Meta‐analysis: pre‐operative infliximab treatment and short‐term post‐operative complications in patients with ulcerative colitis

Aliment Pharmacol Ther 31 , 486–492

Summary

Background Infliximab was approved for use in ulcerative colitis in recent years. It has been debated if infliximab increases the risk of post‐operative complications in patients with ulcerative colitis. Aim To perform a meta‐analysis that examines the relationship between preoperative infliximab treatment and short‐term post‐operative complications in patients with ulcerative colitis. Methods We searched the PubMed and MEDLINE databases to identify observational studies on the impact of pre‐operative infliximab use on short‐term post‐operative complications in ulcerative colitis. Infectious complications mainly included wound infection, sepsis and abscess, whereas non‐infectious complications included intestinal obstruction, thromboembolism and gastrointestinal haemorrhage. Pooled odds ratios (ORs) were calculated for each relationship. Results A total of 5 studies and 706 patients were included in our meta‐analysis. Overall, we did not find a strong association between pre‐operative treatment of infliximab and short‐term infectious [OR 2.24, 95% confidence interval (CI) 0.63–7.95] or non‐infectious (OR 0.85, 95% CI 0.50–1.45) post‐operative complications in ulcerative colitis patients. On the contrary, we discovered that pre‐operative infliximab use increased short‐term total post‐operative complications (OR 1.80, 95% CI 1.12–2.87). Conclusions Pre‐operative infliximab use increased the risk of short‐term post‐operative complications. Subgroup analysis is underpowered to assess the nature of these complications but shows a trend towards increased post‐operative infection.     

Pre‐operative management is associated with low rate of post‐operative morbidity in penetrating Crohn’s disease

Aliment Pharmacol Ther 2010; 32: 459–465

Summary

Background Ileocaecal resection for penetrating Crohn’s disease is still challenging with a high rate of post‐operative morbidity and faecal diversion. Aim To report retrospectively the results of pre‐operative management for penetrating Crohn’s disease focusing on the rate of post‐operative major morbidities and need for faecal diversion. Methods Between 1997 and 2007, 78 patients with penetrating Crohn’s disease underwent a first ileocaecal resection after a pre‐operative management consisting in bowel rest, nutritional therapy, intravenous antibiotics, weaning off steroids and immunosuppressors, and drainage of abscesses when appropriate. Results Resection was performed for terminal ileitis associated with (n = 41), abscesses (n = 37) or both (n = 5). A pre‐operative nutritional therapy was performed in 50 patients (68%) for 23 days (range, 7–69 days) along with a weaning off steroids and immunosuppressors. A diverting stoma was performed for six patients (7.7%). There was no post‐operative death. Post‐operative complications were classified as minor in 10 patients (12.8%), and major in four patients (5%). Overall, the post‐operative course was uneventful in 58 patients (74%). Conclusion Pre‐operative management for penetrating Crohn’s disease allowed ileocaecal resection with low rates of post‐operative morbidity and faecal diversion.     

Obtaining accurate patient‐specific perioperative anaesthetic costs in orthopaedic anaesthesia

□ The aim of the study was to obtain perioperative patient‐specific costs associated with orthopaedic anaesthesia □ A prospective observational study design was used to determine fixed, semi‐fixed, and variable costs □ The preliminary results of the first 60 patients reports a mean total perioperative anaesthetic cost of £291 (SD: £103.9, median: £278.09, IQR: £219.3–£369.5) □ Fixed and semi‐fixed costs are a major cost component of anaesthesia; variable costs account for only 12 per cent of total cost □ The results of this study will be used in an economic evaluation examining the use of different anaesthetic techniques in orthopaedics     

An evaluation of the process‐related medication risks for elective surgery patients from pre‐operative assessment to discharge

Aim — To investigate where the process‐related medication risks occur in an elective surgery service with a pre‐operative assessment clinic (PAC) and make recommendations for how pharmacy services should best be provided. Method — The study involved identification of discrepancies in medication history taking, changes that occurred in patients' medication between PAC and admission, and changes that occurred between admission and discharge. Prescribing errors were identified and classified according to whether they occurred on admission, during the inpatient stay or on discharge, and whether they were identified and rectified by the existing pharmacy service. Setting — Seventy‐six patients recruited from the nurse‐led PAC of a 580‐bed London teaching hospital between May 2 and June 30, 2000. Key findings — The PAC nurse omitted 27 per cent of medications from the medication history; the admitting doctor omitted 37 per cent from the medication history documented in the medical notes and 47 per cent from the inpatient medication chart; the majority of the omissions were complementary and over‐the‐counter preparations. Twenty‐six per cent of patients had changes made to their medication between PAC and admission, and 85 per cent had changes made between admission and discharge. A total of 177 prescribing errors were identified (median of 1 error per patient; interquartile range 0–3), of which 38 per cent occurred on admission, 14 per cent during the inpatient stay and 48 per cent at discharge. Pharmacists made interventions to rectify 59 per cent of the errors. Conclusion — Given the large number of changes to patients' medication that occurred between PAC and admission, we would not support the writing of inpatient medication charts or the supply of medication at this stage. For this group of patients in the study hospital, the greatest process‐related medication risks occurred on admission and discharge, and pharmacy services should be provided accordingly.     

A patient‐held medication record and a patient medication profile to support the continuity of acute cancer care

□ The sharing of care of patients receiving medical oncology care is vulnerable to errors in their documented drug history □ A patient‐held medication record identified over 90 per cent of patients' medications but was ‘forgotten’ by the patient in a third of contacts with a pharmacist □ Discrepancies between the medication records of GPs, community pharmacists and the medical oncology clinic were highly prevalent □ A posted patient medication profile issued by the hospital pharmacist to both the patient's GP and their community pharmacist was associated with a significant convergence in their records (discrepancies reduced from 17 to 6 % P<0.001) □ The patient‐held record had little impact on the accuracy of practitioners' records and its value lies more in facilitating patient education than rectifying errors in documentation     

The microbiological impact of pre-operative biliary drainage on patients undergoing hepato-biliary-pancreatic (HPB) surgery

Background The merit of pre‐operative biliary drainage in managing hepatic, biliary or pancreatic patients remains unclear with previous studies demonstrating significant increases in bacterobilia. Aims To establish if pre‐operative biliary drainage was associated with (i) a change in bacterial flora, (ii) post‐operative sepsis and (iii) to ascertain if a modification of antibiotic prophylaxis was warranted. Methods Data were collected on 331 patients undergoing hepatic, biliary or pancreatic surgery for malignant obstruction between August 2000 and June 2005. Microbiological data from intra‐operative bile, post‐operative wounds, blood cultures, urine and sputum were analysed. All episodes of pre‐operative endoscopic retrograde cholangiopancreatography (ERCP), stenting and percutaneous drainage were documented. Results One hundred and sixty two patients had ERCP prior to surgery and 154 had surgery only. In comparison to patients who had surgery alone stented patients had significantly increased rates of bacterobilia (40 vs. 85%) and fungobilia (8 vs. 34%, both P < 0.001). Pre‐operative biliary drainage significantly increased post‐operative sepsis, wound infections and prolonged in‐patient stay (P < 0.05). The most common organisms cultured were coliforms and enterococcus with percutaneous transhepatic cholangiography (PTC) highly significant for the development of MRSA sepsis. Conclusions Pre‐operative biliary drainage is associated with a high incidence of bacterobilia and fungal colonization. Pre‐operative biliary drainage should be utilized selectively, with modification of antibiotic prophylaxis according to patient characteristics.     

Identification of psychosocial factors which influence patient adherence with antihypertensive medication

□ It is estimated that only 50 per cent of hypertensive patients adhere to medication regimens □ In this study evaluation of self‐efficacy and the theory of planned behaviour was used to identify psychosocial factors which impact on patient adherence to antihypertensives □ High self‐efficacy, intentions to comply with the medication regimen, possessing a positive attitude towards taking medication, perceiving pressure from significant others to take medication as prescribed, and perceiving control over taking medication were determinants of good adherence □ The successful identification of factors which influence adherence will allow health‐care providers to implement interventions, aimed at enhancing adherence with antihypertensive medication.     

Development of a pharmacist‐led cholesterol screening and lipid‐lowering medication review service in coronary artery bypass graft patients

Objective — To assess the effects of pharmacist intervention on lipid management in coronary artery bypass graft (CABG) patients. Method — Open study in which total cholesterol (TC) levels were measured in 43 elective CABG patients at visit 1 (pre‐surgery) and visit 2 (six weeks post‐discharge following surgery). Statin therapy was initiated (using atorvastatin) or statin doses were adjusted according to an agreed protocol. Key findings — Prior to CABG surgery, 19 patients (44 per cent) did not have target TC values. Fourteen (74 per cent) of these patients were already receiving a statin while five patients (26 per cent) were not receiving statin therapy. At visit 2, 33 patients (77 per cent) had achieved target TC. Mean (SD) TC was 5.7 (0.72) mmol/L at visit 1 and 4.8 (0.68) mmol/L at visit 2 in the intervention patients (P<0.01). There was no significant difference between mean TC at visits 1 and 2 in the non‐intervention patients (patients who had target TC values at visit 1). From a previous meta‐analysis, the decrease in TC of 0.9 mmol/L (16 per cent) in the intervention patients equates to a 24 per cent risk reduction in coronary heart disease (CHD) mortality and an 18 per cent risk reduction in total mortality. The recent National Service Framework for CHD has set standards for improving the care of CHD patients. From this study, it appears that the management of raised TC in this high‐risk population is sub‐optimal. Conclusion — This study has shown that the role of the pharmacist can be extended to encompass the management of raised total cholesterol in CABG patients, thereby contributing towards health care benefit.     

Tranexamic Acid in Total Knee Arthroplasty: Mixed Treatment Comparisons and Recursive Cumulative Meta‐Analysis of Randomized,Controlled Trials and Cohort Studies

Tranexamic acid (TXA) has been shown to be effective in patients with total knee arthroplasty (TKA) in clinical studies with no consensus with regard to the most appropriate route of administration. We conducted a network meta‐analysis to compare the evidence available on efficacy and safety of TXA in TKA. Electronic databases were searched for randomized, clinical trials and cohort studies that evaluated TXA in TKA. Publication bias, risk of bias and inconsistencies were assessed. Direct and indirect comparisons were carried out for blood transfusion rate and incidence of thrombotic complications. Sensitivity analyses and grading of evidence were performed for key comparisons. A cumulative meta‐analysis was conducted for comparisons that had a minimum of 10 included studies. A total of 19 studies with 8916 participants were pooled for this network meta‐analysis. No inconsistencies and publication bias were observed. Low risk of bias was observed for the majority of the included studies. When compared to placebo, the pooled estimates for mixed treatment analyses favoured (in the order of higher ranking) the combined pre‐operative oral and topical TXA, intra‐operative intravenous TXA with topical TXA, pre‐operative intravenous TXA, intra‐operative and post‐operative intravenous TXA, intra‐operative intravenous bolus and topical TXA. Additionally, combined intravenous and topical TXA performed better than topical TXA alone. No significant changes were observed in the sensitivity analyses. No significant differences were observed in the risk of thrombotic complications between the interventions. TXA is efficacious and safe in patients with TKA. The combined topical and intra‐operative intravenous TXA may perform better.     

The Effect of the Combined Use of Methylergonovine and Oxytocin during Caesarean Section in the Prevention of Post‐partum Haemorrhage

We aimed to show to patients the benefit of post‐partum haemorrhage prophylaxis treatment and the effectiveness as a uterotonic agent of the combined use of methylergonovine and oxytocin infusion in the prevention of haemorrhage during and after Caesarean section, by comparison with a control group which received oxytocin infusion only. Two groups of patients undergoing Caesarean section at the same clinic were included in the study. A combination of methylergonovine and oxytocin was administered to the first group during the intra‐operative and post‐operative periods. The second group did not receive methylergonovine and was administered only with oxytocin infusion in the intra‐operative and post‐operative periods. Pre‐operative and post‐operative haemogram readings were taken for all patients in each of the groups for comparison. No difference was found between the two groups with regard to mean ages and pre‐operative haemogram values. The decrease in post‐operative haemoglobin values for the group administered with methylergonovine maleate and oxytocin was found to be significantly greater than for the group administered with oxytocin only. Results indicated that prophylactic methylergonovine treatment was clearly successful for the patients and no adverse side effects were found. The routine use of methylergonovine and oxytocin infusion in combination during the intra‐operative period of Caesarean section reduced the level of post‐partum haemorrhage considerably. We believe that this procedure will also reduce the risk of uterine atony, but clearly, prospective studies will be necessary in future to confirm this assumption.     

Poor correlation between predicted ideal and prescribed digoxin dose: a community‐based pharmacokinetic study in the elderly

□ This study assessed if population‐based pharmacokinetics predicted measured plasma digoxin concentrations in elderly community‐managed patients □ Twenty‐seven per cent of the sample showed plasma concentrations consistent with a therapeutic level over an entire 24‐hour dosing schedule; 36 per cent showed therapeutic levels for at least some of the dosing schedule; the remainder showed digoxin concentrations not consistent with achieving a therapeutic plasma concentration for any part of the dosing schedule □ The mean daily prescribed dose of digoxin was significantly lower than that predicted from population kinetics.     

Gender and age influences on prescription and consultation frequency for multiple sclerosis patients

□ The study aimed to examine whether gender and age affects the burden of disease in secondary care in terms of number of prescribed drugs and number of consultations with the general practitioner (GP) for multiple sclerosis and control patients □ Anonymised data for 1996 was obtained for all patients (patient years at risk = 220,538) from 24 GP practices in the GP Morbidity Database who had a Read code of MS at some point from 1993 to 1996 and a randomly selected age, gender and surgery matched control group □ A total of 216 cases was identified, giving a prevalence of 97.9 per 105 (based on patient years at risk in the database for 1996; n=220,538). Sixty‐seven per cent (145/216) of cases were female. The mean age was 46.7 (range 17 to 84 years) □ Gender differences for the MS patients, but not controls were found. For example, although females in both the control and MS population had significantly more consultations than the corresponding males, only the control females had more items prescribed than control males (p=0.033) □ This study warrants further work to elucidate whether specific therapeutic areas or MS‐treated symptoms are influenced by gender     

Variation in the management of PONV and pain in day case surgery: implications for evidence based practice

□ This study aimed to provide information on the variation in perioperative anaesthetic care for principal types of day case adult and paediatric procedures including the use of intraoperative analgesia and the treatment of post‐operative nausea and vomiting □ A structured postal survey comprising closed questions was sent to consultant anaesthetists involved in anaesthetising patients for day case surgery in United Kingdom National Health Service trusts □ This survey found wide variation in the selection of intraoperative analgesics and treatment anti‐emetics for the potential management of patients having three common day surgery procedures □ It is likely that the wide variation in practice seen in this, and previous studies, is due to uncertainty about effectiveness □ The lack of consensus about the preferred choice of analgesia and anti‐emetics provides a challenge to pharmacists and clinicians in the development of evidence based guidelines.     

Educational and Organizational Interventions to Improve the Usefulness of Clinical Pharmacological Advice for Personalized Drug Dosing Based on Therapeutic Drug Monitoring

This study was aimed at increasing the clinical usefulness of clinical pharmacological advice (CPA) for personalized drug dosing based on therapeutic drug monitoring (TDM). Educational and organizational interventions focused on improving the knowledge of clinical pharmacology among hospital healthcare workers and reducing the incidence of errors throughout the process were planned. After a pre‐interventional period of risk assessment, different list forms of the types of error occurring in the various phases of the process (Phase 1, request for CPA and blood sampling for TDM; Phase 2, sample delivery to and check in at the CPU; Phase 3, TDM execution and CPA production) were created. In the interventional period, the errors were collected daily and educational programmes were carried out. The pre‐intervention error rate was 19.5%, and resulted significantly higher for the requests coming from the medical wards compared with those from the surgical wards or the ICUs (26.0% versus 10.5% versus 13.7%, p < 0.001). The educational programme trained 303 nurses and 145 physicians. Afterwards, the error percentage progressively dropped (15.5% in the 2nd trimester; 12.3% in the 3rd one; 10.5% in the 4th one). The adopted strategy resulted in significant improvements which may be useful both to improve quality of patient care and to reduce waste in healthcare costs.     

Co‐Administration of Dextromethorphan and Morphine: Reduction of Post‐Operative Pain and Lack of Influence on Morphine Metabolism

Abstract: We investigated co‐analgesic effect of dextromethorphan in adolescent post‐operative patients with idiopathic scoliosis. In a double‐blind study, 60 patients with ASA physical status I–II were randomised into two groups. Group dextromethorphan (n = 30; age: 15.9 ± 2.4 years) was given oral dextromethorphan 30 or 45 mg 1 hr before surgery and 8, 20 and 32 hr after operation. Group placebo (n = 30; age: 16.5 ± 2.7 years) received placebo at identical times. Post‐operative analgesic requirements were assessed using nurse‐controlled analgesia system. Pain was assessed using numeric rating scale before first administration of morphine and at 2, 3, 4, 6, 24 and 48 hr after operation. Blood samples were taken 20 min. after the first use of morphine (within 1 hr after operation). The total use of analgesics during surgery was lower in the dextromethorphan group. The dose of morphine providing relief immediately after surgery, as well as total analgesic requirements in the first and second day after surgery did not differ between groups. Subjectively evaluated pain intensity score (numeric rating scale) was lower for the dextromethorphan patients in the first 4 hr, but not later after surgery. Plasma levels of morphine, morphine‐6‐glucuronide and morphine‐3‐glucuronide did not differ between groups. Dextromethorphan did not influence morphine glucuronidation, in terms of promotion of formation of any morphine glucuronides. In conclusion, in young patients subjected to spine surgery, addition of dextromethorphan to morphine reduced pain only in early post‐operative period. In such patients, co‐analgesic action of dextromethorphan was not associated with significant changes in plasma levels of morphine metabolites.     

Pre‐clinical and Clinical Safety Studies of CMX‐2043: A Cytoprotective Lipoic Acid Analogue for Ischaemia–Reperfusion Injury

CMX‐2043 is an α‐lipoic acid analogue targeted to reduction of cellular injury and organ damage due to ischaemia–reperfusion injury (IRI). It has been shown to be effective in a rat model of cardiac IRI. The studies here reported evaluate its safety and pharmacokinetic profile in preparation for human clinical studies in procedures associated with IRI. Safety and tolerability were tested in standard pre‐clinical in vitro and animal models and in a Phase 1 human clinical trial. CMX‐2043 did not bind to a wide range of receptors and specific targets at approximately 4 μg/mL (10 μM). It was not mutagenic by Ames assay, did not produce chromosome aberrations in Chinese hamster ovary (CHO) cells, and was negative for clastogenic potential. Toxicological studies in rats including both single and 14‐day repeat intravenous doses and in dogs (single intravenous dose) with a 2‐week recovery period were conducted. The NOAEL in rats and dogs was 30 and >10 mg/kg, respectively. No serious adverse events were reported in a placebo‐controlled, sequential dose escalation Phase 1 clinical trial. The low toxicity in the pre‐clinical studies and the absence of adverse events in the Phase 1 trial have supported investigation of CMX‐2043 in a human efficacy trial.     

A randomised,controlled study to quantify the benefits of community pharmacist interventions on the prescribing of cardiovascular drugs in general practice

□ The impact of a one‐off medication review by a specially trained community pharmacist, with recommendations to the patient's general practitioner was studied □ No differences were observed in any of the physiological or biochemical monitoring indicators □ There was greater improvement post‐intervention in some key quality prescribing indicators (eg, prescribing of antiplatelet and beta blocker or ACE inhibitor post‐MI); others showed equal improvement in both groups (diabetic patients on ACE inhibitor) □ A single review of medication records by a practice‐based pharmacist, with a dependence on the general practitioner to implement change may have limited benefit.     

Assessing patient adherence to anti‐hypertensive drug therapy: can a structured pharmacist‐conducted interview separate the wheat from the chaff?

Objective To identify determinants of adherence and assess the impact of structured pharmacist‐conducted interviews in determining patients' adherence to prescribed anti‐hypertensive medications in a secondary care setting in Nigeria. Method The study was conducted in a secondary care facility located in Ibadan, Southwestern Nigeria. Two methodological approaches were employed. The first phase was pharmacist‐conducted, pre‐physician consultation, cross‐sectional interviews of 400 hypertensive patients who presented at the study site within the 2‐month study period. The second phase was a follow‐up review of case notes of these patients after they had left the physician's office. Key findings The outcome of the pharmacist‐conducted pre‐physician consultation interview shows that financial difficulty was the most frequently identified factor responsible for patients' non‐adherence to anti‐hypertensive drug therapy (64%). A drug holiday, varying from 5–14 days per month, was the coping strategy adopted by patients to circumvent this difficulty. Only 48% (192) of patients were aware of the negative consequences of non‐adherence with anti‐hypertensive drug therapy, and of these, 75% were adherent. The level of awareness was significantly higher in adherent patients (P < 0.001). Sixty‐seven per cent (268) of patients use a daily medication reminder (DMR) to assist them in taking their anti‐hypertensive drugs, and of these 65.7% were adherent. The use of DMRs was significantly higher among adherent patients (P < 0.01). A meal time was the most frequently used DMR (88%). Forty‐one per cent (164) of patients had additional measurement of their blood pressure at pharmacies (65.9%) and neighbourhood private hospital (34.1%), and of these 75.6% were judged to be adherent with their prescribed drug therapy. Additional measurement of blood pressure was significantly higher in adherent patients (P < 0.001). Fifty‐one per cent of the cohort were judged by pharmacists as non‐adherent during pre‐consultation interviews (phase 1), while physicians judged 25% of the same cohort as non‐adherent during consultation (phase 2). The structured pharmacist‐conducted pre‐physician consultation interviews were significantly better at identifying patients who were non‐adherent with prescribed anti‐hypertensive drugs (P < 0.01). Conclusion A brief structured pharmacist‐conducted interview can be a valuable tool in assessing and/or identifying determinants of adherence with anti‐hypertensive drug therapy.