and important increases in survival among cardiac arrest survivors: all-cause mortality was reduced by 23%–28% with their use for secondary prevention, and the rate of sudden cardiac death was reduced by 50% in both meta-analyses.6,7Guidelines from several national and international societies recommend insertion of ICDs in all survivors of cardiac arrest without a reversible cause.8,9 Despite advances in ICD insertion and technology, studies to date suggest that the utilization rate is low, at least in some settings.10,11 Several factors, including patient preference, physician referral, availability and cost, may contribute to the underutilization of ICDs.The Ontario Prehospital Advanced Life Support Study (OPALS)12,13 is a multiphase before–after study designed to systematically evaluate the effectiveness of various prehospital interventions for people experiencing cardiac arrest, trauma or respiratory arrest. As an extension of the OPALS study, we sought to determine the rate of ICD insertion among survivors of cardiac arrest, as well as the factors associated with ICD implantation.  相似文献   

9.

Background

Whether to continue oral anticoagulant therapy beyond 6 months after an “unprovoked” venous thromboembolism is controversial. We sought to determine clinical predictors to identify patients who are at low risk of recurrent venous thromboembolism who could safely discontinue oral anticoagulants.

Methods

In a multicentre prospective cohort study, 646 participants with a first, unprovoked major venous thromboembolism were enrolled over a 4-year period. Of these, 600 participants completed a mean 18-month follow-up in September 2006. We collected data for 69 potential predictors of recurrent venous thromboembolism while patients were taking oral anticoagulation therapy (5–7 months after initiation). During follow-up after discontinuing oral anticoagulation therapy, all episodes of suspected recurrent venous thromboembolism were independently adjudicated. We performed a multivariable analysis of predictor variables (p < 0.10) with high interobserver reliability to derive a clinical decision rule.

Results

We identified 91 confirmed episodes of recurrent venous thromboembolism during follow-up after discontinuing oral anticoagulation therapy (annual risk 9.3%, 95% CI 7.7%–11.3%). Men had a 13.7% (95% CI 10.8%–17.0%) annual risk. There was no combination of clinical predictors that satisfied our criteria for identifying a low-risk subgroup of men. Fifty-two percent of women had 0 or 1 of the following characteristics: hyperpigmentation, edema or redness of either leg; D-dimer ≥ 250 μg/L while taking warfarin; body mass index ≥ 30 kg/m2; or age ≥ 65 years. These women had an annual risk of 1.6% (95% CI 0.3%–4.6%). Women who had 2 or more of these findings had an annual risk of 14.1% (95% CI 10.9%–17.3%).

Interpretation

Women with 0 or 1 risk factor may safely discontinue oral anticoagulant therapy after 6 months of therapy following a first unprovoked venous thromboembolism. This criterion does not apply to men. (http://Clinicaltrials.gov trial register number NCT00261014)Venous thromboembolism is a common, potentially fatal, yet treatable, condition. The risk of a recurrent venous thromboembolic event after 3–6 months of oral anticoagulant therapy varies. Some groups of patients (e.g., those who had a venous thromboembolism after surgery) have a very low annual risk of recurrence (< 1%),1 and they can safely discontinue anticoagulant therapy.2 However, among patients with an unprovoked thromboembolism who discontine anticoagulation therapy after 3–6 months, the risk of a recurrence in the first year is 5%–27%.3–6 In the second year, the risk is estimated to be 5%,3 and it is estimated to be 2%–3.8% for each subsequent year.5,7 The case-fatality rate for recurrent venous thromboembolism is between 5% and 13%.8,9 Oral anticoagulation therapy is very effective for reducing the risk of recurrence during therapy (> 90% relative risk [RR] reduction);3,4,10,11 however, this benefit is lost after therapy is discontinued.3,10,11 The risk of major bleeding with ongoing oral anticoagulation therapy among venous thromboembolism patients is 0.9–3.0% per year,3,4,6,12 with an estimated case-fatality rate of 13%.13Given that the long-term risk of fatal hemorrhage appears to balance the risk of fatal recurrent pulmonary embolism among patients with an unprovoked venous thromboembolism, clinicians are unsure if continuing oral anticoagulation therapy beyond 6 months is necessary.2,14 Identifying subgroups of patients with an annual risk of less than 3% will help clinicians decide which patients can safely discontinue anticoagulant therapy.We sought to determine the clinical predictors or combinations of predictors that identify patients with an annual risk of venous thromboembolism of less than 3% after taking an oral anticoagulant for 5–7 months after a first unprovoked event.  相似文献   

10.
11.

Background

Postoperative delirium after elective surgery is frequent and potentially serious. We sought to determine whether the use of statin medications was associated with a higher risk of postoperative delirium than other medications that do not alter microvascular autoregulation.

Methods

We conducted a retrospective cohort analysis of 284 158 consecutive patients in Ontario aged 65 years and older who were admitted for elective surgery. We identified exposure to statins from outpatient pharmacy records before admission. We identified delirium by examining hospital records after surgery.

Results

About 7% (n = 19 501) of the patients were taking statins. Overall, 3195 patients experienced postoperative delirium; the rate was significantly higher among patients taking statins (14 per 1000) than among those not taking statins (11 per 1000) (odds ratio [OR] 1.30, 95% confidence interval [CI] 1.15–1.47, p < 0.001). The increased risk of postoperative delirium persisted after we adjusted for multiple demographic, medical and surgical factors (OR 1.28, 95% CI 1.12–1.46) and exceeded the increased risk of delirium associated with prolonging surgery by 30 minutes (OR 1.20, 95% CI 1.19– 1.21). The relative risk associated with statin use was somewhat higher among patients who had noncardiac surgery than among those who had cardiac surgery (adjusted OR 1.33, 95% CI 1.16–1.53), and extended to more complicated cases of delirium. We did not observe an increased risk of delirium with 20 other cardiac or noncardiac medications.

Interpretation

The use of statins is associated with an increased risk of postoperative delirium among elderly patients undergoing elective surgery.Delirium is an acute change in mental status that is worrisome to patients and families, especially after elective surgery. This condition may contribute to delays in extubation, a prolonged need for intensive care, increased risk of nosocomial infections and about a 1-week rise in total length of stay in hospital for the average patient.1,2 Delirium also disrupts many specific aspects of care, including the administration of medications, treatment of wounds, physiotherapy, nutrition, hygiene, discharge planning and dignity.3 The management of delirium is awkward and may lead to a cascade of nonspecific testing and sedation, with an average net increase in hospital costs of $2500 per patient.4 In some cases, the delirium never completely disappears, and the patient is left with a degree of permanent disability.5The causes of postoperative delirium are not well understood. Hypoglycemia, hypoxemia and hypotension are all possible and correctable, but they rarely have an immediate resolution.6 Medical imaging studies typically do not show specific changes; however, they may show markers of prior stroke or other lesions. One underlying factor may be cerebral ischemia secondary to inadequate perfusion. Altered cerebral perfusion may result in altered metabolism, an increased predisposition to drug toxicity or other factors during anesthesia and surgery.7 Cerebral ischemia may also explain commonly observed risk factors for postoperative delirium, including advanced age, baseline cognitive dysfunction and the failure of drug antagonists, major tranquilizers or modern volatile anesthetics to prevent postoperative delirium.8,9,10Statins have pleiotropic properties that alter the tone of smooth muscle in small blood vessels. Experiments on endothelial cells indicate that these changes are mediated by expression of endothelial nitric oxide synthase that is unrelated to cholesterol levels or vascular disease.11 In turn, activity of endothelial nitric oxide synthase contributes to arteriolar vasodilation by relaxing the surrounding smooth-muscle cells, thereby shifting the distribution of blood flow in the microvasculature of the brain. This can compromise individual neurons even if aggregate blood flow is maintained.12 These effects can be beneficial for reducing the size of stroke or other long-term neurologic disorders; however, altered cerebral blood flow autoregulation might predispose patients to delirium after anesthesia.13–15We sought to determine whether the use of statins was associated with postoperative delirium among elderly patients undergoing elective surgery.  相似文献   

12.

Background

People with type 2 diabetes mellitus are at high risk for cardiovascular disease. In some studies, the mortality rate among people with this condition has been equivalent to that among people with cardiovascular disease. We compared cardiovascular mortality between incident cases of diabetes and cardiovascular disease.

Methods

The study population was part of a random sample of 4376 men from Quebec, Canada, aged 35 to 64 years, who did not have cardiovascular disease in 1974 and who were followed until 1998. Three groups of incident cases were identified: diabetes without cardiovascular disease, first cardiovascular event (myocardial infarction, unstable angina or stroke) without diabetes, and both cardiovascular disease and diabetes. These cases were age-matched to a control group without diabetes or cardiovascular disease.

Results

During the 24-year follow-up period, new diabetes without cardiovascular disease was documented in 137 men. A first cardiovascular event without diabetes was documented in 527 men. Relative to the 627 controls, men with 1 of the 2 diseases of interest had higher cardiovascular mortality (age-adjusted relative risk [RR] 3.11, 95% confidence interval [CI] 1.96–4.92) for those with diabetes and 4.46 (95% CI 3.15–6.30) for those with cardiovascular disease). However, within the first 5 years after diagnosis, men with cardiovascular disease had higher cardiovascular mortality than men with diabetes (age-adjusted RR 2.03, 95% CI 1.01–4.08).

Interpretation

Men with isolated type 2 diabetes and men with isolated cardiovascular disease had similar cardiovascular mortality rates several years after initial diagnosis of either condition. These findings reinforce the need to prevent and optimally manage diabetes and cardiovascular disease.In 1971, type 2 diabetes mellitus was already considered an epidemic, affecting more than 170 million people worldwide.1 In 2001, it was estimated that diabetes prevalence would increase by nearly 50% by the year 2010.1 Epidemiologic studies performed in randomly sampled populations and initiated in the 1970s and 1980s have shown that diabetes increases the risk of all-cause death, as well as death due to cardiovascular disease and coronary artery disease.2–23 In some studies,12–17 but not all studies,18–23 coronary or cardiovascular mortality among people with type 2 diabetes without previous cardiovascular disease was equivalent to that of people without diabetes who had had a first myocardial infarction or first cardiovascular event. Thus, there is controversy as to whether diabetes alone confers a risk of cardiovascular mortality similar to that associated with having had a first coronary or cardiovascular event. The differences in findings among various studies may be attributable to several factors such as age, sex, duration of diabetes and cardiovascular disease, ethnicity, cardiovascular risk factors and therapies. Furthermore, most studies used prevalent cases without considering the duration of cardiovascular disease or diabetes and did not exclude high-risk patients who had angina or intermittent claudication before the diagnoses of diabetes and cardiovascular disease.The rationale for undertaking the present study was the need for more information about the cardiovascular prognosis of men with type 2 diabetes relative to men with cardiovascular disease. We used incident instead of prevalent cases, without prior angina and without intermittent claudication. We speculated that the adverse prognosis associated with a diagnosis of diabetes would be similar to the prognosis associated with a diagnosis of cardiovascular disease over the long term but would be less similar over the short term. We formulated 2 hypotheses: first, that within the first few years after diagnosis, the risk of a fatal cardiovascular event would be higher among men with a first cardiovascular event and no diabetes than among men with type 2 diabetes and no cardiovascular disease; and second, that over the longer term, the risk of death within these 2 clinical subsets would tend toward equivalence.  相似文献   

13.

Background

Aboriginal Canadians are considered to be at increased risk of major trauma. However, population-based studies characterizing the distribution, determinants and outcomes of major trauma in this group are lacking. We sought to measure the impact of ethnicity, as reflected by Aboriginal status, on the incidence of severe trauma and to broadly define the epidemiologic characteristics of severe trauma among status Aboriginal Canadians in a large health region.

Methods

This population-based, observational study involves all adults (people ≥ 16 years) resident in the Calgary Health Region between Apr. 1, 1999, and Mar. 31, 2002. Stratification of the population into status Aboriginal Canadians and the reference population was performed by Alberta Health and Wellness using an alternate premium arrangement field within the personal health care number. Injury incidence was determined by identifying all injuries with severity scores of 12 or greater in the Alberta Trauma Registry, regional corporate data and the Office of the Medical Examiner.

Results

Aboriginal Canadians were at much higher risk than the reference population in the Calgary Health Region of sustaining severe trauma (257.2 v. 68.8 per 100 000; relative risk [RR] 3.7, 95% confidence interval [CI] 3.0–4.6). Aboriginal Canadians were found to be at significantly increased risk of injuries resulting from motor vehicle crashes (RR 4.8, 95% CI 3.5–6.5), assault (RR 11.1, 95% CI 6.2–18.6) and traumatic suicide (RR 3.1, 95% CI 1.4–6.1). A trend toward higher median injury severity scores was observed among Aboriginal Canadians (21 v. 18, p = 0.09). Although the case-fatality rate among Aboriginal Canadians was less than half that in the reference population (14/93 [15%] v. 531/1686 [31%], p < 0.0001), population mortality was almost 2 times greater (RR = 1.8, 95% CI 1.0–3.0, p = 0.046).

Interpretation

Severe trauma disproportionately affects Aboriginal Canadians.In Canada, injury is the leading cause of death among people under the age of 45 and the leading cause of potential years of life lost.1 Although difficult to quantify, the cost of injury was estimated to be at least $12.7 billion in 1998.2 Trauma has been known, even in industrialized countries, to disproportionately affect the most marginalized members of society.3 Aboriginal Canadians are considered to be particularly at risk, and data showing alarming patterns of trauma mortality in this group are beginning to emerge. Unfortunately, the number of studies looking at injury risk among Aboriginal Canadians is small,4 and little attention has been paid to quantifying the risk of nonfatal injury. Better understanding of the nature of trauma risk and outcome among Aboriginal Canadians could lead to more effective prevention and treatment strategies.In this study, we used a population-based design in an attempt to quantify the impact of injury, both fatal and nonfatal, on the Aboriginal community in a large, heterogeneous Canadian region with over 1 million urban and rural inhabitants. We sought to measure the impact of ethnicity (defined by registered status within the definition of the Indian Act5) on the incidence of severe trauma and to broadly define the epidemiologic characteristics of severe trauma among status Aboriginal Canadians.  相似文献   

14.

Background

Recent lipid guidelines recommend aggressive low-density lipoprotein (LDL) cholesterol lowering in patients with coronary artery disease. To clarify the evidence for this recommendation, we conducted a meta-analysis of randomized controlled trials that compared different intensities of statin therapy.

Methods

We searched electronic databases (MEDLINE, EMBASE, Cochrane Central Registery of Controlled Trials, Web of Science) for randomized controlled trials published up to July 19, 2007, that compared statin regimens of different intensities in adults with coronary artery disease and that reported cardiovascular events or mortality. Data were pooled using random-effects models to calculate odds ratios (OR).

Results

A total of 7 trials (29 395 patients) were included. Compared with less intensive statin regimens, more intensive regimens further reduced LDL levels (0.72 mmol/L reduction, 95% confidence interval [CI] 0.60–0.84 mmol/L), and reduced the risk of myocardial infarction (OR 0.83, 95% CI 0.77–0.91) and stroke (OR 0.82, 95% CI 0.71–0.95). Although there was no effect on mortality among patients with chronic coronary artery disease (OR 0.96, 95% CI 0.80–1.14), all-cause mortality was reduced among patients with acute coronary syndromes treated with more intensive statin regimens (OR 0.75, 95% CI 0.61–0.93). Compared with lower intensity regimens, more intensive regimens were associated with small absolute increases in rates of drug discontinuation (2.5%), elevated levels of aminotransferases (1%) and myopathy (0.5%), and there was no difference in noncardiovascular mortality. All 7 trials reported events by randomization arm rather than by LDL level achieved. About half of the patients treated with more intensive statin therapy did not achieve an LDL level of less than 2.0 mmol/L, and none of the trials tested combination therapies.

Interpretation

Our analysis supports the use of more intensive statin regimens in patients with established coronary artery disease. There is insufficient evidence to advocate treating to particular LDL targets, using combination lipid-lowering therapy to achieve these targets or for using more intensive regimens in patients without established coronary artery disease.Dyslipidemia is the most important modifiable risk factor for myocardial infarction worldwide,1 and serum cholesterol levels are directly related to mortality from coronary artery disease in all populations studied.2–4 Over the past decade, randomized controlled trials enrolling a wide variety of patients have confirmed that for every 1-mmol/L reduction in serum low-density lipoprotein (LDL) cholesterol achieved by statin therapy, the relative risks of cardiovascular events and mortality are reduced (by 21% and 12% respectively).5Statins exert their beneficial effects primarily by reducing the level of LDL cholesterol,6 and the reductions in the relative risk of cardiovascular events achieved by statin therapy appears to be similar regardless of baseline cholesterol levels.5 As a result, attention has increasingly focused on defining optimal target LDL levels, particularly in patients at highest risk (i.e., those with coronary artery disease). Based on the observational studies mentioned above,2,3 the apparent lack of a lower threshold for statin benefit in the randomized controlled trials, and recent trials reporting greater benefits with more intensive statin regimens (compared with less intensive regimens), Canadian7 and American8 guidelines for secondary prevention now recommend target LDL levels below 2.0 mmol/L in patients with coronary artery disease. On the other hand, European guidelines specify a target LDL of 2.5 mmol/L in these patients.9 Questions have been raised about the safety and incremental benefits of more intensive statin regimens.10–12We performed a systematic review and meta-analysis to critically examine the evidence for the safety, efficacy (LDL lowering) and clinical effectiveness from trials comparing more intensive statin therapy with less intensive statin therapy in patients with coronary artery disease.  相似文献   

15.

Background

Patients undergoing hip or knee replacement are at high risk of developing a postoperative venous thromboembolism even after discharge from hospital. We sought to identify hospital and patient characteristics associated with receiving thromboprophylaxis after discharge and to compare the risk of short-term mortality among those who did or did not receive thromboprophylaxis.

Methods

We conducted a retrospective cohort study using system-wide hospital discharge summary records, physician billing information, medication reimbursement claims and demographic records. We included patients aged 65 years and older who received a hip or knee replace ment and who were discharged home after surgery.

Results

In total we included 10 744 patients. Of these, 7058 patients who received a hip replacement and 3686 who received a knee replacement. The mean age was 75.4 (standard deviation [SD] 6.8) years and 38% of patients were men. In total, 2059 (19%) patients received thomboprophylaxis at discharge. Patients discharged from university teaching hospitals were less likely than those discharged from community hospitals to received thromboprophylaxis after discharge (odds ratio [OR] 0.89, 95% confidence interval [CI] 0.80–1.00). Patients were less likely to receive thromboprophylaxis after discharge if they had a longer hospital stay (15–30 days v. 1–7 days, OR 0.69, 95% CI 0.59–0.81). Patients were more likely to receive thromboprophylaxis if they had hip (v. knee) replacement, osteoarthritis, heart failure, atrial fibrillation or hypertension, higher (v. lower) income or if they were treated at medium-volume hospitals (69–116 hip and knee replacements per year). In total, 223 patients (2%) died in the 3-month period after discharge. The risk of short-term mortality was lower among those who received thromboprophylaxis after discharge (hazard ratio [HR] 0.34, 95% CI 0.20–0.57).

Interpretation

Fewer than 1 in 5 elderly patients discharged home after a hip-or knee-replacement surgery received postdischarge thromboprophylaxis. Those prescribed these medications had a lower risk of short-term mortality. The benefits of and barriers to thromboprophylaxis therapy after discharge in this population requires further study.Venous thromboembolism is a leading cause of mortality among patients in hospital.1,2 Major orthopedic surgery (e.g., hip or knee replacement) is associated with a high risk for postoperative venous thromboembolism.1,3,4 Because the clinical diagnosis of venous thromboembolism is unreliable and its first manifestation may be a life-threatening pulmonary embolism,5 it is recommended that patients undergoing hip or knee replacement receive routine thromboprophylaxis with anticoagulant therapy after surgery unless they have contraindications to anticoagulant therapy.1,3,5,6Thromboprophylaxis is commonly administered for the entire hospital stay, which is usually between 4 and 14 days.7 Expert consensus guidelines recommend that patients undergoing hip or knee replacement receive thromboprophylaxis medications for at least 10 days after surgery.6 These guidelines also recommend extended thromboprophylaxis for up to 28–35 days after surgery for patients undergoing hip replacement.6 Although there is evidence that extended thromboprophylaxis after hospital discharge is effective for reducing the risk of venous thromboembolism among patients who undergo hip replacement,8 the benefit among patients who undergo knee replacement has not been established.6 Thromboprophylaxis after discharge is likely to most benefit patients at high risk for venous thromboembolism, such as those with cancer, heart failure or major respiratory disease.6–9 However, given that patients who undergo joint replacement are often elderly and have multiple comorbidities, the risks associated with extended thromboprophylaxis, particularly gastrointestinal bleeding and hemorrhagic strokes, may be substantial and may be relative contraindications for this therapy.10Among patients discharged home after hip-or knee-replacement surgery, we sought characterize the use of thromboprophylaxis after discharge and its consequences on risk of short-term mortality.  相似文献   

16.

Background

Treatment of osteoarthritis with oral NSAID therapy provides pain relief but carries a substantial risk of adverse effects. Topical NSAID therapy offers an alternative to oral treatment, with the potential for a reduced risk of side effects. The objective of this trial was to assess the safety and efficacy of a topical diclofenac solution in relieving the symptoms of primary osteoarthritis of the knee.

Methods

We identified 248 men and women from southern Ontario with primary osteoarthritis of the knee and at least moderate pain. The patients were randomly assigned to apply 1 of 3 solutions to their painful knee for 4 weeks: a topical diclofenac solution (1.5% wt/wt diclofenac sodium in a carrier containing dimethyl sulfoxide [DMSO]); a vehicle-control solution (the carrier containing DMSO but no diclofenac); and a placebo solution (a modified carrier with a token amount of DMSO for blinding purposes but no diclofenac). The primary efficacy end point was pain relief, measured by the Western Ontario and McMaster Universities (WOMAC) LK3.0 Osteoarthritis Index pain subscale. Secondary end points were improved physical function and reduced stiffness (measured by the WOMAC subscales), reduced pain on walking and patient global assessment (PGA). Safety was evaluated with clinical and laboratory assessments.

Results

In the intent-to-treat group the mean change (and 95% confidence interval [CI]) in pain score from baseline to final assessment was significantly greater for the patients who applied the topical diclofenac solution (–3.9 [– 4.8 to –2.9]) than for those who applied the vehicle-control solution (–2.5 [– 3.3 to –1.7]; p = 0.023) or the placebo solution (–2.5 [–3.3 to –1.7]; p = 0.016). For the secondary variables the topical diclofenac solution also revealed superiority to the vehicle-control and placebo solutions, leading to mean changes (and 95% CIs) of –11.6 (–14.7 to –8.4; p = 0.002 and 0.014, respectively) in physical function, –1.5 (–1.9 to –1.1; p = 0.015 and 0.002, respectively) in stiffness and –0.8 (–1.1 to –0.6; p = 0.003 and 0.015, respectively) in pain on walking. The PGA scores were significantly better for the patients who applied the topical diclofenac solution than for those who applied the other 2 solutions (p = 0.039 and 0.025, respectively). The topical diclofenac solution caused some skin irritation, mostly minor local skin dryness, in 30 (36%) of the 84 patients, but this led to discontinuation of treatment in only 5 (6%) of the cases. The incidence of gastrointestinal events did not differ between the treatment groups. No serious gastrointestinal or renal adverse events were reported or detected by means of laboratory testing.

Interpretation

This topical diclofenac solution can provide safe, site-specific treatment for osteoarthritic pain, with only minor local skin irritation and minimal systemic side effects.Osteoarthritis is a degenerative joint disease affecting articular cartilage and underlying bone, commonly of the knee.1 Current treatment includes the oral use of NSAIDs, either nonselective or cyclooxygenase-2 (COX-2)-selective. These agents carry a substantial risk of clinically significant adverse effects, particularly on the gastrointestinal2,3 and renal systems.4 Although the incidence of gastrointestinal complications has been reported to be lower with COX-2-selective NSAIDs than with nonselective NSAIDs,5,6,7 the former have been linked to adverse renal effects8 and an increased risk of cardiovascular complications.9The need for safer treatment of osteoarthritis has led to research into the topical use of NSAIDs.10,11,12 Recent reviews of the few published placebo-controlled studies suggest that topical NSAID therapy can relieve pain13,14,15 with few gastrointestinal side effects.16 Current practice guidelines advocate the use of topical therapy, including NSAIDs, in the management of osteoarthritis.17,18,19 A diclofenac solution containing the absorption enhancer dimethyl sulfoxide (DMSO) was developed for site-specific topical application. The objective of this study was to demonstrate that applying this solution to a painful knee with primary osteoarthritis could provide symptom relief with minimal systemic side effects.  相似文献   

17.

Background

The use of elective cholecystectomy has increased dramatically following the widespread adoption of laparoscopic cholecystectomy. We sought to determine whether this increase has resulted in a reduction in the incidence of severe complications of gallstone disease.

Methods

We examined longitudinal trends in the population-based rates of severe gallstone disease from 1988 to 2000, using a quasi-experimental longitudinal design to assess the effects of the large increase in elective cholecystectomy rates after 1991 among people aged 18 years and older residing in Ontario. We also measured the rate of hospital admission because of acute diverticulitis, to control for secular trends in the use of hospital care for acute abdominal diseases.

Results

The adjusted annual rate of elective cholecystectomy per 100 000 population increased from 201.3 (95% confidence interval [CI] 197.0–205.8) in 1988–1990 to 260.8 (95% CI 257.1– 264.5) in 1992–2000 (rate ratio [RR] 1.35, 95% CI 1.32– 1.38, p 0.001). An anomalously high number of elective cholecystectomies were performed in 1991. Overall, the annual rate of severe gallstone diseases (acute cholecystitis, acute biliary pancreatitis and acute cholangitis) declined by 10% (RR 0.90, 95% CI 0.88– 0.91) for 1992–2000 as compared with 1988–1991. This decline was entirely due to an 18% reduction in the rate of acute cholecystitis (RR 0.82, 95% CI 0.80–0.84).

Interpretation

The increase in the rate of elective cholecystectomy that occurred following the introduction of laparoscopic cholecystectomy in 1991 was associated with an overall reduction in the incidence of severe gallstone disease that was entirely attributable to a reduction in the incidence of acute cholecystitis.After the widespread introduction of laparoscopic cholecystectomy in 1991, the rate of cholecystectomy in North America increased by 30% to 60%,1,2,3 primarily because of higher rates of elective operations.1 Although cholecystectomy is not ordinarily indicated in people with asymptomatic gallstones,4,5 the decision to perform the procedure is highly discretionary.6 It is unclear whether the increased rate of elective cholecystectomy is due to overuse of surgery among people with asymptomatic or minimally symptomatic gallstones, or whether more patients with clinically important gallbladder disease are willing to undergo cholecystectomy with the availability of laparoscopic surgery.7,8Most cholecystectomies are done in people with uncomplicated biliary colic, the most common presentation of symptomatic gallstones.8 Severe complications of gallbladder disease, such as acute cholecystitis, acute biliary pancreatitis and acute cholangitis, are potentially life-threatening conditions that require hospital care. Greater use of elective cholecystectomy in people at risk of severe gallstone complications should result in a lower incidence of such complications. We sought to determine whether the increase in the rate of elective cholecystectomy was associated with a reduction in the incidence of severe complications of gallbladder disease.  相似文献   

18.

Background:

Inuit and First Nations populations have higher rates of stillbirth than non-Aboriginal populations in Canada do, but little is known about the timing and cause of stillbirth in Aboriginal populations. We compared gestational age– and cause-specific stillbirth rates in Inuit and First Nations populations with the rates in the non-Aboriginal population in Quebec.

Methods:

Data included singleton stillbirths and live births at 24 or more gestational weeks among Quebec residents from 1981 to 2009. We calculated odds ratios (ORs), rate differences and 95% confidence intervals (CIs) for the retrospective cohort of Inuit and First Nations births relative to non-Aboriginal births using fetuses at risk (i.e., ongoing pregnancies) as denominators and adjusting for maternal characteristics. The main outcomes were stillbirth by gestational age (24–27, 28–36, ≥ 37 wk) and cause of death.

Results:

Rates of stillbirth per 1000 births were greater among Inuit (6.8) and First Nations (5.7) than among non-Aboriginal (3.6) residents. Relative to the non-Aboriginal population, the risk of stillbirth was greater at term (≥ 37 wk) than before term for both Inuit (OR 3.1, 95% CI 1.9 to 4.8) and First Nations (OR 2.6, 95% CI 2.1 to 3.3) populations. Causes most strongly associated with stillbirth were poor fetal growth, placental disorders and congenital anomalies among the Inuit, and hypertension and diabetes among the First Nations residents.

Interpretation:

Stillbirth rates in Aboriginal populations were particularly high at term gestation. Poor fetal growth, placental disorders and congenital anomalies were important causes of stillbirth among the Inuit, and diabetic and hypertensive complications were important causes in the First Nations population. Prevention may require improvements in pregnancy and obstetric care.Attention has recently been drawn to the paucity of data on rates and causes of stillbirth, a pregnancy outcome that is largely ignored compared with later deaths.1 Aboriginal populations in Canada rank at the top of the list of disadvantaged groups with the highest rates of stillbirth in the Western world.1 First Nations and Inuit, 2 distinct Aboriginal populations in Canada, have stillbirth rates that are 2–3 times that among non-Aboriginal Canadians.1,2 Although these trends are alarming, little data exist to guide prevention efforts among Aboriginal Canadians. Not much is known about how stillbirth rates in Aboriginal populations vary by gestational age or cause of death, despite evidence that prevention requires knowledge on the timing and cause of stillbirth.3 Opportunities for preventing stillbirth are typically greater after 28 weeks of gestation,4 particularly at term, but the absence of gestational age– and cause-specific comparisons between Aboriginal and non-Aboriginal Canadians is a major impediment to reducing stillbirth rates. To gain a better understanding of the timing and causes of stillbirth in Inuit and First Nations populations, we estimated gestational age– and cause-specific fetal death rates in the Aboriginal and non-Aboriginal populations in the province of Quebec, where Inuit and First Nations people can be identified by parental information on birth registration forms.  相似文献   

19.

Background

Alterations in waveforms in the uterine artery are associated with the development of pre-eclampsia and intrauterine growth restriction. We investigated the predictive accuracy of all uterine artery Doppler indices for both conditions in the first and second trimesters.

Methods

We identified relevant studies through searches of MEDLINE, EMBASE, the Cochrane Library and Medion databases (all records to April 2006) and by checking bibliographies of identified studies and consulting with experts. Four of us independently selected studies, extracted data and assessed study validity. We performed a bivariable meta-analysis of sensitivity and specificity and calculated likelihood ratios.

Results

We identified 74 studies of pre-eclampsia (total 79 547 patients) and 61 studies of intrauterine growth restriction (total 41 131 patients). Uterine artery Doppler ultrasonography provided a more accurate prediction when performed in the second trimester than in the first-trimester. Most Doppler indices had poor predictive characteristics, but this varied with patient risk and outcome severity. An increased pulsatility index with notching was the best predictor of pre-eclampsia (positive likelihood ratio 21.0 among high-risk patients and 7.5 among low-risk patients). It was also the best predictor of overall (positive likelihood ratio 9.1) and severe (positive likelihood ratio 14.6) intrauterine growth restriction among low-risk patients.

Interpretation

Abnormal uterine artery waveforms are a better predictor of pre-eclampsia than of intrauterine growth restriction. A pulsatility index, alone or combined with notching, is the most predictive Doppler index. These indices should be used in clinical practice. Future research should also concentrate on combining uterine artery Doppler ultrasonography with other tests.Pre-eclampsia and intrauterine growth restriction remain important causes of maternal and perinatal morbidity and mortality.1–3 Maternal complications of pre-eclampsia include coagulopathy, renal and liver failure, and stroke.1 Adults who were affected by intrauterine growth restriction in utero are at increased risk for cardiovascular disease, hypertension and type 2 diabetes.4,5Pre-eclampsia and intrauterine growth restriction are characterized by abnormal placenta formation,6 which results in inadequate uteroplacental blood flow. This has led to the idea of using Doppler ultrasonography to assess the velocity of uterine artery blood flow as part of routine ultrasound screening.7 Low end-diastolic velocities and an early diastolic notch characterize the waveforms of uterine artery blood flow in women who are not pregnant or are in their first trimester. Persistence of a diastolic notch (beyond 24 weeks'' gestation) or abnormal flow velocity ratios have been associated with inadequate trophoblast invasion.8Accurate prediction of pre-eclampsia and intrauterine growth restriction is crucial to allow judicious allocation of resources for monitoring and preventive treatment to improve maternal and perinatal outcomes.9,10 However, studies investigating the predictive accuracy of uterine artery Doppler indices (Box 1) have revealed considerably varied results. Thus, it is questionable whether uterine artery Doppler ultrasonography should be used as a predictive test. We undertook this review to investigate the accuracy of all uterine artery Doppler indices in predicting pre-eclampsia and intrauterine growth restriction.Open in a separate windowBox 1  相似文献   

20.

Background

The risk association between low-density lipoprotein (LDL) cholesterol and cancer remains controversial and largely unexplored for people not receiving statin therapy.

Methods

We examined the risk association between LDL cholesterol and cancer among patients with type 2 diabetes mellitus who were free of cancer at enrolment and whose statin use was known. We considered a variety of nonlinear relationships in our analysis.

Results

During a median follow-up period of 4.90 years, cancer developed in 270 (4.4%) of 6107 patients. Among the 3800 patients who did not receive statin therapy, the risk association between LDL cholesterol and cancer was represented by a V-shaped curve. Compared with patients whose LDL cholesterol was at least 2.80 mmol/L but less than 3.80 mmol/L, the risk of cancer, death from any cause or the composite outcome of cancer or death was greater among those with an LDL cholesterol level of less than 2.80 mmol/L (hazard ratio for cancer 1.74, 95% confidence interval [CI] 1.20–2.52) and those with an LDL cholesterol level of 3.80 mmol/L or greater (hazard ratio for cancer 1.87, 95% CI 1.29–2.71). Using 3.8 mmol/L as a reference point, we found that the hazard ratio for cancer for every millimole per litre absolute change in LDL cholesterol was 1.54 (95% CI 1.19–1.99) among patients not using statins; the hazard ratio was reduced to 1.24 (1.01–1.53) for the entire sample (statin users and those not using statins). These associations persisted after adjustment for covariates and exclusion of patients with less than 2.5 years of follow-up.

Interpretation

Among patients with type 2 diabetes, the association between LDL cholesterol and cancer was V-shaped, whereby both low and high levels of LDL cholesterol were associated with elevated risk of cancer.Emerging data suggest an association between diabetes mellitus and an increased risk of cancer,1 including breast cancer in women;2 colorectal,3 pancreatic4,5 and liver6 cancer in both men and women; and prostate cancer in men.7 Several prospective analyses, including the US National Health and Nutrition Examination Survey,8 have demonstrated an inverse relation between serum total cholesterol and cancer incidence and mortality in the general population, although few studies have investigated this relation among patients with type 2 diabetes mellitus. In 2004, the US National Cholesterol Education Program Adult Treatment Panel III recommended treatment targets for low-density lipoprotein (LDL) cholesterol of less than 1.81 mmol/L (less than 70 mg/dL) for patients with very high risk of coronary artery disease and less than 2.59 mmol/L (less than 100 mg/dL) for patients with high risk of coronary artery disease;9 these targets were intended for both diabetic and nondiabetic patients.These recommendations remain controversial. Although one recent analysis of a large cohort of patients treated with statins showed a greater risk of cancer with achievement of low LDL cholesterol,10 a more recent study reported otherwise.11 Furthermore, the independent associations between LDL cholesterol level and cancer in both the general population and in patients with type 2 diabetes have not been explored. We conducted a hypothesis-generating study to explore the possible independent association between LDL cholesterol and cancer risk in Chinese patients with type 2 diabetes mellitus.  相似文献   

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