Early constipation predicts faster dementia onset in Parkinson's disease.

Constipation is a common but not a universal feature in early PD, suggesting that gut involvement is heterogeneous and may be part of a distinct PD subtype with prognostic implications. We analysed data from the Parkinson's Incidence Cohorts Collaboration, composed of incident community-based cohorts of PD patients assessed longitudinally over 8 years. Constipation was assessed with the MDS-UPDRS constipation item or a comparable categorical scale. Primary PD outcomes of interest were dementia, postural instability and death. PD patients were stratified according to constipation severity at diagnosis: none (n = 313, 67.3%), minor (n = 97, 20.9%) and major (n = 55, 11.8%). Clinical progression to all three outcomes was more rapid in those with more severe constipation at baseline (Kaplan-Meier survival analysis). Cox regression analysis, adjusting for relevant confounders, confirmed a significant relationship between constipation severity and progression to dementia, but not postural instability or death. Early constipation may predict an accelerated progression of neurodegenerative pathology.

Progression of Neuropsychiatric Symptoms over Time in an Incident Parkinson's Disease Cohort (ICICLE-PD).

BACKGROUND: Cross-sectional studies have identified that the prevalence of neuropsychiatric symptoms (NPS) in Parkinson's disease (PD) ranges from 70-89%. However, there are few longitudinal studies determining the impact of NPS on quality of life (QoL) in PD patients and their caregivers. We seek to determine the progression of NPS in early PD. METHODS: Newly diagnosed idiopathic PD cases (n = 212) and age-matched controls (n = 99) were recruited into a longitudinal study. NPS were assessed using the Neuropsychiatric Inventory with Caregiver Distress scale (NPI-D). Further neuropsychological and clinical assessments were completed by participants, with reassessment at 18 and 36 months. Linear mixed-effects modelling determined factors associated with NPI-D and QoL over 36 months. RESULTS: Depression, anxiety, apathy and hallucinations were more frequent in PD than controls at all time points (p < 0.05). Higher motor severity at baseline was associated with worsening NPI-D scores over time (ß = 0.1, p < 0.05), but not cognition. A higher NPI total score was associated with poorer QoL at any time point (ß = 0.3, p < 0.001), but not changed in QoL scores. CONCLUSION: NPS are significantly associated with poorer QoL, even in early PD. Screening for NPS from diagnosis may allow efficient delivery of better support and treatment to patients and their families.

Discontinuation and non-publication of neurodegenerative disease trials: a cross-sectional analysis.

BACKGROUND AND PURPOSE: Trial discontinuation and non-publication represent major sources of research waste in clinical medicine. No previous studies have investigated non-dissemination bias in clinical trials of neurodegenerative diseases. METHODS: ClinicalTrials.gov was searched for all randomized, interventional, phase II-IV trials that were registered between 1 January 2000 and 31 December 2009 and included adults with Alzheimer's disease, motor neurone disease, multiple sclerosis or Parkinson's disease. Publications from these trials were identified by extensive online searching and contact with authors, and multiple logistic regression analysis was performed to identify characteristics associated with trial discontinuation and non-publication. RESULTS: In all, 362 eligible trials were identified, of which 12% (42/362) were discontinued. 28% (91/320) of completed trials remained unpublished after 5 years. Trial discontinuation was independently associated with number of patients (P = 0.015; more likely in trials with ≤100 patients; odds ratio 2.65, 95% confidence interval 1.21-5.78) and phase of trial (P = 0.009; more likely in phase IV than phase III trials; odds ratio 3.90, 95% confidence interval 1.41-10.83). Trial non-publication was independently associated with blinding status (P = 0.005; more likely in single-blind than double-blind trials; odds ratio 5.63, 95% confidence interval 1.70-18.71), number of centres (P = 0.010; more likely in single-centre than multi-centre trials; odds ratio 2.49, 95% confidence interval 1.25-4.99), phase of trial (P = 0.041; more likely in phase II than phase IV trials; odds ratio 2.88, 95% confidence interval 1.04-7.93) and sponsor category (P = 0.001; more likely in industry-sponsored than university-sponsored trials; odds ratio 5.05, 95% confidence interval 1.87-13.63). CONCLUSIONS: There is evidence of non-dissemination bias in randomized trials of interventions for neurodegenerative diseases. Associations with trial discontinuation and non-publication were similar to findings in other diseases. These biases may distort the therapeutic information available to inform clinical practice.

Leprosy: a 'common' and curable cause of peripheral neuropathy with skin lesions.

Leprosy (or Hansen's disease) is a curable chronic infectious disease caused by the acid-fast bacillus Mycobacterium leprae. While leprosy remains one of the most common causes of neuropathy worldwide, its rarity in the UK means that many doctors are unfamiliar with the typical clinical features. This is problematic because early recognition and treatment is vital in order to minimise disease-related complications such as nerve injury. We describe a 75-year-old man who presented with multiple mononeuropathy (mononeuritis multiplex, particularly affecting the ulnar nerves) and typical granulomatous skin lesions, in whom the diagnosis was made on the basis of skin biopsy. We highlight the clinical features, investigations and treatment of the patient, and provide information about the epidemiology and pathogenesis of leprosy.

Malignant pleural effusion.

Malignant pleural effusion (MPE) refers to the presence of neoplastic cells in the pleural fluid. Approximately 40 000 people per year in the UK are affected by MPE and it is associated with significant morbidity and an overall poor prognosis. Management should be prompt and care plans should be individualized and involve a multidisciplinary team of healthcare professionals. This article reviews the pathophysiology of MPE along with available investigations and management strategies for these patients.

Feasibility of short term drainage for diagnostic thoracoscopy.

BACKGROUND AND AIM: Thoracoscopy is a diagnostic tool superior to other available techniques for the assessment of pleural effusions. There are numerous publications that describe the technique in detail but there is very little published on the optimal time of chest drain removal post procedure. Our aim was to retrospectively study all cases of diagnostic thoracoscopy and to ascertain the time of chest drain removal, length of hospital stay and associated complications. METHODS: All patients who underwent thoracoscopy during a 6-year period were identified from a computerised database. Patients who received talc for pleurodesis were excluded as they required longer drainage time. A review of the remaining patients' charts and radiology was performed to ascertain the predefined outcomes. RESULTS: 124 patients had a diagnostic thoracoscopy. The time to chest drain removal was documented as less than four hours, four to 24 hours, 24 to 48 hours and greater than 48 hours in 66 (53.2%), 29 (23.4%), 12 (9.7%) and 17 (13.7%) of patients respectively. The median length of stay for all patients was one day (interquartile range, 1-4 days). There was a statistically significant difference in overall length of hospital stay between the early (<4 hours) and late (>48 hours) chest drain removal groups, p=0.0028. The overall complication rate was 15.9%. There was no statistical difference in complication rates between the two groups. CONCLUSION: This retrospective series demonstrates that early chest drain removal post diagnostic thoracoscopy is possible and safe. This is likely to confer economic benefits.

Angiosarcoma of the right atrium masquerading as recurrent pulmonary embolism.

Primary cardiac angiosarcoma is a rare tumor that may present with features mimicking venous thromboembolic disease, making the diagnosis particularly challenging. Without a high index of suspicion, the majority of cases will remain undetected until the disease is advanced. As a result, the outlook for most patients remains dismal even with aggressive multimodality treatment. We report a case of angiosarcoma masquerading as recurrent pulmonary embolism successfully treated by radical surgery and adjuvant cytotoxic chemotherapy.

Emergency department evaluation of sudden, severe headache.

AIM: To assess the clinical management of adults presenting with sudden, severe headache. METHODS: We retrospectively reviewed the medical records of consecutive adults presenting with sudden, severe headache to the emergency department (ED) or medical admissions unit at one teaching hospital. RESULTS: Of 12 025 consecutive attendances over 3 months, 91 adults (0.8%, 95% CI 0.6-0.9%) presented with sudden severe headache. Documentation of time to peak headache intensity and headache duration was complete in only 33% of cases. Brain computed tomography was performed in each of the 29 patients (33%) in whom it appeared indicated for the investigation of headaches peaking within 5 min and lasting more than 1 h, as well as 11 patients (13%) who did not meet these criteria. Lumbar puncture was attempted in every patient for whom it appeared indicated (although it was unsuccessful and abandoned on three of 24 patients), as well as one patient in whom it appeared not to be indicated. When subarachnoid haemorrhage was suspected, 81% of patients had spectrophotometry. Of the patients, 52 (60%) were given a specific diagnosis, 17 (33%) of whom were given a diagnosis despite an apparently insufficient history. A further 12 (14%) could have been diagnosed if the International Headache Society classification had been applied to the documented history. Neurological advice was sought for only 20 patients (23%). CONCLUSION: Patients with sudden, severe headache might benefit if EDs used simple protocols, emphasizing the crucial elements of history and examination, appropriate investigation and targeted consultation with neurologists.

Epidemiology, clinical characteristics, and management of adults referred to a teaching hospital first seizure clinic.

BACKGROUND: There are scarce data describing the epidemiology, clinical characteristics, and management of adults who suffer a suspected first seizure. AIM: To describe the epidemiology, clinical characteristics, and management of adults with a suspected first seizure who are referred to a teaching hospital first seizure clinic over a one year period. DESIGN: Prospective descriptive study. METHODS: Data were collected on consecutive adults referred to the Royal Infirmary of Edinburgh between 4 February 2003 and 10 February 2004. RESULTS: 232 patients were referred to the first seizure clinic. Median age was 32 years; 53% of patients were male. Lower socioeconomic groups were more likely to present with a suspected first seizure. Nineteen per cent of patients were admitted to hospital after their suspected seizure episode. Appropriate driving advice was reported in 64% of cases. Seventy two per cent of patients were offered a first seizure clinic appointment within six weeks of referral. Nine per cent of patients had a subsequent seizure while awaiting review. Fifty two per cent of patients were confirmed as having a first seizure at the clinic, of which 56% were provoked by alcohol, recreational drugs, or sleep deprivation. Electroencephalography and computed tomography of the brain were the most common investigations ordered at the first seizure clinic (22% and 22% of patients respectively). CONCLUSION: Adults who suffer a suspected first seizure, and who make a full neurological recovery, can be safely managed as an outpatient. Around half of these patients will have a specialist diagnosis of first seizure and alcohol will be a common precipitating factor.

Early management of adults with an uncomplicated first generalised seizure.

A literature review of first seizures in adults was performed and a management algorithm was constructed. This review highlights the importance of a thorough history and examination, routine biochemistry and haematology, an electrocardiogram, selected neuroimaging, discharge planning with driving and lifestyle advice, and follow-up in a specialist clinic.

Bed usage in a Dublin teaching hospital: a prospective audit.

AIMS AND METHODS: We prospectively audited inpatient bed use in our hospital for the first three months of this year. While 70% (mean age 54 +/- 20.8 years) of our patients went home on the day they were medically discharged, 30% (mean age 70.3 +/- 18.3 years) remained in the hospital awaiting step-down facilities. The total of 486 bed days occupied by overstaying patients would if available, have allowed treatment of 54% more patients without any increase in the hospital complement of beds, preventing the cancellation of elective procedures and preventing patients remaining on trolleys overnight. RESULTS AND CONCLUSION: These prospective data emphasise (1) a highly inefficient use of acute hospital beds; (2) the need for step-down facilities; (3) efficient use of existing hospital beds is the highest priority both for optimal patient care and optimal use of expensive hospital resources; (4) efficient use of existing facilities should be achieved before the construction of additional facilities.

The performance of two intensive care humidifiers at high gas flows.

High continuous flow breathing systems are now available to provide fresh gas flows well in excess of 100 l.min-1 in continuous positive airway pressure systems used for respiratory support. The performance of two commonly used intensive care humidifiers, the Kendal Conchatherm and the Fisher and Paykel FP310 have been assessed at flows of 50, 75, 100, 125 and 150 l.min-1. Their performance when using two humidifiers connected in parallel and in series was also studied. At a fresh gas flow of 100 l.min-1 the single Conchatherm gave an absolute water vapour concentration of 15.6 g.m-3 and the single FP310 11.9 g.m-3. At all flows the best results were achieved using two Conchaterm humidifiers in series. It is concluded that with high continuous flow breathing systems the humidification achieved with conventional humidifiers may be inadequate and it may be necessary to combine two humidifiers to obtain clinically useful humidification.

Anesthesia and Bartter's syndrome: a case report and review.

A 22-year-old female with Bartter's syndrome presented at 40 weeks' gestation for elective cesarean section under general anesthesia. Her usual medication was ibuprofen and potassium supplements. Preoperative potassium was 3.3 mmol/L, and in anticipation of difficulties in fluid, electrolyte, and acid-base management, a central line and urinary catheter were inserted and blood gases measured. In the first 20 hours postdelivery she had a brisk diuresis and required 3.5 L of crystalloid to maintain her central venous pressure and 100 mmol of potassium to prevent significant hypokalemia. The main features of Bartter's syndrome are growth retardation, hypertrophy, and hyperplasia of the juxtaglomerular apparatus, increased angiotensin II, hyperaldosteronism, hypokalemic alkalosis, normal blood pressure, and decreased response to pressors. The precise biochemical lesion is unknown, but it is most probably an abnormality of chloride transport in the loop of Henle. Anesthetic management is a major challenge, requiring a thorough understanding of the pathophysiology of the syndrome. The specific aims of the anesthetist are to maintain cardiovascular stability, control serum potassium, and prevent renal damage. Perioperative fluid balance must be meticulously managed, and drugs dependent on renal excretion must be used with caution. Metabolic alkalosis may interfere with the binding of drugs. The patient's short stature, platelet abnormalities, and reduced responsiveness to pressors all make regional anesthesia theoretically hazardous.

Patient-controlled on-demand epidural fentanyl. A comparison of patient-controlled on-demand fentanyl delivered epidurally or intravenously.

A prospective, open, clinical trial is described in which 20 patients having upper abdominal surgery were randomly allocated to receive fentanyl for postoperative analgesia by patient-controlled demand analgesic computer by either the epidural or intravenous route. Hourly pain, sedation and nausea scores were very similar in the two groups during the first 24 hours after surgery. What few differences there were favoured the epidural group. There was a highly significant difference in fentanyl consumption between the two groups, with the intravenous group demanding consistently more than twice as much as the epidural group.

A continuous high flow intermittent mandatory ventilation system incorporating a Downs venturi device and a modified Nuffield Series 200 ventilator.

Systems for respiratory support are becoming increasingly expensive and complex. Many systems suffer inadequacies when used for spontaneous ventilation. Some modes on newer ventilators are rarely used because of the complex controls and settings. There is no truly universal ventilator that satisfies every intensivist's wishes. CPAP/IMV is becoming accepted as the standard management of many patients with acute respiratory failure and there would be few intensive care units where CPAP/IMV is not used for part of a patient's respiratory support. We describe a cost-effective system that may be used for respiratory support in the spontaneously breathing mode. This system combines a high flow venturi, an efficient humidifier and an inexpensive reliable ventilator that can be used for adult and paediatric patients. The system, primarily for use in patients breathing spontaneously, functions well in patients requiring full ventilation.