Interventions for preventing venous thromboembolism in adults undergoing knee arthroscopy.

BACKGROUND: Knee arthroscopy (KA) is a routine orthopedic procedure recommended to repair cruciate ligaments and meniscus injuries and, in suitable cases, to assist the diagnosis of persistent knee pain. There is a small risk of thromboembolic events associated with KA. This systematic review aims to assess if pharmacological or non-pharmacological interventions may reduce this risk. This is an update of an earlier Cochrane Review. OBJECTIVES: To evaluate the efficacy and safety of interventions - whether mechanical, pharmacological, or a combination of both - for thromboprophylaxis in adults undergoing KA. SEARCH METHODS: We used standard, extensive Cochrane search methods. The latest search date was 1 June 2021. SELECTION CRITERIA: We included randomized controlled trials (RCTs) and controlled clinical trials (CCTs), blinded or unblinded, of all types of interventions used to prevent deep vein thrombosis (DVT) in men and women aged 18 years and older undergoing KA. DATA COLLECTION AND ANALYSIS: We used standard Cochrane methods. Our primary outcomes were pulmonary embolism (PE), symptomatic DVT, asymptomatic DVT, and all-cause mortality. Our secondary outcomes were adverse effects, major bleeding, and minor bleeding. We used GRADE criteria to assess the certainty of the evidence. MAIN RESULTS: We did not identify any new studies for this update. This review includes eight studies involving 3818 adults with no history of thromboembolic disease. Five studies compared daily subcutaneous low-molecular-weight heparin (LMWH) versus no prophylaxis; one study compared oral rivaroxaban 10 mg versus placebo; one study compared daily subcutaneous LMWH versus graduated compression stockings; and one study compared aspirin versus no prophylaxis. The incidence of PE in all studies combined was low, with seven cases in 3818 participants. There were no deaths in any of the intervention or control groups. Low-molecular-weight heparin versus no prophylaxis When compared with no prophylaxis, LMWH probably results in little to no difference in the incidence of PE in people undergoing KA (risk ratio [RR] 1.81, 95% confidence interval [CI] 0.49 to 6.65; 3 studies, 1820 participants; moderate-certainty evidence). LMWH may make little or no difference to the incidence of symptomatic DVT (RR 0.61, 95% CI 0.18 to 2.03; 4 studies, 1848 participants; low-certainty evidence). It is uncertain whether LMWH reduces the risk of asymptomatic DVT (RR 0.14, 95% CI 0.03 to 0.61; 2 studies, 369 participants; very low-certainty evidence). LMWH probably makes little or no difference to the risk of all adverse effects combined (RR 1.85, 95% CI 0.95 to 3.59; 5 studies, 1978 participants; moderate-certainty evidence), major bleeding (RR 0.98, 95% CI 0.06 to 15.72; 1451 participants; moderate-certainty evidence), or minor bleeding (RR 1.79, 95% CI 0.84 to 3.84; 5 studies, 1978 participants; moderate-certainty evidence). Rivaroxaban versus placebo One study with 234 participants compared oral rivaroxaban 10 mg versus placebo. There were no cases of PE reported. Rivaroxaban probably led to little or no difference in symptomatic DVT (RR 0.16, 95% CI 0.02 to 1.29; moderate-certainty evidence). It is uncertain whether rivaroxaban reduces the risk of asymptomatic DVT because the certainty of the evidence is very low (RR 0.95, 95% CI 0.06 to 15.01). The study only reported bleeding adverse effects. No major bleeds occurred in either group, and rivaroxaban probably made little or no difference to minor bleeding (RR 0.63, 95% CI 0.18 to 2.19; moderate-certainty evidence). Aspirin versus no prophylaxis One study compared aspirin with no prophylaxis. There were no PE, DVT or asymptomatic events detected in either group. The study authors reported adverse effects including pain and swelling, but without clarifying which groups these occurred in. There were no bleeds reported. Low-molecular-weight heparin versus compression stockings One study with 1317 participants compared LMWH versus compression stockings. LMWH may lead to little or no difference in the risk of PE compared to compression stockings (RR 1.00, 95% CI 0.14 to 7.05; low-certainty evidence), but it may reduce the risk of symptomatic DVT (RR 0.17, 95% CI 0.04 to 0.75; low-certainty evidence). It is uncertain whether LMWH has any effect on asymptomatic DVT (RR 0.47, 95% CI 0.21 to 1.09; very low-certainty evidence). The results suggest LMWH probably leads to little or no difference in major bleeding (RR 3.01, 95% CI 0.61 to 14.88; moderate-certainty evidence), or minor bleeding (RR 1.16, 95% CI 0.64 to 2.08; moderate-certainty evidence). We downgraded the certainty of the evidence for imprecision due to overall small event numbers, for risk of bias due to concerns about lack of blinding, and for indirectness due to uncertainty about the direct clinical relevance of asymptomatic DVT detection. AUTHORS' CONCLUSIONS: There is a small risk that healthy adults undergoing KA will develop venous thromboembolism (PE or DVT). We found moderate- to low-certainty evidence of little or no benefit from LMWH, or rivaroxaban in reducing this small risk of PE or symptomatic DVT. The studies provided very low-certainty evidence that LMWH may reduce the risk of asymptomatic DVT compared to no prophylaxis, but it is uncertain how this directly relates to incidence of DVT or PE in healthy people undergoing KA. There is probably little or no difference in adverse effects (including major and minor bleeding), but data relating to these outcomes were limited by low numbers of events in the studies reporting these outcomes.

A stress-related transcription factor belonging to the YL-1 family is differently regulated in durum wheat cultivars differing in drought sensitivity.

The Mediterranean area is characterised by unfavorable environmental conditions such as heat stress and drought responsible for yield loss of crops like durum wheat, widely cultivated in this area. The response of plants to stressing environments is mediated by activation of a complex gene network, strictly related to the genetic background. Among the genes induced by drought, those coding for proteins acting as key regulators of signal transduction are of great interest. Characterization of these genes is a crucial point to understand their potential roles in plant stress response, also in view of their possible use in molecular breeding. In this work we have characterised a Triticum durum gene, named TdDRG1, in two commercial cultivars, Primadur and Svevo, differing for drought stress resistance. TdDRG1 codes for a putative transcription factor belonging to the VPS72/YL-1 family, highly conserved in plants and animals. The expression analysis indicates that this gene is expressed at higher level in roots of the resistant cultivar Svevo, than in the susceptible Primadur. The gene structure was determined in both cultivars and the regulatory activity of 5' upstream regions was analyzed by transient expression analysis using tobacco protoplasts. Dissimilar expression level of TdDRG1 in the two cultivars can be explained by the differences observed in gene structure. In particular, differences in 5' upstream regions could account for contrasting ability to cope with drought of the two cultivars. The data obtained in this study provide indications for further insight into the molecular basis of differences in drought stress response.

Characteristics and determinants of high volume dispensing in long-term oral nutritional supplement users in primary care: a secondary analysis.

BACKGROUND: Oral nutritional supplements (ONS) are recommended for patients who are malnourished or at risk of malnutrition. Appropriate ONS prescribing requires regular monitoring to assess its continued requirement. Previous research identified long-term ONS prescriptions (>6 months) without review, with 70% of these influenced by social factors. AIM: To investigate the characteristics of long-term ONS users in Ireland and the determinants of larger volumes of ONS dispensing. DESIGN & SETTING: Secondary analysis of anonymous dispensed pharmacy claims data of patients dispensed standard ONS for 12 consecutive months in 2018 (n = 912). METHOD: Factors showing significant (P<0.05) univariate associations with above the median consumption of ONS units were entered into a multivariable model. RESULTS: Median age was 76 (range 18 to 101) years, with 66.9% of the sample being ≥65 years. Almost 70% of the samples were on polypharmacy (45.6%; ≥5 medications) or excessive polypharmacy (21.5%; ≥10 medications). Younger age and being on polypharmacy for drugs having an effect on the central nervous system (CNS) were significantly associated with being dispensed more ONS units in univariate and multivariate analysis. Those patients in the age range 18 to 44 were 2.5 fold more likely to be prescribed more ONS units (odds ratio [OR] 2.5; 95% confidence interval [CI] 1.5 to 4.3; P<0.001). Patients using CNS drugs or on CNS polypharmacy were more likely to be prescribed more ONS units (ORs 1.2 and 2.4; 95% CI 0.9 to 1.4 and 1.3 to 4.4 respectively; P = 0.029). CONCLUSION: Older age and polypharmacy characterise long-term ONS users in this study. Younger age and CNS medication polypharmacy are predictors of more ONS units prescribed over a year.

Interventions for preventing venous thromboembolism in adults undergoing knee arthroscopy.

BACKGROUND: Knee arthroscopy (KA) is a routine orthopedic procedure recommended to repair cruciate ligaments and meniscus injuries and in eligible patients, to assist the diagnosis of persistent knee pain. KA is associated with a small risk of thromboembolic events. This systematic review aims to assess if pharmacological or non-pharmacological interventions may reduce this risk. This review is the second update of the review first published in 2007. OBJECTIVES: To assess the efficacy and safety of interventions, whether mechanical, pharmacological, or in combination, for thromboprophylaxis in adult patients undergoing KA. SEARCH METHODS: For this update, the Cochrane Vascular Information Specialist searched the Cochrane Vascular Specialised Register, the CENTRAL, MEDLINE, Embase and CINAHL databases, and the World Health Organization International Clinical Trials Registry Platform and ClinicalTrials.gov trials registries, on 14 August 2019. SELECTION CRITERIA: We included randomized controlled trials (RCTs) and controlled clinical trials (CCTs), whether blinded or not, of all types of interventions used to prevent deep vein thrombosis (DVT) in males and females aged 18 years and older undergoing KA. There were no restrictions on language or publication status. DATA COLLECTION AND ANALYSIS: Two authors independently selected studies for inclusion, assessed trial quality with the Cochrane 'Risk of bias' tool, and extracted data. A third author addressed discrepancies. We contacted study authors for additional information when required. We used GRADE to assess the certainty of the evidence. MAIN RESULTS: This update adds four new studies, bringing the total of included studies to eight and involving 3818 adult participants with no history of thromboembolic disease undergoing KA. Studies compared daily subcutaneous (sc) low-molecular-weight heparin (LMWH) versus control (five studies); oral rivaroxaban 10 mg versus placebo (one study); daily sc LMWH versus graduated compression stockings (GCS) (one study); and aspirin versus control (one study). The incidence of pulmonary embolism (PE) in all trials combined was low, with seven cases in 3818 participants.There were no deaths in any of the intervention or control groups. LMWH versus control When compared with control, LMWH probably results in little to no difference in the incidence of PE in patients undergoing KA (risk ratio (RR) 1.81, 95% confidence interval (CI) 0.49 to 6.65; 1820 participants; 3 studies; moderate-certainty evidence). LMWH showed no reduction of the incidence of symptomatic DVT (RR 0.61, 95% CI 0.18 to 2.03; 1848 participants; 4 studies; moderate-certainty evidence). LMWH may reduce the risk of asymptomatic DVT but the evidence is very uncertain (RR 0.14, 95% CI 0.03 to 0.61; 369 participants; 2 studies; very low-certainty evidence). There was no evidence of an increased risk of all adverse events combined (RR 1.85, 95% CI 0.95 to 3.59; 1978 participants; 5 studies; moderate-certainty evidence). No evidence of a clear effect on major bleeding (RR 0.98, 95% CI 0.06 to 15.72; 1451 participants; 1 study; moderate-certainty evidence), or minor bleeding was observed (RR 1.79, 95% CI 0.84 to 3.84; 1978 participants; 5 studies; moderate-certainty evidence). Rivaroxaban versus placebo One study with 234 participants compared oral rivaroxaban 10 mg versus placebo. No evidence of a clear impact on the risk of PE (no events in either group), symptomatic DVT (RR 0.16, 95% CI 0.02 to 1.29; moderate-certainty evidence); or asymptomatic DVT (RR 0.95, 95% CI 0.06 to 15.01; very low-certainty evidence) was detected. Only bleeding adverse events were reported. No major bleeds occurred in either group and there was no evidence of differences in minor bleeding between the groups (RR 0.63, 95% CI 0.18 to 2.19; moderate-certainty evidence). Aspirin versus control One study compared aspirin with control. No PE, DVT or asymptomatic events were detected in either group. Adverse events including pain and swelling were reported but it was not clear what groups these were in. No bleeds were reported. LMWH versus GCS One study with 1317 participants compared the use of LMWH versus GCS. There was no clear difference in the risk of PE (RR 1.00, 95% CI 0.14 to 7.05; low-certainty evidence). LMWH use did reduce the risk of DVT compared to people using GCS (RR 0.17, 95% CI 0.04 to 0.75; low-certainty evidence). No clear difference in effects was seen between the groups for asymptomatic DVT (RR 0.47, 95% CI 0.21 to 1.09; very low-certainty evidence); major bleeding (RR 3.01, 95% CI 0.61 to 14.88; moderate-certainty evidence) or minor bleeding (RR 1.16, 95% CI 0.64 to 2.08; moderate-certainty evidence). Levels of thromboembolic events were higher in the GCS group than in any other group. We downgraded the certainty of the evidence for imprecision resulting from overall small event numbers; risk of bias due to concerns about lack of blinding, and indirectness as we were uncertain about the direct clinical relevance of asymptomatic DVT detection. AUTHORS' CONCLUSIONS: There is a small risk that healthy adult patients undergoing KA will develop venous thromboembolism (PE or DVT). There is moderate- to low-certainty evidence of no benefit from the use of LMWH, aspirin or rivaroxaban in reducing this small risk of PE or symptomatic DVT. There is very low-certainty evidence that LMWH use may reduce the risk of asymptomatic DVT when compared to no treatment but it is uncertain how this directly relates to incidence of DVT or PE in healthy patients. No evidence of differences in adverse events (including major and minor bleeding) was seen, but data relating to this were limited due to low numbers of events in the studies reporting within the comparisons.

General practitioners' views on malnutrition management and oral nutritional supplementation prescription in the community: A qualitative study.

BACKGROUND & AIMS: Malnutrition or undernutrition, arising from a deficiency of energy and protein intake, occurs commonly among community-dwelling individuals in developed countries. Once identified, malnutrition can be effectively treated in the majority of cases with dietary advice and the prescription of oral nutritional supplements (ONS) for patients who can eat and drink orally. However, previous research has reported inadequate screening and treatment of malnutrition in the community. The aim of this qualitative study was to explore general practitioners' (GPs) experiences and opinions on the management of malnutrition and the prescription of ONS in the primary care/community setting in Ireland. METHODS: Sixteen semi-structured interviews including chart stimulated recalls (CSR) were conducted with GPs. The interviews and CSRs explored, among others, the following domains; barriers and facilitators in the management of malnutrition, ONS prescribing in the primary care/community setting, and future directions in the management of malnutrition and ONS prescribing. Recorded interviews were transcribed and analysed following a generic qualitative approach with inductive thematic analysis using NVIVO 12 to facilitate data management. RESULTS: Three main themes were identified. Theme 1: 'Malnutrition is a secondary concern', encapsulating the idea that the identification of malnutrition is usually secondary to other clinical issues or disease rather than an independent clinical outcome. This theme also includes the idea that obesity is viewed as a dominant nutritional issue for GPs. Theme 2: 'Responsibility for malnutrition and ONS management in the community', highlighting that GPs feel they do not know who is responsible for the management of malnutrition in the community setting and expressed their need for more support from other healthcare professionals (HCPs) to effectively monitor and treat malnutrition. Theme 3: 'Reluctance to prescribe ONS', emerging from the GPs reported lack of knowledge to prescribe the appropriate ONS, their concern that ONS will replace the patient's meals and the costs associated with the prescription of ONS. CONCLUSIONS: GPs in Ireland do not routinely screen for malnutrition in their clinics as they feel unsupported in treating and managing malnutrition in the community due to limited or no dietetic service availability and time constraints. GPs also view malnutrition as a secondary concern to disease management and prioritise referral to dietetic services for patients with overweight and obesity. GPs reported that they have insufficient knowledge to change or discontinue ONS prescriptions. This study demonstrates that there is a clear need for primary care training in malnutrition identification, treatment and management and more community dietetic services are needed in order to support GPs and deliver high quality care to patients.

Multiple myeloma and occupation: a pooled analysis by the International Multiple Myeloma Consortium.

OBJECTIVE: We investigated occupational risk of multiple myeloma (MM) in a pooled analysis of five international case-control studies. METHODS: We calculated the odds ratio and its 95% confidence interval for selected occupations with unconditional regression analysis in 1959 MM cases and 6192 controls, by pooling study-specific risks using random-effects meta-analysis. Exposure to organic solvents was assessed with a job-exposure matrix (JEM). RESULTS: Gardeners and nursery workers combined, most likely exposed to pesticides, showed a 50% increase in risk (OR = 1.50, 95% CI 0.9-2.3), while other farming jobs did not. Metal processors (OR = 1.55, 95% CI 0.9-2.3), female cleaners (OR = 1.32, 95% CI 1.0-1.8), and high level exposure to organic solvents (OR = 1.38, 95% CI 0.96-1.8) also showed moderately increased risks. CONCLUSIONS: Additional case-control studies of MM aetiology are warranted to further investigate the nature of the repeatedly reported increase in MM risk in several occupational groups.

Multiple Myeloma and lifetime occupation: results from the EPILYMPH study.

BACKGROUND: The EPILYMPH study applied a detailed occupational exposure assessment approach to a large multi-centre case-control study conducted in six European countries. This paper analysed multiple myeloma (MM) risk associated with level of education, and lifetime occupational history and occupational exposures, based on the EPILYMPH data set. METHODS: 277 MM cases and four matched controls per each case were included. Controls were randomly selected, matching for age (+/- 5 years), centre and gender. Lifetime occupations and lifetime exposure to specific workplace agents was obtained through a detailed questionnaire. Local industrial hygienists assessed likelihood and intensity for specific exposures. The odds ratio and 95% confidence intervals (OR, 95% CI) were calculated for level of education, individual occupations and specific exposures. Unconditional logistic regression models were run for individual occupations and exposures. RESULTS: A low level of education was associated with MM OR=1.68 (95% CI 1.02-2.76). An increased risk was observed for general farmers (OR=1.77; 95% CI 1.05-2.99) and cleaning workers (OR=1.69; 95% CI 1.04-2.72) adjusting for level of education. Risk was also elevated, although not significant, for printers (OR=2.06; 95% CI 0.97-4.34). Pesticide exposure over a period of ten years or more increased MM risk (OR=1.62; 95% CI 1.01-2.58). CONCLUSION: These results confirm an association of MM with farm work, and indicate its association with printing and cleaning. While prolonged exposure to pesticides seems to be a risk factor for MM, an excess risk associated with exposure to organic solvents could not be confirmed.

[Occupational risk of multiple myeloma: results from the EPILYMPH study]. / Rischio occupazionale di mieloma multiplo: risultati dello studio EPILYMPH.

European case-control study evaluates occupational risk of multiple myeloma (MM) in 277MM cases and 1108 matched controls, using logistic regression analysis and adjusting by age, gender, study centre and education. An increase in MM risk was observed for general farmers, cleaners, telephone and radio operators, and printers. Pesticide exposure lasting ten years or more, but not exposure to solvents, was also associated with an elevated MM risk (OR = 1.62; 95% CI 1.01-2.58). Our results confirm an association of multiple myeloma with farm work, and particularly with prolonged exposure to pesticides.

[Risk of multiple myeloma and agricultural exposures]. / Rischio di mieloma multiplo ed esposizioni in agricoltura.

We analyzed risk associated with exposure to pesticides and contact with livestock in 277 multiple myeloma (MM) cases and 2434 controls who participated in the multicentre European EPILYMPH study. Ever exposure to organic pesticides or contact with any species of livestock was not associated with an increase in risk of MM. However, risk associated with ever exposure to pesticides was elevated after adjusting for contact with sheep (OR = 2.0, 95% CI 1.2-3.3). The finding of an excess risk associated with ever exposure to any pesticides after adjusting for contact with breeding animals is most likely due to chance.

Multiple myeloma and farming. A systematic review of 30 years of research. Where next?

BACKGROUND: Multiple myeloma has been linked to farming for over thirty years. However, there is little clarity about the magnitude of the risk, nor about the specific agricultural exposures which contribute to the risk. METHODS: We have carried out a systematic review of case-control studies of multiple myeloma published from 1970 to October 2007. Studies were identified through database searches and from references in the literature.Studies reporting risk estimates from farming, agricultural exposures, and exposure to animals were identified, and details abstracted. The impact of study heterogeneity, publication bias, variation in methods of case identification and exposure ascertainment between studies were considered in analysis. RESULTS: Case control studies showed a pooled odds ratio (OR) for working as a farmer of 1.39 95% CI 1.18 to 1.65. There was no graphic evidence of publication bias, for pesticide exposure 1.47; 95% 1.11 to 1.94, for DDT 2.19; CI 95% 1.30 to 2.95; for exposed to herbicides 1.69; 95 %CI 1.01 to 1.83. For working on a farm for more than ten years OR was 1.87; 95% CI 1.15 to 3.16. CONCLUSION: Farmers seem to have increase risk for MM. However, a major limitation of this analysis is the presence of significant heterogeneity across the studies and the evidence of publication bias in some models.A pooled analysis using individual level data could provide more power and permit the harmonization of occupational and exposure coding data.

Interventions for preventing venous thromboembolism in adults undergoing knee arthroscopy.

BACKGROUND: Knee arthroscopy is a frequent surgical procedure. Arthroscopy procedures are considered minimally invasive. However, some patients will need extended surgical time, suffer injury and immobilization thus increasing the risk for thromboembolic events. Incidence of deep venous thrombosis (DVT) in patients undergoing knee arthroscopy is reported to be from 0.6% to 17.9% depending on the diagnostic method used. Different approaches are available for thromboprophylaxis (mechanical or pharmacological). OBJECTIVES: To assess the effectiveness and safety of thromboprophylaxis to reduce the incidence of DVT in patients undergoing knee arthroscopy. SEARCH STRATEGY: We searched the Cochrane Peripheral Vascular Diseases Group Specialized Register (last searched October 2006) the CENTRAL (last searched Issue 4, 2006), MEDLINE (1966 to 2006), EMBASE (1980 to 2006), and Lilacs (1988 to 2006). We contacted specialists known to be involved in phlebology and interested in post thrombotic syndrome for details of unpublished and ongoing trials. SELECTION CRITERIA: Randomized clinical trials (RCTs) and controlled clinical trials (CCTs), whether blinded or not (i.e. double blinded, single blinded or unblinded) of all type of interventions, whether mechanical or pharmacological, single or in combination, used to prevent DVT in males and females over 18 years old undergoing knee arthroscopy. There was no restriction on language. DATA COLLECTION AND ANALYSIS: Two authors independently assessed trial quality and extracted data. Study authors were contacted for additional information. MAIN RESULTS: Four trials involving 527 predominantly male participants were included. The main weakness of the studies was the lack of correct stratification of the arthroscopic intervention.The relative risk (RR) of thrombotic events was 0.16 (95% confidence interval (CI); 0.05 to 0.52) comparing any type of low molecular weight heparin (LMWH) versus placebo. All thrombotic events but one (pulmonary embolism in the LMWH group) were distal venous thrombosis. Adverse events were most common in the intervention group than in the control group, RR 2.04 (95% CI 1.21 to 3.44). There were 66 episodes of adverse events. The number needed to harm was 20 for any adverse events. AUTHORS' CONCLUSIONS: This meta-analysis suggests that LMWH reduces the incidence of distal DVT diagnosed by sonogram. The clinical benefit of this is uncertain. No strong evidence was found to conclude thromboprophylaxis is effective to prevent thromboembolic events and safe, in people with unknown risk factors for thrombosis, undergoing knee arthroscopy.

Molecular cloning and characterization of an almond 9-hydroperoxide lyase, a new CYP74 targeted to lipid bodies.

Oxylipin metabolism represents one of many defence mechanisms employed by plants. It begins with the oxygenation of polyunsaturated fatty acids by lipoxygenases to form fatty acid hydroperoxides that are substrates for several enzymes, including specialized cytochrome P450s known as CYP74s. The targeting of a new CYP74, a 9-hydroperoxide lyase (HPL) from almonds, to the endomembrane system and lipid bodies, both as enzyme activity in almond seeds and as GFP fusions transiently expressed in tobacco protoplasts, is described. Such association of a CYP74 with lipid bodies has not been reported previously. Also described are the properties of a 9-HPL gene, the developmental regulation of its expression, the production and characterization of recombinant 9-HPL in Escherichia coli, and the developmental correlation between gene expression, enzyme activity, and the appearance of volatile C9 aldehydes from HPL action.