Effect of testing experience and profession on provider acceptability of rapid HIV testing after implementation in public sexual health clinics in Sydney.

OBJECTIVES: Rapid HIV testing (RHT) is well established in many countries, but it is new in Australia since a policy change in 2011. We assessed service provider acceptability of RHT before and after its implementation in four Sydney public sexual health clinics. METHODS: Service providers were surveyed immediately after training in RHT and again 6-12 months later. Differences in mean scores between survey rounds were assessed via t-tests, with stratification by profession and the number of tests performed. RESULTS: RHT was rated as highly acceptable among staff at baseline and acceptability scores improved between survey rounds. Belief in being sufficiently skilled and experienced to perform RHT (P = 0.004) and confidence in the delivery of nonreactive results increased (P = 0.007), while the belief that RHT was disruptive declined (P = 0.001). Acceptability was higher for staff who had performed a greater number of tests regarding comfort with their role in RHT (P = 0.004) and belief that patients were satisfied with RHT (P = 0.007). Compared with nurses, doctors had a stronger preference for a faster rapid test (P = 0.027) and were more likely to agree that RHT interfered with consultations (P = 0.014). CONCLUSIONS: Differences in responses between professions may reflect differences in staff roles, the type of patients seen by staff and the model of testing used, all of which may affect the number of tests performed by staff. These findings may inform planning for how best to implement RHT in clinical services.

Increasing prevalence of gonorrhoea and chlamydia among female sex workers in northern Sydney, 2005-2019.

BACKGROUND: Recent reports indicate increasing gonorrhoea and chlamydia among female sex workers (FSWs) in Australia, with decreasing condom use for oral sex. METHODS: We determined trends in prevalence and positivity of gonorrhoea and chlamydia among FSWs attending our clinic from 2005 to 2019, by analysing data from medical and pathology records. We conducted a sensitivity analysis by using an alternative prevalence definition of first test result only per calendar year. RESULTS: Prevalence of gonorrhoea (all sites: pharynx, genital, rectal) increased from 1/130 (0.8%) in 2005 to 14/166 (8.4%) in 2012, to 31/257 (12.1%) in 2019; rate ratio (RR) 1.19, 95%CI 1.14-1.24, ptrend < 0.001. There were rising trends for pharyngeal (RR 1.11, 95% CI 1.05-1.17, ptrend = 0.001) and genital gonorrhoea (RR 1.17, 95% CI 1.08-1.26, ptrend < 0.001). Prevalence of chlamydia (all sites) increased from 4/130 (3.1%) in 2005 to 8/166 (4.8%) in 2012, to 20/257 (7.8%) in 2019; RR 1.05, 95%CI 1.01-1.09, ptrend = 0.006. This rise reflected predominately pharyngeal chlamydia (RR 1.16, 95%CI 1.04-1.29, ptrend = 0.004). Qualitatively similar trends with similar significant results, were seen for gonococcal and chlamydial infections in the sensitivity analyses, indicating robustness of results to potential changes in testing frequency. Gonorrhoea and chlamydia were significantly associated with FSWs born in China. Chlamydia was significantly associated with age group 18-25. In the 2015-2019 period, of 89 women with gonococcal infections, 56 (62.9%) were pharyngeal-only; of 93 with chlamydial infections, 32 (34.4%) were pharyngeal-only infections. CONCLUSIONS: FSWs require screening for pharyngeal as well as genital infections. Enhanced and sustainable health promotion is required.

Assessing condition and ecological role of deep-water biogenic habitats: Glass sponge reefs in the Salish Sea.

Biogenic habitats play important roles in shallow-water ecosystems, but their roles in deeper waters are less well-studied. We quantitatively assessed 19 glass sponge reefs in the Salish Sea for live reef-building sponge cover and biodiversity, explored potential drivers behind variation observed among reefs, and quantified individual and collective roles the reefs play in filtration and carbon removal. The reefs support diverse and abundant communities of invertebrates and fish, with 115 unique taxonomic groups observed. Sponge cover varied widely between reefs: percent live reef-building sponge cover ranged from 0.2 to 17.5% and proportion of live reef habitat category ranged from 0.2 to 92%. These differences were predominantly driven by the seabed terrain characteristics such as seafloor rugosity, curvature, and depth; human pressure measures explored in this study - density of anthropogenic objects and fishing footprint over the past 17 years - did not mask the natural influence of seabed terrain. The difference in sponge cover between the reefs led to wide variation in ecosystem function with individual reefs processing between 465 and 47,300 L/m2 per day. Collectively, each day the 19 reefs filter 1.04 × 1011 L of water which corresponds to 1% of the total water volume in Strait of Georgia and Howe Sound combined. The reefs remove up to 1 g of carbon per m2 per day, comparable to carbon sequestration rates reported for terrestrial old growth forests and to "blue carbon" sequestration rates by marine vegetation. Implications for sponge reef conservation and monitoring are discussed.

A nontransfusional perioperative management regimen for patients with sickle cell disease undergoing laparoscopic cholecystectomy.

BACKGROUND: Patients with sickle cell disease (SCD) are at increased risk for cholelithiasis. Laparoscopic cholecystectomy is the most frequent general surgical operation performed for this group of patients. Acute chest syndrome (ACS) is the most common cause of postoperative death among SCD patients. This study aimed to evaluate the impact of a novel perioperative management regimen involving prophylactic continuous positive airways pressure (CPAP) ventilation and avoidance of preoperative blood transfusion on postoperative SCD-related complications after laparoscopic cholecystectomy. METHODS: A retrospective study included all SCD patients who underwent laparoscopic cholecystectomy since 1997 at our institution. Medical notes were analyzed to assess the rates of postoperative complications in relation to the severity of SCD. RESULTS: A total of 13 patients were identified. There were no recorded episodes of acute painful crises and only one patient experienced an episode of ACS requiring protracted CPAP. CONCLUSION: Laparoscopic cholecystectomy can be safely performed for SCD patients without prior blood transfusion. A defined perioperative regimen including the use of routine postoperative prophylactic CPAP for these patients helps to reduce SCD-related postoperative complications such as ACS and painful vaso-occlusive crises.

Multi-centre field evaluation of the performance of the Trinity Biotech Uni-Gold HIV 1/2 rapid test as a first-line screening assay for gay and bisexual men compared with 4th generation laboratory immunoassays.

BACKGROUND: The Trinity Biotech Uni-Gold HIV test (Uni-Gold) is often used as a supplementary rapid test in testing algorithms. OBJECTIVE: To evaluate the operational performance of the Uni-Gold as a first-line screening test among gay and bisexual men (GBM) in a setting where 4th generation HIV laboratory assays are routinely used. STUDY DESIGN: We compared the performance of Uni-Gold with conventional HIV serology conducted in parallel among GBM attending 22 testing sites. Sensitivity was calculated separately for acute and established infection, defined using 4th generation screening Ag/Ab immunoassay (EIA) and Western blot results. Previous HIV testing history and results of supplementary 3rd generation HIV Ab EIA, and p24 antigen EIA were used to further characterise cases of acute infection. RESULTS: Of 10,793 specimens tested with Uni-Gold and conventional serology, 94 (0.90%, 95%CI:0.70-1.07) were confirmed as HIV-positive by conventional serology, and 37 (39.4%) were classified as acute infection. Uni-Gold sensitivity was 81.9% overall (77/94, 95%CI:72.6-89.1); 56.8% for acute infection (21/37, 95%CI:39.5-72.9) and 98.2% for established infection (56/57, 95%CI:90.6-100.0). Of 17 false non-reactive Uni-Gold results, 16 were acute infections, and of these seven were p24 antigen reactive but antibody negative. Uni-Gold specificity was 99.9% (10,692/10,699, 95%CI:99.9-100.0), PPV was 91.7% (95%CI:83.6-96.6) and NPV was 99.8% (95%CI:99.7-99.9), respectively. CONCLUSIONS: In this population, Uni-Gold had good specificity and sensitivity was high for established infections when compared to 4th generation laboratory assays, however sensitivity was lower in acute infections. Where rapid tests are used in populations with a high proportion of acute infections, additional testing strategies are needed to detect acute infections.

Implications of increased haemoglobin A2 values in HIV positive women in the antenatal clinic.

Universal antenatal haemoglobinopathy screening in this hospital has identified several women with increased haemoglobin A(2) values, but without hypochromic microcytic red cell indices. This report describes two cases where there is evidence that the raised haemoglobin A(2) value is not caused by heterozygous beta thalassaemia, but rather results from these patients being human immunodeficiency virus (HIV) positive and on antiretroviral therapy. This will have important implications as universal antenatal haemoglobinopathy screening becomes more widespread, and as the number of HIV positive women of childbearing age increases.

The uptake of HIV post-exposure prophylaxis within a sexual assault setting in Sydney, Australia.

Our aim was to compare the assault characteristics of victims presenting to a sexual assault service who were prescribed HIV post-exposure prophylaxis (HIV PEP) with those not prescribed HIV PEP. A retrospective review was carried out of the medical records of victims who were seen over a 12-month period in 1999/2000.HIV PEP may have been potentially appropriate for 117 victims, of whom nine (7.7%) were prescribed PEP (eight women, one man). There was a trend for prescription of PEP to depend on the type of assault, with those suffering anal penetration most likely to be prescribed PEP, followed by those with vaginal, and then oral penetration (P = 0.08). Those who gave a history of oral or vaginal mucosal contact with ejaculate were more likely to receive PEP compared with those in whom ejaculation occurred at a non-mucosal site (P = 0.03). Most prescribed PEP regimens involved three antiretroviral drugs. In this study, HIV PEP, when prescribed, was in accord with existing guidelines. Future studies should aim to better document HIV seroconversions in victims of sexual assault and HIV seroprevalence in assailants.

Bone marrow transplant for sickle cell disease--the dilemma.

Sickle cell disease is the family of clinically significant haemoglobin disorders which have in common the inheritance of the sickle beta haemoglobin chain gene. The homozygous SS condition, also known as sickle cell anaemia, can present a varied clinical picture from asymptomatic through to frequent painful vaso-occlusive crises and even death as a result of complications of the disease. S beta zero thalassaemia and the rate haemoglobin SD disease present a similar picture to SS, while S beta plus thalassaemia and haemoglobin SC disease generally have milder clinical features than SS and present somewhat later in life. The present debate about bone marrow transplant (BMT) for sickle cell disease, among both physicians and community, relates to SS patients, definition and markers of disease severity, the effect of BMT on sickle related organ damage, the efficacy of BMT for SS, and its complications, both early and long-term.

Blood transfusion in sickle cell disease.

Blood transfusion can be life-saving in sickle cell disease. There is an increasing body of literature available to help define its place in this patient population. In this review, we have brought together the reported trials, case reports and our experience to discuss the role of transfusion now and in the future for sickle cell disease. Advances are continually being made in all fields and we have in addition. considered the relevant ones from immunohaematology, virology and clinical medicine so that their impact on the subject is taken into consideration.

The presentation, management and prophylaxis of sickle cell disease.

Sickle cell disease (SCD) is encountered in all parts of the world where plasmodium falciparum has been endemic and has spread by migration to the temperate countries of the world resulting in a heavy caseload in Northern Europe and the United States. These patients in the temperate climates manifest most of the clinical problems associated with SCD in Tropical Africa and the West Indies. There are, however, differences between the groups in both the frequency and presentations of the clinical syndromes. The clinical management of SCD is discussed with particular reference to the potentially fatal sequestration syndromes: splenic, hepatic, 'the girdle syndrome' and 'the chest syndrome'. In all clinical situations encountered in SCD blood transfusions should be by isovolaemic exchange unless there is a marked fall in haematocrit (less than 5 g/dl) as may occur with sequestration and aplasia. The criteria for exchange transfusion in the chest syndrome are a pAO2 of less than 60 mm Hg while breathing air or a rapidly deteriorating clinical picture. Analgesia for vaso-occlusive sickle pain should be adequate and freely available which often requires the parental administration of opiates. We have delineated a small sub-group (6%) of SCD patients, 'the non-copers', who manifest a high demand for analgesia. The prospects for cure, and the techniques and issues for antenatal diagnosis are reviewed demonstrating the importance of education and counselling. The significant reduction in mortality and morbidity of children with SCD taking penicillin prophylaxis is emphasised with the need for its early institution.

The insulin-like growth factor (IGF)-binding proteins and IGF bioactivity in Laron-type dwarfism.

Laron-type dwarfism (LTD) is caused by a variable defect in the GH receptor gene and is, therefore, an ideal model to study the physiology of the insulin-like growth factors (IGFs) and their binding proteins (IGFBPs) in the complete absence of GH action. In this study we examined the overnight variation of the IGFs, IGFBPs, and IGF bioactivity in two prepubertal subjects with LTD. Subject 1 was a 14-yr-old female, 103 cm tall (-8.3 SD), and subject 2 was a 11.5-yr-old male, 103.6 cm tall (-5.9 SD). Both had serum IGF-I levels below 0.07 U/mL and low constant serum IGF-II levels overnight (185 +/- 10 and 232 +/- 8 micrograms/L), despite high serum GH levels [mean GH, 65 (32.5 micrograms/L) and 53 mU/L (26.5 micrograms/L)]. Serum IGFBP-1 levels increased overnight (from 24 and 22 micrograms/L at 2000 h to 83 and 110 micrograms/L at 0800 h) as serum insulin levels fell [from 19 (136 pmol/L) and 17 mU/L (122 pmol/L) at 2000 h to less than 2 (less than 14 pmol/L) and 5 mU/L (36 pmol/L) at 0800 h] in subjects 1 and 2, respectively. Serum IGFBP-2 levels remained constant overnight, as assessed on Western Ligand blotting and, despite the changes in IGFBP-1, remained the most prominent IGFBP throughout. On size separation, most of the IGF-II (greater than 60%) eluted with IGFBP-2 and the other low mol wt IGFBPs. Serum IGFBP-3 levels were reduced, and IGFBP-3 was not the major IGF carrier in LTD serum, in contrast to normal serum. An IGFBP-3-specific protease that was heat sensitive and cation dependent was identified as the cause of an apparent overnight rise of serum IGFBP-3 levels. No IGFBP-3 variation and no proteolytic activity was seen in normal serum or rapidly separated LTD plasma. Serum IGF bioactivity, measured in a porcine cartilage bioassay, was 0.18 and 0.55 U/mL in subjects 1 and 2; differences in bioactivity between subjects did not relate to serum IGF-II levels, but, rather, to differences in IGFBP-3 levels. Serum IGF bioactivity was not constant overnight and varied in a similar fashion in both subjects 1 and 2, with reduction in bioactivity between 0600-0800 h by 55% and 32%, suggesting the presence of inhibitory factors in the LTD serum; this decrease coincided with the rise in serum IGFBP-1 levels.(ABSTRACT TRUNCATED AT 400 WORDS)

Thyrotrophin (TSH)-binding proteins in bacteria and their cross-reaction with autoantibodies against the human TSH receptor.

A screen of a range of bacteria normally found in gut flora identified eight with the ability to bind TSH specifically. These included the previously reported Yersinia enterocolitica, Gram-positive, Gram-negative, pathogenic and commensal organisms. Eleven preparations of TSH-receptor autoantibodies strongly able to displace 125I-labelled TSH from the mammalian TSH receptor differed in their ability to displace the tracer from binding to bacterial extracts. None could displace the tracer from E. coli 06-1, four displaced 125I-labelled TSH from E. coli V21/1 and five displaced the tracer from Y. enterocolitica. Of those immunoglobulin preparations which did react with the bacterial protein, their apparent potency compared with that of TSH in displacing tracer from bacterial binders was an order of magnitude greater than with the mammalian receptor. This is consistent with the autoantibodies having a relatively better fit with the bacterial antigen than with the receptor when compared with TSH. The bacterial-binding activity and mammalian receptor-binding activities in each of two samples co-chromatographed on a Remazol yellow GGL-Sepharose affinity column strongly indicated that the same immunoglobulin species reacts with both antigens. These results are consistent with the proposal that a bacterial protein is the primary immunogen for the TSH-receptor antibodies in at least some patients with Graves' disease.

The induction of a specific protease for insulin-like growth factor binding protein-3 in the circulation during severe illness.

The insulin-like growth factors (IGF-I and IGF-II) are almost completely bound in the circulation to specific binding proteins (IGFBPs). These IGFBPs appear to play a pivotal role in maintaining circulating levels and modulating the delivery of the IGFs to the tissues. A large proportion of the circulating IGFs are bound with high affinity to one of the binding proteins. IGFBP-3. The mechanism by which these IGFs are transferred from the circulatory pool to the tissue receptors is at present unclear. Recent studies in late pregnancy have demonstrated the presence of specific proteases which may modify the IGFBPs such that their affinities for the IGFs are reduced. In this paper, we have demonstrated the presence of a heat-sensitive cation-dependent proteolytic enzyme specific for IGFBP-3 in the serum of five severely ill patients. The activity of this protease was found to vary in these patients, becoming more apparent during fasting than when studied after commencement of parenteral nutrition, indicating that one of the influencing factors in the activity of this protease is the nutritional intake of the patient. Age- and sex-matched healthy adults were also studied in a similar protocol, but no proteolytic modification of any of the IGFBPs was found in any of the samples examined. As the levels of both IGF-I and IGF-II were found to be low in the patients, the presence of a circulatory protease suggests that this may be an adaptive response to increase the bioavailability of the IGFs and possibly to improve the nitrogen retention and counter the catabolic state in severe illness.

The insulin-like growth factors and their binding proteins in a case of non-islet-cell tumour-associated hypoglycaemia.

Non-islet-cell tumours which induce hypoglycaemia are rare. Insulin-like growth factor-II (IGF-II) produced by some tumours is thought to be responsible for the hypoglycaemia and other systemic effects, despite normal or even low serum IGF-II levels. We studied a 44-year-old woman presenting with symptomatic hypoglycaemia associated with a large intraabdominal haemangiopericytoma. The serum IGF-II level was 455 micrograms/l when measured after acid-ethanol extraction (normal range (NR) 450-750 micrograms/l) and 1063 micrograms/l after acid chromatography (normal human serum pool 1068 micrograms/l). Levels of fasting plasma insulin, C-peptide, glucose and serum IGF-I levels were low before the operation (less than 2 mU/l (NR less than 2-14), 0.23 nmol/l (NR 0.4-1.2), 3.1 mmol/l, (NR 3.7-5.9) and 0.02 U/ml respectively). After tumour removal, the symptoms resolved rapidly and the patient made a full recovery. Secretion of both insulin and growth hormone was suppressed before the operation in response to a 75 g glucose meal and to an infusion of 100 micrograms GH-releasing hormone (GHRH) respectively in comparison with studies after the operation. Serum IGF-II levels 6 weeks and 12 weeks after the operation fell to 385 micrograms/l (777 micrograms/l; acid chromatography) and 280 micrograms/l (647 micrograms/l; acid chromatography) and serum IGF-I levels increased to 0.35 U/ml and 0.26 U/ml. Serum before the operation and tumour extract contained chiefly a large molecular weight precursor IGF-II (molecular weight 15,000-20,000) which disappeared from the serum after the operation. The IGF-binding proteins (IGFBP-1, IGFBP-2, IGFBP-3 and IGFBP-4) were examined.(ABSTRACT TRUNCATED AT 250 WORDS)

Sickle cell disease: the transplant issue.

A legal moot (mock trial) was held in London in the Middle Temple Hall on Saturday 31 October 1992 to debate the place of BMT in sickle cell disease. The exact wording of the motion, which allowed a very full discussion to take place, was as follows: Bone marrow transplantation should forthwith be offered to all children in the UK with symptomatic sickle cell anaemia who have HLA compatible siblings.

Detection of fetomaternal haemorrhage by an immunofluorescence technique.

An inexpensive and simple technique for assessing fetomaternal bleeds in cases of Rh(D) incompatibility is described. The method is unlikely to replace the acid elution technique, but it may be of use in cases where results are in doubt owing to the presence of F cells of maternal origin.

Patterns of mortality in sickle cell disease in the United Kingdom.

Eighteen of 384 patients entered on the Brent sickle cell disease register died between 1974 and 1989, a mortality of one per 128 years of follow up. Two children died from acute splenic sequestration and a third died from fulminant pneumococcal septicaemia: none was taking prophylactic penicillin. Acute chest syndrome was the cause of death in eight young adults and one child. Three deaths occurred after surgery. Cerebrovascular accidents contributed to the cause of death in three cases and there were two sudden unexplained deaths. Ten of the deaths occurred at home or within 24 hours of admission to hospital. Post mortem examinations were made in 14 cases, but the histological appearances of acute chest syndrome were often not recognised. In most cases for whom information was available, the cause of death (chest syndrome, pneumococcal sepsis, postoperative complications) could have been prevented.

Outcomes of universal antenatal screening for haemoglobinopathies.

OBJECTIVE: To evaluate universal antenatal screening for haemoglobinopathies. SETTING: District general hospital serving a London borough with 45% ethnic minorities. METHODS: Retrospective cohort study of 1444 women referred in 1688 pregnancies and 95 tertiary referrals during 101 pregnancies. RESULTS: Unselected women at risk for sickle cell disease booked 2.7 weeks (95% confidence interval (CI) 0.14 to 5.1) later in gestation than those at risk for beta thalassaemia were less likely to attend counselling (83% v 93%, relative risk (RR) 0.89; 95% CI 0.85 to 0.94), their partners were less likely to be tested (77% v 95%, RR 0.81; 0.77 to 0.83), and they were less likely to accept prenatal diagnosis (22% v 90%, RR 0.37; 0.24 to 0.57). Over 99% of tertiary referrals attended counselling and had their partners tested. There were no significant differences in acceptance of prenatal diagnosis between those at risk of sickle cell disease and beta thalassaemia (55% v 67%). Unselected women at risk of sickle cell disease were significantly less likely to have their partner tested or to accept prenatal diagnosis than tertiary referrals, but not those at risk of beta thalassaemia. 80% of beta thalassaemia and 16% of SS births were prevented. CONCLUSIONS: Uptake of prenatal diagnosis among unselected women at risk of beta thalassaemia is similar to that reported by tertiary centres. It is considerably lower for sickle cell disease but could increase considerably if screening occurred earlier in gestation. Acceptance of counselling is universally high, suggesting that informed choices are made, and indicating a need to measure these outcomes for cost effectiveness studies.

Costing model for neonatal screening and diagnosis of haemoglobinopathies.

AIM: To compare the costs and cost effectiveness of universal and targeted screening for the haemoglobinopathies; to compare the cost of two laboratory methods; and to estimate the cost effectiveness of programmes at different levels of prevalence and mix of haemoglobinopathy traits. METHODS: A retrospective review of laboratory and follow up records to establish workload and costs, and estimation of costs in a range of circumstances was made in a haematology department and sickle cell and thalassaemia centre, providing antenatal and neonatal screening programmes in Inner London. The costs for 47,948 babies, screened during 1994, of whom 25 had clinically significant haemoglobinopathies and 704 had haemoglobinopathy traits, were retrospectively assessed. RESULTS: The average cost per baby tested (isoelectric focusing and high power liquid chromatography) was 3.51 Pounds /3.83 Pounds respectively; the cost per case of sickle cell disease identified (IEF/HPLC) was 6738 Pounds /7355 Pounds; the cost per trait identified (IEF/HPLC) was 234 Pounds /255 Pounds; the cost per extra case of SCD and trait identified by universal programme varied. CONCLUSIONS: IEF and HPLC are very similar in terms of average cost per test. At 16 traits/1000 and 0.5 SCD/1000 there was no significant identification cost difference between universal and targeted programmes. Below this prevalence, a targeted programme is cheaper but likely to miss cases of SCD. If targeted programmes were 90-99% effective, universal programmes would cease to be good value except at very high prevalence. Greater use of prenatal diagnosis, resulting in termination, and therefore fewer affected births, reduces the cost effectiveness of universal screening. Screening services should aim to cover a screened population which will generate a workload over 25,000 births a year, and preferably over 40,000.