Evaluation of HIV testing recommendations in specialty guidelines for the management of HIV indicator conditions.

OBJECTIVES: European guidelines recommend HIV testing for individuals presenting with indicator conditions (ICs) including AIDS-defining conditions (ADCs). The extent to which non-HIV specialty guidelines recommend HIV testing in ICs and ADCs is unknown. Our aim was to pilot a methodology in the UK to review specialty guidelines and ascertain if HIV was discussed and testing recommended. METHODS: UK and European HIV testing guidelines were reviewed to produce a list of 25 ADCs and 49 ICs. UK guidelines for these conditions were identified from searches of the websites of specialist societies, the National Institute of Clinical Excellence (NICE) website, the NICE Clinical Knowledge Summaries (CKS) website, the Scottish Intercollegiate Guidance Network (SIGN) website and the British Medical Journal Best Practice database and from Google searches. RESULTS: We identified guidelines for 12 of 25 ADCs (48%) and 36 of 49 (73%) ICs. In total, 78 guidelines were reviewed (range 0-13 per condition). HIV testing was recommended in six of 17 ADC guidelines (35%) and 24 of 61 IC guidelines (39%). At least one guideline recommended HIV testing for six of 25 ADCs (24%) and 16 of 49 ICs (33%). There was no association between recommendation to test and publication year (P = 0.62). CONCLUSIONS: The majority of guidelines for ICs do not recommend testing. Clinicians managing ICs may be unaware of recommendations produced by HIV societies or the prevalence of undiagnosed HIV infection among these patients. We are piloting methods to engage with guideline development groups to ensure that patients diagnosed with ICs/ADCs are tested for HIV. We then plan to apply our methodology in other European settings as part of the Optimising Testing and Linkage to Care for HIV across Europe (OptTEST) project.

WHAM-FTOXß - An aquatic toxicity model based on intrinsic metal toxic potency and intrinsic species sensitivity.

We developed a model that quantifies aquatic cationic toxicity by a combination of the intrinsic toxicities of metals and protons and the intrinsic sensitivities of the test species. It is based on the WHAM-FTOX model, which combines the calculated binding of cations by the organism with toxicity coefficients (αH, αM) to estimate the variable FTOX, a measure of toxic effect; the key parameter αM,max (applying at infinite time) depends upon both the metal and the test species. In our new model, WHAM-FTOXß, values of αM,max are given by the product αM* × ß, where αM* has a single value for each metal, and ß a single value for each species. To parameterise WHAM-FTOXß, we assembled a set of 2182 estimates of αM,max obtained by applying the basic model to laboratory toxicity data for 76 different test species, covering 15 different metals, and including results for metal mixtures. Then we fitted the log10αM,max values with αM* and ß values (a total of 91 parameters). The resulting model accounted for 72% of the variance in log10αM,max. The values of αM* increased markedly as the chemical character of the metal changed from hard (average αM* = 4.4) to intermediate (average αM* = 25) to soft (average αM* = 560). The values of log10ß were normally distributed, with a 5-95 percentile range of -0.73 to +0.56, corresponding to ß values of 0.18 to 3.62. The WHAM-FTOXß model entails the assumption that test species exhibit common relative sensitivity, i.e. the ratio αM,max / αM* is constant across all metals. This was tested with data from studies in which the toxic responses of a single organism towards two or more metals had been measured (179 examples for the most-tested metals Ni, Cu, Zn, Ag, Cd, Pb), and statistically-significant (p < 0.003) results were obtained.

Longitudinal characterisation of haematological and biochemical parameters in cancer patients prior to and during COVID-19 reveals features associated with outcome.

BACKGROUND: Cancer patients are at increased risk of death from severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). Cancer and its treatment affect many haematological and biochemical parameters, therefore we analysed these prior to and during coronavirus disease 2019 (COVID-19) and correlated them with outcome. PATIENTS AND METHODS: Consecutive patients with cancer testing positive for SARS-CoV-2 in centres throughout the United Kingdom were identified and entered into a database following local governance approval. Clinical and longitudinal laboratory data were extracted from patient records. Data were analysed using Mann-Whitney U test, Fisher's exact test, Wilcoxon signed rank test, logistic regression, or linear regression for outcomes. Hierarchical clustering of heatmaps was performed using Ward's method. RESULTS: In total, 302 patients were included in three cohorts: Manchester (n = 67), Liverpool (n = 62), and UK (n = 173). In the entire cohort (N = 302), median age was 69 (range 19-93 years), including 163 males and 139 females; of these, 216 were diagnosed with a solid tumour and 86 with a haematological cancer. Preinfection lymphopaenia, neutropaenia and lactate dehydrogenase (LDH) were not associated with oxygen requirement (O2) or death. Lymphocyte count (P < 0.001), platelet count (P = 0.03), LDH (P < 0.0001) and albumin (P < 0.0001) significantly changed from preinfection to during infection. High rather than low neutrophils at day 0 (P = 0.007), higher maximal neutrophils during COVID-19 (P = 0.026) and higher neutrophil-to-lymphocyte ratio (NLR; P = 0.01) were associated with death. In multivariable analysis, age (P = 0.002), haematological cancer (P = 0.034), C-reactive protein (P = 0.004), NLR (P = 0.036) and albumin (P = 0.02) at day 0 were significant predictors of death. In the Manchester/Liverpool cohort 30 patients have restarted therapy following COVID-19, with no additional complications requiring readmission. CONCLUSION: Preinfection biochemical/haematological parameters were not associated with worse outcome in cancer patients. Restarting treatment following COVID-19 was not associated with additional complications. Neutropaenia due to cancer/treatment is not associated with COVID-19 mortality. Cancer therapy, particularly in patients with solid tumours, need not be delayed or omitted due to concerns that treatment itself increases COVID-19 severity.

Systematic analysis of freshwater metal toxicity with WHAM-FTOX.

We used the WHAM chemical speciation model and the WHAM-FTOX toxicity model to analyse the published results of laboratory toxicity experiments covering 52 different freshwater biological test species and 24 different metals, a total of 2037 determinations of EC50 with accompanying data on solution composition. The key extracted parameter was αM, the parameter in WHAM-FTOX that characterises the toxic potency of a metal on the basis of its estimated metabolically active body burden. For 16 data sets applying to metal-test species pairs with appreciable variations in solution composition, values of EC50 back-calculated from averaged values of αM showed significantly (p < 0.001) less deviation from the measured EC50 values than did the simple average EC50, confirming that the modelling calculations could account for some of the dependence of toxicity on chemical speciation. Data for different exposure times permitted a simple parameterisation of temporal effects, enabling values of αM,max (values at infinite exposure time) to be obtained, and the effects of different exposure times to be factored out for further analysis. Comparison of averaged values of αM,max for different metals showed little difference among major taxa (invertebrates, plants, and vertebrates). For Cd, Cu, Ni and Zn (the four metals with most data) there were significant differences among αM,max values for different species, but within-species variabilities were greater. Reasonably similar species sensitivity distributions of standardised αM,max applied to Cd, Cu, Ni and Zn. The average values, over all species, of αM,max increased in the order Al < lanthanides < Zn ∼ UO2 < Ni ∼ Cu < Pb < Cd < Ag. Considering all the αM,max values, there was a strong dependence (r2 = 0.56, p < 0.001) on Pearson's hardness-softness categories, and a slightly stronger relationship (r2 = 0.59) if ionic radius was included in the statistical model, indicating that softer, larger cations are the most effective toxicants.

Renal health after long-term exposure to tenofovir disoproxil fumarate (TDF) in HIV/HBV positive adults in Ghana.

OBJECTIVES: The study assessed markers of renal health in HIV/HBV co-infected patients receiving TDF-containing antiretroviral therapy in Ghana. METHODS: Urinary protein-to-creatinine ratio (uPCR) and albumin-to-protein ratio (uAPR) were measured cross-sectionally after a median of four years of TDF. At this time, alongside extensive laboratory testing, patients underwent evaluation of liver stiffness and blood pressure. The estimated glomerular filtration rate (eGFR) was measured longitudinally before and during TDF therapy. RESULTS: Among 101 participants (66% women, median age 44 years, median CD4 count 572 cells/mm3) 21% and 17% had detectable HIV-1 RNA and HBV DNA, respectively. Overall 35% showed hypertension, 6% diabetes, 7% liver stiffness indicative of cirrhosis, and 18% urinary excretion of Schistosoma antigen. Tubular proteinuria occurred in 16% of patients and was independently predicted by female gender and hypertension. The eGFR declined by median 1.8 ml/min/year during TDF exposure (IQR -4.4, -0.0); more pronounced declines (≥ 5 ml/min/year) occurred in 22% of patients and were associated with receiving ritonavir-boosted lopinavir rather than efavirenz. HBV DNA, HBeAg, transaminases, and liver stiffness were not predictive of renal function abnormalities. CONCLUSIONS: The findings mandate improved diagnosis and management of hypertension and suggest targeted laboratory monitoring of patients receiving TDF alongside a booster in sub-Saharan Africa.

Management of biochemical failure following radical prostatectomy: salvage radiotherapy - a case series.

A retrospective analysis of the outcome of radical prostatectomy (RP) for prostate cancer in a single centre and assessment of the role of salvage radiotherapy (RT) for patients with biochemical relapse. Hundred and thirty-seven patients underwent RP for adenocarcinoma of the prostate in our centre between December 1994 and June 2003. Fifty-four of these patients developed a biochemical relapse prostate-specific antigen (PSA > or = 0.2 ng/ml). Thirty-two patients including five from elsewhere (one with a palpable local recurrence) received salvage RT. Twenty-five of these had positive margins at resection and four had involvement of seminal vesicles. Nine had Gleason score > or = 8. Median PSA before RT was 0.55 ng/ml (range 0.2-5.0). Median age at surgery was 63.5 years (range 52-71). Median age at RT was 65 years (range 53-73). Median time from surgery to biochemical relapse was 11 months (range 0-37) and median interval from surgery to RT was 22 months (range 3-71). Twenty-seven patients received 64 Gy in 32 fractions, three patients received 55 Gy in 20 fractions and two patients received 50 Gy in 20 fractions. Twenty-seven patients were managed by observation or hormone therapy. Twenty-seven patients (84%) achieved complete biochemical remission following RT. Eighteen (56%) remain in complete remission with a median follow-up since RT for the whole group of 30 months (range 8-85). Fourteen patients have relapsed, eight of whom had either clear margins or PSA >1.0 ng/ml at the time of RT (PSA > or = 0.2 ng/ml). Salvage RT is an effective treatment for achieving biochemical remission in selected patients who relapse following RP.

Radiotherapy and conservative surgery in the management of musculo-aponeurotic fibromatosis.

Fifty-four patients with musculo-aponeurotic fibromatosis treated with surgery, surgery and planned post-operative radiotherapy, or radiotherapy alone between 1936 and 1982 have been retrospectively reviewed. Twenty-seven patients had a previous excision before definitive treatment. All patients in whom surgery was known to be incomplete and who had no further treatment relapsed. Nine patients had a complete surgical excision alone and 1 relapsed. Twenty-nine patients were treated with surgery and post-operative radiotherapy and 7 relapsed. Relapse was associated with small field size, orthovoltage irradiation, and doses less than 50 Gy. Radiotherapy was effective in preventing relapse in 6 of 8 cases incompletely excised and in all of these cases the total dose was more than 50 Gy. In 13 assessable patients with clinically evident disease, 14 fields were treated with radiotherapy. Complete response was achieved in 9 fields (although one subsequently relapsed and 2 had a marginal relapse), partial response in 4, and disease stasis in one. Complete resolution took up to 21 months and total doses ranged from 35.2 Gy to 64 Gy. Radiotherapy is indicated in cases of incomplete excision and inoperable disease. Doses should be radical and fields should be sufficiently generous to encompass the anatomical limits of the infiltrated tissues.

The role of the gastroenterologist in the provision of artificial nutrition support.

BACKGROUND: Nutrition support is required for the prevention or treatment of malnutrition in patients with intestinal failure and those who are unable to eat. AIMS: To determine the demands upon gastroenterologists for nutrition support, the available resources, and compliance with the British Society of Gastroenterology (BSG) guidelines. METHOD: A questionnaire was circulated to all 483 consultant physician members of the BSG. RESULTS: There were 336 (70%) replies. Fifty-three per cent of respondents reported malnutrition in 20% or more of their patients. Seventy-nine per cent of consultants supervised patients on enteral feeding, and 64% supervised parenteral feeding. Feeding jejunostomy was used by 61% of Teaching Hospital (TH) consultants but only 38% of District General Hospital (DGH) consultants (P < 0.001). Twenty-seven per cent of respondents headed, or were members of, a nutrition support team (NST). Forty-five and 38% of respondents did not follow written protocols for peripheral and central parenteral nutrition, respectively. Fifty-five per cent monitored catheter complications, of whom 44% reported catheter infections in 5% or more of their patients. Weights of inpatients were obtained by 76% of DGH consultants and 91% of TH consultants (P < 0.001). Fifty-eight per cent of respondents did not arrange for nutritional screening. Ninety-six per cent of consultants could access a dietitian, 55% had access to an NST and 36% had a nutrition nurse specialist (NNS). An NNS was available to 57% of TH consultants but only 23% of DGH consultants (P < 0.001). CONCLUSIONS: Gastroenterologists have a major role in nutrition support. Facilities are suboptimal. Observing guidelines may improve nutritional care. These findings have implications for resources and training.

Abdominal wall metastasis following laparoscopy: a case report.

Laparoscopy is commonly used for diagnosis and follow up of malignant disease. Metastatic infiltration of the scar is very rare. We report a case which presented as acute inflammation within 8 days of the procedure.

Public understanding of genetics and Alzheimer disease.

It is generally thought that public understanding of science is inadequate. The definitions of "the public," "understanding," and "science" all need careful consideration in this formulation, with a greater focus on who should understand what and for what purposes. Improved public understanding depends on experts being reflective about the limits of their own expertise and the different needs of the many potential consumers of genetic knowledge. Media coverage of genetic discoveries has been extensive in recent years, but this coverage is often not useful and may even be misleading to families at risk for genetic disease. The Internet provides an alternative source of information as well as an interactive forum, one that has been widely used by persons interested in Alzheimer disease (AD). Internet-based activities hold great promise for providing interested members of the public with useful information and facilitating more substantive dialogue among physicians, researches, and laypersons regarding the genetic aspects of AD.

Radiotherapy: an effective treatment for extramammary Paget's disease.

Extramammary Paget's disease is a rare condition. Simple excision may result in local relapse, wide local excision may not be appropriate in elderly patients with extensive disease. The case records of six patients with extramammary Paget's disease treated by radiotherapy were reviewed retrospectively. Radical radiotherapy to the skin controlled the disease in four patients.

Sarcoma of the prostate treated with radiotherapy.

Sarcoma of the prostate is a rare primary tumour in adults. We report a 73-year-old man who presented with urinary outflow obstruction. He had histologically proven prostatic sarcoma and probably derived some benefit from radiotherapy. A brief review of the literature is included.

Merkel cell (trabecular) carcinoma of skin treated by radiotherapy.

Merkel cell tumour is a recently described aggressive primary neoplasm of the skin. It is commonly seen in the elderly, on the head and neck or extremities. Surgical excision is the recommended treatment, but local recurrence or dissemination is not an uncommon consequence of this form of therapy. Radiotherapy is usually used as a palliative treatment for metastatic disease. We present two patients, in one an extensive primary was controlled by superficial X-ray, in the other, lymph node metastases were controlled with radiotherapy after excision of the primary.

Primary care physician management, referral, and relations with specialists concerning patients at risk for cancer due to family history.

BACKGROUND: Risk stratification based on family history is a feature of screening guidelines for a number of cancers and referral guidelines for genetic counseling/testing for cancer risk. AIMS: Our aim was to describe primary care physician perceptions of their role in managing cancer risk based on family history. METHODS: Structured interviews were conducted by a medical anthropologist with primary care physicians in 3 settings in 2 north-eastern states. Transcripts were systematically analyzed by a research team to identify major themes expressed by participants. RESULTS: Forty interviews were conducted from May 2003 through May 2006. Physicians provided a diversity of views on roles in management of cancer risk based on family history, management practices and patient responses to risk information. They also provided a wide range of perspectives on criteria used for referral to specialists, types of specialists referred to and expected management roles for referred patients. CONCLUSION: Some primary care physicians appeared to make effective use of family history information for cancer risk management, but many in this sample did not. Increased focus on efficient assessment tools based on recognized guidelines, accessible guides to management options, and patient education and decision aids may be useful directions to facilitate broader use of family history information for cancer risk management.

An audit of acute bacterial meningitis in a large teaching hospital 2005-10.

BACKGROUND: Acute bacterial meningitis (ABM) is a rare disease associated with severe neurological sequelae and death. Clinical features on admission may be subtle and thus delay recognition. Previous studies have shown association between early administration of antibiotics and favourable outcomes. AIM: To examine the presenting clinical features of patients aged >15 years with ABM admitted to a University teaching hospital. To audit investigations and treatment including lumbar puncture (LP), computed tomography (CT) and antibiotics against British Infection Association guidelines. DESIGN: Retrospective observational audit. METHODS: Hospital records were reviewed for presenting clinical features and timing of CT scan, LP and antibiotics. RESULTS: Records of 39 patients with ABM were reviewed. The classical triad of fever, neck stiffness and altered mental state was present on admission in only 21% of cases. LP was contraindicated in 69% of cases. Immediate LP was carried out in only 17% of those who had no contraindication. Antibiotics were administered after a median of 79 min (interquartile range 24-213 min); 65% were given within 3 h after arrival. Eighty-five percent of patients had antibiotics in accordance with local guidelines. CONCLUSION: In patients with ABM, the classical clinical features are uncommon on arrival to hospital and frequently evolve following admission. The majority of patients have contraindications to immediate LP. Efforts should be made to facilitate immediate LP performed in the Emergency Department when there are no contraindications. Earlier administration of antibiotics in cases of suspected ABM and close review following admission is recommended.