A challenge to the evidence behind noise guidelines for UK hospitals.

BACKGROUND: Teams assessing hospital noise against international guidelines regularly find that noise exceeds perceived safe levels in clinical settings. The care of sick people may be inherently noisy but recent efforts to tackle the problem propose a wider scope to identify sources and qualities of noise as well as more precision with noise recording. AIMS: We sought to challenge the scientific evidence cited in the four major documents pertaining to hospital noise in the UK to clarify if evidence of harm from noise included in guidelines is available, contemporary and of high quality. METHODS: Our team of hearing-health clinicians, acoustic scientists and acoustic engineers have conducted a narrative scoping review focused on critically appraising four of the most cited guidelines against which noise is measured in healthcare settings in the UK. RESULTS: There is a lack of high-quality evidence for commonly accepted consequences of noise cited in current guidelines. CONCLUSIONS: The current evidence base for noise guidelines in a healthcare setting is largely based on subjective heterogeneous and inconclusive research. Whilst reduced noise is not disputed as potentially beneficial for patient care, further hypothesis-driven research and interventions assessing the benefits or outcomes of any such intervention should be sought to produce high-quality evidence of relevance on the clinical coalface.

Prone en bloc sacrectomy with proctectomy: a surgical approach to the inaccessible and hostile pelvis.

AIM: Reoperative pelvic surgery is rarely hostile and unsafe. Kraske's procedure has historically been used to approach the mid-rectum and to resect retrorectal tumors. However, it provides limited access to the pelvis and is best in the 'virgin' pelvis. We have encountered a select group of patients who required completion proctectomy or resection of a disconnected ileoanal J-pouch where trans-abdominal access to the pelvis was not possible and access to the pelvis could only be safely gained by a prone en bloc sacrectomy. METHOD: We describe a prone approach that provides an alternative route of access to the hostile pelvis. After exposure of the sacrum and coccyx and transection of the sacrum, access to the mesorectal plane is achieved and a proctectomy (or resection of an ileoanal J-pouch) can be completed. The procedure is similar to the Kraske approach but requires a higher and wider exposure similar to the extent of an abdominal resection; however, the operation is performed in 'reverse'. RESULTS: We found that this approach was feasible and safe in the previously operated, hostile pelvis. We employed it in one patient to excise a disconnected J-pouch with chronic sepsis and in another patient for a completion proctectomy. Both patients had an uneventful recovery and clear margins were obtained with no complications. CONCLUSION: The en bloc prone sacrectomy approach is a useful alternative in a very select group of patients with difficult trans-abdominal access to the pelvis. Experience in pelvic surgery and identification of clear anatomical landmarks is paramount to avoid catastrophic uncontrollable bleeding.

Prognostic factors and patterns of failure after surgery for T4 rectal cancer in the beyond total mesorectal excision era.

BACKGROUND: Despite advances in the rates of total mesorectal excision (TME) for rectal cancer surgery, decreased local recurrence rates and increased 5-year survival, there still exists large variation in the quality of treatment received. Up to 30 per cent of rectal cancers are locally advanced at presentation and approximately 5-10 per cent still breach the mesorectal plane and invade adjacent structures despite neoadjuvant therapy. With the evolution of extended resections for rectal cancers beyond the TME plane, proponents advocate that these resections should be performed only in specialist centres. The aim was to assess the prognostic factors and patterns of failure after beyond TME surgery for T4 rectal cancers. METHODS: Data were collected from prospective databases at three high-volume institutions specializing in beyond TME surgery for T4 rectal cancers between 1990 and 2013. The primary outcome measures were overall survival, local recurrence and patterns of first failure. RESULTS: Three hundred and sixty patients were identified. The negative resection margin (R0) rate was 82·8 per cent (298 patients) and the local recurrence rate was 12·5 per cent (45 patients). The type of surgical procedure (Hartmann's: hazard ratio (HR) 4·49, 95 per cent c.i. 1·99 to 10·14; P = 0·002) and lymphovascular invasion (HR 2·02, 1·08 to 3·77; P = 0·032) were independent predictors of local recurrence. The 5-year overall survival rate for all patients was 61 (95 per cent c.i. 55 to 67) per cent. The 5-year cumulative incidence of first failure was 8 per cent for local recurrence, 6 per cent for local and distant disease, and 18 per cent for distant disease. CONCLUSION: This study has demonstrated that a coordinated approach in specialist centres for beyond TME surgery can offer good oncological and long-term survival in patients with T4 rectal cancers.

ANTECEDENTES: A pesar de las mejoras en los porcentajes de extirpación total del mesorrecto (total mesorectal excision, TME) en la cirugía de cáncer de recto, la disminución de los porcentajes de recidiva local y el aumento de la supervivencia a 5 años, todavía existe una gran variabilidad en la calidad del tratamiento recibido. Hasta el 30% de los cánceres de recto están localmente avanzados en el momento del diagnóstico y aproximadamente el 5-10% sobrepasarán el plano mesorrectal e invadirán las estructuras adyacentes a pesar del tratamiento neoadyuvante. Con la evolución de las resecciones ampliadas para los cánceres de recto que sobrepasan el plano de la TME, los defensores recomiendan que estas resecciones solo se realicen en centros especializados. El objetivo fue evaluar los factores pronósticos y los patrones de recidiva después de la cirugía ampliada más allá de la TME para los cánceres de recto T4. MÉTODOS: Los datos se recogieron a partir de bases de datos prospectivas de tres instituciones de alto volumen especializadas en resecciones ampliadas más allá de la TME para el cáncer de recto T4 entre 1990 y 2013. Los criterios de valoración principal fueron la supervivencia global, la recidiva local y los patrones de la primera recidiva. RESULTADOS: Se identificaron 360 pacientes. El margen de resección fue negativo (R0) en el 82,8% (n = 298) y el porcentaje de recidiva local fue de 12,5% (n = 45). El tipo de cirugía realizada (Hartmann: cociente de riesgos instantáneos, hazard ratio, HR 4,49; i.c. del 95%: 1,99-10,14; P = 0,002) y la invasión linfovascular (HR 2,02; i.c. del 95%: 1,08-3,77; P = 0,032) fueron factores predictivos independientes de recidiva local. La supervivencia global a 5 años para todos los pacientes fue del 61% (i.c. del 95%: 55-67). La incidencia acumulada a los 5 años de la primera recidiva fue de 8% para la recidiva local, 6% para la recidiva local y a distancia, y 18% para la recidiva a distancia. CONCLUSIÓN: Este estudio demuestra que un abordaje coordinado en centros especializados para cirugía más allá de la TME puede ofrecer una buena supervivencia oncológica y a largo plazo en pacientes con cáncer de recto T4.

A functional macrophage migration inhibitory factor promoter polymorphism is associated with reduced diffusing capacity.

Cigarette smoke exposure is the leading modifiable risk factor for chronic obstructive pulmonary disease (COPD); however, the clinical and pathologic consequences of chronic cigarette smoke exposure are variable among smokers. Macrophage migration inhibitory factor (MIF) is a pleiotropic cytokine implicated in the pathogenesis of COPD. Within the promoter of the MIF gene is a functional polymorphism that regulates MIF expression (-794 CATT5-8 microsatellite repeat) ( rs5844572 ). The role of this polymorphim in mediating disease susceptibility to COPD-related traits remains unknown. We performed a cross-sectional analysis of DNA samples from 641 subjects to analyze MIF-794 CATT5-8 ( rs5844572 ) polymorphism by standard methods. We generated multivariable logistic regression models to determine the risk of low expressing MIF alleles for airflow obstruction [defined by forced expiratory volume in 1 s (FEV1)/forced vital capacity ratio <0.70] and an abnormal diffusion capacity [defined by a diffusion capacity for carbon monoxide (DLCO) percent predicted <80%]. We then used generalized linear models to determine the association of MIF genotypes with FEV1 percent predicted and DLCO percent predicted. The MIF-794 CATT5 allele was associated with an abnormal diffusion capacity in two cohorts [odds ratio (OR): 9.31, 95% confidence interval (CI): 1.97-4.06; and OR: 2.21, 95% CI: 1.03-4.75]. Similarly, the MIF-794 CATT5 allele was associated with a reduced DLCO percentage predicted in these two cohorts: 63.5 vs. 70.0 ( P = 0.0023) and 60.1 vs. 65.4 ( P = 0.059). This study suggests an association between a common genetic polymorphism of an endogenous innate immune gene, MIF, with reduced DLCO, an important measurement of COPD severity.

Interleukin-18 mediates cardiac dysfunction induced by western diet independent of obesity and hyperglycemia in the mouse.

Obesity and diabetes are independent risk factors for heart failure and are associated with the consumption of diet rich in saturated fat and sugar, Western diet (WD), known to induce cardiac dysfunction in the mouse through incompletely characterized inflammatory mechanisms. We hypothesized that the detrimental cardiac effects of WD are mediated by interleukin-18 (IL-18), pro-inflammatory cytokine linked to cardiac dysfunction. C57BL/6J wild-type male mice and IL-18 knockout male mice were fed high-saturated fat and high-sugar diet for 8 weeks. We measured food intake, body weight and fasting glycemia. We assessed left ventricular (LV) systolic and diastolic function by Doppler echocardiography and cardiac catheterization. In wild-type mice, WD induced a significant increase in isovolumetric relaxation time, myocardial performance index and left ventricular end-diastolic pressure, reflecting an impairment in diastolic function, paired with a mild reduction in LV ejection fraction. IL-18 KO mice had higher food intake and greater increase in body weight without significant differences in hyperglycemia. Despite displaying greater obesity, IL-18 knockout mice fed with WD for 8 weeks had preserved cardiac diastolic function and higher left ventricular ejection fraction. IL-18 mediates diet-induced cardiac dysfunction, independent of food intake and obesity, thus highlighting a disconnect between the metabolic and cardiac effects of IL-18.

Posterior high sacral segmental disconnection prior to anterior en bloc exenteration for recurrent rectal cancer.

This article describes a novel technique for en bloc resection of locally recurrent rectal cancer that invades the high sacral bone (above S3). The involved segment of the sacrum is mobilised with osteotomes during an initial posterior approach before an anterior abdominal phase where the segment of sacral bone is delivered with the specimen. This allows en bloc resection of the involved sacrum while preserving uninvolved distal and contralateral sacral bone and nerve roots. The goal is to obtain a clear bony margin and offer a chance of cure while improving functional outcomes by maintaining pelvic stability and minimising neurological deficit.

Survival after pelvic exenteration for T4 rectal cancer.

BACKGROUND: The purpose of this study was to analyse retrospectively the pooled results after pelvic exenteration for locally advanced T4 rectal cancer. Historically, patients with T4 rectal cancers requiring pelvic exenteration have been offered only palliative surgery or no operation. METHODS: The basic treatment principle was preoperative (chemo)radiotherapy, radical surgery and, in some patients, adjuvant chemotherapy. Risk factors for local recurrence, distant metastases and overall survival were studied in univariable and multivariable analyses. RESULTS: Ninety-five patients with T4 rectal cancer who underwent pelvic exenteration in two tertiary referral centres up to 2013 were studied. Clear margins (R0) were achieved in 87 per cent of patients. Adjuvant chemotherapy was administered in 33 per cent, independent of the resection margin, lymph node status and postoperative T category. The 5-year local recurrence rate was 17 per cent, with a distant metastasis rate of 16 per cent and overall survival rate of 62 per cent. In multivariable analysis the only factor associated with death was omission of adjuvant chemotherapy (P = 0.016). The effect of adjuvant chemotherapy was more pronounced in the elderly: patients aged over 70 years who had chemotherapy had a 5-year overall survival rate of 80 per cent, compared with 39 per cent of elderly patients who did not receive chemotherapy (P = 0.019). CONCLUSION: Pelvic exenteration led to an R0 resection rate of 87 per cent for T4 rectal cancer, giving good local control and overall survival comparable to population-based colorectal cancer survival rates. Adjuvant chemotherapy may improve overall survival further, even in the elderly.

A laboratory study for assessing speech privacy in a simulated open-plan office.

UNLABELLED: The aim of this study is to assess speech privacy in open-plan office using two recently introduced single-number quantities: the spatial decay rate of speech, DL(2,S) [dB], and the A-weighted sound pressure level of speech at a distance of 4 m, L(p,A,S,4) m [dB]. Open-plan offices were modeled using a DL(2,S) of 4, 8, and 12 dB, and L(p,A,S,4) m was changed in three steps, from 43 to 57 dB.Auditory experiments were conducted at three locations with source­receiver distances of 8, 16, and 24 m, while background noise level was fixed at 30 dBA.A total of 20 subjects were asked to rate the speech intelligibility and listening difficulty of 240 Korean sentences in such surroundings. The speech intelligibility scores were not affected by DL(2,S) or L(p,A,S,4) m at a source­receiver distance of 8 m; however, listening difficulty ratings were significantly changed with increasing DL(2,S) and L(p,A,S,4) m values. At other locations, the influences of DL(2,S) and L(p,A,S,4) m on speech intelligibility and listening difficulty ratings were significant. It was also found that the speech intelligibility scores and listening difficulty ratings were considerably changed with increasing the distraction distance (r(D)). Furthermore, listening difficulty is more sensitive to variations in DL(2,S) and L(p,A,S,4) m than intelligibility scores for sound fields with high speech transmission performances. PRACTICAL IMPLICATIONS: The recently introduced single-number quantities in the ISO standard, based on the spatial distribution of sound pressure level, were associated with speech privacy in an open-plan office. The results support single-number quantities being suitable to assess speech privacy, mainly at large distances. This new information can be considered when designing open-plan offices and making acoustic guidelines of open-plan offices.

Isotropic round-wire multifilament cuprate superconductor for generation of magnetic fields above 30 T.

Magnets are the principal market for superconductors, but making attractive conductors out of the high-temperature cuprate superconductors (HTSs) has proved difficult because of the presence of high-angle grain boundaries that are generally believed to lower the critical current density, J(c). To minimize such grain boundary obstacles, HTS conductors such as REBa2Cu3O(7-x) and (Bi, Pb)2Sr2Ca2Cu3O(10-x) are both made as tapes with a high aspect ratio and a large superconducting anisotropy. Here we report that Bi2Sr2CaCu2O(8-x) (Bi-2212) can be made in the much more desirable isotropic, round-wire, multifilament form that can be wound or cabled into arbitrary geometries and will be especially valuable for high-field NMR magnets beyond the present 1 GHz proton resonance limit of Nb3Sn technology. An appealing attribute of this Bi-2212 conductor is that, being without macroscopic texture, it contains many high-angle grain boundaries but nevertheless attains a very high J(c) of 2,500 A mm(-2) at 20 T and 4.2 K. The large potential of the conductor has been demonstrated by building a small coil that generated almost 2.6 T in a 31 T background field. This demonstration that grain boundary limits to high Jc can be practically overcome underlines the value of a renewed focus on grain boundary properties in non-ideal geometries.

The kidney as a new target for antidiabetic drugs: SGLT2 inhibitors.

WHAT IS KNOWN AND OBJECTIVE: A novel class of antidiabetic drugs - SGLT2 (Na(+) /glucose cotransporter type 2) inhibitors - target renal reabsorption of glucose and promote normal glucose levels, independent of insulin production or its action at receptors. We review this new mechanistic approach and the reported efficacy and safety of clinical testing of lead compounds. METHODS: Information was obtained from various bibliographic sources, including PubMed and others, on the basic science and the clinical trials of SGLT2 inhibitors. The information was then summarized and evaluated from the perspective of contribution to a fuller understanding of the potential and current status of the lead clinical candidates. RESULTS AND DISCUSSION: Diabetes mellitus is a spectrum of disorders that involves inadequate insulin function resulting in adverse health sequelae due to acute and chronic hyperglycaemia. Current antidiabetic pharmacotherapy primarily addresses either insulin production at the pancreatic ß-cells or insulin action at insulin receptors. These drugs have less than full clinical effectiveness and sometimes therapy-limiting adverse effects. The third major component of glucose balance, namely elimination, has not been a significant therapeutic target to date. SGLT2 inhibitors are a novel approach. WHAT IS NEW AND CONCLUSION: A sufficient number of clinical trials have been conducted on sufficiently chemically diverse SGLT2 inhibitors to reasonably conclude that they have efficacy (HbA1c reductions of 0·4-1%), and thus far, the majority of adverse effects have been mild and transitory or treatable, with the caveat of possible association with increased risk of breast cancer in women and bladder cancer in men.

Pelvic exenteration for recurrent squamous cell carcinoma of the pelvic organs arising from the cloaca--a single institution's experience over 16 years.

AIM: Minimal data are available on the role of pelvic exenteration in patients with recurrent squamous cell carcinoma (SCC) of the pelvic organs. This study aimed to highlight our experience of pelvic exenteration in patients with recurrent and re-recurrent SCC of the pelvic organs. METHOD: A retrospective review of all patients who underwent pelvic exenteration for recurrent SCC of the pelvic organs arising from the embryological cloaca from 1994 to 2010 was performed. RESULTS: Twenty-four patients (median age 59, range, 27-79 years) underwent pelvic exenteration for recurrent SCC of the anus (18), cervix and upper vagina (2), lower vagina (1) and the vulva (3). Nine patients with anal SCC had undergone abdominoperineal excision prior to pelvic exenteration. Ten (41.7%) patients underwent a complete pelvic exenteration procedure, while sacrectomy was performed in 13 (54.2%) patients. There was no 30-day inpatient mortality. An R0 resection was achieved in 15 (62.5%) patients. Three (12.5%) had R1 resections while 6 (25%) had R2 resections. In the 15 patients with an R0 resection, 7 (46.7%) developed metastatic disease at a median of 18 (range 10-131) months. After a median follow-up of 26 (range 4-169) months, 1- and 2-year overall survival rates were 64% [95% confidence interval (CI), 44-84%] and 57% (95% CI 35-79%), respectively. CONCLUSION: Pelvic exenteration for recurrent SCC of the cloaca is safe and feasible even after previous salvage surgery. An R0 resection can be achieved in 62.5% of the patients with reasonable early survival though less than published recurrent rectal cancer studies.

Costs and outcomes over 36 years of patients with phenylketonuria who do and do not remain on a phenylalanine-restricted diet.

BACKGROUND: To quantify the costs and consequences of managing phenylketonuria (PKU) in the UK and to estimate the potential implications to the UK's National Health Service (NHS) of keeping patients on a phenylalanine-restricted diet for life. METHOD: A computer-based model was constructed depicting the management of PKU patients over the first 36 years of their life, derived from patients suffering from this metabolic disorder in The Health Improvement Network database (a nationally representative database of patients registered with general practitioners in the UK). The model was used to estimate the incidence of co-morbidities and the levels of healthcare resource use and corresponding costs over the 36 years. RESULTS: Patients who remained on a phenylalanine-restricted diet accounted for 38% of the cohort. Forty-seven per cent of patients discontinued their phenylalanine-restricted diet between 15 and 25 years of age. Of these, 73% remained off diet and 27% restarted a restricted diet at a mean 30 years of age. Fifteen per cent of the cohort had untreated PKU. Eleven per cent of patients who remained on a phenylalanine-restricted diet for 36 years received the optimum amount of prescribed amino acid supplements. Patients had a mean 12 general practitioner visits per year and one hospital outpatient visit annually, but phenylalanine levels were only measured once every 18 to 24 months. The mean NHS cost (at 2007/08 prices) of managing a PKU sufferer over the first 36 years of their life was estimated to range between £21 000 and £149 000, depending on the amount of prescribed nutrition they received. CONCLUSION: The findings suggest that the majority of patients with PKU were under-treated. The NHS cost of patient management should not be an obstacle to encouraging patients to remain on a restricted diet until further information becomes available about the long-term clinical impact of stopping such a diet. Nevertheless, patients require counselling and managed follow up regardless of the choices they make about their diet.

Vitamin D and type 2 diabetes mellitus.

WHAT IS KNOWN AND OBJECTIVE: The deleterious effect of vitamin D deficiency on bone health has long been known. More recent studies suggest a deleterious effect of low vitamin D (hypovitaminosis D) on general health. And specific studies propose an association between hypovitaminosis D and the aetiology and progression of type 2 diabetes (T2DM). Given a commonly assumed lack of toxicity of vitamin D, routine measurement of plasma vitamin D and supplementation is rapidly becoming accepted general practice. COMMENT: Authoritative practice guidelines have raised the level of vitamin D that is to be considered minimal for optimum health. This recommendation was based on a wealth of information and definitive evidence for skeletal benefits of vitamin D, but there was a lack of compelling evidence that hypovitaminosis D is causally related to extra-skeletal health outcomes such as diabetes. Hence, vitamin D supplementation for the purpose of achieving a level consistent with good health is evidence based, but measurement and supplementation for the purpose of preventing or treating T2DM is not. WHAT IS NEW AND CONCLUSION: Although the maintenance of adequate vitamin D levels is desirable for all patients, we conclude that routine measurement of vitamin D level in every patient or initiating high-dose supplementation for the purpose of preventing or treating T2DM is not evidence based.

T helper cells promote disease progression of osteoarthritis by inducing macrophage inflammatory protein-1γ.

OBJECTIVE: Immune cells are involved in the pathogenesis of osteoarthritis (OA). We examined the effects of T helper (Th) cells, which induce the expression of macrophage inflammatory protein (MIP-1γ), on the progression of OA. DESIGN: Using anterior cruciate ligament-transection (ACLT), we induced OA in one hind-leg knee joint of B6 mice. The CD4(+) T cells from splenocytes and synovium were flow-cytometrically and immunochemically evaluated, respectively. The knee joints were histologically assessed for manifestations of OA. MIP-1γ levels and nuclear factor-κB (NF-κB) in the knee joints were measured using enzyme-linked immunosorbent and immunoblotting assays, respectively; osteoclastogenesis was detected by tartrate-resistant acid phosphatase (TRAP) staining. The inflammatory responses and MIP-1γ expression were examined using immunohistochemistry. RESULTS: The number of CD4(+) T cells and the expression of interferon-γ (IFN-γ) increased during OA onset (30 days after ACLT) and then decreased at a later stage of OA (90 days after ACLT). Tissue damage induced by CD4(+) T cells was evident at the later stage. The activation of CD4(+) T cells induced the expression of MIP-1γ and NF-κB. The expression of MIP-1γ can be detected in synovium which CD4(+) T cells were infiltrated. The increased MIP-1γ expression caused an increase in the number of osteoclasts in joints. The regulation of CD4(+) T cells was accompanied by increased macrophage infiltration and matrix metalloproteinase (MMP)-9 expression. Histopathological examinations revealed that CD4(+) T cell knockout (CD4(-/-)) mice had less expression of MIP-1γ and slower cartilage degeneration than control mice had. CONCLUSIONS: CD4(+) T cells were activated during the onset of OA, but cartilage damage was more prominent at a later stage. CD4(+) T cells were involved in the pathogenesis of OA: they induced MIP-1γ expression and subsequent osteoclast formation.

Safety of zoledronic acid and incidence of osteonecrosis of the jaw (ONJ) during adjuvant therapy in a randomised phase III trial (AZURE: BIG 01-04) for women with stage II/III breast cancer.

The AZURE trial is an ongoing phase III, academic, multi-centre, randomised trial designed to evaluate the role of zoledronic acid (ZOL) in the adjuvant therapy of women with stage II/III breast cancer. Here, we report the safety and tolerability profile of ZOL in this setting. Eligible patients received (neo)adjuvant chemotherapy and/or endocrine therapy and were randomised to receive neither additional treatment nor intravenous ZOL 4 mg. ZOL was administered after each chemotherapy cycle to exploit potential sequence-dependent synergy. ZOL was continued for 60 months post-randomisation (six doses in the first 6 months, eight doses in the following 24 months and five doses in the final 30 months). Serious (SAE) and non-serious adverse event (AE) data generated during the first 36 months on study were analysed for the safety population. 3,360 patients were recruited to the AZURE trial. The safety population comprised 3,340 patients (ZOL 1,665; control 1,675). The addition of ZOL to standard treatment did not significantly impact on chemotherapy delivery. SAE were similar in both treatment arms. No significant safety differences were seen apart from the occurrence of osteonecrosis of the jaw (ONJ) in the ZOL group (11 confirmed cases; 0.7%; 95% confidence interval 0.3-1.1%). ZOL in the adjuvant setting is well tolerated, and can be safely administered in addition to adjuvant therapy including chemotherapy. The adverse events were consistent with the known safety profile of ZOL, with a low incidence of ONJ.

Lemierre's and Lemierre's-like syndromes in association with infectious mononucleosis.

OBJECTIVE: This study aimed to review cases of Lemierre's and Lemierre's-like syndromes in paediatric patients, to examine a possible association with Epstein-Barr virus as a predisposing factor, and to assess the impact of this virus on the severity of illness. METHODS: We performed a retrospective analysis of data from the in-patient database at Winthrop University Hospital, from January 2001 to October 2007. We reviewed clinical and laboratory findings as well as the outcome of infection in patients aged 21 years or less with a diagnosis of Lemierre's syndrome. An additional case of Lemierre's-like syndrome was also included. The illness severity and duration of in-patient management of those testing positive for heterophile antibody were then compared with the same parameters in patients who tested negative. RESULTS: Of the five patients diagnosed with Lemierre's syndrome, two had concomitant acute infection with Epstein-Barr virus. Additionally, a 19-year-old adolescent was admitted during this period with acute infectious mononucleosis, Fusobacterium necrophorum sepsis, sinusitis, frontal lobe abscess and ophthalmic vein thrombosis. The clinical presentation of all patients included fever, sore throat, and ear or neck pain. The duration of symptoms ranged from two days to three weeks prior to admission. The patients with acute Epstein-Barr virus infection had been diagnosed with infectious mononucleosis prior to admission, and tested positive for heterophile antibody. These patients subsequently underwent more extensive in-patient treatment, including intensive care management and ventilator support. The patients who tested negative for heterophile antibody experienced a milder course of illness, with a shorter duration of in-patient management. CONCLUSION: Two patients diagnosed with Lemierre's syndrome, and a third with Fusobacterium necrophorum sepsis, had coexisting acute Epstein-Barr virus infection. Patients who tested positive for heterophile antibody experienced a more severe course of illness. These observations suggest a possible association between Epstein-Barr virus infection and the severity of concomitant Lemierre's syndrome.

Long-term needs of adult patients with organic acidaemias: outcome and prognostic factors.

BACKGROUND: With improvements in the treatment of children with organic acidaemias (OA), the number surviving to adulthood is increasing. To plan appropriate services for their care it is important to know what their needs are. OBJECTIVE: To describe the clinical and social problems affecting adult patients with OA. PATIENTS AND METHODS: We reviewed the medical records of 15 adult patients diagnosed with OA. Social attainment (housing, schooling and occupation) was analysed. Nutritional status was evaluated by body mass index (BMI) and laboratory studies. Neurological and visceral complications were noted. Cognitive outcome was evaluated by psychometric testing and/or educational attainment. RESULTS: Seven had methylmalonic acidaemia (MMA), 4 isovaleric acidaemia (IVA) and 4 propionic acidaemia (PA). Ten were female, and median age was 23.5 years (range 18-48). All but three had late-onset disease. Two patients became pregnant during follow up. Four patients had obtained university degrees and were working. Three-quarters of the patients required some kind of social support. All had a good nutritional status. Height was normal in IVA and 3 PA patients. Osteoporosis was present in 2 out of 8 patients assessed. A variety of neurocognitive or visceral complications were seen in two-thirds of the patients. Metabolic decompensations were unusual. CONCLUSIONS: The approach to adult patients with OA has to be multidisciplinary, with the clinician and dietician as the core of the team, but with the collaboration of clinical nurses specialists, social workers and other specialist services and the support of a biochemical and molecular laboratory.