Mindfulness-based psychotherapies: a review of conceptual foundations, empirical evidence and practical considerations

OBJECTIVE: This paper, composed by an interest group of clinicians and researchers based in Melbourne, presents some background to the practice of mindfulness-based therapies as relevant to the general professional reader. We address the empirical evidence for these therapies, the principles through which they might operate, some practical questions facing those wishing to commence practice in this area or to refer patients into mindfulness-based therapies, and some considerations relevant to the conduct and interpretation of research into the therapeutic application of mindfulness. METHOD: Databases (e.g. PsycINFO, MEDLINE) were searched for literature on the impact of mindfulness interventions, and the psychological and biological mechanisms that underpin the effects of mindfulness practice. This paper also draws upon the clinical experience of the author group. RESULTS: Mindfulness practice and principles have their origins in many contemplative and philosophical traditions but individuals can effectively adopt the training and practice of mindfulness in the absence of such traditions or vocabulary. A recent surge of interest regarding mindfulness in therapeutic techniques can be attributed to the publication of some well-designed empirical evaluations of mindfulness-based cognitive therapy. Arising from this as well as a broader history of clinical integration of mindfulness and Western psychotherapies, a growing number of clinicians have interest and enthusiasm to learn the techniques of mindfulness and to integrate them into their therapeutic work. This review highlights the importance of accurate professional awareness and understanding of mindfulness and its therapeutic applications. CONCLUSIONS: The theoretical and empirical literatures on therapeutic applications of mindfulness are in states of significant growth and development. This group suggests, based on this review, that the combination of some well-developed conceptual models for the therapeutic action of mindfulness and a developing empirical base, justifies a degree of optimism that mindfulness-based approaches will become helpful strategies to offer in the care of patients with a wide range of mental and physical health problems.     

Lapses in a prefrontal-extrastriate preparatory attention network predict mistakes

Mistakes are common to all forms of behavior but there is disagreement about what causes errors. We recorded electrophysiological and behavioral measures in a letter discrimination task to examine whether deficits in preparatory attention predicted subsequent response errors. Error trials were characterized by decreased frontal-central preparatory attention event-related potentials (ERPs) prior to stimulus presentation and decreased extrastriate sensory ERPs during visual processing. These findings indicate that transient lapses in a prefrontal-extrastriate preparatory attention network can lead to response errors.     

BK virus-associated nephropathy in sirolimus-treated renal transplant patients: incidence, course, and clinical outcomes

BACKGROUND: Because the course of polyoma virus-associated nephropathy (PVAN) has not been evaluated in a large cohort of patients receiving sirolimus (SRL)-based regimens, we have herein presented the incidence, clinical characteristics, and outcomes of 378 renal transplant recipients treated with SRL-based immunosuppression. METHODS: This retrospective single center study evaluated 344 kidney alone (KTX) and 34 simultaneous pancreas-kidney (SPK) transplantations performed between June 2000 and December 2004. RESULTS: At a mean follow-up of 43.3 months, six kidney (1.7%) and three kidney-pancreas (9.0%) transplanted patients displayed biopsy-proven PVAN. The mean time to diagnosis after transplantation was 18.2 months (range: 3.5-31.1 months), with a higher incidence among patients exposed (4.23%) versus not exposed to rabbit antithymocyte globulin (rATG; 0.53%; P=0.019) or SPK (9.0%) versus KTX (1.7%) recipients (odds ratio: 5.43; confidence interval: 1.29-22.8; P=0.038). Despite treatment with cidofovir, reduced immunosuppression and maintenance therapy with no agents other than SRL (C0=10.2+/-2.7 ng/dL) plus modest doses of prednisone (< or =5 mg), five patients (55.5%) experienced renal allograft failure. No rejection episodes were documented during the PVAN treatment and pancreatic function continued to be excellent among the SPK patients. CONCLUSIONS: Patients treated with SRL-based immunosuppression showed an incidence at the lower end of the range described with various other contemporaneous immunosuppressive regimens and with other cohorts not undergoing BK virus polymerase chain reaction surveillance. Exposure to rATG and SPK transplantation represented risk factors for the occurrence of PVAN, which showed a pernicious course despite withdrawal of calcineurin antagonists and/or mycophenolate mofetil.     

Pediatric robotic surgery: lessons from a clinical experience

PURPOSE: Robotic surgery may improve minimally invasive surgery at high magnification by tremor filtration, motion-scaling, and improved dexterity with the provision of a wrist at the end of the robotic instrument. MATERIALS AND METHODS: We chose the Zeus Microwrist robotic surgical system as more applicable to small children than the competing da Vinci surgical system. We attempted 57 surgical procedures and completed 54. RESULTS: Completed procedures included Nissen fundoplication (n = 25), cholecystectomy (n = 18), Heller myotomy (n = 2), splenectomy (n = 2), Morgagni hernia repair (n = 2), and single cases of complex pyloroplasty in the chest, bowel resection, left Bochdalek congenital diaphragmatic hernia repair, esophageal atresia and tracheoesophageal fistula repair, and choledochal cyst excision. There were no complications related to the use of the robot. The mean time for the surgeon at the console using the robot was 117 +/- 39 minutes for Nissen fundoplication, and the total operating room time was 250 +/- 60 minutes. Surgeons found dissection, suturing, and knot tying easier than with conventional laparoscopy. None of the surgeons thought the lack of touch feedback (haptics) was crucial. CONCLUSION: Robotic surgery offers increased dexterity to the pediatric minimally invasive surgeon, but procedures require more time, and there is no defined patient benefit. The fact that robotic surgery digitalizes minimally invasive surgery creates exciting possibilities for training surgeons, planning operations, and performing surgery at great distances from the operator.     

Randomized, double-blind comparison of patient-controlled epidural infusion vs nurse-administered epidural infusion for postoperative analgesia in patients undergoing colonic resection

BACKGROUND: There is little published evidence of the analgesic efficacyof patient-controlled epidural analgesia (PCEA) for postoperativepain relief. The aim of this study was to compare the analgesicefficacy of epidural infusion of bupivacaine 0.125% and fentanyl4 µg ml^–1 administered by either PCEAwith a background infusion or nurse-administered continuousepidural infusion (CEI) after major intra-abdominal surgery. METHODS: In a double-blind, randomized clinical trial, 205 adult patientsundergoing colonic resection by laparotomy received either PCEAor CEI. Pain scores were recorded via a four-point verbal ratingscale at 1, 2, 3, 4, 8, 12, 24, 48, and 72 h after surgery.The administration of epidural top-ups and systemic analgesiaover the same period was also recorded, and patient satisfactionquestionnaires completed. RESULTS: The median area under the curve of pain against time was significantlylower in the PCEA group (2 vs 24, P<0.001) as were mediansummary pain scores on movement (0.67 vs 1.33, P<0.001).Significantly fewer patients in the PCEA group received oneor more epidural top-ups (13 vs 36%, P = 0.0002) or any systemicanalgesics (41 vs 63%, P = 0.0021). Patients in the PCEA groupwere significantly more likely to be very satisfied than inthe CEI group (76 vs 43%, P<0.0001). CONCLUSIONS: PCEA provides greater analgesic efficacy than CEI for postoperativeanalgesia after major intra-abdominal surgery, and a decreasedrequirement for physician or nurse intervention.     

Preservation solutions for static cold storage of kidney allografts: a systematic review and meta-analysis

Static cold storage is the most prevalent method for renal allograft preservation. Several solutions have been designed to counteract the detrimental effects of cold ischemia and reperfusion. The aim of this study was to appraise the evidence for the currently available preservation solutions. We performed a systematic literature search using MEDLINE, EMBASE, the Cochrane Library, the Transplant Library and trial registries. Inclusion criteria specified any comparative, prospective study for deceased donor renal allografts. Studies were assessed for methodological quality. The primary outcome was delayed graft function (DGF). Fifteen trials with a total of 3584 kidneys were included. Eurocollins was associated with a higher risk of DGF than University of Wisconsin solution (UW) in two randomized controlled trials (RCTs) and histidine-tryptophan-ketoglutarate (HTK) in two RCTs. UW was associated with an equal risk of DGF compared with Celsior in three RCTs and HTK in two RCTs. There was limited data regarding other comparisons and outcomes. The choice of preservation solution has an effect on the incidence of DGF, which might, in turn, affect long-term outcomes. Both UW and HTK have lower rates of DGF than Eurocollins. There is no difference in the incidence of DGF with the use of Celsior, HTK and UW. These findings are supported by registry data.     

Modified Ollier transtrochanteric approach for the treatment of acetabular fractures

The purpose of this retrospective clinical study was to evaluate the rates of wound and neurologic complications and clinically significant heterotopic ossification, Brooker stage 3 and 4, with the modified Ollier transtrochanteric approach for the treatment of acetabular fractures. The study group comprised 94 consecutive patients (95 acetabuli) who had unstable acetabular fractures requiring surgical fixation. All patients were treated with open reduction internal fixation via the Ollier approach by a single surgeon (L.E.D.). Demographic and clinical information regarding rates of wound and neurologic complications and remaining articular stepoff at fixation was obtained from a chart review. The degree of heterotopic ossification was graded from standard anteroposterior pelvis radiographs according to the Brooker classification. Six (6%) patients underwent reoperation for infection; however, only 3 (3%) of these patients had deep infections. Three (3%) patients had iatrogenic sciatic nerve injuries; only 1 patient had persistent sensory changes at final follow-up. Thirteen (18%) of the 73 patients with radiographs available for review at a minimum of 3-month follow-up had Brooker grade III heterotopic ossification and 1 (1%) patient had grade IV. Five (5%) patients underwent excision of heterotopic ossification. Fourteen (17%) of 81 patients had no radiographic union of the greater trochanteric osteotomy, but none of these patients required further surgery. The complication rates of the Ollier approach in this study compare favorably with alternative surgical approaches reported in large series. We believe this approach provides excellent exposure without increasing the risk of complications.     

Thymoglobulin,sirolimus, and reduced-dose cyclosporine provides excellent rejection prophylaxis for pancreas transplantation

BACKGROUND: We investigated a novel immunosuppressive protocol including thymoglobulin induction in combination with sirolimus and corticosteroids, followed by introduction of markedly reduced exposures to cyclosporine to prevent pancreas-transplant rejection. METHODS: A 7-day course of thymoglobulin (1.5 mg/kg per day) was begun on postoperative day (POD) 0, together with 15 mg of sirolimus on POD 1, and followed by 5 mg per day, targeting these doses to achieve a trough of 10 to 20 ng/mL. When the serum creatinine was below 2.5 mg/dL, cyclosporine was introduced at 50 mg twice daily with dose adjustment to maintain a trough concentration of 100 to 125 ng/mL. RESULTS: The 18 patients included 14 simultaneous pancreas-kidney and 4 pancreas-after-kidney transplant recipients. Two patients were African-American, three patients had a pretransplant panel reactive antibody greater than 20%, and the human leukocyte antigen (HLA) mismatch was 4.5+/-1 (mean+/-standard deviation). With a mean follow-up of 13.6+/-4.7 months, patient, kidney, and pancreas graft survivals are 100%, 100%, and 94%, respectively. A single pancreas graft was lost to thrombosis. There were no acute rejection episodes and no opportunistic infections. Mean hospital stay was 9+/-3 days. At 3 months posttransplantation, the mean value of serum creatinine was 1.2+/-0.3 mg/dL, fasting glucose was 88+/-15 mg/dL, and sirolimus dose at month 3 was 6.3+/-3 mg per day and at month 12 2.7+/-1 mg per day. The average total daily cyclosporine A dose at month 3 was 208+/-62 mg per day and 133+/-13 mg per day at 1 year. CONCLUSIONS: This immunosuppressive regimen provided excellent prophylaxis against acute rejection with no opportunistic infections. We believe that careful monitoring of sirolimus and cyclosporine levels was critical to success of this protocol.     

Unusual absence of endothelium-dependent or -independent vasodilatation to purines or pyrimidines in the rat renal artery

BACKGROUND: Adenosine triphosphate (ATP) is a cotransmitter with noradrenaline (NA) in sympathetic perivascular nerves. It has a dual role in the maintenance of vascular tone as ATP, released from endothelial cells during shear stress or hypoxia, induces vasodilatation via endothelial P2Y receptors or by direct action on smooth muscle. The role and distribution of P2 receptors is well characterized for many blood vessels but not for the rat renal artery. This study aims to determine whether ATP is a vasoconstrictor cotransmitter with NA and whether ATP induces vasodilatation via the endothelium or smooth muscle. METHODS: On isolated rat renal arteries, electrical field stimulation (EFS) in the absence and presence of antagonists to P2X receptors and alpha1-adrenoceptors was examined. Concentration-response curves were constructed to NA, ATP, alpha,beta-methylene ATP (alpha,beta-meATP), uridine triphosphate (UTP), and 2-methylthio ADP (2-MeSADP) on low tone. Curves to acetylcholine (ACh), 2-MeSADP, and UTP were constructed on raised tone. Immunofluorescent localization of P2X and P2Y receptor subtypes was performed. RESULTS: Electrical field stimulation induced vasoconstriction, partially inhibited by the P2X receptor antagonist, pyridoxalphosphate-6-azophenyl-2',4'-disulfonic acid, and predominantly by prazosin. Exogenous NA and ATP mimicked EFS; immunostaining for P2X1 and P2X2 receptors was expressed on vascular smooth muscle. Unusually, ATP, 2-MeSADP, and UTP failed to induce vasodilatation. Acetylcholine induced vasodilatation. alpha,beta-meATP, 2-MeSADP, and UTP induced vasoconstriction via P2X1, P2Y1, and P2Y2 receptors, respectively. Immunostaining for P2X1, P2Y1, and P2Y2 receptors was expressed on the vascular smooth muscle. CONCLUSION: Adenosine triphosphate and NA are cotransmitters in sympathetic nerves supplying the rat renal artery, NA being the dominant partner. The novel feature of this vessel is that purines and pyrimidines do not produce either endothelium-dependent or -independent vasodilatation; P2X1, P2Y1, and P2Y2 receptors on the smooth muscle all mediate vasoconstriction.     

The place of sirolimus in kidney transplantation: can we reduce calcineurin inhibitor renal toxicity?

Sirolimus, a macrocylic lactone, blocks T-cell activation by a mechanism of action distinct from calcineurin inhibitors (CNIs). Therefore, it may be expected that sirolimus would display a safety profile without the vasomotor form of nephrotoxicity characteristic of CNIs. Initial studies in rodent models and in psoriasis patients showed that sirolimus alone did not impair renal function. Subsequently, two pivotal, randomized double dummy, phase III trials in human renal transplantation demonstrated that sirolimus exacerbated the nephrotoxicity of full doses of CNIs. Both pharmacokinetic and pharmacodynamic mechanisms have been implicated in the pathogenesis of this disorder. Subsequent experience has shown that cyclosporin A dose reduction, elimination, or avoidance mitigates these effects, particularly in patients distant from the transplant procedure. However, there is concern about recovery from ischemia-reperfusion injury. Animal models suggesting that sirolimus may delay recovery in this setting have been supported by non-randomized experiences at single centers, which have observed an increased incidence of delayed graft function among sirolimus-treated recipients. In contrast, large single- and multi-center studies have not confirmed this finding; impaired renal recovery has been observed in only occasional instances. Thus, present data indicate that sirolimus does not impair the function of an uninjured kidney, but whether the drug acts alone or potentiates conditions that delay recovery after ischemic injury remains to be established by large randomized trials specifically targeted to recipients at high risk for this complication.