The quality of reporting of phase II and III trials for new antipsychotics: a systematic review.

BACKGROUND: The findings of the Clinical Antipsychotic Trials of Intervention Effectiveness (CATIE) study and the Cost Utility of the Latest Antipsychotic Drugs in Schizophrenia Study (CUtLASS) called previous trials of antipsychotics into question, including pre-licensing trials. Concerns regarding methodological robustness and quality of reporting increased. This systematic review aimed to examine the quality of reporting of phase II and III trials for new antipsychotics in the aftermath of the CATIE and CUtLASS studies. METHOD: Electronic searches were conducted in EMBASE, Medline and Cochrane databases and also ClinicalTrials.gov for antipsychotic trials (published between January 2006 and February 2012). Phase II and III randomized controlled trials (RCTs) for iloperidone, asenapine, paliperidone, olanzapine, lurasidone and pomaglumetad methionil were selected for schizophrenia and schizoaffective disorder. The reporting of the methodology was evaluated in accordance with Consolidated Standards of Reporting Trials (CONSORT) guidelines. RESULTS: Thirty-one articles regarding 32 studies were included. There was insufficient reporting of design in 47% of studies and only 13% explicitly stated a primary hypothesis. Exclusion criteria were poorly reported for diagnosis in 22% of studies. Detail regarding comparators, particularly placebos, was suboptimal for 56% of studies, and permitted concomitant medication was often not reported (19%). Randomization methods were poorly described in 56% of studies and reporting on blinding was insufficient in 84% of studies. Sample size calculations were insufficiently reported in 59% of studies. CONCLUSIONS: The quality of reporting of phase II and III trials for new antipsychotics does not reach the standards outlined in the CONSORT guidelines. Authors often fail to adequately report design and methodological processes, potentially impeding the progress of research on antipsychotic efficacy. Both policymakers and clinicians require high quality reporting before decisions are made regarding licensing and prescribing of new antipsychotics.

Efficacy of incisional negative pressure therapy in preventing post-sternotomy wound complications.

BACKGROUND: Sternal wound infections represent a source of significant morbidity and mortality following median sternotomy. The use of incisional negative pressure wound therapy in prevention has yet to be elucidated. METHODS: A retrospective study was conducted before and after a universal wound care protocol was implemented including the prophylactic use of negative pressure wound therapy (NPWT). The primary endpoint was sternal infections within 90 days of the index operation. RESULTS: In the control period, there was a 3.0% rate of sternal infection within 90 days compared to 0.8% in the intervention period (p < 0.001). An odds ratio of 0.25 (95% confidence interval 0.11, 0.57; p < 0.001) in the intervention period as compared to the control period was demonstrated. CONCLUSIONS: The use of a standardized wound care protocol including the universal application of NPWT for patients undergoing cardiac surgery with median sternotomy was an independent predictor of decreased rates of sternal infection.

Synthesis of novel N-(2-hydroxy-2-p-tolylethyl)-amide and N-(2-oxo-2-p-tolylethyl)-amide derivatives and their antidyslipidemic and antioxidant activity.

In continuation of our drug discovery program on metabolic diseases, we identified an alkaloidal amide, that is, Aegeline (V) from the plant Aegle marmelos leaves as a dual acting agent (antihyperlipidemic and antihyperglycemic). We therefore synthesized a series of alkaloidal amides [N-(2-hydroxy-2-p-tolylethyl)-amides and N-(2-oxo-2-p-tolylethyl)-amide derivatives] related to Aegeline and screened for their in vivo antihyperlipidemic activity in Triton induced hyperlipidemia model. The synthetic compounds 4, 17 and 20 showed equipotent activity to the natural product, that is, Aegeline (V). These compounds also showed strong antioxidant activity, which support their antihyperlipidemic activity. Compound 12 showed better antihyperlipidemic and antioxidant profile than the natural product V.

Double blind placebo control trial of large neutral amino acids in treatment of PKU: effect on blood phenylalanine.

Large neutral amino acids (LNAA) have been used on a limited number of patients with phenylketonuria (PKU) with the purpose of decreasing the influx of phenylalanine (Phe) to the brain. In an open-label study using LNAA, a surprising decline of blood Phe concentration was found in patients with PKU in metabolic treatment centres in Russia, the Ukraine, and the United States. To validate the data obtained from this trial, a short-term double-blind placebo control study was done using LNAA in patients with PKU, with the participation of three additional metabolic centres--Milan, Padua and Rio de Janeiro. The results of the short trial showed significant lowering of blood Phe concentration by an average of 39% from baseline. The data from the double-blind placebo control are encouraging, establishing proof of principle of the role of orally administered LNAA in lowering blood Phe concentrations in patients with PKU. Long-term studies will be needed to validate the acceptability, efficacy and safety of such treatment.

Large neutral amino acids in the treatment of phenylketonuria (PKU).

Large neutral amino acids (LNAAs) have been used on a limited number of patients with phenylketonuria (PKU) with the purpose of decreasing the influx of phenylalanine (Phe) to the brain. In earlier studies on mice with PKU (ENU(2)/ENU(2)), LNAAs were given and a surprising decline in blood Phe concentrations was observed. The formula used in the mouse experiment (PreKUnil) lacked lysine. Therefore, a new formulation of LNAAs (NeoPhe) was developed, introducing changes in the concentration of some amino acids and adding lysine, so that such a mixture could be used in humans. The new formula was found to be effective in reducing blood Phe concentration in mice by about 50% of the elevated levels. Patients with PKU were given LNAAs and blood Phe concentrations were determined in an open-label study. Three centers--in Russia, the Ukraine and the USA--took part in the study. NeoPhe was given at 0.5 g/kg per day in three divided doses to eight subjects with PKU and at 1.0 g/kg per day to three patients, for one week. The NeoPhe resulted in decrease of elevated blood Phe by 50% in both groups. The preliminary data from this study are encouraging and a double blind placebo-controlled trial will be required to show long-term efficacy and tolerance of LNAAs in the treatment of PKU.

Elisa kit evaluation for IGG and IGM antibodies to A-60 tubercular protein antigen.

AIMS: The purpose of this study is to evaluate the A-60 antigen-based enzyme-linked immuno sorbent assay (ELISA) test for its sensitivity, specificity, and other related statistical parameters. SETTINGS AND DESIGN: Sera from 114 healthy volunteers, 105 bacteriologically confirmed cases of pulmonary tuberculosis (PTB), 59 sera from family contacts of PTB, and 40 sera from cases of lung infections other than tuberculosis collected from September to December 2003 were used for the kit evaluation. METHODS AND MATERIALS: Enzyme-linked immuno sorbent assay test using tuberculosis A-60 antigen-based kit manufactured by Anda Biologicals, France was used for the evaluation. STATISTICAL ANALYSIS: Differences in the optical density (OD) values for immunoglobulins G (IgG), and immunoglobulins M (IgM) antibodies in various groups were studied using t-test. RESULTS: On the basis of the findings the threshold value was setup as 400 U for IgG and mean OD for sera from healthy volunteers +2SD as the threshold for IgM. The sensitivity was 80% and specificity 95.8% for the IgG antibody test. The efficiency and predictive values were also high. The sensitivity for IgM was low (28.5%) but the specificity was high (95.7%). None of the 40 nontubercular lung infection cases were positive for the IgG and IgM antibody test for A-60, whereas five and three cases of 59 family contacts of PTB were positive for IgG and IgM antibody test. The test reproducibility was good for both IgG and IgM. CONCLUSION: IgG antibody test using A-60 antigen has good sensitivity and specificity, whereas IgM antibody test had high specificity but low sensitivity. Multicentric trials suggested evaluation of the diagnostic utility of the test for the extra-PTB.

Synthesis, characterization and anticancer activity of gold(I) complexes that contain tri-tert-butylphosphine and dialkyl dithiocarbamate ligands.

Two new gold(I) complexes that contain tri-ter-butylphosphine and dialkyl dithiocarbamate ligands were synthesized and characterized by FTIR, NMR spectroscopy, Cyclic voltammetry, elemental analysis and X-ray diffraction. The in vitro cytotoxicity of both complexes was examined against A549 (lung cancer), MCF7 (breast cancer), and HeLa (cervical cancer) human cancer cell lines. Both complexes exhibit very strong in vitro cytotoxic effects against A549, MCF7 and HeLa cell lines. The screening of the cytotoxic activity based on IC50 data against the A549, MCF7, and HeLa lines shows that the synthesized gold(I) complexes are highly effective, particularly against HeLa cancer cell line. Based on IC50 data, the cytotoxic activity of both complexes is better than well-known commercial anticancer drug cisplatin against all the three cancer lines tested.

Prevalence of measles antibodies in adults with HIV infection: possible risk factors of measles seronegativity.

OBJECTIVES: To determine the prevalence of measles (rubeola) immunity in a group of HIV-1-infected adults and to examine predictors of measles seronegativity in this population. SETTING: County hospital outpatient clinic and public-health department early HIV intervention clinic. PATIENTS: A total of 262 HIV-infected adults presenting to outpatient clinics between September 1990 and January 1991. INTERVENTIONS: Patients were screened for the presence of measles immunoglobulin G antibody, as measured by an enzyme-linked immunosorbent assay (ELISA). Pertinent clinical and immunologic information was recorded. Univariate and multivariate analyses were performed to identify possible risk factors for measles seronegativity. MAIN OUTCOME MEASURE: Measles seronegativity, as defined by a lack of detectable antibody (ELISA predicted index value < 1.0). RESULTS: Thirteen (5%) patients lacked serologic evidence of immunity. Risk factors for measles seronegativity included year of birth in 1957 or later, Caucasian (non-Hispanic) race and oral hairy leukoplakia. Factors associated with progressive HIV disease (other than hairy leukoplakia) were not associated with a lack of existing immunity. CONCLUSIONS: A high prevalence (95%) of measles antibody was found in this large group of HIV-infected adults. Young, white individuals born in 1957 or later were at the greatest risk for measles seronegativity, but declining immunity due to progressive HIV infection did not appear to be associated with a lack of antibody. Self-reported histories of measles infection or immunization were not reliable predictors of measles immunity.

Pancreatic cystadenocarcinoma associated with strongyloides.

A 60-year-old woman presented with a mass in the left upper abdominal quadrant. Noninvasive studies showed a cystic structure arising from the pancreas. Pathologic studies of the tumor revealed pancreatic cystadenocarcinoma; the fluid contained Strongyloides larvae. There was no evidence of disseminated Strongyloides or immunosuppression. Results of stool examinations were also negative for Strongyloides. Were these larvae the etiologic agent for the carcinoma? Other parasitic infestations have been associated with carcinoma. This is the first reported association between Strongyloides and cystadenocarcinoma.

Effect of epinephrine and norepinephrine on immuno-reactive insulin secretion from isolated islets of Langerhans.

Earlier studies have demonstrated the inhibitory nature of epinephrine and norepinephrine on pancreatic insulin release. The present study reports their effect on beta-cell IRI release in an isolated islet system. Results show that epinephrine and norepinephrine inhibit islet-IRI release at the 100-10 microM level. The alpha adrenergic blocker phentolamine (100 microM) but not the beta adrenergic blocker propranolol (100 microM) can reverse this catecholamine induced inhibition of islet-IRI release. This clearly suggests that epinephrine and norepinephrine inhibit insulin release via alpha-adrenergic pathway.

Control of olefin geometry in the bryostatin B-ring through exploitation of a C(2)-symmetry breaking tactic and a Smith-Tietze coupling reaction.

A completely stereocontrolled asymmetric synthesis of an advanced B-ring synthon for the bryostatin family of antitumor agents is reported. Noteworthy features of our synthesis include the Smith-Tietze bis-alkylation reaction between 12 and 13 en route to C(2)-symmetrical ketone 10 and the totally stereoselective conversion of 10 into triol 18 via a Grignard addition tactic. Triol 18 was converted to epoxide 3 in nine steps, and an acid-catalyzed intramolecular Williamson etherification reaction completed the synthesis of 2.

Chronic toxicity of styrene maleic anhydride, a male contraceptive, in rhesus monkeys (Macaca mulatta).

A newly developed male contraceptive, styrene maleic anhydride (SMA), was injected in the vas deferens of male rhesus monkeys for safety evaluation at the dose of 100 mg (contraceptive dose, CD), 250 mg (CD x 2.5) and 500 mg (CD x 5.0), and the monkeys were kept under observation for one year. The observed behavioural, haematological, biochemical and histopathological parameters in treated monkeys were comparable to controls. The results suggest the polymer SMA to be safe up to 5 times CD in monkeys.

Quantification of facial surface change using a structured light scanner.

Three-dimensional surface changes that accompany facial surgical procedures were measured noninvasively and evaluated quantitatively. An optical three-dimensional surface scanner with 360-degree surface coverage of a subject's head and a subsecond data acquisition was used. The scanner employs six pairs of "white light" pattern projectors and digital TV cameras. A noncontact optical method to quantify facial surface morphology and objectively assess change resulting from reconstructive or cosmetic plastic surgery has been developed. This quantification technique was implemented and tested with the three-dimensional range scanner. This technique defines the entire surface of the head and face, as opposed to the conventional manual method of measuring surface points or facial landmarks. The method allows facial volume change assessment. The method was tested by repeatedly scanning a volunteer who was injected subcutaneously with known volumes of anesthetic solution. The measured and injected volumes were compared and showed little difference.

Patterns of use of unconventional therapies in the medical outpatient department of a tertiary care hospital in India.

Unconventional, alternative or unorthodox systems of treatment have become increasingly popular in recent years. We interviewed patients visiting the Internal Medicine outpatient department (OPD) for a period of 6 months regarding their use of unconventional therapies. Overall 76% of patients visiting the OPD had used one or more of the unconventional therapies in the past 1 year. Homeopathy was found to be the most frequently used alternative therapy (38.6%). A large number of patients used more than one unconventional therapy. Digestive problems, backache, joint pains and bronchial asthma were the most frequent conditions for which alternative therapies were used. Most patients who used alternative therapies used them on their own, without actually visiting a provider of such therapies. Because of the widespread use of alternative systems of medicine, efforts to enhance understanding about these forms of treatment have to be made.

Assessment of mass properties of human head using various three-dimensional imaging modalities.

Better methods are needed to analyse personal protective devices, such as helmets or facemasks, before they are used in practice. Software tools to quantify three-dimensional craniofacial mass properties are developed to improve our understanding of craniofacial impact biomechanics, supplement existing knowledge of osseous structure and provide a comprehensive description of human head morphology. The application of state-of-the-art imaging systems, solid modelling and other software tools are studied to determine the associated errors in mass property estimation by spiral computed tomography, three-dimensional magnetic resonance and optical surface scanning using phantoms and cadaver head studies. Volume, centre of gravity and principal moments of inertia are determined from solid mathematical models for each scanning modality. Landmark-based registration is used to register scans of the same object obtained from the three imaging modalities to a common reference co-ordinate system. Physically and analytically determined mass properties are used as the standard for truth. Although this comparative study does not lend itself to statistical analysis owing to the small sample size, results indicate that any of the three imaging modalities can be used to predict mass properties within the uncertainty of existing methods. Applying these techniques in vivo is practical and feasible.

Visualization and quantitative analysis of talocrural joint kinematics.

The three dimensional (3D) in vivo kinematic behavior of the ankle joint was evaluated using spiral volumetric CT scanning of a normal adult foot. The CT data were reconstructed and interpolated to create an isotropic 3D data volume. These data were rendered, visualized, segmented into their bony elements, labeled, and exported to disk using Mayo Analyze software. The labeled 3D CT datasets were analyzed to determine relative orientation, translation, and rotation of the tibia-talus, tibia-calcaneus and calcaneus-talus. Using these results, the 3D motion characteristics during normal adult foot flexion/extension were described quantitatively.

Management of the obstetric patient with tuberculosis.

Tuberculosis in obstetric patients presents a challenging nursing problem to facilities caring for populations at high risk: the economically disadvantaged, minorities, the foreign-born, and patients with human immunodeficiency virus. Coordination of public health, outpatient, and inpatient services is essential for obtaining the desired outcome of a healthy family unit with a minimum of interruption of the attachment process. This article presents issues related to nursing care and medical management of tuberculosis in the perinatal period.

Validation of spiral CT and optical surface scanning for lower limb stump volumetry.

Spiral X-ray Computed Tomography (SXCT), Optical Surface Scanning (OSS), and hydrostatic weighing methods were used to measure stump volume of trans-tibial amputees. The precision and accuracy of these methods were assessed in a validation study. A repeated measures analysis of variance statistical design was employed that required each participant to be measured (scanned) twice at each of two separate measurement sessions. For OSS and SXCT, each scan was segmented twice to determine intra-observer error. Plaster cast replicas of subject stumps were formed by certified prosthetists to serve as a reference standard. Accuracy (bias) of SXCT and OSS was determined by comparison to volumetry by hydrostatic weighing. Ten trans-tibial amputees were recruited for this study and nine completed both sessions. Plaster replica measurement precision error relative to the mean was found to be less than 1% for all modalities. The precision was slightly inferior on subjects, 1.1% and 2.2% error for hydrostatic weighting and OSS respectively, due to patient instability during measurement, but was better with SXCT where the subjects' stumps were stabilized during scan acquisition. The OSS and SXCT methods offer advantages over hydrostatic weighing and other volumetry methods since the volume data are represented digitally and can be analyzed in multiple ways. SXCT enables study of the stump and its internal tissues with the prosthesis in place. It was found that SXCT is comparable to hydrostatic weighing in both precision and accuracy. While OSS had a high precision and reproducibility, it was found to have an associated bias.