Validation of the TNM-8 AJCC classification for HPV-positive oropharyngeal cancers in patients undergoing trans-oral robotic surgery.

High-risk human papillomaviruses (HPV) are associated with some oropharyngeal squamous cell carcinomas (OPSCC). HPV-OPSCC have better survival outcomes compared to HPV negative tumours. The new TNM-8 AJCC staging (2018) is based on ICON-S data with 98% of patients treated with primary chemoradiation. To validate the TNM-8 AJCC classification in HPV-OPSCC treated primarily with surgery (trans-oral robotic surgery or open). There were 102 patients with HPV-OPSCC treated between July 2009 and December 2014 at the Royal Adelaide Hospital. The median age was 57 years (range: 38-83) and mostly males (84.5%). 27.2% were active smokers and 50.5% reformed smokers. Early T-stage cancer in 72.8%. Primary treatment was surgery & adjuvant therapy (70%) while primary chemoradiation (30%). Survival analyses were performed for the 7th and 8th AJCC systems. The reclassification to the AJCC 8th edition staging system resulted in a change of 54 patients from stage 4 to stages 1 and 2. This was mainly an effect of changes with N2a and N2b nodal disease being reclassified to N1. Survival outcomes were comparable with the ICON-S data. The new TNM-8 classification is, therefore, validated in a cohort treated, predominantly, with primary surgery and adjuvant therapy.

Cross validated serum small extracellular vesicle microRNAs for the detection of oropharyngeal squamous cell carcinoma.

BACKGROUND: Oropharyngeal squamous cell carcinoma (OPSCC) is often diagnosed at an advanced stage because the disease often causes minimal symptoms other than metastasis to neck lymph nodes. Better tools are required to assist with the early detection of OPSCC. MicroRNAs (miRNAs, miRs) are potential biomarkers for early head and neck squamous cell cancer diagnosis, prognosis, recurrence, and presence of metastatic disease. However, there is no widespread agreement on a panel of miRNAs with clinically meaningful utility for head and neck squamous cell cancers. This could be due to variations in the collection, storage, pre-processing, and isolation of RNA, but several reports have indicated that the selection and reproducibility of biomarkers has been widely affected by the methods used for data analysis. The primary analysis issues appear to be model overfitting and the incorrect application of statistical techniques. The purpose of this study was to develop a robust statistical approach to identify a miRNA signature that can distinguish controls and patients with inflammatory disease from patients with human papilloma virus positive (HPV +) OPSCC. METHODS: Small extracellular vesicles were harvested from the serum of 20 control patients, 20 patients with gastroesophageal reflux disease (GORD), and 40 patients with locally advanced HPV + OPSCC. MicroRNAs were purified, and expression profiled on OpenArray™. A novel cross validation method, using lasso regression, was developed to stabilise selection of miRNAs for inclusion in a prediction model. The method, named StaVarSel (for Stable Variable Selection), was used to derive a diagnostic biomarker signature. RESULTS: A standard cross validation approach was unable to produce a biomarker signature with good cross validated predictive capacity. In contrast, StaVarSel produced a regression model containing 11 miRNA ratios with potential clinical utility. Sample permutations indicated that the estimated cross validated prediction accuracy of the 11-miR-ratio model was not due to chance alone. CONCLUSIONS: We developed a novel method, StaVarSel, that was able to identify a panel of miRNAs, present in small extracellular vesicles derived from blood serum, that robustly cross validated as a biomarker for the detection of HPV + OPSCC. This approach could be used to derive diagnostic biomarkers of other head and neck cancers.

Elective neck dissection for the node-negative neck during salvage laryngectomy: an analysis of survival outcomes and complication rates.

OBJECTIVES: This study aimed to evaluate the effect of neck dissection on survival and complication rates in patients with no clinical or radiological evidence of cervical nodal disease (N0) undergoing salvage laryngectomy. METHODS: A retrospective study was conducted of patients with squamous cell carcinoma of the larynx following primary radiotherapy that required salvage laryngectomy. Disease-free and overall survival rates were compared over three years using Kaplan-Meier analysis. Pharyngocutaneous fistula rate, hospitalisation length and the requirement for further surgical intervention were also compared across cohorts. RESULTS: Twenty-three cases met the inclusion criteria (17 neck dissections, 6 undissected). No significant differences in survival outcomes were identified. One patient who underwent neck dissection for advanced, recurrent transglottic squamous cell carcinoma showed evidence of occult lymph node metastases. Fistula rates did not differ significantly between dissected and non-dissected groups; however, two patients required surgical repair of post-operative pharyngocutaneous fistula following neck dissection. CONCLUSION: In this study, elective neck dissection did not appear to alter survival outcomes or complication rates during salvage laryngectomy. Given the small but significant risk of occult neck metastases, its true value remains unclear.

Clinical validity assessment of genes frequently tested on hereditary breast and ovarian cancer susceptibility sequencing panels.

PURPOSE: Several genes on hereditary breast and ovarian cancer susceptibility test panels have not been systematically examined for strength of association with disease. We employed the Clinical Genome Resource (ClinGen) clinical validity framework to assess the strength of evidence between selected genes and breast or ovarian cancer. METHODS: Thirty-one genes offered on cancer panel testing were selected for evaluation. The strength of gene-disease relationship was systematically evaluated and a clinical validity classification of either Definitive, Strong, Moderate, Limited, Refuted, Disputed, or No Reported Evidence was assigned. RESULTS: Definitive clinical validity classifications were made for 10/31 and 10/32 gene-disease pairs for breast and ovarian cancer respectively. Two genes had a Moderate classification whereas, 6/31 and 6/32 genes had Limited classifications for breast and ovarian cancer respectively. Contradictory evidence resulted in Disputed or Refuted assertions for 9/31 genes for breast and 4/32 genes for ovarian cancer. No Reported Evidence of disease association was asserted for 5/31 genes for breast and 11/32 for ovarian cancer. CONCLUSION: Evaluation of gene-disease association using the ClinGen clinical validity framework revealed a wide range of classifications. This information should aid laboratories in tailoring appropriate gene panels and assist health-care providers in interpreting results from panel testing.

Reviewing indications for panendoscopy in the investigation of head and neck squamous cell carcinoma.

BACKGROUND: The role of panendoscopy in the modern investigation of head and neck cancer is changing with the development of improved radiological techniques, in-office biopsy capabilities and the low rate of synchronous primary tumours. This study aimed to review the indications for panendoscopy in the investigation of newly diagnosed head and neck cancer. METHOD: A retrospective review was conducted of 186 patients with newly diagnosed head and neck cancer, between January 2014 and December 2015, at two tertiary centres. RESULTS: Obtaining a tissue diagnosis was the most common indication for panendoscopy (65 per cent), followed by surgical planning including transoral robotic surgery suitability assessment (22.6 per cent), and the investigation of carcinoma of an unknown primary (11.3 per cent). Two synchronous primary tumours were identified, generating a yield of 1.1 per cent. CONCLUSION: Panendoscopy remains integral in the assessment of transoral robotic surgery suitability. Refining indications for modern panendoscopy could reduce the need for this procedure in this cohort of patients.

"Possibly positive or certainly uncertain?": participants' responses to uncertain diagnostic results from exome sequencing.

PurposeClinical genome sequencing produces uncertain diagnostic results, raising concerns about how to communicate the method's inherent complexities in ways that reduce potential misunderstandings and harm. This study investigates clinicians' communications and patient/participant responses to uncertain diagnostic results arising from a clinical exome sequencing research study, contributing empirical data to the debate surrounding disclosure of uncertain genomic information.MethodsWe investigated the communication and impact of uncertain diagnostic results using ethnographic observations of result disclosures with 21 adults and 11 parents of child patients, followed by two semistructured interviews with these same participants.ResultsParticipants understood their uncertain results in ways that were congruent with clinical geneticists' communications. They followed recommendations for further consultation, although family testing to resolve uncertainty was not always done. Participants were prepared for learning an uncertain result and grasped the key concept that it should not be used to guide health-care or other decisions. They did not express regret for having learned the uncertain result; most regarded it as potentially valuable in the future.ConclusionThis study suggests that uncertain diagnostic results from genome sequencing can be relayed to patients in ways they can understand and consistent with providers' interpretations, without causing undue harm.

A comparison of oncological outcomes between transoral surgical and non-surgical treatment protocols in the management of oropharyngeal squamous cell carcinoma.

BACKGROUND: The incidence of oropharyngeal squamous cell carcinoma in the Western world is increasing, with the human papillomavirus epidemic implicated in this observed trend. The optimal treatment modality is yet undetermined regarding oncological outcomes. METHODS: This study comprised 98 patients with oropharyngeal squamous cell carcinoma, treated with either primary transoral surgery with adjuvant therapy or primary chemoradiotherapy with curative intent, between 2008 and 2012. Clinicopathological characteristics including tumour-node-metastasis stage, human papillomavirus status, treatment modality, recurrence and overall survival were collated. RESULTS: Five per cent of primary surgical patients had locoregional recurrences compared with 25 per cent of primary chemoradiotherapy patients. A lower rate of locoregional recurrence was observed in the human papillomavirus positive group. CONCLUSION: This paper reports higher rates of overall survival and local control for oropharyngeal squamous cell carcinoma treated with primary surgery compared with primary chemoradiotherapy. This reflects overall lower tumour stage and higher human papillomavirus status in this group.

Heat and moisture exchanger use reduces in-hospital complications following total laryngectomy: a case-control study.

BACKGROUND: Total laryngectomy (TL) is an appropriate oncologic operation for many patients with laryngeal cancer delivering excellent oncologic outcomes, however it remains beset with significant functional consequences. Following TL, the upper and lower airways are permanently disconnected, which causes unfiltered, cold air with reduced humidity to enter the tracheobronchial tree, resulting in mucus overproduction and an increase in the viscosity of the mucus. In response to this, Heat and moisture exchangers were developed to compensate for the lost functions of the upper respiratory tract and their effect on the patients' respiratory performance in addition to their quality of life. METHODS: The case records of 48 patients undergoing total laryngectomy were reviewed and data concerning demographics, surgical details, post-operative care requirements and adverse events was retrieved. Post hoc analysis of the case patients was undertaken to identify any benefit of using a heat and moisture exchanger (HME) system with particular reference to post-operative respiratory outcomes. RESULTS: There was no significant difference between case and control subjects based on demographics, extent of surgery or need for flap repair. 16 patients had used a HME and 32 patients had used external humidification (EH). Of those experiencing mucous plugging, only 3/24 (12.5 %) had used a HME system, in contrast to 21/24 (87.5 %) who used EH (Chi square = 9.375, p = 0.002). The odds ratio of having an adverse event if not using HME was 8.27 (CI = 1.94 - 35.71). Use of HME also significantly reduced the number of days requiring physiotherapy (1.75 days vs. 3.20 days, p = 0.034). CONCLUSION: Use of an HME system can reduce in-hospital complications, in particular episodes of mucus plugging, and post-operative care requirements. Furthermore, there is a cost benefit to using HME systems that warrants more widespread introduction of these devices in head and neck surgery centers.

Surgical management of airway stenosis by radiofrequency coblation.

BACKGROUND: Acquired airway stenosis can be challenging to manage endoscopically because of difficult field visualisation, instrument limitations and the risk of laser fire. At our institution, radiofrequency coblation has been successfully used for the resection of subglottic and tracheal stenosis in adults. This paper presents our experience with this technique. METHOD: A retrospective case note analysis of all cases of airway stenosis in adults from 2007 to 2012 was performed. RESULTS: Ten adult patients underwent coblation resection for airway stenosis. All lesions were classified as McCaffrey stage I (i.e. less than 1 cm long). Causes of stenosis included: idiopathic stenosis (40 per cent), previous tracheostomy (30 per cent) and endotracheal intubation (20 per cent). Six patients (60 per cent) required a single procedure and 4 (40 per cent) required multiple interventions. All patients reported significant improvement in their symptoms following treatment. All patients were alive at the time of writing and none have required open resection. CONCLUSION: Radiofrequency coblation is an attractive alternative technique for the treatment of idiopathic or acquired airway stenosis in adults.

Adaptive immune responses in Staphylococcus aureus biofilm-associated chronic rhinosinusitis.

BACKGROUND: The etiopathogenesis of chronic rhinosinusitis (CRS) is currently an area of intense debate. Recently, biofilms have been proposed as a potential environmental trigger in this disease. In particular, Staphylococcus aureus biofilms appear to be a predictor of severe disease recalcitrant to current treatment paradigms. However, direct causal links between biofilms and host immune activation are currently lacking. This study aimed to document both the adaptive immune responses that characterize S. aureus biofilm-associated CRS and the relative contributions of staphylococcal superantigens and S. aureus biofilms in the inflammatory make-up of this disease. METHODS: A total of 53 disease subjects and 15 controls were recruited. Sinonasal mucosa was collected for the determination of S. aureus and Haemophilus influenzae biofilms and presence of total and superantigen-specific IgE and for the measurement of cytokines that characterize the T-helper pathways. RESULTS: Staphylococcus aureus biofilms and superantigens are significantly associated in CRS patients, suggesting the biofilm may be a nidus for superantigen-eluting bacteria. The presence of S. aureus biofilms is associated with eosinophilic inflammation, across the spectrum of CRS, on the back of a T-helper(2) skewing of the host's adaptive immune response (elevated Eosinophilic Cationic Protein and IL-5). This can be distinguished from the superantigenic effect resulting in the induction of IgE. CONCLUSION: This study provides novel evidence of a link between S. aureus biofilms and skewing of the T-cell response toward the T-helper(2) pathway that is independent of superantigen activities. Further research is required to confirm the cause-effect relationship of this association.

Nearly complete regression of tumors via collective behavior of magnetic nanoparticles in hyperthermia.

One potential cancer treatment selectively deposits heat to the tumor through activation of magnetic nanoparticles inside the tumor. This can damage or kill the cancer cells without harming the surrounding healthy tissue. The properties assumed to be most important for this heat generation (saturation magnetization, amplitude and frequency of external magnetic field) originate from theoretical models that assume non-interacting nanoparticles. Although these factors certainly contribute, the fundamental assumption of 'no interaction' is flawed and consequently fails to anticipate their interactions with biological systems and the resulting heat deposition. Experimental evidence demonstrates that for interacting magnetite nanoparticles, determined by their spacing and anisotropy, the resulting collective behavior in the kilohertz frequency regime generates significant heat, leading to nearly complete regression of aggressive mammary tumors in mice.

Assessment of intratumor non-antibody directed iron oxide nanoparticle hyperthermia cancer therapy and antibody directed IONP uptake in murine and human cells.

Hyperthermia, as an independent modality or in combination with standard cancer treatments such as chemotherapy and radiation, has been established in vitro and in vivo as an effective cancer treatment. However, despite efforts over the past 25 years, such therapies have never been optimized or widely-accepted clinically. Although methods continue to improve, conventionally-delivered heat (RF, ultrasound, microwave etc) can not be delivered in a tumor selective manner. The development of antibody-targeted, or even nontargeted, biocompatible iron oxide nanoparticles (IONP) now allows delivery of cytotoxic heat to individual cancer cells. Using a murine mouse mammary adenocarcinoma (MTGB) and human colon carcinoma (HT29) cells, we studied the biology and treatment of IONP hyperthermia tumor treatment. METHODS: Cancer cells (1 × 106) with or without iron oxide nanoparticles (IONP) were studied in culture or in vivo via implanted subcutaneously in female C3H mice, Tumors were grown to a treatment size of 150 mm3 and tumors volumes were measured using standard 3-D caliper measurement techniques. Mouse tumors were heated via delivery of an alternating magnetic field, which activated the nanoparticles, using a cooled 36 mm diameter square copper tube induction coil which provided optimal heating in 1.5 cm wide region of the coil. The IONPs were dextran coated and had a hydrodynamic radius of approximately 100 nm. For the in vivo studies, intra-tumor, peritumor and rectal (core body) temperatures were continually measured throughout the treatment period. RESULTS: Although some eddy current heating was generated in non-target tissues at the higher field strengths, our preliminary IONP hyperthermia studies show that whole mouse AMF exposure @160 KHz and 400 or 550 Oe, for a 20 minutes (heat-up and protocol heating), provides a safe and efficacious tumor treatment. Initial electron and light microscopic studies (in vitro and in vivo) showed the 100 nm used in our studies are rapidly taken up and retained by the tumor cells. Additional in vitro studies suggest antibodies can significantly enhance the cellular uptake of IONPs.

NanoFerrite particle based radioimmunonanoparticles: binding affinity and in vivo pharmacokinetics.

Dextran and PEG-coated iron oxide nanoparticles (NP), when suitably modified to enable conjugation with molecular targeting agents, provide opportunities to target cancer cells. Monoclonal antibodies, scFv, and peptides conjugated to 20 nm NP have been reported to target cancer for imaging and alternating magnetic field (AMF) therapy. The physical characteristics of NPs can affect their in vivo performance. Surface morphology, surface charge density, and particle size are considered important factors that determine pharmacokinetics, toxicity, and biodistribution. New NanoFerrite (NF) particles having improved specific AMF absorption rates and diameters of 30 and 100 nm were studied to evaluate the variation in their in vitro and in vivo characteristics in comparison to the previously studied 20 nm superparamagnetic iron oxide (SPIO) NP. SPIO NP 20 nm and NF NP 30 and 100 nm were conjugated to (111)In-DOTA-ChL6, a radioimmunoconjugate. Radioimmunoconjugates were conjugated to NPs using 25 microg of RIC/mg of NP by carbodiimide chemistry. The radioimmunonanoparticles (RINP) were purified and characterized by PAGE, cellulose acetate electrophoresis (CAE), live cell binding assays, and pharmacokinetics in athymic mice bearing human breast cancer (HBT 3477) xenografts. RINP (2.2 mg) were injected iv and whole body; blood and tissue data were collected at 4, 24, and 48 h. The preparations used for animal study were >90% monomeric by PAGE and CAE. The immunoreactivity of the RINP was 40-60% compared to (111)In-ChL6. Specific activities of the doses were 20-25 microCi/2.2 mg and 6-11 microg of mAb/2.2 mg of NP. Mean tumor uptakes (% ID/g +/- SD) of each SPIO 20 nm, NF 30 nm, and 100 nm RINP at 48 h were 9.00 +/- 0.8 (20 nm), 3.0 +/- 0.3 (30 nm), and 4.5 +/- 0.8 (100 nm), respectively; the ranges of tissue uptakes were liver (16-32 +/- 1-8), kidney (7.0-15 +/- 1), spleen (8-17 +/- 3-8), lymph nodes 5-6 +/- 1-2), and lung (2.0-4 +/- 0.1-2). In conclusion, this study demonstrated that 100 nm NF NP could be conjugated to (111)In-mAb so that the resulting RINP had characteristics suitable for AMF therapy. Although 100 nm RINP targeted tumor less than 20 nm SPIO RINP, their heating capacity is typically 6 times greater, suggesting the 100 nm NF RINP could still deliver better therapy with AMF.

Children's OMNI scale of perceived exertion: mixed gender and race validation.

PURPOSE: The newly developed Children's OMNI Scale of Perceived Exertion (category range: 0 to 10) was validated using separate cohorts of female and male, African American and white subjects. Each of the four cohorts contained 20 clinically normal, nonobese children, 8-12 yr of age. METHODS: A cross-sectional, perceptual estimation paradigm using a single multi-stage cycle ergometer test protocol was used. Oxygen uptake (VO2; mL x min(-1)), heart rate (HR; beats x min(-1)) and ratings of perceived exertion for the overall body (RPE-Overall), legs (RPE-Legs), and chest (RPE-Chest) were determined at the end of each continuously administered 3-min power output (PO) (i.e., 25, 50, 75, and 100 W) test stage. RESULTS: The range of responses over the four POs for all cohorts was VO2: 290.8 to 1204.0 mL x min(-1); HR: 89.2 to 164.4 beats x min(-1); and RPE-Overall, RPE-Legs, and RPE-Chest: 0.85 to 9.1. First-order correlation and linear regression analyses were performed for each cohort separately and the total sample using a repeated measures paradigm over the four POs. For all correlation/regression paradigms RPE-Overall, RPE-Legs, and RPE-Chest distributed as a positive linear function of both VO2 and HR; r = 0.85 to 0.94; P < 0.01. Differences between RPE-Overall, RPE-Legs, and RPE-Chest were examined with ANOVA for the repeated measures paradigm. RPE-Legs was higher (P < 0.01) than RPE-Chest and RPE-Overall at 25, 50, 75, and 100 W. RPE-Chest did not differ from RPE-Overall at 25 and 50 W but was lower (P < 0.01) than RPE-Overall at 75 and 100 W. CONCLUSION: The psycho-physiological responses provide validity evidence for use of the Children's OMNI Scale over a wide range of dynamic exercise intensities.

Utility of kindergarten teacher judgments in identifying early learning problems.

Most existing research on early identification of learning difficulties has examined the validity of methods for predicting future academic problems. The present study focused instead on the sensitivity of kindergarten teachers to learning problems in their students and on the continuity of teacher-identified problems over time. To identify early learning problems, kindergarten teachers in a suburban school district rated student progress toward six academic objectives as satisfactory or unsatisfactory. Twenty percent of the district's 303 kindergarten children received unsatisfactory ratings in at least one area. Thirty-eight of these children (identified group) were matched to 34 children with satisfactory ratings in all areas (nonidentified group). Results of testing conducted during kindergarten revealed poorer academic achievement in identified children than in nonidentified children. Children from the identified group also performed more poorly than children from the nonidentified group on tests of phonological processing and working memory/executive function and were rated by teachers as having more behavior and attention problems and lower social competence. Follow-up of the sample to first grade documented continued learning problems in the identified group. These findings support the use of teacher judgements in early detection of learning problems and argue against reliance on discrepancy criteria.

The relationship of coping style to dysphoria, anxiety, and anger.

This study examines Problem-focused Coping and Emotion-focused Coping, as measured by the Revised Ways of Coping Checklist, in relation to Dysphoria, Anxiety, Anger, Social Support, and course grades in psychology. Women university students (N = 245) were assessed two times six weeks apart. Problem-focused Coping was significantly negatively correlated with scores on the Center for Epidemiological Studies-Depression scale and with scores on the Self-rating Anxiety Scale at both time periods. Emotion-focused Coping was significantly positively correlated with scores on these scales and with scores on the State-Trait Anger scale at both times. Emotion-focused Coping was significantly negatively correlated with scores on the Social Support Questionnaire at both times and significantly negatively correlated with grades.

The effect of esmolol on ST-segment depression and arrhythmias after electroconvulsive therapy.

Electroconvulsive therapy (ECT) induces sympathetically mediated hemodynamic alterations that can be associated with myocardial ischemia and arrhythmia generation. Esmolol, a short-acting beta-blocker, blunts the hypertension and tachycardia seen with ECT. The purpose of this study is to determine whether esmolol use during ECT reduces the incidence of myocardial ischemia or arrhythmias after ECT. In a randomized, double-blind, placebo-controlled protocol, with each patient acting as his/her own control, the effects of esmolol on the incidence of myocardial ischemia and arrhythmias were studied using two-lead Holter monitoring for at least 2 h post-ECT. Nineteen patients underwent 71 ECT treatments (34 placebo, 37 esmolol), recording 746 h of Holter data. The esmolol group had significantly reduced heart rate and mean arterial pressure immediately after ECT. There was no difference in the incidence of ECG defined ischemia post-ECT between groups, with 7 of 19 (36.8%) patients in the esmolol group showing ST-segment depression compared with 5 of 19 (26.3%) in the placebo group. There was no difference between groups in arrhythmia detection. This experiment demonstrates that (a) ECT is associated with a significant incidence of ST-segment depression, (b) esmolol blunts the sympathetic discharge during ECT, and (c) esmolol does not reduce the incidence of post-ECT ischemia or arrhythmia.

Clinical features of AIDS in the Edinburgh City Hospital cohort.

In order to describe the clinical features of AIDS, particularly injection drug use (IDU) related AIDS in patients attending the Regional Infectious Diseases Unit in Edinburgh a prospective review of the 680 HIV-positive patients, 30% of whom were women and 68% were infected via IDU was undertaken. The commonest AIDS-related clinical problem in Edinburgh was Pneumocystis carinii pneumonia (PCP). Whilst gender differences were not apparent in terms of clinical problems, differences were observed in risk groups as previously reported; Kaposi's sarcoma (KS), cytomegalovirus (CMV) and toxoplasmosis were commoner in homo/ bisexuals whilst oesophageal candidiasis was commoner in drug users. Extrapulmonary tuberculosis was uncommon unlike cohorts from the USA or Italy. Each patient with AIDS can expect 1-2 AIDS-related clinical events per year of survival. Considerable differences in mortality rates by risk group but not by gender were observed and explanations for this difference need to be considered further. The mortality rates for drug users were however remarkably similar to published rates from Amsterdam and the Bronx, New York.

Clinical features of early HIV in the Edinburgh City Hospital cohort.

In order to describe the clinical features of HIV (non-AIDS), particularly injection drug use (IDU) related HIV, in patients attending the Regional Infectious Diseases Unit in Edinburgh, a prospective review utilizing the WHO staging system of the 680 HIV positive patients, 30% of whom were women and 68% were infected via IDU, was undertaken. Despite the fact that the majority of drug users and heterosexuals enrolled asymptomatic, by 1993, 71% of the patients had developed some HIV related clinical problem. The important clinical problems observed for the cohort were; minor skin problems, minor bacterial infections, major bacterial sepsis, oral thrush, oral hairy leucoplakia, significant weight loss of > 10%, HIV related thrombocytopenia and of course AIDS. Unlike previous reports from other areas, in Edinburgh drug users were not more likely than other risk groups to develop severe bacterial disease. Differences in morbidity and mortality rates by risk group but not by gender were noted but these may well be affected by the very different enrolment pattern observed in the various risk groups. The pre-AIDS mortality rates for drug users were remarkably similar to published rates from other centres.