Delirium in HIV-infected patients admitted to acute medical wards post universal access to antiretrovirals in South Africa.

BACKGROUND: Delirium is associated with increased mortality and length of hospital stay. Limited data are available from HIV-infected acute hospital admissions in developing countries. We conducted a prospective study of delirium among acute medical admissions in South Africa (SA), a developing country with universal antiretroviral therapy (ART) access and high burdens of tuberculosis (TB) and non-communicable disease. OBJECTIVES: To identify the prevalence of, risk factors for and outcomes of delirium in HIV-infected individuals in acute general medical admissions. METHODS: Three cohorts of adult acute medical admissions to Groote Schuur and Victoria Wynberg hospitals, Cape Town, SA, were evaluated for prevalent delirium within 24 hours of admission. Reference delirium testing was performed by either consultant physicians or neuropsychologists, using the Confusion Assessment Method. RESULTS: The study included 1 182 acute medical admissions, with 318 (26.9%) HIV-infected. The median (interquartile range) age and CD4 count were 35 (30 - 43) years and 132 (61 - 256) cells/µL, respectively, with 140/318 (44.0%) using ART on admission. The prevalence of delirium was 17.6% (95% confidence interval (CI) 13.7 - 22.1) among HIV-infected patients, and delirium was associated with increased inpatient mortality. In multivariable logistic regression analysis, factors associated with delirium were age ≥55 years (adjusted odds ratio (aOR) 6.95 (95% CI 2.03 - 23.67); p=0.002), and urea ≥15 mmol/L (aOR 4.83 (95% CI 1.7 - 13.44); p=0.003), while ART use reduced risk (p=0.014). A low CD4 count, an unsuppressed viral load and active TB were not predictors of delirium; nor were other previously reported risk factors such as non-opportunistic acute infections or polypharmacy. CONCLUSIONS: Delirium is common and is associated with increased mortality in HIV-infected acute medical admissions in endemic settings, despite increased ART use. Older HIV-infected patients with renal dysfunction are at increased risk for inpatient delirium, while those using ART on admission have a reduced risk.

The N-formyl peptide receptors: contemporary roles in neuronal function and dysfunction.

N-formyl peptide receptors (FPRs) were first identified upon phagocytic leukocytes, but more than four decades of research has unearthed a plethora of non-myeloid roles for this receptor family. FPRs are expressed within neuronal tissues and markedly in the central nervous system, where FPR interactions with endogenous ligands have been implicated in the pathophysiology of several neurodegenerative diseases including Alzheimer's disease and Parkinson's disease, as well as neurological cancers such as neuroblastoma. Whilst the homeostatic function of FPRs in the nervous system is currently undefined, a variety of novel physiological roles for this receptor family in the neuronal context have been posited in both human and animal settings. Rapid developments in recent years have implicated FPRs in the process of neurogenesis and neuronal differentiation which, upon greater characterisation, could represent a novel pharmacological target for neuronal regeneration therapies that may be used in the treatment of brain/spinal cord injury, stroke and neurodegeneration. This review aims to summarize the recent progress made to determine the physiological role of FPRs in a neuronal setting, and to put forward a case for FPRs as a novel pharmacological target for conditions of the nervous system, and for their potential to open the door to novel neuronal regeneration therapies.

The formyl peptide receptor agonist FPRa14 induces differentiation of Neuro2a mouse neuroblastoma cells into multiple distinct morphologies which can be specifically inhibited with FPR antagonists and FPR knockdown using siRNA.

The N-formyl peptide receptors (FPRs) have been identified within neuronal tissues and may serve as yet undetermined functions within the nervous system. The FPRs have been implicated in the progression and invasiveness of neuroblastoma and other cancers. In this study the effects of the synthetic FPR agonist FPRa14, FPR antagonists and FPR knockdown using siRNA on mouse neuroblastoma neuro2a (N2a) cell differentiation plus toxicity were examined. The FPRa14 (1-10µM) was found to induce a significant dose-dependent differentiation response in mouse neuroblastoma N2a cells. Interestingly, three distinct differentiated morphologies were observed, with two non-archetypal forms observed at the higher FPRa14 concentrations. These three forms were also observed in the human neuroblastoma cell-lines IMR-32 and SH-SY5Y when exposed to 100µM FPRa14. In N2a cells combined knockdown of FPR1 and FPR2 using siRNA inhibited the differentiation response to FPRa14, suggesting involvement of both receptor subtypes. Pre-incubating N2a cultures with the FPR1 antagonists Boc-MLF and cyclosporin H significantly reduced FPRa14-induced differentiation to near baseline levels. Meanwhile, the FPR2 antagonist WRW4 had no significant effect on FPRa14-induced N2a differentiation. These results suggest that the N2a differentiation response observed has an FPR1-dependent component. Toxicity of FPRa14 was only observed at higher concentrations. All three antagonists used blocked FPRa14-induced toxicity, whilst only siRNA knockdown of FPR2 reduced toxicity. This suggests that the toxicity and differentiation involve different mechanisms. The demonstration of neuronal differentiation mediated via FPRs in this study represents a significant finding and suggests a role for FPRs in the CNS. This finding could potentially lead to novel therapies for a range of neurological conditions including neuroblastoma, Alzheimer's disease, Parkinson's disease and neuropathic pain. Furthermore, this could represent a potential avenue for neuronal regeneration therapies.

A new approach to preferred provider selection in health care.

In January 2015 Zilveren Kruis, the largest health insurer in The Netherlands, engaged in a new three-year, unlimited volume contract with five carefully selected providers of cataract surgery. Zilveren Kruis used a novel method, designed to identify the top expert providers in a certain discipline. This procedure for provider selection uses the principles of Best Value Procurement (BVP), and puts the provider in charge of defining key performance indicators for health care quality. The procedure empowers the professional and acknowledges that the provider, not the purchaser, is the true expert in defining what is high quality care. This new approach focuses purely on provider selection and is thus complementary to innovations in health care reimbursement, such as value-based hospital purchasing or outcome-based financing. We describe this novel approach to preferred provider selection and show how it makes affordable quality the core topic in negotiations with providers.

Clinical outcomes of Ahmed Glaucoma valve in posterior segment versus anterior chamber.

PURPOSE: To compare the intermediate-term intraocular pressure (IOP) control and complication profile of the Ahmed Glaucoma Valve (AGV) implanted posteriorly through the pars plana in eyes undergoing concurrent pars plana vitrectomy (PPV) with device implantation in the anterior chamber (AC) in nonvitrectomized eyes. METHODS: : We retrospectively reviewed the medical records of 31 case eyes (30 patients) with refractory glaucoma that underwent posterior implantation of AGV after complete PPV and compared them to 31 control eyes (31 patients) with refractory glaucoma that underwent implantation of AGV in the AC. Case-control patients were matched one-to-one on the basis of principal glaucoma diagnosis. All surgeries were performed at 1 institution using a silicone-plate device. Success was defined as intraocular pressure (IOP)≥ 5 mm Hg and ≤ 21 mm Hg with or without glaucoma medications at final follow-up, no additional glaucoma surgery, no removal of the implant, and no loss of light perception. RESULTS: The average follow-up was 20.9 months (range, 6 to 54 mo) for the posterior group and 20.5 months (range, 4 to 48 mo) for the anterior group. The reduction in IOP was similar in both groups at all postoperative time points. The number of postoperative glaucoma medications in both groups was not statistically different at final follow-up. Success rates at final follow-up were identical, 83.9% in both groups, and Kaplan-Meier survival curve analysis showed no significant difference between the 2 groups (P=0.96). Postoperative complications were similar between the 2 groups, except there were more instances of early postoperative flat AC in the anterior group than the posterior group (P=0.01). CONCLUSIONS: The AGV can similarly control IOP in the majority of cases, whether the tube is placed in the posterior segment after PPV or in the AC of nonvitrectomized eyes.

Multifactorial intervention with nurse practitioners does not change cardiovascular outcomes in patients with chronic kidney disease.

Strict implementation of guidelines directed at multiple targets reduces vascular risk in diabetic patients. Whether this also applies to patients with chronic kidney disease (CKD) is uncertain. To evaluate this, the MASTERPLAN Study randomized 788 patients with CKD (estimated GFR 20-70 ml/min) to receive additional intensive nurse practitioner support (the intervention group) or nephrologist care (the control group). The primary end point was a composite of myocardial infarction, stroke, or cardiovascular death. During a mean follow-up of 4.62 years, modest but significant decreases were found for blood pressure, LDL cholesterol, anemia, proteinuria along with the increased use of active vitamin D or analogs, aspirin and statins in the intervention group compared to the controls. No differences were found in the rate of smoking cessation, weight reduction, sodium excretion, physical activity, or glycemic control. Intensive control did not reduce the rate of the composite end point (21.3/1000 person-years in the intervention group compared to 23.8/1000 person-years in the controls (hazard ratio 0.90)). No differences were found in the secondary outcomes of vascular interventions, all-cause mortality or end-stage renal disease. Thus, the addition of intensive support by nurse practitioner care in patients with CKD improved some risk factor levels, but did not significantly reduce the rate of the primary or secondary end points.

Cloud and fog processing enhanced gas-to-particle partitioning of trimethylamine.

An aerosol time-of-flight mass spectrometer (ATOFMS) was used to detect trimethylamine (TMA) in 0.52-1.9 µm particles at urban and rural sites in Southern Ontario during the summer and winter of 2007. During the summer, TMA-containing particles were observed exclusively during high relative humidity or fog events at both the urban and rural sites. In the wintertime, greater concentrations of TMA-containing particles were linked to cloud processing of aerosol in air masses originating from over agricultural and livestock areas. A laboratory study revealed that, at high relative humidity (∼ 100%), gas phase TMA at concentrations ranging from 2 to 20,000 ppt partitions preferentially to acidic particles present in the ambient air. On the basis of the field and laboratory studies, it appears that gas phase TMA present in ambient air partitions onto pre-existing particles preferentially during periods of acidic cloud/fog processing, leading to the presence of TMA-containing particles in the 0.52-1.9 µm size range.

Intravitreal injection of tissue plasminogen activator as treatment for an occluded pars plana glaucoma tube.

Implanting glaucoma tubes through the pars plana in the setting of a corneal transplant is becoming more common, and there are unique problems associated with such a procedure. A 42-year-old man with multiple previous eye surgeries presented with a nonfunctioning pars plana glaucoma tube. There was no view to the tube tip, but it was presumed to be clogged with fibrin. Intravitreal tissue plasminogen activator (tPA) was injected through the pars plana which resulted in intraocular pressure control without further surgery. This new application of intravitreal tPA has not been reported previously. Future research should investigate the optimal effective and safe dose of intravitreal tPA injection to relieve such occlusions.

Comparison of trabeculectomy with Ex-PRESS miniature glaucoma device implanted under scleral flap.

PURPOSE: To evaluate the Ex-PRESS miniature implant (Model R 50) placed under partial-thickness scleral flap compared with standard trabeculectomy. METHODS: In this retrospective comparative series of 100 eyes, we compared 50 eyes in 49 patients treated with the Ex-PRESS miniature glaucoma implant under a scleral flap with 50 matched control eyes in 47 patients treated with trabeculectomy. Success was defined as intraocular pressure (IOP) > or =5 mm Hg and < or =21 mm Hg, with or without glaucoma medications, without further glaucoma surgery or removal of implant. Early postoperative hypotony was defined as IOP <5 mm Hg during the first postoperative week. RESULTS: The average follow-up was 10.8 months (range 3.5 to 18) for the Ex-PRESS group and 11.2 months (range 3 to 15) for the trabeculectomy group. Although the mean IOP was significantly higher in the early postoperative period in the Ex-PRESS group compared with the trabeculectomy group, the reduction of IOP was similar in both groups after 3 months. The number of postoperative glaucoma medications in both groups was not significantly different. Kaplan-Meier survival curve analysis showed no significant difference in success between the 2 groups (P=0.594). Early postoperative hypotony and choroidal effusion were significantly more frequent after trabeculectomy compared with Ex-PRESS implant under scleral flap (P<0.001). CONCLUSIONS: The Ex-PRESS implant under a scleral flap had similar IOP-lowering efficacy with a lower rate of early hypotony compared with trabeculectomy.

Medical therapy of pediatric glaucoma and glaucoma in pregnancy.

Although surgery remains the definitive treatment for congenital and other childhood glaucomas, medical therapy can be effective in lowering intraocular pressure as a temporizing measure before surgery or as long-term adjunctive treatment in disease refractory to surgical measures. Carbonic anhydrase inhibitors, beta-blockers, cholinergic drugs, and the prostaglandin-related drugs all play an effective role in pediatric glaucoma management. The usefulness and safety profile of the adrenergic agonists and the osmotic agents are less well established. In medically treating the pediatric patient or the pregnant woman for glaucoma, the clinician must be mindful of the possibility of adverse effects and be prepared to alter or terminate treatment if needed.

A modified technique of reconstruction for complete acromioclavicular dislocation: a prospective study.

BACKGROUND: Many procedures, both nonoperative and operative, have been described for treatment of complete acromioclavicular dislocations. The best primary treatment, however, still remains unclear. PURPOSE: We present a new surgical technique in which the clavicle is reduced to an anatomic position, the coracoacromial ligament is transferred to the clavicle, and acromioclavicular joint fixation is accomplished with the use of absorbable, braided suture cord. METHODS: Twenty-one patients underwent the modified technique of reconstruction. Patients were included only if they had sustained a Rockwood type V acromioclavicular dislocation and were extremely active in competitive sports before dislocation occurred. RESULTS: Eighteen patients returned to their sports without pain within 2.5 months after operation. The mean follow-up was 35.7 months. The average Constant score at last follow-up was 97. Radiographs taken at this time confirmed anatomic reduction in 18 patients, residual subluxation in 2 patients, and, in 1 patient, redislocation of the joint that occurred because of infection. Six patients had radiographic evidence of coracoclavicular ossifications. All patients developed a wide scar. CONCLUSIONS: Considering its operative simplicity, the advantage of absorbable augmentation of the clavicular reduction, and the low rate of recurrence, this technique may be an attractive alternative in this particular group of patients.

Complications after colorectal surgery without mechanical bowel preparation.

BACKGROUND: The current practice of mechanical bowel preparation (MBP) before colorectal surgery is questionable. Mechanical bowel preparation is unpleasant for the patient, often distressful, and potentially harmful. The results are often less than desired, increasing the risk of contamination. Cleansing the colon and rectum before surgery has never been shown in clinical trials to benefit patients. In animal experiments MBP has a detrimental effect on colonic healing. STUDY DESIGN: To investigate the outcomes of colorectal surgery without MBP, we prospectively evaluated a consecutive series of patients who underwent resection and primary anastomosis of the colon and upper rectum, including emergency operations. One surgeon performed all operations. Endpoints were wound infection, anastomotic failure, and death. Late signs and symptoms that might be secondary to leakage of the anastomosis were considered as an anastomotic failure as well, during a followup of 1 year. RESULTS: Two hundred fifty operations were performed, of which 199 (79.6%) were elective. Colectomies were left-sided in 65.6%. Anastomoses were ileocolic in 32%, colocolic in 20.8%, colorectal intraperitoneal in 34.4%, and extraperitoneal in 12.8%. No patient suffered from fecal impaction. Followup was complete in 97.2%. Eight patients (3.3%; 95% confidence interval [CI]: 1.4-6.4) developed superficial wound infections. In three patients there was leakage from an extraperitoneal colorectal anastomosis, in two of them after hospital discharge. The overall anastomotic failure rate was 1.2% (95% CI: 0.3-3.6). The in-hospital mortality rate was 0.8% (95% CI: 0.1-2.9) and was not related to abdominal or septic complications. CONCLUSION: Mechanical bowel preparation is not a sine qua non for safe colorectal surgery.