Rothia aeria vertebral discitis/osteomyelitis in an immunocompetent adult: Case report and literature review.

Rothia aeria is a gram-positive, pleomorphic bacteria forming part of human oral microflora usually only causing periodontal and dental infections. We describe the case of a 68-year-old immunocompetent male with lumbar vertebral discitis/osteomyelitis caused by R. aeria. A review of the literature demonstrated seventeen cases of non-dental R. aeria infection of which only six were in immunocompetent individuals. This is the first reported case of R. aeria vertebral discitis/osteomyelitis.

Investigating Conceptual Models for the Relationship Between Depression and Condomless Sex Among Gay, Bisexual, and Other Men Who have Sex with Men: Using Structural Equation Modelling to Assess Mediation.

The aim of this study is to investigate five hypothesized mechanisms of causation between depression and condomless sex with ≥ 2 partners (CLS2+) among gay, bisexual, and other men who have sex with men (GBMSM), involving alternative roles of self-efficacy for sexual safety and recreational drug use. Data were from the AURAH cross-sectional study of 1340 GBMSM attending genitourinary medicine clinics in England (2013-2014). Structural equation modelling (SEM) was used to investigate which conceptual model was more consistent with the data. Twelve percent of men reported depression (PHQ-9 ≥ 10) and 32% reported CLS2+ in the past 3 months. AURAH data were more consistent with the model in which depression was considered to lead to CLS2+ indirectly via low self-efficacy for sexual safety (indirect Beta = 0.158; p < 0.001) as well as indirectly via higher levels of recreational drug use (indirect Beta = 0.158; p < 0.001). SEM assists in understanding the relationship between depression and CLS among GBMSM.

Accuracy of self-report of HIV viral load among people with HIV on antiretroviral treatment.

OBJECTIVES: The aim of the study was to assess, among people living with HIV, knowledge of their latest HIV viral load (VL) and CD4 count. METHODS: Agreement between self-report and clinic record was assessed among 2771 HIV-diagnosed individuals on antiretroviral treatment (ART) in the UK Antiretrovirals, Sexual Transmission Risk and Attitudes Study (2011-2012). A confidential self-completed questionnaire collected information on demographic, socioeconomic, HIV-related and health-related factors. Participants were asked to self-report their latest VL [undetectable (≤ 50 copies/mL), detectable (> 50 copies/mL) or "don't know"] and CD4 count (< 200, 200-350, 351-500 or > 500 cells/µL, or "don't know"). Latest clinic-recorded VL and CD4 count were documented. RESULTS: Of 2678 participants on ART, 434 (16.2%) did not accurately report whether their VL was undetectable. Of 2334 participants with clinic-recorded VL ≤ 50 copies/mL, 2061 (88.3%) correctly reported undetectable VL; 49 (2.1%) reported detectable VL; 224 (9.6%) did not know their VL. Of 344 participants with clinic-recorded VL > 50 copies/mL, 183 (53.2%) correctly reported detectable VL; 76 (22.1%) reported undetectable VL; 85 (24.7%) did not know their VL. Of 2137 participants who reported undetectable VL, clinic-recorded VL was ≤ 50 copies/mL for 2061 (96.4%) and <1000 copies/mL for 2122 (99.3%). In analyses adjusted for gender/sexual orientation, ethnicity, age and time since starting ART, factors strongly associated with inaccurate self-report of VL (including "don't know") included socioeconomic disadvantage [prevalence ratio (95% CI) for "not" vs. "always" having enough money for basic needs: 2.4 (1.9, 3.1)], poor English fluency [3.5 (2.4, 5.1) vs. UK born], nondisclosure of HIV status [1.7 (1.3, 2.1)], ART nonadherence [2.1 (1.7, 2.7) for three or more missed doses vs. none in the past 2 weeks] and depressive symptoms (PHQ-9 score ≥ 10) [1.9 (1.6, 2.2)]. Overall, 612 (22.9%) of 2667 participants on ART did not accurately self-report whether or not their CD4 count was ≤ 350 cells/µL. CONCLUSIONS: There is a high level of accuracy of a self-report of undetectable VL in people on ART in the UK. Overall, accurate knowledge of personal VL level varied according to demographic, socioeconomic, HIV-related and health-related factors. Active identification of people who may benefit from increased levels of support and engagement in care is important.

Tertiary paediatric hospital admissions in children and young people with cerebral palsy.

BACKGROUND: Many previous studies that have investigated hospital admissions in children and young people with cerebral palsy lack information on cerebral palsy severity and complexity. Consequently, little is known about factors associated with the frequency and type of hospital admissions in this population. This study used hospital admission data available for all children and young people known to a population-based cerebral palsy register to describe the patterns of use of tertiary paediatric hospital services over a 5-year period. METHODS: This was a retrospective cohort analysis of routinely collected admission data from the two tertiary paediatric hospitals in the Australian state of Victoria. Data on admissions of individuals born between 1993 and 2008 registered on the Victorian Cerebral Palsy Register were analysed (n = 2183). RESULTS: Between 2008 and 2012, 53% of the cohort (n = 1160) had at least one same-day admission, and 46% (n = 996) had one or more multi-day admissions. Those with a moderate to severe motor impairment and those with a co-diagnosis of epilepsy had more admissions, and for multi-day admissions, longer lengths of stay, P < 0.05. Across all severity levels, respiratory and musculoskeletal diseases were the most frequently reported reasons for medical and surgical admissions, respectively. All-cause readmission rates for urgent multi-day stays within 7, 30 and 365 days of an index admission were 10%, 23% and 63%, respectively. CONCLUSIONS: The reasons for hospital admissions reported here reflect the range of comorbidities experienced by children and young people with cerebral palsy. This study highlights priority areas for prevention, early diagnosis and medical management in this group. Improved primary and secondary prevention measures may decrease non-elective hospital admissions and readmissions in this group and reduce paediatric inpatient resource use and healthcare expenditure attributable to cerebral palsy.

Expanded blood borne virus testing in a tuberculosis clinic. A cost and yield analysis.

OBJECTIVES: Testing for HIV is a standard of care for people with active tuberculosis (TB). People investigated for TB in the UK often originate from areas with a high prevalence of HIV and other blood borne viruses (BBV). However, assessment for these infections is patchy. We determined the yield and costs of different testing strategies for BBV in a UK TB clinic. METHODS: Since 2009, it has been routine to test all TB clinic attendees. Demographic, clinical and virological data were retrospectively extracted from patient notes and hospital databases. RESULTS: Over 3 years, 1036 people were assessed in the TB service. 410 had a final diagnosis of active TB. HIV testing of the latter population diagnosed 27 new HIV cases at a cost of £3017. When BBV testing was offered to all clinic attendees, a further 6 (total 33) new HIV, 5 Hepatitis B (HBV) and 2 Hepatitis C (HCV) diagnoses were made at a total cost of £22,170. CONCLUSIONS: We have identified previously undiagnosed HIV, HBV and HCV in a TB clinic population. Our data suggest that despite increasing upfront expense, the associated yield argues strongly for BBV testing to be offered to all patients being investigated for possible TB, irrespective of their final diagnosis.

Meta-analysis: antibiotic therapy for small intestinal bacterial overgrowth.

BACKGROUND: Small intestinal bacterial overgrowth (SIBO) is an under-recognised diagnosis with important clinical implications when untreated. However, the optimal treatment regimen remains unclear. AIM: To perform a systematic review and meta-analysis comparing the clinical effectiveness of antibiotic therapies in the treatment of symptomatic patients with documented SIBO. METHODS: Four databases were searched to identify clinical trials comparing effectiveness of: (i) different antibiotics, (ii) different doses of the same antibiotic and (iii) antibiotics compared with placebo. Data were independently extracted according to predetermined inclusion and exclusion criteria. Study quality was independently assessed. The primary outcome was normalisation of post-treatment breath testing. The secondary outcome was post-treatment clinical response. RESULTS: Of 1356 articles identified, 10 met inclusion criteria. Rifaximin was the most commonly studied antibiotic (eight studies) with overall breath test normalisation rate of 49.5% (95% confidence interval, CI 44.0-55.1) (44.0%-55.1%) then (46.7%-55.5%), then (4.6%-17.8%). Antibiotic efficacy varied by antibiotic regimen and dose. Antibiotics were more effective than placebo, with a combined breath test normalisation rate of 51.1% (95% CI 46.7-55.5) for antibiotics compared with 9.8% (95% CI 4.6-17.8) for placebo. Meta-analysis of four studies favoured antibiotics over placebo for breath test normalisation with an odds ratio of 2.55 (95% CI 1.29-5.04). Clinical response was heterogeneously evaluated among six studies, but tended to correlate with breath test normalisation. CONCLUSIONS: Antibiotics appear to be more effective than placebo for breath test normalisation in patients with symptoms attributable to SIBO, and breath test normalisation may correlate with clinical response. Studies were limited by modest quality, small sample size and heterogeneous design. Additional higher quality clinical trials of SIBO therapy are warranted.

Nutrient digestion and performance by lambs and steers fed thermochemically treated crop residues.

Five studies were conducted to determine nutrient digestibility and performance of lambs and steers fed thermochemically treated crop residues and distillers dried grains with solubles (DDGS) as a corn replacement pellet (CRP; 75% residue:25% DDGS, DM basis). Fifteen Hampshire, Suffolk, or Dorset wethers (BW 33.3 +/- 5.0 kg) were utilized to evaluate nutrient digestibility of the unprocessed native (NAT) and CRP [Exp. 1: wheat straw (WS); Exp. 2: corn stover (CS); Exp. 3: switchgrass (SWG) and corn fiber:wheat chaff (CFWC)] when limit fed (Exp. 1 and 2: 1.8% of BW daily; Exp. 3: 2.5% of BW daily) compared with a 60% corn diet. In Exp. 4, 56 individually fed Dorset-cross wether lambs (BW 32.0 +/- 1.4 kg) were utilized to compare performance and digestibility of WS, wheat chaff (WC), corn fiber (CF), a 3:1 blend of corn fiber:wheat straw (CFWS), a 3:1 blend of CFWC, and SWG-CRP fed for ad libitum intake compared with a 45% corn diet. In Exp. 5, 32 individually fed Holstein steers (BW 185.2 +/- 0.9 kg) were used to evaluate performance and digestibility of diets containing corn, WS-CRP, CFWC-CRP, or NAT-WS fed for ad libitum intake. Crop residues were processed with 5% calcium oxide (DM basis) and 35% water in a double-shaft enclosed mixer (Readco Kurimoto Continuous Processor, York, PA) and subsequently pelleted with DDGS to form CRP. Feeding lambs WS-CRP (Exp. 1) or CS-CRP (Exp. 2) increased digestion of DM, NDF, and ADF compared with NAT (P < 0.05). In Exp. 3, feeding CFWC-CRP increased total tract NDF digestibility and ADF digestibility (P < 0.05). Experiment 4 final BW were greatest for control lambs and least for lambs fed CFWS-CRP or SWG-CRP. Body weight gains for lambs fed CRP averaged 15.9% less than control (P < 0.05). Lambs fed CRP diets had greater (P < 0.05) NDF and ADF intake and output. In Exp. 5, steers fed the corn or 2 CRP diets gained similarly and faster (P < 0.05) than those fed the NAT-WS diet. Steers fed the control corn diet were more efficient (P < 0.05) than steers fed other treatments. Steers fed the corn diet, CFWC-CRP, and WS-CRP had greater (P < 0.01) DM digestibility than NAT. The results confirm benefits for nutrient digestion and subsequent animal performance when crop residues are thermochemically processed. Processed crop residues may be fed in combination with DDGS to partially replace corn in ruminant diets.

Clinician's perspectives of the relocation of a regional child and adolescent mental health service from co-located to stand alone premises.

INTRODUCTION: Australia's National Mental Health Strategy's statement of rights and responsibilities states that children and adolescents admitted to a mental health facility or community program have the right to be separated from adult patients and provided with programs suited to their developmental needs. However, in rural Australia, where a lack of healthcare services, financial constraints, greater service delivery areas and fewer mental healthcare specialists represent the norm, Child and Adolescent Mental Health Services (CAMHS) are sometimes co-located with adult mental health services. The aim of the present study was to evaluate the impact of a recent relocation of a regional CAMHS in Victoria from co-located to stand alone premises. METHOD: Six CAMHS clinicians who had experienced service delivery at a co-located setting and the current stand-alone CAMHS setting were interviewed about their perceptions of the impact of the relocation on service delivery. An exploratory interviewing methodology was utilized due to the lack of previous research in this area. Interview data were transcribed and analysed according to interpretative phenomenological analysis techniques. RESULTS: Findings indicated a perception that the relocation was positive for clients due to the family-friendly environment at the new setting and separation of CAMHS from adult psychiatric services. However, the impact of the relocation on clinicians was marked by a perceived loss of social capital from adult psychiatric service clinicians. CONCLUSION: These results provide increased understanding of the effects of service relocation and the influence of co-located versus stand-alone settings on mental health service delivery - an area where little prior research exists.

Mothers of Africa--an anaesthesia charity.

An anaesthetic charity 'Mothers of Africa' has been established as a link between the academic departments of anaesthesia in Togo and Benin and the University Hospital of Wales. Visits by UK consultant anaesthetists have identified a number of clinical areas where collaborative working in both classroom and theatre has the potential to improve outcomes in maternal mortality and morbidity.

The effect of a therapeutic trial of high-dose rabeprazole on symptom response of patients with non-cardiac chest pain: a randomized, double-blind, placebo-controlled, crossover trial.

BACKGROUND: Therapeutic trials with high-dose lansoprazole and omeprazole have been shown to be sensitive clinical tools for diagnosing patients with gastro-oesophageal reflux disease-related non-cardiac chest pain. AIM: To determine the clinical value of a therapeutic trial of high-dose rabeprazole over 7 days in detecting patients with gastro-oesophageal reflux disease-related non-cardiac chest pain. METHODS: Double-blind, randomized, placebo-controlled, crossover study. Patients referred by a cardiologist after a comprehensive cardiac work-up were enrolled into the study. Oesophageal mucosal disease was determined by upper endoscopy and 24-h oesophageal pH monitoring assessed acid exposure. Patients were then randomized to either placebo or rabeprazole 20 mg am and 20 mg pm for 7 days. After a washout period of 1 week, patients crossed over to the other arm of the study for an additional 7 days. Patients completed a daily diary assessing severity and frequency of chest pain throughout the baseline, treatment and wash-out periods. The rabeprazole therapeutic trial was considered as a diagnostic tool, if chest pain scores improved > or =50% from baseline. RESULTS: Of the 35 patients enrolled, 16 (46%) were diagnosed as gastro-oesophageal reflux disease-positive and 19 (54%) as gastro-oesophageal reflux disease-negative. Of the gastro-oesophageal reflux disease-positive patients, 12 of 16 (75%) had a significant symptom improvement on rabeprazole when compared with 3 of 16 (19%) on placebo (P = 0.029). Of the gastro-oesophageal reflux disease-negative group, only two of 19 (11%) improved significantly on the medication and four of 19 (21%) on placebo (P = 0.6599). The calculated sensitivity and specificity of the rabeprazole therapeutic trial was 75% and 90%, respectively. CONCLUSIONS: A rabeprazole therapeutic trial is highly sensitive and specific for diagnosing gastro-oesophageal reflux disease-related non-cardiac chest pain patients.

Systematic review: proton-pump inhibitor failure in gastro-oesophageal reflux disease--where next?

Proton-pump inhibitor failure has become a common clinical dilemma in gastrointestinal clinics and has been increasingly encountered at the primary care level as well. Underlying mechanisms are diverse and may overlap. Most patients who have proton-pump inhibitor failure are likely to originate from the non-erosive reflux disease phenotype. Currently, available diagnostic modalities provide limited clues to the exact underlying cause. Treatment relies primarily on escalating dosing of proton-pump inhibitors. However, new insights into the pathophysiology of proton-pump inhibitor failure are likely to provide alternative therapeutic options.

The mechanism of action of Kahalalide F: variable cell permeability in human hepatoma cell lines.

Kahalalide F (KF) is a small natural peptide that showed activity in vitro and in vivo. The dose-limiting toxicity in clinical trials was transaminitis. We investigated the cytotoxicity of KF in cell lines from breast, ovary, prostate and colon cancers, but focused on hepatoma cell lines, performing mechanistic studies in HepG2 (IC50 = 0.3 microM) and PLC/PRF/5C (IC50 = 5 microM). Following KF exposure, HepG2 cells demonstrated profound ATP depletion, associated with cell swelling and cell blebbing, and increased permeability to propidium iodide (PI), annexin V (AV) and release of lactate dehydrogenase (LDH). PLC/PRF/5C cells retained their cell structure, but were permeable to PI and, following exposure to high concentrations of KF, to AV. The pattern of cell permeability is similar to maitotoxin, another small cytotoxic peptide, but the differential effects on the cell membrane induced by KF in HepG2 and PLC/PRF/5C suggest specific interactions with membranes or proteins. This could lead to better drug design aimed at exploiting the potential for cell selectivity.

Derivation of preliminary three-dimensional pharmacophoric maps for chemically diverse intravenous general anaesthetics.

BACKGROUND: The molecular basis of i.v. general anaesthetic activity was investigated using comparative molecular field analysis (CoMFA). METHODS: The free plasma concentrations that abolish movement to a noxious stimulus for 14 structurally diverse i.v. anaesthetics were obtained from the literature. The compounds were randomly divided into a training set (n=10) to derive the activity model, and a separate test set (n=4) used to assess its predictive capability. The anaesthetic structures were aligned so as to maximize their similarities in molecular shape and electrostatic potential to conformers of the most active agent in the group, eltanolone. The conformers and alignments that showed the maximum similarity (calculated using combined Carbo indices) were retained, and used to derive the CoMFA models. RESULTS: The final model explained 94.0% of the variance in the observed activities of the training set (n=10, P<0.0001) and was a good predictor of test set activity (n=4, r(2)=0.799). In contrast, a model based on non-polar solubility (LogP) explained only 78.3% of the variance in the observed activities of the training set (n=10, P=0.0007) and was a poor predictor for the test set (n=4, r(2)=0.272). Further analysis of the CoMFA results identified the spatial distribution of key areas where steric and electrostatic interactions are important in determining the activity of the 14 anaesthetics considered. CONCLUSIONS: A single activity model can be formulated for i.v. general anaesthetics and preliminary pharmacophoric maps derived, which describe the molecular basis of their in vivo potency.

Can molecular similarity-activity models for intravenous general anaesthetics help explain their mechanism of action?

BACKGROUND: The importance of molecular shape and electrostatic potential in determining the activities of 11 structurally-diverse i.v. general anaesthetics was investigated using computational chemistry techniques. METHODS: The free plasma anaesthetic concentrations that abolished the response to noxious stimulation were obtained from the literature. The similarities in the molecular shapes and electrostatic potentials of the agents to eltanolone (the most potent anaesthetic agent in the group) were calculated using Carbo indices, and correlated with in vivo potency. RESULTS: The best model obtained was based on the similarities of the anaesthetics to two eltanolone conformers (r2=0.820). This model correctly predicted the potencies of the R- and S-enantiomers of ketamine, but identified alphaxalone as an outlier. Exclusion of alphaxalone substantially improved the activity correlation (r2=0.972). A bench mark model based on octanol/water partition coefficients (r2=0.647) failed to predict the potency order of the ketamine enantiomers. CONCLUSIONS: The results demonstrate that a single activity model can be formulated for chiral and non-chiral i.v. anaesthetic agents using molecular similarity indices.

Targeting the EGF receptor in ovarian cancer with the tyrosine kinase inhibitor ZD 1839 ("Iressa").

The modulating effects of the orally active epidermal growth factor receptor-specific tyrosine kinase inhibitor ZD 1839 ("Iressa") on cell growth and signalling were evaluated in four ovarian cancer cell lines (PE01, PE04, SKOV-3, OVCAR-5) that express the epidermal growth factor receptor, and in A2780, which is epidermal growth factor receptor-negative. Transforming growth factor-alpha stimulated growth was completely inhibited by concentrations of ZD 1839 > or =0.3 microM in the epidermal growth factor receptor-expressing cell lines, as were transforming growth factor-alpha stimulated phosphorylation of the epidermal growth factor receptor and downstream components of the MAP kinase and PI-3 kinase signalling cascades. Growth inhibition in the absence of added transforming growth factor-alpha was also observed which could be consistent with suppression of action of autocrine epidermal growth factor receptor-activating ligands by ZD 1839. In support of this, transforming growth factor-alpha, EGF and amphiregulin mRNAs were detected by RT-PCR in the epidermal growth factor receptor-expressing cell lines. ZD 1839 inhibited growth of the PE04 ovarian cancer xenograft at 200 mg kg(-1)day(-1). These data lend further support to the view that targeting the epidermal growth factor receptor in ovarian cancer could have therapeutic benefit.

The use of panoramic radiography in a dental accident and emergency department.

OBJECTIVES: To determine the rate of appropriate requests for panoramic radiography (PR) in a Dental Accident and Emergency Department and the implications for patient dose. METHODS: Two hundred and seventy-one requests for PR during July 1998 were assessed by two dental radiologists and categorised as appropriate or inappropriate based on established selection criteria. Incidental findings that might alter patient management were also noted. RESULTS: One hundred and fifty-seven requests (58%) were considered appropriate and 114 (42%) inappropriate. The most common inappropriate request was to assess disease localised to one or two teeth. Dental students were involved in 186 requests and 76 of these (41%) were inappropriate. The estimated saving in collective radiation dose over the month of the study if appropriate radiographs had been taken, would have been approximately 540 microSv, a reduction of 70%. Three out of 114 (3%) inappropriate, PRS showed minor incidental findings. CONCLUSIONS: A considerable proportion of requests for PR were inappropriate. In most of these cases, periapical radiographs would have provided more detail with less radiation dose. The large number of inappropriate requests involving dental students has implications for educators. The use of local selection criteria based on currently accepted guidelines would have reduced the dose substantially.