Prognostic value of the Quick Sepsis-related Organ Failure Assessment (qSOFA) score among critically ill medical and surgical patients with suspected infection in a resource-limited setting.

Background: The Quick Sequential Organ Failure Assessment (qSOFA) score is a simple bedside tool validated outside of the intensive care unit (ICU) to identify patients with suspected infection who are at risk for poor outcomes. Objectives: To assess qSOFA at the time of ICU referral as a mortality prognosticator in adult medical v. surgical patients with suspected infection admitted to an ICU in a resource-limited regional hospital in South Africa (SA). Methods: We conducted a retrospective cohort study on adult medical or surgical patients that were admitted to an ICU in a resource-limited hospital in SA. We performed univariate and multivariable logistic regression and compared nested models using likelihood ratio test, and we calculated the area under the receiver operating characteristic curve (AUROC). Results: We recruited a total of 1 162 (medical n=283 and surgical n=875) participants in the study who were admitted to the ICU with suspected infection. qSOFA at the time of ICU referral was highly associated with but poorly discriminant of in-ICU mortality among medical (odds ratio (OR) 2.60, 95% confidence interval (CI) 1.19 - 5.71; p=0.02; AUROC 0.60; 95% CI 0.53 - 0.67; p=0.02) and surgical (OR 2.74; 95% CI 1.73-4.36; p<0.001; AUROC 0.60; 95% CI 0.55 - 0.65; p=0.04) patients. qSOFA model performance was similar between medical and surgical subgroups (p≥0.26). Addition of qSOFA to a baseline risk factor model including age, sex, and HIV status improved the model discrimination in both subgroups (medical AUROC 0.64; 95% CI 0.56 - 0.71; p=0.049; surgical AUROC 0.69; 95% CI 0.64 - 0.74; p<0.0001). Conclusion: qSOFA was highly associated with, but poorly discriminant for, poor outcomes among medical and surgical patients with suspected infection admitted to the ICU in a resource-limited setting. These findings suggest that qSOFA may be useful as a tool to identify patients at increased risk of mortality in these populations and in this context.

A Combined Study of Headspace Volatiles using Human Sensory, Mass Spectrometry and Chemometrics.

Smokeless tobacco products (STPs) are widely used in certain parts of the world, yet there is limited understanding of how they are consumed, particularly the impact of chemosensory characteristics on their use. In order to develop an understanding of the drivers of STP use and product acceptability we conducted both human sensory panel testing and chemical analyses on a range of STPs. Free-sorting paired odour testing using sensory panellists identified similarities and clear differences between eleven different STPs. Headspace volatiles, analysed by headspace solid-phase microextraction gas chromatography mass spectrometry (HS-SPME-GC-MS), identified 20 to 70 components depending upon the STP. Key differences in headspace volatiles were found between STPs. For example, the headspace of Skoal Bandits Wintergreen was dominated by methyl salicylate, while Marlboro Spice consists of a more complex profile including pinene, nicotine, eugenol and cymene. Chemometric Target Factor Analysis (TFA) and Hierarchical Cluster Analysis (HCA) of chemistry and sensory data was used to deduce chemical drivers of sensory perceptions. The chemometric strategy used showed that headspace analysis is a complementary screening tool to sensory analysis in classification studies. This study is generic with applications across various product sectors that require routine human sensory panel evaluation.

Bovid ecomorphology and hominin paleoenvironments of the Shungura Formation, lower Omo River Valley, Ethiopia.

The Shungura Formation in the lower Omo River Valley, southern Ethiopia, has yielded an important paleontological and archeological record from the Pliocene and Pleistocene of eastern Africa. Fossils are common throughout the sequence and provide evidence of paleoenvironments and environmental change through time. This study developed discriminant function ecomorphology models that linked astragalus morphology to broadly defined habitat categories (open, light cover, heavy cover, forest, and wetlands) using modern bovids of known ecology. These models used seven variables suitable for use on fragmentary fossils and had overall classification success rates of >82%. Four hundred and one fossils were analyzed from Shungura Formation members B through G (3.4-1.9 million years ago). Analysis by member documented the full range of ecomorph categories, demonstrating that a wide range of habitats existed along the axis of the paleo-Omo River. Heavy cover ecomorphs, reflecting habitats such as woodland and heavy bushland, were the most common in the fossil sample. The trend of increasing open cover habitats from Members C through F suggested by other paleoenvironmental proxies was documented by the increase in open habitat ecomorphs during this interval. However, finer grained analysis demonstrated considerable variability in ecomorph frequencies over time, suggesting that substantial short-term variability is masked when grouping samples by member. The hominin genera Australopithecus, Homo, and Paranthropus are associated with a range of ecomorphs, indicating that all three genera were living in temporally variable and heterogeneous landscapes. Australopithecus finds were predominantly associated with lower frequencies of open habitat ecomorphs, and high frequencies of heavy cover ecomorphs, perhaps indicating a more woodland focus for this genus.

Neurological, visual, and MRI brain scan findings in 87 South African patients with HIV-associated cryptococcal meningoencephalitis.

BACKGROUND: HIV-associated cryptococcal meningoencephalitis (CM) is a leading cause of adult meningitis in sub-Saharan Africa. Neuroradiological data is however limited to case reports and small case series from developed countries and/or immunocompetent patients. METHODS: Eighty seven patients aged ≥18 hospitalized with a first episode of CM had magnetic resonance (MRI) imaging during the first two weeks of admission. A subset of eleven patients had follow-up scans approximately one month from their initial MRI scan. All had prospectively-recorded detailed neurological and visual examinations. RESULTS: An abnormal finding on neurological examination was detected in 33 (39%) patients. 38 (48%) patients experienced some visual loss. Neuroradiological lesions presumed to be cryptococcosis-related, as defined by the presence of dilated Virchow Robin spaces, pseudocysts or cryptococcomas, enhancing nodules, hydrocephalus, meningitis, focal perilesional oedema and infarcts, were detected in 55 (63%) patients. MRI findings suggestive of a second diagnosis were found in 18 (21%) patients. Visual loss was associated with the presence of cryptococcal-related lesions (p = 0.02). Blindness was associated with raised intracranial pressure (ICP) (p = 0.02). Of eleven patients with paired scans, brain swelling was identified on the initial scan in only one patient. CONCLUSION: The majority of patients had MRI brain scan abnormalities presumed secondary to CM. Dilated Virchow Robin spaces were the commonest neuroradiological lesion. Visual loss was associated with the degree of cerebral involvement as reflected by the presence of MRI abnormalities. Blindness was associated with the presence of raised ICP. Initial generalised brain swelling does not appear to be common, but further studies with paired scans are needed.

Outbreak investigation and case-control study: penta-resistant Salmonella Typhimurium DT104 associated with biltong in London in 2008.

In August 2008 an outbreak of Salmonella Typhimurium DT104 occurred in South West London. Sixteen cases were identified with a particular multilocus variable number tandem repeat analysis (MLVA) pattern. In a matched case-control study 14 primary cases were included. These were defined as individuals with gastrointestinal symptoms and Salmonella Typhimurium DT104 isolated from a stool specimen, with a characteristic antibiotic resistance profile and MLVA pattern, and diagnosed in a local laboratory. Four controls per case were matched on age, gender and area of residence. Cases were 26 times more likely than controls to have eaten beef biltong, a South African speciality meat product (odds ratio 25·83, 95% confidence interval 4·92­135·59, P < 0·01). Although environmental investigation failed to identify Salmonella in the food product we conclude that beef biltong consumption led to this outbreak. This conclusion has importance in informing the ongoing risk assessment relating to uncontrolled foodstuffs.

Epidemiology of internal contamination with polonium-210 in the London incident, 2006.

BACKGROUND: More than 700 UK residents were tested for possible contamination with polonium-210 ((210)Po) following the alleged poisoning of Mr Alexander Litvinenko in London in November 2006. This paper describes the epidemiology of internal contamination with the radionuclide in this group. METHODS: 11 locations in London had been identified as sufficiently environmentally contaminated with (210)Po to present a health risk to people associated with them. Public health consultant teams identified individuals at risk and offered 24-h urine testing for (210)Po excretion. Prevalence of internal contamination was estimated, and a retrospective cohort analysis was completed for each location. RESULTS: Overall 139 individuals (prevalence 0.19 (95% CI 0.13 to 0.27)) showed evidence of internal contamination with (210)Po, although none with uptakes likely to cause adverse health effects. Substantial prevalence was seen among specific hotel service staff, customers, staff and other users of a hotel bar, office and hospital staff, staff of one restaurant and residents of and visitors to the family home. Increased risks of contamination were seen for a hotel bar in association with occupational, behavioural and temporal factors. Occupational and guest exposure to contaminated areas of hotels were also associated with increased contamination risk. Nurses were more likely to become contaminated than other staff involved in direct patient care. CONCLUSIONS: Uptake of trace amounts of radionuclide in this incident was frequent. Occupational, behavioural and temporal gradients in contamination risk were mostly consistent with a priori site risk assessments. Utility of the investigation methods and findings for future accidental or deliberate environmental contamination incidents are discussed.

Burden of meticillin-resistant Staphylococcus aureus colonization and infection in London acute hospitals: retrospective on a voluntary surveillance programme.

Although meticillin-resistant Staphylococcus aureus (MRSA) is recognized as an important cause of hospital and community healthcare-associated morbidity, and colonization as a precursor to infection, few studies have attempted to assess the burden of both colonization and infection across acute healthcare providers within a defined health economy. This study describes the prevalence and incidence of MRSA colonization and infection in acute London hospital Trusts participating in a voluntary surveillance programme in 2000-2001. Hospital infection control staff completed a weekly return including details on incident and prevalent colonizations, bacteraemias and other significant infections due to MRSA. Incidence and prevalence rates were calculated for hospitals with sufficient participation across both years. Colonizations accounted for 79% of incident MRSA cases reported; 4% were bacteraemias, and 17% other significant infections. There was no change in incidence of colonization of hospital patients between 2000 and 2001. By contrast, there was an unexplained 49% increase in prevalence of colonizations over this period. For any given month, prevalent colonizations outnumbered incident colonizations at least twofold. This MRSA surveillance programme was unusual for prospective ascertainment of incident and prevalent cases of both colonization and infection within an English regional health economy. Consistent with other studies, the incidence and prevalence of colonization substantially exceeded infection. Given the small contribution of bacteraemias to the overall MRSA burden, and the surveillance, screening and control interventions of recent years, it may be appropriate to review the present reliance on bacteraemia surveillance.

Antibiotic administration longer than eight hours after triage and mortality of community-acquired pneumonia in patients with diabetes mellitus.

Studies have established that diabetic patients with community-acquired pneumonia (CAP) may have increased mortality. The primary objective of this study was to investigate if time to first appropriate antibiotic in the emergency department (ED) was associated with in-hospital mortality of CAP in patients with diabetes mellitus (DM). This was a retrospective cohort study of adult diabetic patients who were admitted with CAP. Patients were stratified into two groups: those who received first dose of appropriate antibiotic within 8 hours of triage and those who received it later than 8 hours. A multiple logistic regression analysis was performed. Two hundred six patients were included in the study. Fifty-nine patients (28.6%) had complications of CAP on admission and 31 patients (16%) died. In-hospital mortality was higher in patients who received their initial appropriate antibiotic after 8 hours of triage than those who received it within 8 hours [18 (35.3%), 15 (9.7%), p < 0.0001]. Time to first appropriate antibiotic later than 8 hours of triage was associated with increased in-hospital mortality (OR 4, 95% CI 1.2-13.1, p = 0.02). Antibiotic administration later than 8 hours of triage in the ED was associated with increased in-hospital mortality of CAP among patients with DM.

Assessing public health risk in the London polonium-210 incident, 2006.

OBJECTIVES: Mr Alexander Litvinenko died in a London hospital on 23 November 2006, allegedly from poisoning with the radionuclide polonium-210 ((210)Po). Associated circumstances required an integrated response to investigate the potential risk of internal contamination for individuals exposed to contaminated environments. STUDY DESIGN: Descriptive study. METHODS: Contaminated locations presenting a potential risk to health were identified through environmental assessment by radiation protection specialists. Individuals connected with these locations were identified and assessed for internal contamination with (210)Po. RESULTS: In total, 1029 UK residents were identified, associated with the 11 most contaminated locations. Of these, 974 were personally interviewed and 787 were offered urine tests for (210)Po excretion. Overall, 139 individuals (18%) showed evidence of probable internal contamination with (210)Po arising from the incident, but only 53 (7%) had assessed radiation doses of 1mSv or more. The highest assessed radiation dose was approximately 100mSv. CONCLUSIONS: Although internal contamination with (210)Po was relatively frequent and was most extensive among individuals associated with locations judged a priori to pose the greatest risk, a high degree of assurance could be given to UK and international communities that the level of health risk from exposure to the radionuclide in this incident was low.

Prospective comparative study of the scarf and Ludloff osteotomies in the treatment of hallux valgus.

BACKGROUND: This study compares two diaphyseal osteotomies (scarf and Ludloff) which correct moderate to severe metatarsus primus varus. This is a single surgeon, prospective cohort study with clinical and radiological follow~up at 12 months. MATERIALS AND METHODS: There were 57 patients in each group. Both groups were similar in terms of age, gender and preoperative deformity. Clinical assessment included visual analogue scale questionnaires for subjective assessment and functional activities and the American Orthopaedic Foot and Ankle Society (AOFAS) score. Standardized weight bearing radiographs were analyzed. RESULTS: There was no statistically significant difference between the two groups at 6 and 12 months in subjective satisfaction, AOFAS score, improvement in functional activities and range of movements. The improvement in pain (at best) and transfer lesions at 12 months was significantly better in the scarf group (p < 0.05). The radiological results at 6 and 12 months including intermetatrsal angle (p < 0.001), hallux valgus angle (p < 0.01), distal metatarsal articular angle and seasmoid position (p < 0.05) were significantly better in the scarf osteotomy group. There were three cases (5%) of delayed union in the Ludloff group. Two of these healed with dorsiflexion malunion. One patient in the Ludloff osteotomy group developed a complex regional pain syndrome. There were two wound complications in the scarf group. CONCLUSION: Overall the patients who had a scarf osteotomy had a superior outcome at 6 and 12 months.

Guidelines on the insertion and management of central venous access devices in adults.

Central venous access devices are used in many branched of medicine where venous access is required for either long-term or a short-term care. These guidelines review the types of access devices available and make a number of major recommendations. Their respective advantages and disadvantages in various clinical settings are outlined. Patient care prior to, and immediately following insertion is discussed in the context of possible complications and how these are best avoided. There is a section addressing long-term care of in-dwelling devices. Techniques of insertion and removal are reviewed and management of the problems which are most likely to occur following insertion including infection, misplacement and thrombosis are discussed. Care of patients with coagulopathies is addressed and there is a section addressing catheter-related problems.

Emergence of methicillin resistant Staphylococcus aureus (MRSA) bacteraemia among children in England and Wales, 1990-2001.

Methicillin resistant Staphylococcus aureus (MRSA) is now a major cause of adult bacteraemia. All reports of Staphylococcus aureus bacteraemia to the Health Protection Agency were analysed from 1990 to 2001. There were 376 cases of MRSA bacteraemia in children <15 years over this time. The proportion of Staphylococcus aureus bacteraemia due to MRSA increased steadily from 0.9% in 1990 to 13% in 2000. The proportion was higher in infants. MRSA bacteraemia is now a serious problem in children in England and Wales. More data on the risk factors for acquisition and spread of MRSA in children are required.

Outcome of follicular lymphoma grade 3: is anthracycline necessary as front-line therapy?

A grading system (grades 1-3) for follicular lymphoma (FL) is used in the WHO classification for lymphoid malignancies based on the absolute number of centroblasts in the neoplastic follicles. Grade 3 FL is further subdivided into 3a and 3b depending on the presence or absence of centrocytes. A total of 231 patients with FL, referred from 1970 to 2001, were identified from our prospectively maintained database. Original diagnostic materials were available for review on 215 patients and these were reclassified according to the WHO grading system. Follicular lymphoma grades 1, 2 and 3 accounted for 92, 68 and 55 patients, respectively. No significant overall survival (OS) differences were observed among FL grades 1-3 (log rank P=0.25) or between grades 3a and 3b (log rank P=0.20). No significant failure-free survival (FFS) differences were observed among FL grades 1-3 (log rank P=0.72) or between grades 3a and 3b (log rank P=0.11). First-line anthracyclines did not influence OS or FFS (log rank P=0.86, P=0.58, respectively) in patients with FL grade 3. There are long-term survivors among patients with FL grade 3 with a continuing risk of relapse. Anthracyclines did not appear to influence survival or disease relapses when given as front-line therapy in our series. The role of anthracyclines should be further evaluated in large randomised studies.

Rapid access multidisciplinary lymph node diagnostic clinic: analysis of 550 patients.

Lymphadenopathy is common, affecting patients of all ages. The current referral pattern for investigating patients with lymphadenopathy varies widely with no universally practised pathway. Our institution set up a lymph node diagnostic clinic (LNDC) accepting direct referrals from primary care physicians. Details of clinical presentation and investigations were recorded prospectively. Between December 1996 and July 2001, 550 patients were referred (M: 203; F:347). The median age was 40 years (range 14-90). The median time between initial referral and the first clinic visit was 6 days. Of 95 patients diagnosed to have malignant diseases, the median time from the first clinic visit to reaching malignant diagnosis was 15 days. Multivariate logistic regression analysis identified five significant predictors for malignant nodes: male gender (risk ratio (RR)=2.72; 95% confidence interval (CI): 1.63-4.56), increasing age (RR=1.05; 95% CI: 1.04-1.07), white ethnicity (RR=3.01; 95% CI: 1.19-7.6) and sites of lymph nodes: supraclavicular region (RR=3.72; 95% CI: 1.52-9.12) and > or = 2 regions of lymph nodes (RR=6.41; 95% CI: 2.82-14.58). Ultrasound and fine-needle aspiration cytology of palpable lymph nodes were performed in 154 and 289 patients, respectively. An accuracy of 97 and 84% was found, respectively. In conclusion, a multidisciplinary lymph node diagnostic clinic enables a rapid, concerted approach to a common medical problem and patients with malignant diseases were diagnosed in a timely fashion.

Gastrin-cholecystokinin(B) receptor expression in AGS cells is associated with direct inhibition and indirect stimulation of cell proliferation via paracrine activation of the epidermal growth factor receptor.

BACKGROUND: Activation of the gastrin-cholecystokinin(B) (CCK(B)) receptor stimulates cell proliferation and increases production of ligands for the epidermal growth factor receptor (EGF-R). AIMS: To determine the role of gastrin-CCK(B) activation in stimulation of cell proliferation via paracrine activation of EGF-R. METHODS: AGS cells were transfected with the gastrin-CCK(B) receptor (AGS-G(R) cells) or with green fluorescent protein (AGS-GFP cells). Proliferation was determined by [(3)H] thymidine incorporation, flow cytometry, and cell counting. RESULTS: Gastrin inhibited proliferation of AGS-G(R) cells by delaying entry into S phase. However, when AGS-G(R) cells were cocultured with AGS-GFP cells, gastrin stimulated proliferation of the latter. Immunoneutralisation and pharmacological studies using metalloproteinase and kinase inhibitors indicated that the proliferative response was mediated by paracrine stimulation of EGF-R and activation of the mitogen activated protein kinase pathway through release of heparin binding EGF. CONCLUSIONS: Gastrin can directly inhibit, and indirectly stimulate, proliferation of gastric AGS cells.

Comparative context of Plio-Pleistocene hominin brain evolution.

One of the distinguishing features of Homo sapiens is its absolutely and relatively large brain. This feature is also seen in less extreme form in some fossil Homo species. However, are increases in brain size during the Plio-Pleistocene only seen in Homo, and is brain enlargement among Plio-Pleistocene primates confined to hominins? This study examines evidence for changes in brain size for species and lineage samples of three synchronic East African fossil primate groups, the two hominin genera Homo and Paranthropus, and the cercopithecoid genus Theropithecus. Hominin endocranial capacity data were taken from the literature, but it was necessary to develop an indirect method for estimating the endocranial volume of Theropithecus. Bivariate and multivariate regression equations relating measured endocranial volume to three external cranial dimensions were developed from a large (ca. 340) sample of modern African cercopithecoids. These equations were used to estimate the endocranial volumes of 20 Theropithecus specimens from the African Plio-Pleistocene. Spearman's rho and the Hubert nonparametric test were used to search for evidence of temporal trends in both the hominin and Theropithecus data. Endocranial volume apparently increased over time in both Homo and Paranthropus boisei, but there was no evidence for temporal trends in the endocranial volume of Theropithecus. Thus, hypotheses which suggest a mix of environmental, social, dietary, or other factors as catalysts for increasing brain in Plio-Pleistocene primates must accommodate evidence of brain enlargement in both Homo and Paranthropus, and explain why this phenomenon appears to be restricted to hominins.

Randomized trial of folic acid supplementation and serum homocysteine levels.

BACKGROUND: Lowering serum homocysteine levels with folic acid is expected to reduce mortality from ischemic heart disease. Homocysteine reduction is known to be maximal at a folic acid dosage of 1 mg/d, but the effect of lower doses (relevant to food fortification) is unclear. METHODS: We randomized 151 patients with ischemic heart disease to 1 of 5 dosages of folic acid (0.2, 0.4, 0.6, 0.8, and 1.0 mg/d) or placebo. Fasting blood samples for serum homocysteine and serum folate analysis were taken initially, after 3 months of supplementation, and 3 months after folic acid use was discontinued. RESULTS: Median serum homocysteine level decreased with increasing folic acid dosage, to a maximum at 0.8 mg of folic acid per day, when the homocysteine reduction (placebo adjusted) was 2.7 micromol/L (23%), similar to the known effect of folic acid dosages of 1 mg/d and above. The higher a person's initial serum homocysteine level, the greater was the response to folic acid, but there were statistically significant reductions regardless of the initial level. Serum folate level increased approximately linearly (5.5 nmol/L for every 0.1 mg of folic acid). Within-person fluctuations over time in serum homocysteine levels, measured in the placebo group, were large compared with the effect of folic acid, indicating that monitoring of the reduction in an individual is impractical. CONCLUSIONS: A dosage of folic acid of 0.8 mg/d appears necessary to achieve the maximum reduction in serum homocysteine level across the range of homocysteine levels in the population. Current US food fortification levels will achieve only a small proportion of the achievable homocysteine reduction.

Measurement of secretory vesicle pH reveals intravesicular alkalinization by vesicular monoamine transporter type 2 resulting in inhibition of prohormone cleavage.

1. The acidic interior of neuroendocrine secretory vesicles provides both an energy gradient for amine-proton exchangers (VMATs) to concentrate small transmitter molecules, for example catecholamines, and an optimal pH for the prohormone convertases which cleave hormone precursors. There is evidence that VMAT activity modulates prohormone cleavage, but in the absence of measurements of pH in secretory vesicles in intact cells, it has not been possible to establish whether these effects are attributable to raised intravesicular pH due to proton transport through VMATs. 2. Clones were generated of the hamster insulinoma cell line HIT-T15 expressing a pH-sensitive form of green fluorescent protein (GFP-F64L/S65T) targeted to secretory vesicles, with and without co-expression of VMAT2. In order to study prohormone cleavage, further clones were generated that expressed preprogastrin with and without co-expression of VMAT2. 3. Confocal microscopy of GFP fluorescence indicated that the pH in the secretory vesicles was 5.6 in control cells, compared with 6.6 in cells expressing VMAT2; the latter was reduced to 5.8 by the VMAT inhibitor reserpine. 4. Using a pulse-chase labelling protocol, cleavage of 34-residue gastrin (G34) was found to be inhibited by co-expression with VMAT2, and this was reversed by reserpine. Similar effects on vesicle pH and G34 cleavage were produced by ammonium chloride. 5. We conclude that VMAT expression confers the linked abilities to store biogenic amines and modulate secretory vesicle pH over a range influencing prohormone cleavage and therefore determining the identity of regulatory peptide secretory products.