Graduated compression stockings for prevention of deep vein thrombosis.

BACKGROUND: Hospitalised patients are at increased risk of developing deep vein thrombosis (DVT) in the lower limb and pelvic veins, on a background of prolonged immobilisation associated with their medical or surgical illness. Patients with DVT are at increased risk of developing a pulmonary embolism (PE). The use of graduated compression stockings (GCS) in hospitalised patients has been proposed to decrease the risk of DVT. This is an update of a Cochrane Review first published in 2000, and last updated in 2014. OBJECTIVES: To evaluate the effectiveness and safety of graduated compression stockings in preventing deep vein thrombosis in various groups of hospitalised patients. SEARCH METHODS: For this review the Cochrane Vascular Information Specialist searched the Cochrane Vascular Specialised Register, the Cochrane Central Register of Controlled Trials (CENTRAL), and trials registries on 21 March 2017; and the Cochrane Vascular Specialised Register, CENTRAL, MEDLINE Ovid, Embase Ovid, CINAHL Ebsco, AMED Ovid , and trials registries on 12 June 2018. SELECTION CRITERIA: Randomised controlled trials (RCTs) involving GCS alone, or GCS used on a background of any other DVT prophylactic method. We combined results from both of these groups of trials. DATA COLLECTION AND ANALYSIS: Two review authors (AS, MD) assessed potentially eligible trials for inclusion. One review author (AS) extracted the data, which a second review author (MD) cross-checked and authenticated. Two review authors (AS, MD) assessed the methodological quality of trials with the Cochrane 'Risk of bias' tool. Any disagreements were resolved by discussion with the senior review author (TL). For dichotomous outcomes, we calculated the Peto odds ratio and corresponding 95% confidence interval. We pooled data using a fixed-effect model. We used the GRADE system to evaluate the overall quality of the evidence supporting the outcomes assessed in this review. MAIN RESULTS: We included 20 RCTs involving a total of 1681 individual participants and 1172 individual legs (2853 analytic units). Of these 20 trials, 10 included patients undergoing general surgery; six included patients undergoing orthopaedic surgery; three individual trials included patients undergoing neurosurgery, cardiac surgery, and gynaecological surgery, respectively; and only one trial included medical patients. Graduated compression stockings were applied on the day before surgery or on the day of surgery and were worn up until discharge or until the participants were fully mobile. In the majority of the included studies DVT was identified by the radioactive I125 uptake test. Duration of follow-up ranged from seven to 14 days. The included studies were at an overall low risk of bias.We were able to pool the data from 20 studies reporting the incidence of DVT. In the GCS group, 134 of 1445 units developed DVT (9%) in comparison to the control group (without GCS), in which 290 of 1408 units developed DVT (21%). The Peto odds ratio (OR) was 0.35 (95% confidence interval (CI) 0.28 to 0.43; 20 studies; 2853 units; high-quality evidence), showing an overall effect favouring treatment with GCS (P < 0.001).Based on results from eight included studies, the incidence of proximal DVT was 7 of 517 (1%) units in the GCS group and 28 of 518 (5%) units in the control group. The Peto OR was 0.26 (95% CI 0.13 to 0.53; 8 studies; 1035 units; moderate-quality evidence) with an overall effect favouring treatment with GCS (P < 0.001). Combining results from five studies, all based on surgical patients, the incidence of PE was 5 of 283 (2%) participants in the GCS group and 14 of 286 (5%) in the control group. The Peto OR was 0.38 (95% CI 0.15 to 0.96; 5 studies; 569 participants; low-quality evidence) with an overall effect favouring treatment with GCS (P = 0.04). We downgraded the quality of the evidence for proximal DVT and PE due to low event rate (imprecision) and lack of routine screening for PE (inconsistency).We carried out subgroup analysis by speciality (surgical or medical patients). Combining results from 19 trials focusing on surgical patients, 134 of 1365 (9.8%) units developed DVT in the GCS group compared to 282 of 1328 (21.2%) units in the control group. The Peto OR was 0.35 (95% CI 0.28 to 0.44; high-quality evidence), with an overall effect favouring treatment with GCS (P < 0.001). Based on results from seven included studies, the incidence of proximal DVT was 7 of 437 units (1.6%) in the GCS group and 28 of 438 (6.4%) in the control group. The Peto OR was 0.26 (95% CI 0.13 to 0.53; 875 units; moderate-quality evidence) with an overall effect favouring treatment with GCS (P < 0.001). We downgraded the evidence for proximal DVT due to low event rate (imprecision).Based on the results from one trial focusing on medical patients admitted following acute myocardial infarction, 0 of 80 (0%) legs developed DVT in the GCS group and 8 of 80 (10%) legs developed DVT in the control group. The Peto OR was 0.12 (95% CI 0.03 to 0.51; low-quality evidence) with an overall effect favouring treatment with GCS (P = 0.004). None of the medical patients in either group developed a proximal DVT, and the incidence of PE was not reported.Limited data were available to accurately assess the incidence of adverse effects and complications with the use of GCS as these were not routinely quantitatively reported in the included studies. AUTHORS' CONCLUSIONS: There is high-quality evidence that GCS are effective in reducing the risk of DVT in hospitalised patients who have undergone general and orthopaedic surgery, with or without other methods of background thromboprophylaxis, where clinically appropriate. There is moderate-quality evidence that GCS probably reduce the risk of proximal DVT, and low-quality evidence that GCS may reduce the risk of PE. However, there remains a paucity of evidence to assess the effectiveness of GCS in diminishing the risk of DVT in medical patients.

Factors that influence nurses' assessment of patient acuity and response to acute deterioration.

BACKGROUND: nurses play a crucial role in the early recognition and management of the deteriorating patient. They are responsible for the care they provide to their patients, part of which is the monitoring of vital signs (blood pressure, pulse, respiratory rate and temperature), which are fundamental in the surveillance of deterioration. The aim of this study was to discover what factors influence how nurses assess patient acuity and their response to acute deterioration. METHODS: a generic qualitative approach was used. Some 10 nurses working in an acute NHS trust were interviewed using a semi- structured approach, with equal representation from medical and surgical inpatient wards. RESULTS: the main themes identified were collegial relationships, intuition, and interpretation of the MEWS system (Modified Early Warning Score). Collegial relationships with the medical staff had some influence on the nurses' assessment, as they tended to accept the medical peers' assessment as absolute, rather than their own assessment. It was also highlighted that nurses relied on the numerical escalation of the MEWS system to identify the deteriorating patient, instead of their own clinical judgement of the situation. Interestingly, the nurses found no difficulty in escalating the patient's care to medical staff when the patient presented with a high MEWS score. The difficulty arose when the MEWS score was low-the participants found it challenging to authenticate their findings. CONCLUSION: this study has identified several confounding factors that influence the ways in which nurses assess patient acuity and their response to acute deterioration. The information provides a crucial step forward in identifying strategies to develop further training.

Graduated compression stockings for prevention of deep vein thrombosis.

BACKGROUND: One of the settings where deep vein thrombosis (DVT) in the lower limb and pelvic veins occurs is in hospital with prolonged immobilisation of patients for various surgical and medical illnesses. Using graduated compression stockings (GCS) in these patients has been proposed to decrease the risk of DVT. This is an update of a Cochrane review first published in 2000 and updated in 2010. OBJECTIVES: To evaluate the effectiveness and safety of graduated compression stockings in preventing DVT in various groups of hospitalised patients. SEARCH METHODS: For this update the Cochrane Peripheral Vascular Diseases Group Trials Search Co-ordinator searched the Specialised Register (last searched March 2014) and CENTRAL (2014, Issue 2). SELECTION CRITERIA: Randomised controlled trials (RCTs) involving GCS alone; or GCS used on a background of any other DVT prophylactic method. Results from both these groups of trials were combined in this update. DATA COLLECTION AND ANALYSIS: For this update one review author (AS) extracted the data. These were cross-checked and authenticated by a second author (MJD). Two review authors (AS and MJD) assessed the quality of trials. Disagreements were resolved by discussion. MAIN RESULTS: Nineteen RCTs were identified involving 1681 individual patients and 1064 individual legs (2745 analytic units). Of these 19 trials, nine included patients undergoing general surgery, six included patients undergoing orthopaedic surgery, and only one trial included medical patients. Graduated compression stockings were applied on the day before surgery or on the day of surgery and were worn up until discharge or until the patients were fully mobile. In the majority of the included studies DVT was identified by the radioactive I(125) uptake test. Overall, included studies were of good quality.In the treatment group (GCS) of 1391 units 126 developed DVT (9%) in comparison to the control group (without GCS) of 1354 units where 282 (21%) developed DVT. The Peto odds ratio (OR) was 0.33 (95% confidence interval (CI) 0.26 to 0.41) with an overall effect favouring treatment with GCS (P < 0.00001).Based on results from eight included studies, the incidence of proximal DVT was 7 of 517 (1%) units in the treatment group and 28 of 518 (5%) units in the control group. The Peto OR was 0.26 (95% CI 0.13 to 0.53) with an overall effect favouring treatment with GCS (P = 0.0002). Based on results from five included studies, the incidence of PE was 5 of 283 (2%) participants in the treatment group and 14 of 286 (5%) in the control group. The Peto OR was 0.38 (95% CI 0.15 to 0.96) with an overall effect favouring treatment with GCS (P = 0.04). Limited data were available to accurately assess the incidence of adverse effects and complications with the use of GCS. AUTHORS' CONCLUSIONS: GCS are effective in diminishing the risk of DVT in hospitalised patients, with strong evidence favouring their use in general and orthopaedic surgery. However, evidence for their effectiveness in medical patients is limited to one trial.

Perceptions of the advanced nurse practitioner role in a hospital setting.

AIM: To explore perceptions of junior doctors, nurses and advanced nurse practitioners (ANP) in relation to the role of the ANP. METHOD: A qualitative cross-sectional design was used, embedded in an interpretative philosophy. A non-probability sample of six junior doctors, six ward nurses and six ANPs took part in focus groups and individual semi-structured interviews. A mixture of phenomenological and grounded theory approaches were used to collect the data. FINDINGS: Four major themes were identified - diverse definitions of the ANP role between medical and surgical wards in the hospital at day compared to hospital at night work; role vagueness and ambiguity; communication and education needs; and constraints and barriers. The study found varied perceptions and understanding of the role of the ANP within the hospital at day. Conversely, the hospital at night concept seemed correctly perceived - the role appeared well-established, organised and orchestrated the appropriate responses as required in both medicine and surgery. During the hospital at day, nurses on medical wards were more inclined to use the medical staff as their first responders. The absence of the bleep filtering system in medicine during the day was identified as one of the main barriers. A definitive understanding of the role during the hospital at day has been recognised as the second main barrier. A constraint well known to the ANP team was the inability to provide a bleep filter system in medicine during the day. CONCLUSION: The study finds the need for improved education, clinical support and system management during the hospital at day, with more of an emphasis within medical wards.

Elastic compression stockings for prevention of deep vein thrombosis.

BACKGROUND: One of the settings where deep vein thrombosis (DVT) in the lower limb and pelvic veins occurs is in hospital with prolonged immobilisation of patients for various surgical and medical illnesses. Using graduated compression stockings (GCS) in these patients has been proposed to decrease the risk of DVT. This is an update of a Cochrane review first published in 2000 and updated in 2003. OBJECTIVES: To determine the magnitude of effectiveness of GCS in preventing DVT in various groups of hospitalised patients. SEARCH STRATEGY: For this update the Cochrane Peripheral Vascular Diseases Group searched their Specialised Register and the Cochrane Central Register of Controlled Trials (CENTRAL) (The Cochrane Library 2009, Issue 4) for randomised controlled trials of elastic or graduated compression stockings for prevention of DVT. SELECTION CRITERIA: Randomised controlled trials (RCTs) involving GCS alone; or GCS used on a background of any other DVT prophylactic method. DATA COLLECTION AND ANALYSIS: One author extracted the data, assessed the quality of trials and analysed the results; which were cross-checked and authenticated by a second author. MAIN RESULTS: Eighteen RCTs were identified. GCS were applied on the day before surgery or on the day of surgery and were worn up until discharge or until the patients were fully mobile. In the majority of the included studies DVT was identified by the radioactive I(125) uptake test.For GCS alone, eight RCTs were identified involving 1279 analytic units (887 patients). In the treatment group (GCS), of 662 units, 86 developed DVT (13%) in comparison to the control group (without GCS) of 617 units where 161 (26%) developed DVT. The Peto's odds ratio (OR) was 0.35 (95% confidence interval (CI) 0.26 to 0.47) with an overall effect favouring treatment with GCS (P < 0.00001). For GCS on a background of another prophylactic method, 10 RCTs were identified involving 1248 analytic units (576 patients). In the treatment group (GCS plus another method), of 621 units, 26 (4%) developed DVT, in the control group (the other method alone), of 627 units, 99 (16%) developed DVT (OR 0.25, 95% CI 0.17 to 0.36). The overall effect also favoured treatment with GCS on a background of another DVT prophylactic method (P < 0.00001). AUTHORS' CONCLUSIONS: GCS are effective in diminishing the risk of DVT in hospitalised patients. Data examination also suggests that GCS on a background of another method of prophylaxis is more effective than GCS on its own.

Pharmacologic optimization of protease inhibitors and nonnucleoside reverse transcriptase inhibitors (POPIN)--a randomized controlled trial of therapeutic drug monitoring and adherence support.

We evaluated the feasibility and effectiveness of therapeutic drug monitoring (TDM) and adherence support (collectively, AT) vs standard of care (SOC) in patients receiving HIV protease inhibitors (PIs) and nonnucleoside reverse transcriptase inhibitors (NNRTIs) within a nurse-led clinic. Primary end points were failure to achieve viral load of <50 copies/mL at 24 weeks, viral rebound, or development of treatment limiting toxicity. One hundred twenty-two patients (AT 63 and SOC 59) were followed-up every 12 weeks, for a median of 72 weeks. No difference was observed between arms in risk of reaching a study end point or between groups of patients with abnormal vs "therapeutic" drug concentrations. Interindividual variabilities (coefficient of variation) were the following: efavirenz, 77.5%; nevirapine, 74.5%; lopinavir, 73.4%; nelfinavir, 83.7%; indinavir, 80.8%; saquinavir, 112.4%. Intraindividual variabilities (median coefficient of variation) were the following: NNRTIs, approximately 25%; PIs, 48.4%. Despite persistently abnormal results in 26 of patients in the AT arm (38%), dosage adjustment was only undertaken in 9 patients (35%).A significant proportion of patients had drug concentrations outside the therapeutic range. The Pharmacologic Optimization of PIs and NNRTIs (POPIN) study confirms that TDM trials are complex to interpret and statistically underpowered, with effectiveness better assessed through the clinical utility of a TDM result, whether normal or abnormal. Although TDM of PIs and NNRTIs may be useful in selected patients, routine and unselected use is not supported by current evidence.

Intracellular and plasma pharmacokinetics of nevirapine in human immunodeficiency virus-infected individuals.

BACKGROUND AND OBJECTIVE: Plasma concentrations of nevirapine have been linked to human immunodeficiency virus (HIV) treatment outcome. However, because the site of action of nevirapine is within HIV-infected cells, intracellular concentrations may better relate to antiviral exposure. Investigation of factors that alter the intracellular pharmacokinetics of nevirapine may also aid in our understanding of therapeutic failure. Our objective was to determine intracellular (or cell-associated) nevirapine concentrations over the full dosing interval and to relate protein binding and P-glycoprotein (P-gp) expression to intracellular exposure. METHODS: Plasma and peripheral blood mononuclear cells were isolated from blood samples taken from 10 HIV-infected patients at 0, 2, 4, 8, and 12 hours after dosing. Intracellular and plasma (total and unbound) concentrations were determined by liquid chromatography-tandem mass spectrometry, and the ratios of intracellular to total plasma exposure (area under the concentration-time curves) were calculated. P-gp expression was measured by flow cytometry. RESULTS: The median intracellular accumulation ratio was 0.005 (range, 0.001-0.054) and remained unchanged over the dosing interval. There was an association between higher plasma concentrations and lower cellular concentrations of nevirapine (total r(2) = 0.62, P = .007). There was no relationship between percent unbound nevirapine and intracellular nevirapine. There was a correlation between higher plasma nevirapine exposure and higher P-gp expression (r(2) = 0.77, P = .03), whereas intracellular nevirapine exposure decreased with higher P-gp expression (r(2) = 0.62, P = .01). CONCLUSIONS: The intracellular accumulation of nevirapine was low, did not change over the dosing interval, and was not related to protein binding. In this small study, cells with higher P-gp expression had lower cellular concentrations of nevirapine. Further studies are required to explore the influx and efflux transporter profile of this drug.

The prevalence of urinary tract infections and sexually transmitted disease in women with symptoms of a simple urinary tract infection stratified by low colony count criteria.

OBJECTIVES: Urinary tract infections (UTIs) and early pelvic infections due to sexually transmitted disease (STD) may cause similar symptoms. Therefore, a simple history and urine dip to establish a diagnosis of UTI may result in overtreatment of UTIs and undertreatment of STDs. The objective of this study was to determine the proportion of women with symptoms suggestive of a UTI who are urine culture positive versus urine culture negative, the prevalence of STDs between groups, and if elements of the history or examination may predict those requiring STD screening. METHODS: This was a prospective cohort study in an urban emergency department. Women 18-55 years of age with urinary frequency, urgency, dysuria, and no new vaginal discharge or change in discharge were enrolled. The following were performed: detailed history; bladder catheterization for urinalysis, urine dip, and urine culture; pelvic examination and cervical samples for gonorrhea and Chlamydia trachomatis DNA ligase; and wet mount examinations. Main outcome measurements were the percentage of women who were urine culture positive (using low count criteria of 10(2) colony-forming units [CFU]/mL), the proportion of STDs between urine culture groups, and univariate analysis and logistic regression of historical and examination elements. RESULTS: Ninety-two patients were enrolled; the mean age was 26 years (range, 18-51 years). All had samples for DNA ligase (one quantity not sufficient) and urinalysis or urine dip, while 75 of 92 had urine cultures performed. A total of 57.3% (43/75) were urine culture positive at 10(2) CFU/mL, while the STD rate for those with urine cultures was 17.3% (13/75). There was no statistically significant difference in the number of STDs between urine culture positive and urine culture negative groups. The only variable on logistic regression predictive of an STD (based on all 91 patients) was more than one sex partner in the past year (p = 0.013). No other element of the history or pelvic examination helped differentiate those who tested positive for an STD. CONCLUSIONS: A total of 17.3% of women with symptoms of a UTI in this study had an STD, while only 57.3% were urine culture positive by catheterization using low count criteria. The proportion of STDs between those with and without a UTI was not significantly different.

BLNK: molecular scaffolding through 'cis'-mediated organization of signaling proteins.

Assembly of intracellular macromolecular complexes is thought to provide an important mechanism to coordinate the generation of second messengers upon receptor activation. We have previously identified a B cell linker protein, termed BLNK, which serves such a scaffolding function in B cells. We demonstrate here that phosphorylation of five tyrosine residues within human BLNK nucleates distinct signaling effectors following B cell antigen receptor activation. The phosphorylation of multiple tyrosine residues not only amplifies PLCgamma-mediated signaling but also supports 'cis'-mediated interaction between distinct signaling effectors within a large molecular complex. These data demonstrate the importance of coordinate phosphorylation of molecular scaffolds, and provide insights into how assembly of macromolecular complexes is required for normal receptor function.