Haloperidol for delirium in critically ill patients - protocol for a systematic review.

BACKGROUND: In the intensive care unit, the prevalence of delirium is high. Delirium has been associated with morbidity and mortality including more ventilator days, longer intensive care unit stay, increased long-term mortality, and cognitive impairment. Thus, the burden of delirium for patients, relatives, and societies is considerable. The objective of this systematic review was to critically access the evidence of randomised clinical trials on the effects of haloperidol vs. placebo or any other agents for delirium in critically ill patients. METHODS: We will search for randomised clinical trials in the following databases: Cochrane Library, MEDLINE, EMBASE, Science Citation Index, BIOSIS, Cumulative Index to Nursing and Allied Health Literature, Latin American and Caribbean Health Sciences Literature, and Allied and Complementary Medicine Database. Two authors will independently screen and select references for inclusion using Covidence, extract data and assess the methodological quality of the included randomised clinical trials using the Cochrane risk of bias tool. Any disagreement will be resolved by consensus. We will analyse the extracted data using Review Manager, STATA 15, and Trial Sequential. ANALYSIS: The aim of this study was to assess the quality of the evidence, we will create a 'Summary of Findings' table containing our primary and secondary outcomes using the GRADE assessment. DISCUSSION: Our ambition with this systematic review is to provide reliable and powered evidence to better inform decision makers on the use of or future trials with haloperidol for the management of delirium in critically ill patients.

Tolterodine extended release is well tolerated in older subjects.

OBJECTIVES: To investigate the tolerability of tolterodine extended release (ER) in older subjects with overactive bladder (OAB). METHODS: This was a retrospective analysis of pooled data from five large, randomised, double-blind, placebo-controlled trials. Subjects with OAB symptoms, including urinary frequency and urgency (and nocturia in two studies) with or without urgency urinary incontinence, received qd treatment with tolterodine ER (4 mg) or placebo for 8-12 weeks. Data were stratified post hoc by age group: < 65 (n = 2531), 65-74 (n = 1059) and > or = 75 years (n = 573). Tolerability was assessed by evaluating the occurrence of adverse events (AEs). AE occurrences from each study were mapped to the MedDRA coding dictionary of preferred terms. RESULTS: Discontinuation rates were slightly higher among subjects > or = 75 years of age vs. those < 65 years of age; however, this was observed in subjects treated with placebo as well as tolterodine ER. Overall, there were no significant differences in the occurrence of dry mouth, headache, constipation, nausea, urinary tract infection, blurred vision, dry eye, dizziness and micturition disorder in older (65-74 or > or = 75 years) vs. younger (< 65 years) subjects treated with tolterodine ER relative to placebo (treatment x age; all p > 0.1). Dry mouth was the only AE consistently associated with tolterodine ER treatment (< 65 years, 17%; 65-74 years, 16%; > or = 75 years, 15%). The occurrence of all other AEs was < or = 5% in most age and treatment cohorts. Most AEs were mild or moderate in all age and treatment cohorts. CONCLUSION: The nature and frequency of AEs associated with tolterodine ER treatment were similar across age groups in subjects with OAB, suggesting that tolterodine ER was not associated with an increased risk of AEs in older vs. younger subjects and, thus, is a suitable first-line pharmacotherapy treatment for OAB in this population.

Oxybutynin extended release for the management of overactive bladder: a clinical review.

Overactive bladder (OAB) is a common condition which negatively impacts the quality of life of afflicted patients. This can result in alterations in social interactions at home, in the workplace and in the community, often leading to depression and poor self esteem as well as loss of productivity. Traditional mainstays of treatment include both behavioral therapy and pharmacotherapy. Oxybutynin immediate release (IR) represents the first such medication approved by the FDA specifically for treatment of OAB in 1975. Nevertheless, bothersome side effects in addition to thrice daily dosing often led to treatment cessation which raised the question that patients may actually prefer to live with their OAB symptoms rather than incur side effects or complex dosing schemes. Pharmacological advances ultimately led to development of a long-acting formulation of oxybutynin in the form of oxybutynin extended release (ER) with the hope that this drug would maintain efficacy while decreasing bothersome side effects and improve compliance with the convenience of once daily dosing regimen. This paper will review the major clinical studies involving oxybutynin ER as well as its role in different patient populations and potential concerns with its use.

Quality of life after surgery for stress incontinence.

This study investigated changes in condition-specific quality of life (QOL) after surgery for stress urinary incontinence. Data from 655 women in a clinical trial comparing the Burch and fascial sling were examined. Improvement in QOL, measured with the Incontinence Impact Questionnaire (mean decrease 133.1; SD 109.8), was observed 6 months after surgery and persisted at 24 months. Women for whom surgery was successful (regardless of surgery type) had greater improvement in QOL (mean decrease 160.0; SD 103.9) than did women for whom surgery was not successful (mean decrease 113.6; SD 110.9; p < 0.0001), although not statistically significant after adjusting for covariates. Multivariable analysis showed that QOL improvement was related to decreased urinary incontinence (UI) symptom bother, greater improvement in UI severity, younger age, Hispanic ethnicity, and receiving Burch surgery. Among sexually active women, worsening sexual function had a negative impact on QOL. Improved QOL was explained most by UI symptom improvement.

Management of impending penile prosthesis erosion with a polytetrafluoroethylene distal wind sock graft.

PURPOSE: Erosion of penile prostheses can be calamitous, often leaving patients unable to accommodate further implants. There is a paucity of literature describing impending erosion of penile prosthesis. We report on 5 patients with impending erosion of a penile prosthesis who underwent polytetrafluoroethylene distal wind sock graft placement. MATERIALS AND METHODS: From 1993 to 1997, 5 patients with a mean age of 49 years and impending penile prosthesis erosion underwent 6 revisions using a polytetrafluoroethylene distal wind sock graft. Two patients underwent simultaneous bilateral grafts while 1 patient underwent separate right and left grafts 3 years apart. Indications for reconstruction included distal migration of the prosthetic cylinders into the glans in 4 patients and impingement of the distal urethra in 2. Of the patients 3 were spinal cord injured, 1 had lumbar radiculopathy and 1 had a history of pelvic irradiation. Inflatable prostheses were implanted in 4 patients, while 1 received a malleable prosthesis. RESULTS: Patients underwent a mean of 1.5 penile prosthetic revisions (0 to 4) before diagnosis of impending erosion. An interval of 8 to 144 months (mean 66) elapsed from the most recent penile prosthesis insertion until distal wind sock graft placement. Mean operative time was 1 hour 51 minutes (1.3 to 2.5 hours). Mean hospital stay was 6.3 days (3 to 12). At a mean followup of 32 months (0.7 to 5.2 years) all patients had satisfactory and functional erections with no pain or evidence of impending erosion or penile prosthesis infection. CONCLUSIONS: Erosion of a penile prosthesis can have disastrous consequences. We describe a safe and effective technique for managing impending penile prosthesis erosion using a polytetrafluoroethylene distal wind sock graft.

Video urodynamic findings in men with the central cord syndrome.

PURPOSE: The central cord syndrome reportedly has a favorable prognosis and rehabilitation outcome. However, to our knowledge the status of the lower urinary tract in patients with the central cord syndrome is unclear. We report on 22 men with the central cord syndrome who were evaluated by video urodynamics. MATERIALS AND METHODS: From 1986 to the present we identified 22 men with a mean age of 51 years who had the central cord syndrome and were included in the Houston Veterans Affairs spinal cord registry. All patients underwent video urodynamic evaluation a mean of 34.5 months after injury. RESULTS: Video urodynamic testing for vesicourethral dysfunction was normal in 3 patients, while it showed bladder outlet obstruction secondary to benign prostatic hyperplasia in 2, detrusor areflexia in 4, external detrusor-sphincter dyssynergia in 11, detrusor hyperreflexia with a synergistic external urethral sphincter in 1 and detrusor hypocontractility in 1. Urinary tract infection recurred in 3 patients with external detrusor-sphincter dyssynergia and urolithiasis developed in 2. CONCLUSIONS: Urodynamic testing revealed a high incidence of external detrusor-sphincter dyssynergia in men with the central cord syndrome. Due to the potential for upper tract deterioration all patients with the central cord syndrome should undergo baseline urodynamic studies. Those at high risk for upper tract deterioration with external detrusor-sphincter dyssynergia or a loss of compliance should be treated more aggressively with clean intermittent catheterization and anticholinergic medication when possible.

A new senescence-inducing mitochondrial linear plasmid in field-isolated Neurospora crassa strains from India.

Several field-collected strains of Neurospora crassa from the vicinity or Aarey, Bombay, India, are prone to precocious senescence and death. Analysis of one strain, Aarely-1e, demonstrated that the genetic determinants for the predisposition to senescence are maternally inherited. The senescence-prone strains contain a 7-kb, linear, mitochondrial DNA plasmid, maranhar, which is not present in long-lived isolates from the same geographical location. The maranhar plasmid has inverted terminal repeats with protein covalently bound at the 5' termini. Molecular hybridization experiments have demonstrated no substantial DNA sequence homology between the plasmid and the normal mitochondrial (mtDNA) and nuclear genomes of long-lived strains of N. crassa. Integrated maranhar sequences were detected in the mtDNAs of two cultures derived from Aarey-1e, and mtDNAs with the insertion sequences accumulated during subculturing. Nucleotide sequence analysis of cloned fragments of the two insertion sequences demonstrates that they are flanked by long inverted repeats of mtDNA. The senescence syndrome of the maranhar strains, and the mode of integration of the plasmid, are reminiscent of those seen in the kalilo strains of N. intermedia. Nonetheless, there is no detectable nucleotide sequence homology between the maranhar and kalilo plasmids.

alpha-Glucosidase and N-acetylglucosamine-6-sulphatase are the major mannose-6-phosphate glycoproteins in human urine.

Most newly synthesized lysosomal enzymes contain a transient carbohydrate modification, mannose 6-phosphate (Man-6-P), which signals their vesicular transport from the Golgi to the lysosome via Man-6-P receptors (MPRs). We have examined Man-6-P glycoproteins in human urine by using a purified soluble fragment of the soluble cation-independent MPR (sCI-MPR) as a preparative and analytical affinity reagent. In a survey of urine samples from seven healthy subjects, the pattern of Man-6-P glycoproteins detected with iodinated sCI-MPR as a probe in a blotting assay was essentially identical in each, regardless of sex or age. Two bands of approx. 100 and 110 kDa were particularly prominent. Man-6-P glycoproteins in human urine were purified by affinity chromatography on immobilized sCI-MPR. Seven distinct bands revealed by SDS/PAGE and Coomassie Blue staining were subjected to N-terminal sequence analysis. The prominent 100 and 110 kDa Man-6-P glycoproteins were identified as N-acetylglucosamine-6-sulphatase and alpha-glucosidase respectively. This identification was confirmed by molecular mass determinations on the two major bands after deglycosylation. Sequence analysis revealed arylsulphatase A and several previously unidentified proteins as minor species. Man-6-P glycoproteins were also purified on an analytical scale to determine the proportion of a number of lysosomal enzyme activities represented by the mannose-6-phosphorylated forms. The lysosomal enzymes in urine containing the highest proportion of mannose-6-phosphorylated form were beta-mannosidase (82%), hexosaminidase (27%) and alpha-glucosidase (24%). The profiles of Man-6-P glycoproteins detected by blotting in urine and plasma were not similar, suggesting that the urinary species are not derived from the bloodstream.

Double stranded RNA in natural isolates of Neurospora.

Thirty-six wild type isolates of Neurospora were surveyed for the presence of dsRNA. The survey identified seven strains which contain dsRNA molecules. These seven strains are all from different geographic locations. The sizes of the dsRNAs range from 500 bp to 18 kb and a total of seven distinct dsRNA species was identified. Cross homologies of some of the dsRNAs were apparent. There was homology between the 9.0 kb dsRNA and genomic DNA prepared from all strains in the survey, indicating a possible cellular rather than viral origin for this dsRNA species. None of the other dsRNAs hybridized with genomic DNA suggesting a viral origin for these dsRNAs.