Dose rationale for gabapentin and tramadol in pediatric patients with chronic pain.

Despite off-label use, the efficacy and safety of gabapentin and tramadol in pediatric patients (3 months to <18 years old) diagnosed with chronic pain has not been characterized. However, generating evidence based on randomized clinical trials in this population has been extremely challenging. The current investigation illustrates the use of clinical trial simulations (CTSs) as a tool for optimizing doses and protocol design for a prospective investigation in pediatric patients with chronic pain. Pharmacokinetic (PK) modeling and CTSs were used to describe the PKs of gabapentin and tramadol in the target population. In the absence of biomarkers of analgesia, systemic exposure (AUC, Css) was used to guide dose selection under the assumption of a comparable exposure-response (PKPD) relationship for either compound between adults and children. Two weight bands were identified for gabapentin, with doses titrated from 5 to 63 mg/kg. This yields gabapentin exposures (AUC0-8 ) of approximately 35 mg/L*h (1200 mg/day adult dose equivalent). For tramadol, median steady state concentrations between 200 and 300 ng/mL were achieved after doses of 2-5 mg/kg, but concentrations showed high interindividual variability. Simulation scenarios showed that titration steps are required to explore therapeutically relevant dose ranges taking into account the safety profile of both drugs. Gabapentin can be used t.i.d. at doses between 7-63 and 5-45 mg/kg for patients receiving gabapentin weighing <15 and ≥15 kg, respectively, whereas a t.i.d. regimen with doses between 1 and 5 mg/kg can be used for tramadol in patients who are not fast metabolisers.

Effect of intraoperative botulinum toxin injection on delayed gastric emptying and need for endoscopic pyloric intervention following esophagectomy: a systematic review, meta-analysis, and meta-regression analysis.

The aim of this study was to evaluate the effect of intraoperative botulinum toxin (BT) injection on delayed gastric emptying (DGE) and need for endoscopic pyloric intervention (NEPI) following esophagectomy. In compliance with Preferred Reporting Items for Systematic reviews and Meta-Analyses statement standards, a systematic review of studies reporting the outcomes of intraoperative BT injection in patients undergoing esophagectomy for esophageal cancer was conducted. Proportion meta-analysis model was constructed to quantify the risk of the outcomes and direct comparison meta-analysis model was constructed to compare the outcomes between BT injection and no BT injection or surgical pyloroplasty. Meta-regression was modeled to evaluate the effect of variations in different covariates among the individual studies on overall summary proportions. Nine studies enrolling 1070 patients were included. Pooled analyses showed that the risks of DGE and NEPI following intraoperative BT injection were 13.3% (95% confidence interval [CI]: 7.9-18.6%) and 15.2% (95% CI: 7.9-22.5%), respectively. There was no difference between BT injection and no BT injection in terms of DGE (odds ratio [OR]: 0.57, 95% CI: 0.20-1.61, P = 0.29) and NEPI (OR: 1.73, 95% CI: 0.42-7.12, P = 0.45). Moreover, BT injection was comparable to pyloroplasty in terms of DGE (OR: 0.85, 95% CI: 0.35-2.08, P = 0.73) and NEPI (OR: 8.20, 95% CI: 0.63-105.90, P = 0.11). Meta-regression suggested that male gender was negatively associated with the risk of DGE (coefficient: -0.007, P = 0.003). In conclusion, level 2 evidence suggests that intraoperative BT injection may not improve the risk of DGE and NEPI in patients undergoing esophagectomy. The risk of DGE seems to be higher in females and in early postoperative period. High quality randomized controlled trials with robust statistical power are required for definite conclusions. The results of the current study can be used for hypothesis synthesis and power analysis in future prospective trials.

The impossible gallbladder: aspiration as an alternative to conversion.

BACKGROUND: Laparoscopic cholecystectomy is the standard of care for symptomatic gallstone disease but when laparoscopic removal proves impossible the standard advice is to convert to open surgery. This jettisons the advantages of laparoscopy for a procedure which surgeons no longer perform routinely, so it may no longer be the safest practice. We hypothesised that gallbladder aspiration would be a safer alternative when laparoscopic removal is impossible. METHODS: A retrospective analysis was performed of all laparoscopic cholecystectomies attempted under one surgeon's care over 19 years, and the outcomes of gallbladder aspiration were compared with the standard conversion-to-open procedure within the same institution. RESULTS: Of 757 laparoscopic cholecystectomies attempted, 714 (94.3%) were successful, while 40 (5.3%) were impossible laparoscopically and underwent gallbladder aspiration. Interval cholecystectomy was later performed in 34/40 (85%). Only 3/757 (0.4%) were converted to open. No aspiration-related complications occurred and excessive bile leakage from the gallbladder was not observed. During this time 1209 laparoscopic cholecystectomies were attempted by other surgeons in the institution of which 55 (4.55%) were converted to open and 22 (40%) had procedure-associated complications. There was a significant difference in the mean (± SEM) post-operative hospital stay between laparoscopic gallbladder aspiration [3.12 (± 0.558) days] and institutional conversion-to-open cholecystectomy [9.38 (± 1.04) days] (p < 0.001), with attendant cost savings. CONCLUSION: Laparoscopic gallbladder aspiration is a safe alternative to conversion when inflammation makes cholecystectomy impossible laparoscopically, especially in the sickest patients and for surgeons with limited open surgery experience. This approach minimises morbidity and permits laparoscopic cholecystectomy in the majority after a suitable interval or referral of predicted difficult cases to specialist hepatobiliary centres.

Virtual outpatient clinic as an alternative to an actual clinic visit after surgical discharge: a randomised controlled trial.

BACKGROUND: It is standard practice to review all patients following discharge at a follow-up clinic but demands on all health services outweigh resources and unnecessary review appointments may delay or deny access to patients with greater needs. AIMS: This randomised trial aimed to establish whether a virtual outpatient clinic (VOPC) was an acceptable alternative to an actual outpatient clinic (OPC) attendance for a broad range of general surgical patients following a hospital admission. PATIENTS AND METHODS: All patients admitted under one general surgical service over the study period were assessed. If eligible for inclusion the rationale, randomisation and follow-up methods were explained, consent was sought and patients randomised to receive either a VOPC or an OPC appointment. RESULTS: Two-hundred and nine patients consented to study inclusion, of which 98/107 (91.6%) in the VOPC group and 83/102 (81.4%) in the OPC group were successfully contacted. Only 6 patients in the OPC group and 10 in the VOPC group reported ongoing issues. A further follow-up indicated 78 of 82 (95%) VOPC patients were very happy with their overall experience compared with 34/61 (56%) in the actual OPC group (p<0.001). A significant proportion of both cohorts-68/82 (83%) in VOPC group and 41/61 (67%) in OPC group (p = 0.029)-preferred a VOPC appointment as their future follow-up of choice. CONCLUSIONS: The majority of patients discharged from a surgical service could be better followed up by a virtual clinic with a significant proportion of patients reporting a preference for and a greater satisfaction with such a service.

Rethinking the doctor-patient relationship: toward a hermeneutically-informed epistemology of medical practice.

Although typically implicit, clinicians face an inherent conflict between their roles as medical healers and as providers of technical biomedicine (Scott et al. in Philos Ethics Humanit Med 4:11, 2009). This conflict arises from the tension between the physicalist model which still predominates in medical training and practice and the extra-physicalist dimensions of medical practice as epitomised in the concept of patient-centred care. More specifically, the problem is that, as grounded in a "borrowed" physicalist philosophy, the dominant "applied scientist" model exhibits a number of limitations which severely restrict its ability to underwrite the effective practice of care. Moreover, being structural in character, these problems cannot be resolved by piecemeal modifications of the existing model, nor by an appeal to evidence-based medicine (Miles in J Eval Clin Pract 15(6):887-890, 2009; Miles in Folia Med 55(1):5-24, 2013; Miles et al. in J Eval Clin Pract 14(5):621-649, 2008). Hence, the need for medical theorists to "partner with experts in the humanities to build a sui generis philosophy of medicine" (Whatley in J Eval Clin Pract 20(6):961-964, 2014, p. 961). In response, the present paper seeks to vindicate the merits of hermeneutically-informed template in providing the requisite grounding. While capable of correcting for the limitations of the applied scientist model, a hermeneutically-informed template is a "both/and" approach, which seeks to complement rather than exclude the physicalist dimension, and thereby aspires to reconcile technical mastery with patient-centred care, rather than eschew one in favour of the other. As such, it can provide a cogent philosophical template for current best practice, which does justice to the art as well as the science of medical care.

Contextual Factors Influencing Cost and Quality Decisions in Health and Care: A Structured Evidence Review and Narrative Synthesis.

BACKGROUND: Decisions affecting cost and quality are taken across health and care but investigation of the mediating role of context in these is in its infancy. This paper presents a synthesis of the evidence on the contextual factors that influence 'decisions of value' - defined as those characterised by having a significant and demonstrable impact on both quality and resources - in health and care. The review considers the full range of resource/quality decisions and synthesises knowledge on the contextual drivers of these. METHODS: The method involved structured evidence review and narrative synthesis. Literature was identified through searches of electronic databases (HMIC, Medline, Embase, CINAHL, NHS Evidence, Cochrane, Web of Knowledge, ABI Inform/Proquest), journal and bibliography hand-searching and snowball searching using citation analysis. Structured data extraction was performed drawing out descriptive information and content against review aims and questions. Data synthesis followed a thematic approach in accordance with the varied nature of the retrieved literature. RESULTS: Twenty-one literature items reporting 14 research studies and seven literature reviews met the inclusion criteria. The review shows that in health and care contexts, research into decisions of value in health and care is in its infancy and contains wide variation in approach and remit. The evidence is drawn from a range of service and country settings and this reduces generalisability or transferability of findings. An area of relative strength in the published evidence is inquiry into factors influencing coverage and commissioning decisions in health care systems. Allocative decisions have therefore been more consistently researched than technical decisions. We use Pettigrew's (1985) distinction between inner and outer context to structure analysis of the range of factors reported as being influential. These include: evidence/information, organisational culture and governance regimes, and; economic and political conditions. CONCLUSION: Decisions of value in health and care are subject to range of intersecting influences that often lead to a departure from narrow notions of rational decision-making. Future research should pay greater attention to the relatively under-explored area of technical, as opposed to allocative, decision-making.

The implications of endemic IMP-4 carbapenemase for clinical laboratory susceptibility testing.

A local predominance of carbapenemase producing Enterobacteriaceae with low minimum inhibitory concentrations (MIC) to meropenem prompted a review of methods available for carbapenemase detection. We report on results using two selective media, temocillin discs, CarbaNP test, GeneXpert Carba-R assay and an in-house PCR assay.

Inpatient management of gout in a New Zealand hospital: a retrospective audit.

AIM: To review inpatient management of acute gout in a New Zealand hospital. METHODS: A retrospective file review of all acute episodes of gout at Hutt Hospital, Wellington, New Zealand over a 1 year period. RESULTS: In the course of a year, there were 90 admissions for, or complicated by, acute gout. In 31 cases, gout was the primary diagnosis. Median length of stay was 5 days and readmissions were common. The majority of patients (87%) were known to have gout before admission, yet only 50% of these patients were on uric acid lowering treatment. Serum urate was measured in only 60% of patients with a mean level of 0.471 mmol/L. Treatment for the acute attack was evenly split between monotherapy (49%) and polytherapy (49%). Treatment modalities used were: prednisone (61%), non-steroidal anti-inflammatories (40%), colchicine (40%), adrenocorticotrophic hormone (ACTH) (15%) and intrarticular steroids (7%). Patients were generally treated in a timely manner with few patients experiencing delays. Patients seen by the Rheumatology Department were more likely to receive polytherapy, be treated with intra-articular steroids or ACTH and to start allopurinol. The 'treat-to-target' approach to the management of elevated serum urate was mentioned in only 9% of cases. CONCLUSION: There was considerable variability in the investigation and management of acute gout, with significant deviation from published protocols. The 'treat-to-target' approach to the management of elevated urate has not yet been widely adopted by the physicians in this New Zealand hospital.

Complications of bariatric surgery--What the general surgeon needs to know.

Obesity is an important cause of physical and psychosocial morbidity and it places a significant burden on health system costs and resources. Worldwide an estimated 200 million people over 20 years are obese and in the U.K. the Department of Health report that 61.3% of people in the U.K. are either overweight or obese. Surgery for obesity (bariatric surgery) is being performed with increasing frequency in specialist centres both in the U.K. and Ireland and abroad due to the phenomenon of health tourism. Its role and success in treating medical conditions such as diabetes mellitus and hypertension in obese patients will likely lead to an even greater number of bariatric surgery procedures being performed. Patients with early postoperative complications may be managed in specialist centres but patients with later complications, occurring months or years after surgery, may present to local surgical units for assessment and management. This review will highlight the late complications of the 3 most commonly performed bariatric surgery procedures that the emergency general surgeon may encounter. It will also highlight the complications that require urgent intervention by the emergency general surgeon and those that can be safely referred to a bariatric surgeon for further management after initial assessment and investigations.

Investigation of Suspected Pulmonary Embolism at Hutt Valley Hospital with CT Pulmonary Angiography: Current Practice and Opportunities for Improvement.

Aims. To study the use of CT pulmonary angiography (CTPA) at Hutt Hospital and investigate the use of pretest probability scoring in the assessment of patients with suspected pulmonary embolism (PE). Methods. We studied patients with suspected PE that underwent CTPA between January and May 2012 and collected data on demographics, use of pretest probability scoring, and use of D Dimer and compared our practice with the British Thoracic Society (BTS) guideline. Results. 105 patients underwent CTPA and 15% of patients had PE. 13% of patients had a Wells score prior to their scan. Wells score calculated by researchers revealed 54%, 36%, and 8% patients had low, medium, and high risk pretest probabilities and 8%, 20%, and 50% of these patients had positive scans. D Dimer was performed in 58% of patients and no patients with a negative D Dimer had a PE. Conclusion. The CTPA positive rate was similar to other contemporary studies but lower than previous New Zealand studies and some international guidelines. Risk stratification of suspected PE using Wells score and D Dimer was underutilised. A number of scans could have been safely avoided by using accepted guidelines reducing resources use and improving patient safety.

Malignant tumours of the small intestine.

Adenocarcinoma, neuroendocrine tumours, sarcomas and lymphomas are the four most common malignant tumours arising in the small intestine, although over forty different histological subtypes are described. Collectively these account for only 2% of cancers of the digestive system. The incidence of small bowel cancer has increased in recent decades with a four-fold increase in carcinoid tumours. Risk factors for small bowel tumours include coeliac disease, inflammatory bowel disease and a number of genetic abnormalities. The non-specific nature of their symptoms and the difficulty in visualising these tumours with normal endoscopic techniques often results in late diagnosis. Furthermore the paucity of literature on this topic has made it difficult to standardise management. There has however been marked improvement in imaging methods resulting in earlier diagnosis in many cases. As expected, early detection of localised, well differentiated tumours followed by surgical resection with negative margins offers the best chance of long term survival. Better adjuvant treatment, notably for gastrointestinal stromal tumours, has improved 5-year survival rates significantly. Development of surveillance guidelines for at risk populations may be a valuable way of improving early diagnosis of this challenging group of conditions.

Drug-induced subacute cutaneous lupus erythematosus due to treatment with interferon beta-1a.

Drug-induced subacute cutaneous lupus is a very rare adverse reaction to medications. This case report describes onset of this condition caused by Interferon beta-1a, which has been rarely reported previously.

The development of candidate composite disease activity and responder indices for psoriatic arthritis (GRACE project).

OBJECTIVE: To develop new composite disease activity indices for psoriatic arthritis (PsA). METHODS: Data from routine clinic visits at multiple centres were collected in a systematic manner. Data included all domains identified as important in randomised controlled trials in PsA. Decisions to change treatment were used as surrogates for high disease activity. New indices were developed by multiple linear regression (psoriatic arthritis disease activity score: PASDAS) and empirically, utilising physician-defined cut-offs for disease activity (arithmetic mean of desirability functions: AMDF). These were compared with existing composite measures: Composite Psoriatic arthritis Disease Activity Index (CPDAI), Disease Activity for PSoriatic Arthritis (DAPSA), and Disease Activity Score for rheumatoid arthritis (DAS28). RESULTS: 161/503 (32%) subjects had treatment changes. Although all measures performed well, compared with existing indices, PASDAS was better able to discriminate between high and low disease activity (area under receiver operating curves (ROC)) curve with 95% CI: PASDAS 0.773 (0.723, 0.822); AMDF 0.730 (0.680, 0.780); CPDAI 0.719 (0.668, 0.770); DAPSA 0.710 (0.654, 0.766); DAS28 0.736 (0.680, 0.792). All measures were able to discriminate between disease activity states in patients with oligoarthritis, although area under the receiver operating curves (AUC) were generally smaller. In patients with severe skin disease (psoriasis area and severity index>10) both nonparametric and AUC curve statistics were nonsignificant for all measures. CONCLUSIONS: Two new composite measures to assess disease activity in PsA have been developed. Further testing in other datasets, including comparison with existing measures, is required to validate these instruments.

Use of matrix-assisted laser desorption/ionization time-of-flight mass spectrometry analysis for rapid confirmation of Burkholderia pseudomallei in septicemic melioidosis.

Burkholderia pseudomallei was quickly identified from blood cultures collected from septicemic patients by matrix-assisted laser desorption/ionization time-of-flight mass spectrometry analysis using an in-house reference library. This procedure reduced the time to definitive identification by more than 24 hours. This analysis is a useful addition to laboratory methods for early recognition of septicemic melioidosis in non-endemic settings.

DSM diagnosis and beyond: on the need for a hermeneutically-informed biopsychosocial framework.

While often dubbed "the bible of contemporary psychiatry" and widely hailed as providing "a benchmark" for the profession, on closer inspection the DSM is seen to be shot through with philosophical assumptions that restrict its theoretical cogency and limit it clinical efficacy. Hence, in the interests of enhanced patient-care it is important to think critically about the DSM, with a view to maximising its diagnostic strengths while minimising its weaknesses. The critical analysis undertaken in the present paper underscores the importance of not construing the DSM as a self-contained diagnostic tool but of viewing it, rather, as an indispensable component in a more comprehensive, multidimensional diagnostic process. More specifically, the contention is that the DSM's diagnostic limitations evoke a biopsychosocial framework of application as their necessary corrective, notwithstanding the entrenched tendency to construe these approaches as oppositional. Further, it is contended that a hermeneutically informed biopsychosocial template has particular advantages as an integrating framework.