Clindamycin adjunctive therapy for severe Staphylococcus aureus treatment evaluation (CASSETTE)-an open-labelled pilot randomized controlled trial.

BACKGROUND: Combination antibiotic therapy with an antitoxin agent, such as clindamycin, is included in some guidelines for severe, toxin-mediated Staphylococcus aureus infections. The evidence to support this practice is currently limited to in vitro, animal and observational human case-series data, with no previous randomized controlled trials (RCTs). OBJECTIVES: This pilot RCT aimed to determine the feasibility of conducting a clinical trial to examine if adjunctive clindamycin with standard therapy has greater efficacy than standard therapy alone for S. aureus infections. METHODS: We performed an investigator-initiated, open-label, multicentre, pilot RCT (ACTRN12617001416381p) in adults and children with severe S. aureus infections, randomized to standard antibiotic therapy with or without clindamycin for 7 days. RESULTS: Over 28 months, across nine sites, 127 individuals were screened and 34 randomized, including 11 children (32%). The primary outcome-number of days alive and free of systemic inflammatory response syndrome ≤14 days-was similar between groups: clindamycin (3 days [IQR 1-6]) versus standard therapy (4 days [IQR 0-8]). The 90 day mortality was 0% (0/17) in the clindamycin group versus 24% (4/17) in the standard therapy group. Secondary outcomes-microbiological relapse, treatment failure or diarrhoea-were similar between groups. CONCLUSIONS: As the first clinical trial assessing adjunctive clindamycin for S. aureus infections, this study indicates feasibility and that adults and children can be incorporated into one trial using harmonized endpoints, and there were no safety concerns. The CASSETTE trial will inform the definitive S. aureus Network Adaptive Platform (SNAP) trial, which includes an adjunctive clindamycin domain and participants with non-severe disease.

Biocontrol potential and genetic diversity of Metarhizium anisopliae lineage in agricultural habitats.

AIMS: To assess phylogenetic and genotypic diversity of Metarhizium anisopliae lineage within diverse agroecosystems in the Karnataka State of India and to compare their chitinase activity and pathogenicity against insect pest of field crops subterranean termite, Odontotermes obesus. METHODS AND RESULTS: Three phylogenetic and 27 microsatellite markers were used to assess the genetic diversity of M. anisopliae lineage within multiple agroecosystems. Multilocus phylogeny of the Metarhizium isolates identified two species: Metarhizium pingshaense and Metarhizium guizhouense. Multilocus phylogeny and microsatellite markers resolved two phylogenetic species of M. pingshaense, Mp_1 and Mp_2, and one phylogenetic species of M. guizhouense, Mg_1. Phylogenetic species, Mp_2 and Mg_1, were detected with one genotype each and Mp_1 with eleven genotypes. Metarhizium pingshaense GKVK 02_16 isolate caused significantly high mortality of O. obesus in bioassays and detected with high chitinase activity. CONCLUSIONS: The study revealed phylogenetic and genotypic diversity of M. anisopliae lineage in agroecosystems of Karnataka State. Findings of pathogenicity and chitinase activity suggest that M. pingshaense GKVK 02_16 isolate provides effective control of O. obesus. SIGNIFICANCE AND IMPACT OF THE STUDY: The investigation provided an understanding of the genetic diversity and biocontrol efficiency of M. anisopliae lineage in agroecosystem. These data will serve as a resource in the future pest management strategies at a regional scale.

Multidrug-resistant tuberculosis in Australia, 1998-2012.

OBJECTIVE: To describe the epidemiology and outcomes of multidrug-resistant tuberculosis (MDR-TB) diagnosed in Australia between 1998 and 2012. DESIGN: A retrospective review was undertaken involving all patients with laboratory-confirmed MDR-TB notified in Australia between 1998 and 2012 inclusive. Demographic, clinical and laboratory features are described. Clinical outcomes were defined according to World Health Organization definitions of treatment success (cure and treatment completion), treatment failure, death, loss to follow-up (including transfer out), or not evaluated at treatment completion. RESULTS: A total of 244 cases of MDR-TB were diagnosed in Australia during the study period, representing 1.4% of all TB cases notified. The majority were born outside Australia, including one third in Papua New Guinea. Of those with treatment outcome data available, treatment success was demonstrated in 81%. Treatment success was positively associated with use of a second-line injectable agent. Those born in Papua New Guinea were less likely to achieve treatment success. CONCLUSION: MDR-TB is uncommon in Australia. The large number of cases born in Papua New Guinea, and the poorer outcomes in this cohort, represent challenges with cross-border management of MDR-TB in the Torres Strait. Australia has an ongoing role in the prevention and management of MDR-TB locally and in the region.

Challenges to delivery of isoniazid preventive therapy in a cohort of children exposed to tuberculosis in Timor-Leste.

OBJECTIVES: To evaluate the number and geographic location of children aged <5 years exposed to sputum smear-positive tuberculosis (TB) in Timor-Leste, to determine the proportion evaluated for isoniazid preventive therapy (IPT) and to review the programmatic challenges present in delivering IPT to this cohort. METHODS: A total of 256 consecutive sputum smear-positive TB index cases diagnosed at Bairo Pite Clinic between August 2013 and July 2014 were interviewed about places of residence and household contacts <5 years of age in the 3 months preceding diagnosis. Attendance of these contacts for screening and the outcome of screening were recorded prospectively. RESULTS: The majority (225 of 256, 88%) of index cases resided in Dili, but 73 of 225 (32%) of these also had a second address outside the capital. A total of 255 contacts were identified; 172 of 255 (67%) of whom lived in Dili district and 83 of 255 (33%) of whom resided in remote districts. Only 66 of 255 (26%) contacts attended for evaluation for IPT, of whom 46 of 255 (18%) started IPT and nine of 255 (3.5%) were diagnosed with TB. Attendance was significantly less likely when the index case was not the parent of the child contact. CONCLUSIONS: Sputum smear-positive pulmonary TB cases frequently result in household exposure of children <5 years in Timor-Leste, and provision of IPT is suboptimal. Contacts are located in diverse and distant locations. Further studies to delineate access barriers to IPT and review programmatic models that will facilitate IPT scale up in Timor-Leste are needed.

Heterotopic ossification in unidentified skeletal remains.

Heterotopic ossification is a benign, ectopic bone growth that develops in muscle and other soft tissue. The exact cause is poorly understood, but it is a rarely serious complication of soft tissue trauma. Its most common form, myositis ossifications traumatica, occurs as a secondary complication of direct muscle injury. However, other forms are less common and can result from specific pathologic conditions, such as spinal cord trauma and metabolic disorders. In patients who have had spinal cord injury and subsequent paraplegia, heterotopic ossification often results in ankylosis of the hip and a loss in range of motion. Ectopic ossification occurs below the injury site, and, although the specific muscle groups can vary, it usually involves those for which the origin and insertion involve the anterior pelvis and proximal femur. In dried bone, heterotopic ossification can appear as a smooth, irregularly shaped benign tumor of mature bone, extending from the surface but not invading the cortical bone. These tumors range in size from a few millimeters to several centimeters. Because heterotopic ossification is often associated with specific types of injuries, it has a unique anthropological use in forensic cases.

Use of significance image to determine patterns of cortical blood flow abnormality in pathological and at-risk groups.

UNLABELLED: The purpose of this work was to determine whether certain pathological groups and other groups at risk for neurological damage exhibited distinctive patterns of regional cerebral blood flow (rCBF) abnormality. METHODS: HMPAO SPECT images obtained from six groups of subjects were compared with a normal cortical rCBF atlas, based on multivariate, voxel-by-voxel methods. In each case, a significance image was outputted, highlighting voxels with deficits of > or =3 s.d. of normal. Abnormal patterns were examined for the six groups, which comprised a further 40 normal volunteers, 18 diver controls, 50 divers with decompression illness (DCI), 34 boxers, 23 schizophrenics and 21 subjects with Alzheimer's disease. RESULTS: The percentages of abnormal cortical voxels for each group were 0.41%, 0.53%, 1.38%, 1.05%, 0.56% and 2.24%, respectively. The percentages of images in each group with at least one lesion of 10 or more connected abnormal voxels and at least 10 lesions of two or more connected voxels, respectively, were 8% and 8% (normal volunteers), 17% and 11% (diver controls), 38% and 38% (divers with DCI), 41% and 29% (boxers), 26% and 13% (schizophrenics) and 90% and 48% (subjects with Alzheimer's disease). This suggests that multiple small lesions are as common as single large lesions for divers with DCI but not for patients with Alzheimer's disease or schizophrenia. Large lesions are located predominantly in the parietal and inferior temporal regions for Alzheimer's disease, in the parietal and occipital regions for divers with DCI and boxers and in the inferior frontal region for schizophrenia. CONCLUSION: It appears that the groups considered here do have different rCBF patterns and that the significance image is a useful way of demonstrating this fact.

The viability of an abbreviated version of the Holtzman Inkblot Technique with older adults.

Multiple regression analyses of Holtzman Inkblot Technique (HIT; Holtzman, Thorpe, Swartz, & Herron, 1961) factor scores were conducted to empirically determine the viability of a short form of the HIT with older adults. Although R2 values were acceptable, the contribution of individual cards to total factor scores was dubious at best. These data suggest that the development of a short form of the HIT for use with older adults is premature and requires more systematic research to justify its viability.

Dental health and dental care requirements for young handicapped adults in Wessex.

The dental health status and treatment requirements of 195 young handicapped adults living in the Wessex Health Region are reported. These young adults, aged 25-34 years, attended adult training centres on a daily basis in each of the districts in Wessex Region. The amount of untreated caries was higher and the periodontal status worse for this group than would normally be expected in young adults in this age range. The dental care received was related to the ability of the subject to comprehend and co-operate with the operator. Nearly half the subjects could receive routine treatment in a normal surgery and about a quarter were likely to require hospitalisation and general anaesthesia to achieve any treatment. The community dental service should play an important role in organising and supervising preventive strategies, with the aim of improving oral hygiene for these young handicapped adults, which should materially improve their periodontal health.

Toward the equivalence of the HIT and HIT 25 in community-residing older adults.

In a study by the first author wherein 102 community-residing older adults were administered the Holtzman Inkblot Technique (HIT), data collected were analyzed regarding the equivalence of the HIT and the HIT 25. Although alpha coefficients and split-half correlations were low when single-response-per-card data were analyzed, corrected Spearman-Brown coefficients were more supportive of the use of the HIT 25 with older adults. These data suggest that although a shortened form of the HIT may be useful with aged persons, research exploring the substantive bases for creating a shortened version of the HIT is nevertheless necessary.

Communicative efficacy of psychotherapy research.

Practitioners have claimed that information relevant to psychotherapy application is not regularly provided in professional journals. A survey of the 1985-1987 psychotherapy outcome literature investigated the extent of specific points of information in journal reports. Results partially support the complaint that pertinent information is not routinely available. No content area addressed found consistent representation. Noticeable deficiencies were tabulated for specific categories of patient demographics, disorder description, and replication studies. This suggests an underacknowledgement of the practical utility, both clinical and empirical, of common points of fact.

The credibility and legitimation of science: A loss of faith in the scientific narrative.

The presence of scientific misconduct challenges the authority of science to regulate itself. This paper examines the basis for scientific self-regulation, a basis which forms an ideology of science that has served to publicly legitimate the authority and autonomy of science. It is argued that the conventional scientific narrative overstates quality control and, as a consequence, that there is a potential crisis of legitimation in science. In particular, the dichotomy that is constructed between (1) the structure of science and (2) the individual scientist, is seen as problematic and cannot be used to shift the responsibility for misconduct onto individuals while at the same time preserving the sanctity of the structure of scientific practices-the two are inseparable. This analysis helps to locate the data audit/quality assurance movement and to clarify its role within the structure of scientific practices. The continued public support and legitimation of science requires that the scientific community critically examine and strengthen the structure of scientific practices. The re-examination should not focus overtly on controlling individual scientists. Rather, given the communal nature of science, the appropriate focus is on the social units that constitute and control the structure of scientific practices: laboratories, institutions, scientific societies and journals, and funding agencies. The First International Conference on Scientific Data Audit Policies and Quality Assurance should be viewed, then, as the beginning of a serious and difficult conversation among scientists on how to improve quality control in science and achieve public accountability while at the same time retaining the vitality of scientific practices.

A comparison of three delivery methods of chlorhexidine in handicapped children. I. Effects on plaque, gingivitis, and toothstaining.

In handicapped groups, the maintenance of oral hygiene can be a major problem, and chemical plaque control offers many advantages. This study compared the effectiveness of chlorhexidine gluconate, delivered as a 0.2% mouthrinse, a 0.2% spray, and a 1% gel in trays, in controlling dental plaque and gingival bleeding in a group of 49 spastic children. All three delivery methods produced an improvement in plaque and gingival bleeding scores. However, the gel was significantly more effective than either the mouthwash or the spray. There was no significant difference between delivery methods in the amount of tooth staining.

A comparison of three delivery methods of chlorhexidine in handicapped children. II. Parent and house-parent preferences.

As part of a study of chlorhexidine used for plaque control in handicapped children, preferences and difficulties with the three delivery methods were evaluated by questionnaire. The delivery methods were a 0.2% mouthwash, 0.2% spray, and 1% gel in trays. Responses from parents and house parents revealed the least preference for, and most difficulties with, the gel in trays. The spray was the most popular and 96% of the respondents would be prepared to use this indefinitely as a method of oral hygiene. The most effective method was the gel in trays, but results of the questionnaire suggested that the respondents would be unwilling to use it for prolonged periods. The importance of user acceptance and compliance to the long-term success of oral hygiene methods was evident.

Bed load transport by submerged jets.

Some similarities are presented between the bed load transport of noncohesive grains in long rivers and at a local, jet-induced scour. Experiments are described in which a submerged two-dimensional slot nozzle, inclined downward, eroded a deep sand bed. The rate of erosion at the very beginning of a scour was evaluated and compared with river data by use of the idea of "stream-power." Empirical relationships for the two cases are similar, although the geometry of the boundaries is quite different.

Urinary excretion of c-hydroxy derivatives of methaqualone in man.

1. Six monohydroxy metabolites of methaqualone have been identified by g.l.c.-mass spectrometry in the urine of healthy human subjects who received therapeutic doses (250 mg) of the drug (Melsed) daily for ten day. 2. The three major metabolites were 2-methyl-3-(2'-hydroxymethylphenyl)-4(3H)-quinazolinone, 2-methyl-3-(2'-methyl-3'-hydroxyphenyl)-4(3H)-quinazolinone and 2-methyl-3-(2'-methyl-4'-hydroxyphenyl)-4(3H)-quinazolinone. Three minor metabolites in descending order of importance were 2-hydroxymethyl-3-o-tolyl-4(3H)-quinazolinone, 2-methyl-6-hydroxy-3-o-tolyl-4(3H)-quinazolinone and 2-methyl-8-hydroxy-3-o-tolyl-4(3H)-quinazolinone. 3. The 8-hydroxy metabolite is identified as a urinary metabolite or methaqualone in humans for the first time.