Accelerated care versus standard care among patients with hip fracture: the HIP ATTACK pilot trial

Background:

A hip fracture causes bleeding, pain and immobility, and initiates inflammatory, hypercoagulable, catabolic and stress states. Accelerated surgery may improve outcomes by reducing the duration of these states and immobility. We undertook a pilot trial to determine the feasibility of a trial comparing accelerated care (i.e., rapid medical clearance and surgery) and standard care among patients with a hip fracture.

Methods:

Patients aged 45 years or older who, during weekday, daytime working hours, received a diagnosis of a hip fracture requiring surgery were randomly assigned to receive accelerated or standard care. Our feasibility outcomes included the proportion of eligible patients randomly assigned, completeness of follow-up and timelines of accelerated surgery. The main clinical outcome, assessed by data collectors and adjudicators who were unaware of study group allocations, was a major perioperative complication (i.e., a composite of death, preoperative myocardial infarction, myocardial injury after noncardiac surgery, pulmonary embolism, pneumonia, stroke, and life-threatening or major bleeding) within 30 days of randomization.

Results:

Of patients eligible for inclusion, 80% consented and were randomly assigned to groups (30 to accelerated care and 30 to standard care) at 2 centres in Canada and 1 centre in India. All patients completed 30-day follow-up. The median time from diagnosis to surgery was 6.0 hours in the accelerated care group and 24.2 hours in the standard care group (p < 0.001). A major perioperative complication occurred in 9 (30%) of the patients in the accelerated care group and 14 (47%) of the patients in the standard care group (hazard ratio 0.60, 95% confidence interval 0.26–1.39).

Interpretation:

These results show the feasibility of a trial comparing accelerated and standard care among patients with hip fracture and support a definitive trial. Trial registration: ClinicalTrials.gov, no. {"type":"clinical-trial","attrs":{"text":"NCT01344343","term_id":"NCT01344343"}}NCT01344343.Annually in North America, 0.8% of women and 0.4% of men aged 65 years or older experience a hip fracture.¹ Patients who sustain a hip fracture face a high risk of serious complications (i.e., cardiovascular, venous thrombotic, infectious and hemorrhagic)^2,3 that can result in a prolonged hospital stay and death: 30-day mortality is 9% among men and 5% among women.¹ Among surviving patients who were community-dwelling before their fracture, 11% become bed-ridden and 16% are admitted to a long-term care facility.⁴A hip fracture results in pain, bleeding and immobility. These factors initiate inflammatory, hypercoagulable, catabolic and stress states that can precipitate medical complications.^5–11 Early surgery shortens the exposure to these harmful states and, therefore, may reduce morbidity and mortality. Furthermore, earlier surgery may shorten the period of immobility, which may improve functional outcomes and reduce costs.A meta-analysis of observational studies evaluating the timing of surgery for a hip fracture included 5 studies (involving 4208 patients and 721 deaths) that reported the adjusted risk of mortality.¹² Earlier surgery, irrespective of the cut-off for delay (24, 48 or 72 h), was associated with significantly lower mortality (adjusted relative risk 0.81, 95% confidence interval [CI] 0.68–0.96, p = 0.01). Although these data are encouraging, the apparent benefit may be a result of residual confounding (e.g., sicker patients may have had surgery delayed for medical optimization, which may not have been adequately adjusted for in the analyses). Conversely, the real potential of early surgery may be underestimated because the greatest impact may occur when a hip fracture is treated much more quickly than the timelines assessed in the observational studies (24, 48 or 72 h), similar to how treatment of an acute myocardial infarction or stroke within hours has the most dramatic impact.^13,14In many countries, including Canada, most patients with a hip fracture wait longer than 24 hours to undergo surgery. The 2 main reasons for delay are preoperative medical clearance and operating room access,^15–21 both of which are potentially modifiable. We undertook a pilot trial to determine the feasibility (as assessed by the proportion of eligible patients randomly assigned, completeness of follow-up and timeliness of accelerated surgery) of a large randomized controlled trial (RCT) comparing accelerated care and standard care among adults with a hip fracture.     

Determinants of Mortality and Loss to Follow-Up among Adults Enrolled in HIV Care Services in Rwanda

Background

Antiretroviral therapy (ART) improves morbidity and mortality in patients with HIV, however high rates of loss to follow-up (LTF) and mortality have been documented in HIV care and treatment programs.

Methods

We analyzed routinely-collected data on HIV-infected patients ≥15 years enrolled at 41 healthcare facilities in Rwanda from 2005 to 2010. LTF was defined as not attending clinic in the last 12 months for pre-ART patients and 6 months for ART patients. For the pre-ART period, sub-distribution hazards models were constructed to estimate LTF and death to account for competing risks. Kaplan-Meier (KM) and Cox proportional hazards models were used for patients on ART.

Results

31,033 ART-naïve adults were included, 64% were female and 75% were WHO stage I or II at enrollment. 17,569 (56%) patients initiated ART. Pre-ART competing risk estimates of LTF at 2 years was 11.2% (95%CI, 10.9–11.6%) and 2.9% for death (95%CI 2.7–3.1%). Among pre-ART patients, male gender was associated with higher LTF (adjusted sub-hazard ratio (aSHR) 1.3, 95%CI 1.1–1.5) and death (aSHR 1.7, 95%CI 1.4–2.1). Low CD4 count (CD4<100 vs. ≥350 aSHR 0.2, 95%CI 0.1–0.3) and higher WHO stage (WHO stage IV vs. stage I aSHR 0.4, 95%CI 0.2–0.6) were protective against pre-ART LTF. KM estimates for LTF and death in ART patients at 2 years were 4.4% (95%CI 4.4–4.5%) and 6.3% (95%CI 6.2–6.4%). In patients on ART, male gender was associated with LTF (adjusted hazard ratio (AHR) 1.4, 95%CI 1.2–1.7) and death (AHR1.3, 95%CI 1.2–1.5). Mortality was higher for ART patients ≥40 years and in those with lower CD4 count at ART initiation.

Conclusions

Low rates of LTF and death were founds among pre-ART and ART patients in Rwanda but greater efforts are needed to retain patients in care prior to ART initiation, particularly among those who are healthy at enrollment.     

Household Transmission of Influenza A(H1N1)pdm09 in the Pandemic and Post-Pandemic Seasons

Background

The transmission of influenza viruses occurs person to person and is facilitated by contacts within enclosed environments such as households. The aim of this study was to evaluate secondary attack rates and factors associated with household transmission of laboratory-confirmed influenza A(H1N1)pdm09 in the pandemic and post-pandemic seasons.

Methods

During the 2009–2010 and 2010–2011 influenza seasons, 76 sentinel physicians in Navarra, Spain, took nasopharyngeal and pharyngeal swabs from patients diagnosed with influenza-like illness. A trained nurse telephoned households of those patients who were laboratory-confirmed for influenza A(H1N1)pdm09 to ask about the symptoms, risk factors and vaccination status of each household member.

Results

In the 405 households with a patient laboratory-confirmed for influenza A(H1N1)pdm09, 977 susceptible contacts were identified; 16% of them (95% CI 14–19%) presented influenza-like illness and were considered as secondary cases. The secondary attack rate was 14% in 2009–2010 and 19% in the 2010–2011 season (p = 0.049), an increase that mainly affected persons with major chronic conditions. In the multivariate logistic regression analysis, the risk of being a secondary case was higher in the 2010–2011 season than in the 2009–2010 season (adjusted odds ratio: 1.72; 95% CI 1.17–2.54), and in children under 5 years, with a decreasing risk in older contacts. Influenza vaccination was associated with lesser incidence of influenza-like illness near to statistical significance (adjusted odds ratio: 0.29; 95% CI 0.08–1.03).

Conclusion

The secondary attack rate in households was higher in the second season than in the first pandemic season. Children had a greater risk of infection. Preventive measures should be maintained in the second pandemic season, especially in high-risk persons.     

Epidemiology and Outcome of Severe Sepsis and Septic Shock in Intensive Care Units in Mainland China

Introduction

Information about sepsis in mainland China remains scarce and incomplete. The purpose of this study was to describe the epidemiology and outcome of severe sepsis and septic shock in mixed ICU in mainland China, as well as the independent predictors of mortality.

Methods

We performed a 2-month prospective, observational cohort study in 22 closed multi-disciplinary intensive care units (ICUs). All admissions into those ICUs during the study period were screened and patients with severe sepsis or septic shock were included.

Results

A total of 484 patients, 37.3 per 100 ICU admissions were diagnosed with severe sepsis (n = 365) or septic shock (n = 119) according to clinical criteria and included into this study. The most frequent sites of infection were the lung and abdomen. The overall ICU and hospital mortality rates were 28.7% (n = 139) and 33.5% (n = 162), respectively. In multivariate analyses, APACHE II score (odds ratio[OR], 1.068; 95% confidential interval[CI], 1.027–1.109), presence of ARDS (OR, 2.676; 95%CI, 1.691–4.235), bloodstream infection (OR, 2.520; 95%CI, 1.142–5.564) and comorbidity of cancer (OR, 2.246; 95%CI, 1.141–4.420) were significantly associated with mortality.

Conclusions

Our results indicated that severe sepsis and septic shock were common complications in ICU patients and with high mortality in China, and can be of help to know more about severe sepsis and septic shock in China and to improve characterization and risk stratification in these patients.     

The effect of aluminium concentration on root hairs in white clover (Trifolium repens L.)

The effect of aluminium (Al) on root hair length and number is quantified using solution culture techniques with genotypes from white clover cultivar Tamar, that had previously been selected for long and short root hairs. The population differences were maintained in control (0 Al) treatments, with the long-haired population having hairs three times longer than the short-haired population. At an activity of 2.2 µM Al³⁺, root hair length decreased in both populations, the magnitude of the decrease being greater for the long-haired population. Root hair numbers decreased in a similar manner for both populations. At an activity of 4.4 µM Al³⁺ or higher, root hairs virtually disappeared and root growth was very stunted. The effect of Al on root hair development has not been previously quantified, however other workers have observed reduced root hair development in other species at activities of Al greater than 2.5 µM Al³⁺.     

Cell Elongation and Revolving Movement in Phaseolus vulgaris L. Twining Shoots

In Phaseolus vulgaris L., the shoot displays a revolving movementthat occurs rhythmically in a highly regular manner. Previousdata led to think that revolving movement is driven by turgorand volume changes in the epidermal cells of the bending zone.To document this hypothesis, the time course of in situ celllength variations in the bending zone was measured during themovement of the shoot and related to the phase of the revolvingmovement. Each ten minutes, a photograph of cells was takenand the revolving movement was simultaneously recorded usingtime-lapse microphotography and video-monitoring. In the movingpart of the shoot, epidermal cells displayed partly reversiblelength variations during their growth. Data were processed byFourier analysis to determine whether or not a periodicity exists.Rhythm in cell length variations was evidenced only when initialcell lengths were ranged between 60 and 120 µM. In thiscase, the period corresponds to that of the revolving movement. Thus, revolving movement is related to partly reversible lengthvariations in the cells of the bending zone. These results agreewith the hypothesis of an involvement of turgor mediated volumechanges in the revolving movement (Received September 16, 1997; Accepted June 18, 1998)     

Essential role for IL-10 in resistance to lipopolysaccharide-induced preterm labor in mice

IL-10 is highly expressed in the uterus and placenta and is implicated in controlling inflammation-induced pathologies of pregnancy. To investigate the role of IL-10 in regulating preterm labor, the response of IL-10 null mutant mice to low-dose LPS in late gestation was evaluated. When IL-10 null mutant C57BL/6 (IL-10(-/-)) and control (IL-10(+/+)) mice were administered LPS on day 17 of pregnancy, the dose of LPS required to elicit 50% preterm fetal loss was 10-fold lower in IL-10(-/-) mice than in IL-10(+/+) mice. Surviving fetuses in IL-10(-/-) mice exhibited fetal growth restriction at lower doses of LPS than IL-10(+/+) mice. Marked elevation of LPS-induced immunoactive TNF-alpha and IL-6 was evident in the serum, uterus, and placenta of IL-10(-/-) mice, and TNF-alpha and IL-6 mRNA expression was elevated in the uterus and placenta, but not the fetus. Serum IL-1alpha, IFN-gamma, and IL-12p40 were increased and soluble TNFRII was diminished in the absence of IL-10, with these changes also reflected in the gestational tissues. Administration of rIL-10 to IL-10(-/-) mice attenuated proinflammatory cytokine synthesis and alleviated their increased susceptibility to preterm loss. Exogenous IL-10 also protected IL-10(+/+) mice from fetal loss. These data show that IL-10 modulates resistance to inflammatory stimuli by down-regulating proinflammatory cytokines in the uterus and placenta. Abundance of endogenous IL-10 in gestational tissues is therefore identified as a critical determinant of resistance to preterm labor, and IL-10 may provide a useful therapeutic agent in this common condition.     

The MET3 promoter: a new tool for Candida albicans molecular genetics

A central technique used to investigate the role of a Candida albicans gene is to study the phenotype of a cell in which both copies of the gene have been deleted. To date, such investigations can only be undertaken if the gene is not essential. We describe the use of the Candida albicans MET3 promoter to express conditionally an essential gene, so that the consequences of depletion of the gene product may be investigated. The effects of environmental conditions on its expression were investigated, using GFP as a reporter gene. The promoter showed an approximately 85-fold range of expression, according to the presence or absence of either methionine or cysteine in concentrations in excess of 1 mM. In the presence of either amino acid, expression was reduced to levels that were close to background. We used URA3 as a model to demonstrate that the MET3 promoter could control the expression of an essential gene, provided that a mixture of both methionine and cysteine was used to repress the promoter. We describe an expression vector that may be used to express any gene under the control of the MET3 promoter and a vector that may be used to disrupt a gene and simultaneously place an intact copy under the control of the MET3 promoter. During the course of these experiments, we discovered that directed integration into the RP10 locus gives a high frequency of transformation, providing a means to solve a long-standing problem in this field.