In-depth analysis of delays to patient discharge: a metropolitan teaching hospital experience.

Delayed patient discharge will likely exacerbate bed shortages. This study prospectively determined the frequency, causes and potential cost implications of delays for 83 consecutive patients, who were inpatients for a total of 888 days. 65% of patients experienced delay whilst awaiting a service. 48% of patients experienced delays that extended their discharge date. Discharge delays accounted for 21% of the cohort's inpatient stay, at an estimated cost of 565 sterling pounds per patient; 77% of these hold-ups resulted from delays in the provision of social and therapy requirements. Discharge delays are costly for hospitals and depressing for patients. Investment is required to enable health and social-care professionals to work more closely to improve the patient journey.

Importance and challenge of making an early diagnosis in LMNA-related muscular dystrophy.

OBJECTIVE: To identify the most useful clinical and histologic markers that facilitate early diagnosis in LMNA-related muscular dystrophy and to assess the usefulness of Western blotting (WB) for lamin A/C. METHODS: We analyzed the clinical and histologic features and WB results of all patients with laminopathies diagnosed in a research-based diagnostic service over 8 years. RESULTS: Although patients with congenital muscular dystrophy (MDCL) (n = 5) and Emery-Dreifuss muscular dystrophy (EDMD) (n = 5) had distinctive early clinical features, the lack of a suggestive clinical phenotype significantly delayed diagnosis in 2 of 3 patients with limb-girdle muscular dystrophy (LGMD) (n = 3). In addition, 6 of 20 muscle biopsy samples were considered nondystrophic, which contributed to delays in diagnosis in some patients. Neck extensor involvement (weakness or contractures) was the most consistent clinical sign, present in all patients. Reduced lamin A/C levels on WB were seen in 5 of 9 patients with laminopathies. CONCLUSION: Clinical features provide the best clues for diagnosing MDCL and EDMD early in the disease, and we urge clinicians to become familiar with those phenotypes. WB for lamin A/C may contribute to diagnosis but requires technical expertise, and results are normal in many individuals with LMNA mutations. Because of the survival benefit of early diagnosis and treatment, we recommend that LMNA gene sequencing be performed in all patients with undiagnosed congenital muscular dystrophy and neck extensor weakness, all patients with genetically undiagnosed LGMD, and those with suggestive clinical signs and nonspecific histologic abnormalities.

Anti-tumour necrosis factor-alpha therapy for severe enteropathy in patients with common variable immunodeficiency (CVID).

We present three common variable immunodeficiency (CVID) patients with severe inflammatory bowel disease of unknown aetiology, resistant to steroid treatment, treated with infliximab. After exclusion of any infection, infliximab was given at a dose of 5 mg/kg every 4 weeks for a 3 month induction followed by every 4-8 weeks depending on clinical response. Two of these patients had predominantly small bowel disease; they both showed clinical response to infliximab with weight gain and improvement of quality of life scores. The third patient had large bowel involvement with profuse watery diarrhea; this patient improved dramatically within 48 hours of having infliximab treatment. All three patients have been maintained on infliximab treatment for between 5 and 53 months (mean 37 months) with no evidence of increased susceptibility to infections in the patients with small bowel disease, although the third patient developed two urinary tract infections and a herpes zoster infection following therapy. This is the first small case series to show that infliximab is a useful addition to current therapy in this rare group of patients with potentially life threatening enteritis.

Impaired neutrophil chemotaxis in Crohn's disease relates to reduced production of chemokines and can be augmented by granulocyte-colony stimulating factor.

BACKGROUND: Defective neutrophil recruitment has been described as a primary pathogenic abnormality in Crohn's disease. Cantharidin-induced blisters provide a novel investigative tool to assess cellular influx and inflammatory mediator production during acute inflammation and allows the effects of therapy on these parameters to be measured. AIMS: To determine whether reduced neutrophil tissue penetration in Crohn's disease relates to impaired production of inflammatory mediators, and whether it can be reversed by granulocyte-colony stimulating factor (G-CSF). METHODS: Neutrophil and monocyte/macrophage populations and inflammatory mediators were measured in cantharidin blisters at 24 h. Neutrophil chemotaxis was assessed in vitro using blister fluid as the chemoattractant. The effect of s.c. G-CSF on blister phenotype was determined. RESULTS: Significantly fewer neutrophils migrated into blisters in Crohn's patients. The production of neutrophil chemokines, but not other inflammatory mediators, was reduced. This significantly correlated with reduced chemotaxis in vitro. Differences were unrelated to caspase-recruitment domain 15 genotype. G-CSF significantly increased blister neutrophil concentrations in control subjects and Crohn's patients. CONCLUSIONS: Reduced neutrophil migration during acute inflammation in Crohn's disease is associated with impaired production of appropriate chemoattractants. G-CSF therapy increases neutrophil tissue migration, which may partially account for its observed therapeutic effect.

Conditional haploinsufficiency of NCF1 (encoding p47(phox)), a signaling gene with a heterozygous phenotype potentially subject to natural selection.

Even a minor degree of haploinsufficiency could eventually reduce the frequency of an autosomal immunodeficiency disease. Searching for such a condition, we have re-examined the phenotype of mice +/- for the NCF1 gene encoding p47(phox) and humans +/- for NCF1 and NCF2 using a procedure that allowed the respiratory burst of granulocytes and macrophages to be measured simultaneously. The mice showed significant haploinsufficiency in granulocytes but not in macrophages (i.e. conditional haploinsufficiency). Our human data were obtained from blister cells, and were too scattered to allow a firm conclusion. In view of recent re-evaluation of the role of the respiratory burst these findings are compatible with the view that haploinsufficiency occurs particularly among rate-limiting genes that operate in regulatory/signaling pathways.

Use of intranasal midazolam to treat acute seizures in paediatric community settings.

OBJECTIVES: To evaluate the acceptability of intranasal midazolam (INM) in acute seizure management in the community. METHODS: Parents and staff in residential and educational settings were trained in first aid and seizure management and the administration of INM. Feedback was obtained from those who had given INM over the 30-month period September 2000-March 2003. RESULTS: Intranasal midazolam was administered to 22 children for a total of 54 seizures (range 1-6 seizures each). The dose was 0.2-0.3 mg/kg rounded down to 1 or 2 of the 5 mg in 1-mL plastic ampoules, with the anticonvulsant instilled into the child's nose directly from the plastic ampoule. Seizures were effectively stopped on 48 occasions, i.e. 89%, while no respiratory arrests occurred. Thirty carers had given INM to a convulsing child and 27 (90%) reported no difficulty in administering it. Fifteen people had also previously administered rectal diazepam and INM was considered easier to administer than rectal diazepam by 13 while a preference to use INM rather than rectal diazepam was indicated by 14. CONCLUSION: This study has shown that INM is an acceptable treatment option as a first aid response for acute seizures. We believe that INM should be considered as the preferred alternative in the community setting, as it is easier to administer and is more dignified for the patient than rectal diazepam.

Paediatric narcolepsy: complexities of diagnosis.

Narcolepsy is a sleep disorder that is characterized by excessive daytime sleepiness and the inappropriate intrusion of aspects of rapid eye movement sleep into wakefulness. While the disorder emerges from an interplay of genetic and environmental factors, recent findings suggest that abnormalities in the neurotransmission of hypocretin may be implicated in its pathogenesis. Although narcolepsy has typically been associated with adulthood, there is a growing evidence base for the emergence of the disorder in childhood. We report suspected narcolepsy in early infancy, highlighting both the complexities of presentation and subsequent diagnosis associated with paediatric narcolepsy, and the significant psychosocial difficulties experienced by children and families managing this disorder.

Cantharidin blisters: a technique for investigating leukocyte trafficking and cytokine production at sites of inflammation in humans.

A skin blister technique is described which allows the investigation of acute inflammation in humans in vivo. Filter paper discs are placed on the skin, impregnated with cantharidin and covered with impermeable film held by adhesive tape. The assembly is easily applied, unobtrusive, stable and may be worn during normal activities. The blister formed at 24 h contains approximately 5x10(5)-5x10(6) cells, predominantly neutrophils and macrophages. Inflammatory cytokines and chemotactic factors are detectable in the blister fluid. The technique is useful for characterizing the acute inflammatory response in health and disease.

Levodopa responsive Parkinsonism in adults with Angelman Syndrome.

Two intellectually disabled adults with Angelman Syndrome are reported who developed intermittent episodes of a severe resting tremor, cogwheel rigidity and bradykinesia in their late teens. The Parkinsonism was not due to medications and there was a dramatic improvement with levodopa therapy. The association between Angelman Syndrome and Parkinsonism has not previously been described.

Correlation between the immune responses to collagens type I, III, IV and V and Klebsiella pneumoniae in patients with Crohn's disease and ankylosing spondylitis.

BACKGROUND: Increased levels of collagen types I, III and V are found in strictures of patients with Crohn's disease (CD) compared with normal gut tissue. Type IV collagen is present in the basement membranes, basal lamina, retina and cornea. Elevated levels of antibody to Klebsiella pneumoniae are found in both active CD and active ankylosing spondylitis (AS) patients compared with healthy controls. METHODS: Reactivities for immunoglobulin class-specific antibodies (IgM, IgG and IgA) against collagen types I, III, IV, V and whole K. pneumoniae were measured by ELISA in nine patients with early CD and 10 with late CD from King's College Hospital and 12 late CD patients and 36 HLA-B27-positive AS patients from Middlesex Hospital and was compared with values for 26 healthy controls from the Blood Transfusion Service in London. RESULTS: Levels of class-specific IgM, IgG and IgA antibodies to collagen types I, III, IV, V and K. pneumoniae were significantly elevated in early and late CD patients compared with healthy controls (P<0.001). Levels of IgM, IgG antibody to the four collagen types and K. pneumoniae were also significantly elevated (P<0.001) in AS patients compared with healthy controls. In addition, the level of IgA antibody to K. pneumoniae was elevated in AS patients (P<0.001). Furthermore, a positive correlation between antibody levels to collagen types I, III, IV and K. pneumoniae was demonstrated in both early and late CD patients and in those with AS, whilst a positive correlation to type V was found in early CD. CONCLUSION: The role of K. pneumoniae and anti-collagen antibodies in the aetiopathogenesis of CD and AS requires further study.

Significant anticonvulsant side-effects in children and adolescents.

The anticonvulsant (AED) history for 216 children and adolescents with epilepsy was reviewed to determine the incidence and types of significant side effects (SSE) which warranted ceasing the drug (not due to a lack of response or a high dose). All parents of patients with epilepsy seen by the author over a 2 year period (March 1996 - March 1998) were questioned about SSE to previous AEDs, and the child's current therapy was also monitored prospectively to determine SSE. There were 107 girls and 109 boys ranging in age from 3 months - 18 years. Eighty-three patients had been exposed to a single AED while 133 had multiple AED exposures: mean 3.6 drugs; range 2-10 drugs. They were exposed to a total of 568 AEDs with SSE occurring in 15% of drug contacts: 7% due to behavioural changes such as irritability, aggression or hyperactivity; 8% were due to other factors such as a rash, headache, gastrointestinal disturbance or drowsiness. Fifty-seven children (26%) had experienced at least one SSE with 19 (9%) having SSE to more than one AED (range 2-4). Global developmental delay or an intellectual disability (ID) were present in 67 patients, and 27 (40%) of these experienced SSE compared with 30 (20%) of the group with normal cognition. This difference was principally due to the higher incidence of behavioural SSE in the ID group 28% versus 6% for the normal cognition group. Allowing for the higher number of AEDs used in the ID group (implying that their epilepsy was more difficult to control), behavioural SSE were still significantly more likely to occur in this group, i.e. 1: 9.6 drug exposures compared with 1: 31. 8 exposures for the normal cognition group (P<0.001). Monotherapy trials underestimate the true incidence of SSE in clinical practice as 26% of children had experienced at least one SSE and 9% had SSE to more than one AED. Those with ID were three times more likely to have behavioural SSE than children with normal cognition.

Aortic dissection, patent ductus arteriosus, iris hypoplasia and brachytelephalangy in a male adolescent.

We describe a 14-year-old male with dissection of the descending aorta, bilateral iris hypoplasia, striae distensae and brachytelephalangy, the latter being most marked in the thumbs. Inguinal herniae and a patent ductus arteriosus were surgically repaired in infancy. The pattern of abnormalities may constitute a previously undescribed syndrome. The proband died suddenly at the age of 17 years.

A child with hemimegalencephaly, hemihypertrophy, macrocephaly, cutaneous vascular malformation, psychomotor retardation and intestinal lymphangiectasia--a diagnostic dilemma.

Although the clinical delineation of the majority of overgrowth syndromes is straightforward, we believe there is a subset of patients with overlapping features from a number of overgrowth syndromes. We report a patient with hemimegalencephaly, hemihypertrophy, macrocephaly, vascular lesions, psychomotor retardation and intestinal lymphangiectasia. The clinical history and findings posed a diagnostic dilemma as the features overlapped between several conditions, namely macrocephaly-cutis marmorata telangiectatica congenita (M-CMTC), Klippel-Trenaunay-Weber syndrome (KTWS), Proteus syndrome and a provisional unique syndrome described by Reardon et al. (1996, Am J Med Genet 66:144-149). We anticipate that only when the molecular basis is delineated will it become clear whether these disorders are separate entities or merely differing ends of the same spectrum.

The effect of cisapride on dyspepsia symptoms and the electrogastrogram in patients with non-ulcer dyspepsia.

BACKGROUND: The electrogastrogram (EGG), which records gastric myoelectrical activity, is abnormal in one-third of adult patients with non-ulcer dyspepsia (NUD). AIM: To observe the effects of cisapride on EGG in adults with NUD. METHODS: Twenty-seven NUD patients who had undergone a pre- and post-prandial EGG were entered into an open study. All patients completed a dyspepsia symptom questionnaire and were then treated with cisapride 10 mg t.d.s. The dyspepsia questionnaire was repeated in all those completing 4 weeks of treatment. Those with an initial abnormal EGG (< 70% of slow wave activity at 2-4 cycles per minute) had a repeat EGG at the end of the study. RESULTS: Treatment with cisapride was associated with a significant improvement in the post-prandial EGG (P = 0.007). After 4 weeks of treatment, 7 of 13 abnormal EGGs normalized. Symptom scores improved significantly in the 13 patients with an abnormal EGG who completed treatment (P < 0.0003), but not in NUD patients with a normal EGG (P = 0.48). CONCLUSION: In this open study, treatment of NUD with cisapride was associated with significant symptom improvement in patients with an abnormal pre-treatment EGG, but not those with a normal EGG, with a significant improvement of the post-prandial EGG.

Ictal single photon emission computed tomography in seizures induced by eye closure.

Ictal single photon emission computer tomography (SPECT) studies were performed on a 12 year old child with reflex seizures induced by eye closure. EEGs had shown generalised polyspike waves during eye closure. A magnetic resonance head scan was normal. There was no photosensitive induction of the seizure. Comparison between ideal and post treatment (ethosuximide) interictal SPECT revealed increased ictal perfusion in the basal ganglis, lateral frontal region and superior temporal lobe in the left hemisphere. It is suggested that the reflex epilepsy in this case was triggered by sensory afferents from the orbicularis oculi and mediated via the thalamus.

Bilateral occipital calcification associated with celiac disease, folate deficiency, and epilepsy.

In a patient with celiac disease, folate and iron deficiency, and epilepsy, CT over a 4-month period showed parietoocipital calcifications in the corticomedullary junctions. The calcification was progressive, but it and the seizures stabilized after institution of a gluten-free diet and iron and folic acid supplements.