Individualized prediction of the effect of angiotensin receptor blockade on renal and cardiovascular outcomes in patients with diabetic nephropathy.

AIMS: To predict individualized treatment effects of angiotensin receptor blockers (ARBs) on cardiovascular and renal complications in order to help clinicians and patients assess the benefit of treatment (or adherence) and estimate remaining disease risk. MATERIALS AND METHODS: In patients with diabetic nephropathy, the 3-year treatment effect of ARBs was predicted in terms of absolute risk reduction (ARR) for end-stage renal disease (ESRD) and cardiovascular disease (CVD; i.e. myocardial infarction, stroke, hospitalization for heart failure) and all-cause mortality. Competing-risk-adjusted proportional hazard models were developed based on the Irbesartan Diabetic Nephropathy Trial (IDNT) and externally validated in the Reduction of Endpoints NIDDM with Angiotensin II Antagonist Losartan (RENAAL) trial. RESULTS: Predictors included in the model were age, sex, smoking sex, systolic blood pressure, urinary albumin/creatinine ratio, estimated glomerular filtration rate, albumin and phosphorus. The median predicted 3-year risk without treatment was 6.0% for ESRD and 28.0% for CVD and mortality. The median [interquartile range (IQR)] predicted 3-year ARR was 1.2 (0.4-3.1)% for ESRD and 2.2 (1.8-2.6)% for CVD and mortality, resulting in a combined ARR of 3.4 (2.4-5.5)%. The remaining disease risk was 4.7 (IQR 1.7-12.8)% for ESRD and 25.8% (IQR 20.3-31.9)% for CVD and mortality. CONCLUSIONS: The combined effects of ARBs on ESRD and CVD and mortality in patients with diabetic nephropathy vary considerably between patients. A substantial proportion of patients remain at high risk for both outcomes despite ARB treatment.

Venous thromboembolism and underutilisation of anticoagulant thromboprophylaxis in hospitalised patients with inflammatory bowel disease.

BACKGROUND: Venous thromboembolism (VTE) is a well-recognised extra-intestinal manifestation of inflammatory bowel disease (IBD). Despite the widespread support for anticoagulant prophylaxis in hospitalised IBD patients, the utilisation and efficacy in clinical practice are unknown. AIMS: The aim of this study was to assess the prevalence and clinical features of VTE among hospitalised IBD patients and ascertain whether appropriate thromboprophylaxis had been administered. METHODS: All patients with a discharge diagnosis of Crohn disease or ulcerative colitis and VTE were retrospectively identified using International Classification of Diseases, tenth revision codes from medical records at our institution from July 1998 to December 2009. Medical records were then reviewed for clinical history and utilisation of thromboprophylaxis. Statistical analysis was performed by Mann-Whitney test and either χ(2) tests or Fisher's exact tests. RESULTS: Twenty-nine of 3758 (0.8%) IBD admissions suffered VTE, 13 preadmission and 16 during admission. Of these 29 admissions (in 25 patients), 24% required intensive care unit and 10% died. Of the 16 venous thrombotic events that occurred during an admission, eight (50%) did not receive anticoagulant thromboprophylaxis and eight (50%) occurred despite thromboprophylaxis. Most thromboembolism despite prophylaxis occurred post-intestinal resection (n = 5, 63%). CONCLUSION: Thromboprophylaxis is underutilised in half of IBD patients suffering VTE. Prescription of thromboprophylaxis for all hospitalised IBD patients, including dual pharmacological and mechanical prophylaxis in postoperative patients, may lead to a reduction in this preventable complication of IBD.

Neurosarcoidosis-related intracranial haemorrhage: three new cases and a systematic review of the literature.

BACKGROUND AND PURPOSE: Intracranial haemorrhage in neurosarcoidosis (NS-ICH) is rare, poorly understood and the diagnosis of NS may not be immediately apparent. METHODS: The clinical features of three new NS-ICH cases are described including new neuropathological findings and collated with cases from a systematic literature review. CASES: (i) A 41-year-old man with headaches, hypoandrogenism and encephalopathy developed a cerebellar haemorrhage. He had neuropathological confirmation of NS with biopsy-proven angiocentric granulomata and venous disruption. He responded to immunosuppressive therapy. (ii) A 41-year-old man with no history of hypertension was found unconscious. A subsequently fatal pontine haemorrhage was diagnosed. Liver biopsy revealed sarcoid granulomas. (iii) A 36-year-old man with raised intracranial pressure headaches presented with a seizure and a frontal haemorrhage. Hilar lymph node biopsy confirmed sarcoidosis, and he was treated successfully. Systematic review: Twelve other published cases were identified and collated with our cases. Average age was 36 years and M:F = 2.3:1; 46% presented with neurological symptoms and 31% had CNS-isolated disease. Immediate symptoms of ICH were acute/worsening headache or seizures (60%). ICH was supratentorial (62%), infratentorial (31%) or subarachnoid (7%). Forty percent had definite NS, 53% probable NS and 7% possible NS (Zajicek criteria). Antigranulomatous/immunosuppressive therapy regimens varied and 31% died. CONCLUSIONS: This series expands our knowledge of the pathology of NS-ICH, which may be of arterial or venous origin. One-third have isolated NS. Clinicians should consider NS in young-onset ICH because early aggressive antigranulomatous therapy may improve outcome.

Impact of introducing consultant resident on-call in a district general hospital.

Introduction of structured competency-based training for specialty registrars and implementation of European Working Time Directives (EWTD) have affected the quality of maternity care. In York District Hospital, consultant resident on-call (CRO) without registrar cover was introduced in July 2010 to address the long-standing problem of middle-grade out-of-hours coverage. To examine the impact of introducing out-of-hours consultant resident on-call on maternity care, data from 486 deliveries including 59 CRO and 59 registrar shifts were collected retrospectively, from July 2010 to April 2011. Main outcome measures include mode of delivery, second-stage management, maternal and neonatal outcomes. Feedback from consultants, junior trainees and midwives on the impact of CRO were collated through semi-structured interviews. More normal vaginal deliveries (71.8% vs 63.0%) and fewer emergency caesarean sections (12.5% vs 20.6%) were performed in the CRO shifts compared with registrar on-call. Instrumental delivery rates in labour rooms vs theatre were higher when compared with the registrar group. Overall, good patient and staff experience was reflected during interviews. Our work shows that introduction of CRO in out-of-hours settings is acceptable among staff and is associated with fewer obstetric interventions. However, improved job descriptions may be needed in order to make the CRO post more attractive.

Dog Bites to the Head; Neck and Face in Children

Dog bites are a poorly understood and complex public health problem. Children are most frequently the victims of dog bites and the face is often the favoured target. A review of dog bite wounds in small children presenting to the Red Cross War Memorial Children's Hospital was carried out over a period of 13.5 years (1991-2004). One thousand eight hundred and seventy-one dog bite wounds were admitted from a total of 125;677 patients treated. From 1;871 patients presenting with dog bite injuries; we identified 596 children who sustained injuries to the head; face or neck. Dog bites to the head; face or neck were responsible for 0.5of all trauma unit presentations and 32of all dog bite injuries. The mean age of the children was 5.1 years. Male children accounted for 68of the patients. The peak incidence was noted in children aged 2 to 4 years old. One hundred and seventy-two (29) bites occurred between the summer months of December and February. Two hundred and forty-nine (42) patients presented to hospital between the hours of 12:00 and 18:00 hours and 275 (46) children presented between 18:00 and 0:00 hours. A large proportion of all attacks occurred either inside or outside the victim's own home and at the home of friends or family. Superficial injuries were treated with wound cleaning; suturing and dressing. There were no fatalities. Dog bites are relatively common in small children; but do not represent a major cause of morbidity and mortality

An integrative framework for stochastic, size-structured community assembly.

We present a theoretical framework to describe stochastic, size-structured community assembly, and use this framework to make community-level ecological predictions. Our model can be thought of as adding biological realism to Neutral Biodiversity Theory by incorporating size variation and growth dynamics, and allowing demographic rates to depend on the sizes of individuals. We find that the species abundance distribution (SAD) is insensitive to the details of the size structure in our model, demonstrating that the SAD is a poor indicator of size-dependent processes. We also derive the species biomass distribution (SBD) and find that the form of the SBD depends on the underlying size structure. This leads to a prescription for testing multiple, intertwined ecological predictions of the model, and provides evidence that alternatives to the traditional SAD are more closely tied to certain ecological processes. Finally, we describe how our framework may be extended to make predictions for more general types of community structure.

Dog bite injuries in children--a review of data from a South African paediatric trauma unit.

BACKGROUND AND OBJECTIVE: Dog bites are a major cause of preventable traumatic injury in the paediatric population. We aimed to determine the epidemiology of dog bite injuries in a group of South African children with a view to developing potential preventive strategies. DESIGN, SETTING, SUBJECTS: A retrospective review was done of patients presenting with dog bite injuries to the trauma unit at the Red Cross War Memorial Children's Hospital in Cape Town over a 13.5-year period. RESULTS: We identified 1,871 children treated for 2,021 dog bite injuries during the study period. Dog bites accounted for 1.5% of all trauma unit presentations. Male children accounted for 68% of the patients. Children under 6 years of age were more likely to have sustained injuries to the head, face or neck, while children older than 6 years more commonly received injuries to the perineum, buttocks, legs or feet. Younger children were more likely to be attacked at home and older children outside the home. The most frequent injuries were superficial, and the majority of patients were treated with simple medication, dressing or suturing. There were no dog bite-related fatalities. CONCLUSION: The relationship between the geographical location of dog attacks on children and the age groups attacked suggests that strategies to prevent dog bites should target both parents supervising younger children at home, and older children who encounter dogs outside the home.

Chronic myeloid leukemia-associated membranoproliferative glomerulonephritis that responded to imatinib mesylate therapy.

There is no known clinical association between chronic myelogenous leukemia (CML) and membranoproliferative glomerulonephritis (MPGN). We present a patient who was followed in the renal clinic for proteinuria of unknown etiology (3.2 g/24 h) and normal renal function who was diagnosed with CML as well as MPGN and acute renal failure at the same time. The patient's renal function and proteinuria improved when his CML was treated with imatinib mesylate, suggesting that CML either caused or exacerbated existing MGPN. To the best of our knowledge, this is the first reported case of MPGN associated with CML that improved with imatinib mesylate therapy.

Sensory abnormalities in unaffected relatives in familial adult-onset dystonia.

Somatosensory abnormalities are found in adult-onset primary torsion dystonia (PTD). Therefore we assessed spatial discrimination thresholds (SDT), a measure of spatial acuity, in four multiplex families with adult-onset PTD. In family members aged 20 to 45 years vs controls (mean + 2.5 SD), abnormal SDTs were found in four of five affected with adult-onset PTD and in 12 of 49 unaffected relatives. Sensory abnormalities may be an endophenotype, possibly expressed later as adult-onset PTD.

Continuous measurement of systemic vascular resistance.

We have successfully linked a standard patient monitor system (Hewlett Packard M1166A-A66) with the Baxter Edwards Critical-Care Swan Ganz Intellicath continuous cardiac output catheter and the Vigilance continuous cardiac output monitor system to produce continuous values of systemic vascular resistance. Six cases are presented in which marked changes in indexed systemic vascular resistance were observed as a result of clinical interventions. The continuous derivation of systemic vascular resistance has much potential as a diagnostic and research tool as well as allowing rapid accurate assessment of the response of patients to therapy.

The use of esmolol to attenuate the haemodynamic response when extubating patients following cardiac surgery--a double-blind controlled study.

We have assessed the cardiovascular changes associated with emergence from anaesthesia, reversal of neuromuscular blockade and extubation in a group of 14 patients immediately after coronary artery bypass graft surgery had been completed. Patients were randomly allocated to receive either esmolol 500 micrograms.kg-1 over 1 min followed by 100 micrograms.kg-1.min-1 or placebo starting prior to reversal. Significant hypertension and tachycardia occurred in the placebo group, whilst these changes were prevented by the administration of esmolol.

Upper oesophageal sphincter pressure during inhalational anaesthesia.

Upper oesophageal sphincter pressure was recorded with a Dent sleeve in 30 patients breathing nitrous oxide, oxygen and halothane. Twenty-three patients, after thiopentone induction, received suxamethonium and had their trachea intubated either before (group A, n = 11), or after (group B, n = 11), a study period of inhalational anaesthesia. Group C (n = 8) received an inhalational induction. Mean (SD) sphincter pressure after loss of consciousness was 8 (7) mmHg (group A), 6 (5) mmHg (group B) and 24 (13) mmHg (group C) increasing to 19 (7) mmHg in group A immediately after intubation. With an end-tidal halothane concentration of 1.5%, mean sphincter pressure in group B, 16 (7) mmHg, was significantly lower than in group A, 45 (21) mmHg (p < 0.001) and group C, 27 (14) mmHg (p < 0.05). Halothane had no dose-related effect on sphincter pressure. Insertion of a laryngeal mask in group C (n = 7) had no significant effect on sphincter pressure. Induction and maintenance of anaesthesia with halothane, unlike thiopentone or suxamethonium, maintained a degree of upper oesophageal sphincter tone, although three patients in this study had sphincter pressures of less than 10 mmHg and would therefore have been at risk of regurgitation in the presence of gastro-oesophageal reflux.

Upper oesophageal sphincter pressure and the intravenous induction of anaesthesia.

The upper oesophageal sphincter can prevent regurgitation of oesophageal contents into the pharynx following gastrooesophageal reflux in the awake patient. Upper oesophageal sphincter pressure was recorded with a Dent sleeve after hypnosis with midazolam (n = 7) and also during the rapid intravenous induction of anaesthesia with thiopentone (n = 16) or ketamine (n = 7). Thiopentone decreased mean (SD) sphincter pressure from an awake value of 43 (19) to 9 (7) mmHg (p less than 0.001) and midazolam from 38 (25) to 7 (3) mmHg (p less than 0.02). Mean (SD) sphincter pressures before and after ketamine were not significantly different at 29 (15) and 32 (21) mmHg respectively. After suxamethonium mean (SD) sphincter pressure in all patients (n = 30) was 7 (4) mmHg. Laryngoscopy (n = 30) caused a small increase in mean (SD) sphincter pressure to 13 (10) mmHg (p less than 0.001). Thiopentone caused a rapid fall in upper oesophageal sphincter pressure which usually started before loss of consciousness. These findings have implications for the timing of cricoid pressure application.

Upper oesophageal sphincter pressure and the effect of cricoid pressure.

Upper oesophageal sphincter pressure has been measured in 24 patients with a sleeve device. The median sphincter pressure when awake was 38 mmHg, and when anaesthetized and paralysed was 6 mmHg. After tracheal intubation, cricoid pressure was applied at measured values between 5 and 50 N using a hand-held cricoid yoke while the sphincter pressure was recorded in two head and neck positions: with and without a standard intubating pillow with neck support. A cricoid force of 40 N increased sphincter pressure to above 38 mmHg in all the patients and the use of the pillow did not alter this effect. With the application of cricoid pressure, operating department assistants raised sphincter pressure to above 38 mmHg in only 50% of patients. Laryngoscopy made little difference to the effect of cricoid pressure except in one patient in whom it reduced the sphincter pressure by 27 mmHg.

Milrinone and the pulmonary vascular system.

In a multicentre study of 99 adult patients undergoing cardiac surgery, if post-operative cardiac failure was demonstrated (pulmonary capillary wedge pressure greater than 8 mmHg, cardiac index less than 2.5 litre min-1 m-2), then a bolus dose of milrinone (50 micrograms kg-1) was given, followed by an infusion at one of three rates (0.375, 0.5 or 0.75 microgram kg-1 min-1), and haemodynamic effects were assessed. Mean pulmonary artery pressures fell by 15% initially (P less than 0.001), and this significant reduction was maintained throughout the infusion period and reversed with the withdrawal of milrinone. Mean pulmonary vascular resistance fell progressively throughout the infusion period, the maximum change (30-40%) being evident at the 12 h point (P less than 0.05). Reversal of this effect after terminating the milrinone infusion was less marked than with pulmonary capillary wedge pressure or mean pulmonary artery pressure. A group of 39 of these patients from two centres were retrospectively divided into three groups: 1. Mitral valve replacement with high baseline pulmonary vascular resistance (greater than 200 dyne s cm-5) 2. Coronary revascularization with lower baseline pulmonary vascular resistance (100-200 dyne s cm-5) 3. Coronary revascularization with high baseline pulmonary vascular resistance (greater than 200 dyne s cm-5). There was a significant reduction in pulmonary vascular resistance and increase in cardiac index in all patients. At the 15 min point, there was significant between-group variation, the fall in pulmonary vascular resistance and increase in cardiac index being greater in Group 1 than in Groups 2 or 3. This difference between groups was not maintained during the infusion.

Exaggerated radiation-induced fibrosis in patients with systemic sclerosis.

Four patients with stable systemic sclerosis and limited skin involvement received radiation for the treatment of solid malignant neoplasms. Following localized irradiation, each patient developed an exaggerated cutaneous and internal fibrotic reaction in the irradiated areas. The surface area of fibrosis extended beyond the radiation portals employed, and the fibrotic process was poorly responsive to antifibrotic therapy. Three of the patients died of complications caused by fibrous encasement of internal organs. The extent and severity of postradiation fibrosis in these patients was distinctly unusual. These observations suggest that patients with systemic sclerosis are particularly susceptible to developing excessive radiation-induced fibrosis.

Acceptable cancer risks: probabilities and beyond.

The acceptability of cancer risk requires consideration of factors that extend beyond mere numerical representations, such as either individual lifetime risk in excess of background and excess incidence. Recently, use of these numbers has been tempered by the addition of qualitative weights-of-evidence that describe the degree of support provided by animal and epidemiologic results. Nevertheless, many other factors, most of which are not quantitative, require incorporation but remain neglected by the analyst eager to use quantitative results. In this paper we show that simple risk measures are often fraught with problems. Moreover, these measures do not incorporate the very essence of acceptability, which includes notions of responsibility, accountability, equity, and procedural legitimacy, among others. We link the process of risk assessment to those legal and regulatory standards that shape it. These standards are among the principal means to resolve risk-related disputes and to enhance the balancing of competing interests when science and law meet on uncertain and often conjectural ground. We conclude the paper with a proposal for the portfolio approach to manage cancer risks and to deal with uncertain scientific information. This approach leads to the concept of "provisional acceptability," which reflects the choices available to the decisionmaker, and the trade-offs inherent to such choices.