Experimental demonstration of optical data links using a hybrid CAP/QAM modulation scheme.

The first known experimental demonstrations of a 10 Gb/s hybrid CAP-2/QAM-2 and a 20 Gb/s hybrid CAP-4/QAM-4 transmitter/receiver-based optical data link are performed. Successful transmission over 4.3 km of standard single-mode fiber (SMF) is achieved, with a link power penalty ∼0.4 dBo for CAP-2/QAM-2 and ∼1.5 dBo for CAP-4/QAM-4 at BER=10(-9).

Developing a strategy for accreditation of clinical services.

Accreditation is one method of assuring quality. Accreditation requires the setting of standards and the creation of a robust and reliable process for assessing them. Accreditation offers different advantages to different groups, eg quality assurance to commissioners and the boards of provider organisations, confidence and choice for patients, and a quality improvement pathway for services to follow. This paper is focused on service accreditation and it proposes that service accreditation be professionally led.

A study of the reproducibility and etiology of diffusion anisotropy differences in developmental stuttering: a potential role for impaired myelination.

Several diffusion tensor imaging (DTI) studies have reported fractional anisotropy (FA) reductions within the left perisylvian white matter (WM) of persistent developmental stutterers (PSs). However, these studies have not reached the same conclusions in regard to the presence, spatial distribution (focal/diffuse), and directionality (elevated/reduced) of FA differences outside of the left perisylvian region. In addition, supplemental DTI measures (axial and radial diffusivities, diffusion trace) have yet to be utilized to examine the potential etiology of these FA reductions. Therefore, the present study sought to reexamine earlier findings through a sex- and age-controlled replication analysis and then to extend these findings with the aforementioned non-FA measures. The replication analysis showed that robust FA reductions in PSs were largely focal, left hemispheric, and within late-myelinating associative and commissural fibers (division III of the left superior longitudinal fasciculus, callosal body, forceps minor of the corpus callosum). Additional DTI measures revealed that these FA reductions were attributable to an increase in diffusion perpendicular to the affected fiber tracts (elevated radial diffusivity). These findings suggest a hypothesis that will be testable in future studies: that myelogenesis may be abnormal in PSs within left-hemispheric fiber tracts that begin a prolonged course of myelination in the first postnatal year.

Care of patients with psoriasis: an audit of U.K. services in secondary care.

BACKGROUND: Medical professionals require data about the structure and delivery of dermatological services in primary and secondary care in order to identify and tackle variations in standards and monitor the impact of healthcare reforms. The British Association of Dermatologists (BAD) commissioned an audit of the provision of care for patients with psoriasis. OBJECTIVES: To assess the staffing and facilities in dermatology units in the U.K. with a focus on the provision of care for patients with psoriasis. METHODS: Data were collected from 100 dermatology units in the U.K. for 1 year using a questionnaire and a web-based collection system. RESULTS: Key results are as follows. Eighteen per cent (18/98) of units had fewer than 2.0 whole-time equivalent consultants and 20% had no specialist dermatology nurse. Only 23% of units collected diagnostic data on outpatients, and half were unable to supply details about the number of attendances for psoriasis. Seventy-seven units reported admitting patients to dedicated dermatology beds, general medical beds, or both; three-quarters of units had access to dedicated adult dermatology beds. Pharmacy services were not always available for dermatology patients. Only 21 units (21%) had dedicated clinics for patients with psoriasis and 56% of units lacked a clinical psychology service willing to accept adult dermatology patients; 59% (55/93) lacked psychological services for children. Fifty-five per cent had no systemic drug monitoring clinic. Phototherapy was run by dermatology nurses in 93% (88/95) of the units and by physiotherapists in 11% (10/94). Biologics for psoriasis were prescribed in 75% (73/97) of units and in 88% (64/73) of these the BAD guidelines for the use of biologics were known to be followed. Of the seventy-three units prescribing biologic therapies, 64% had a nurse trained in the assessment and administration of biologics, 71% had facilities for outpatient infusions (e.g. for infliximab) and 39% were restricted in prescribing biologic agents because of financial constraints. A quality-of-life score was either inadequately or never recorded in outpatient records in 81% of units, increasing to 88% for inpatient records. The Psoriasis Area and Severity Index score was inadequately or never recorded in 79% of outpatient records and 82% of inpatient records. CONCLUSIONS: Units varied in their capacity to meet BAD guidelines and standards. Among the most significant deficiencies identified were a shortage of specialist dermatology nurses, treatment delivery by untrained nurses and financial constraints on the prescription of biologics for psoriasis. Gaps in data collection and record keeping jeopardize efforts to improve standards of care.

The ophthalmic blade perfectly made to create an oral antral communication blockade; a technical note.

Oral antral fistulas are commonly referred to the Oral and Maxillofacial department for surgical management. Though conventional methods of repair are well established, we present a technical note highlighting the novel use of an ophthalmic blade in raising palatal mucoperiosteal flaps. We have experienced much success with this instrument and believe it represents a very useful and complimentary addition to the oral and maxillofacial surgeon's kit.

Onabotulinum toxin A in children with refractory idiopathic overactive bladder: medium-term outcomes.

INTRODUCTION: Botulinum toxin-A (BtA) has been used for refractory idiopathic overactive bladder (IOAB) in children. Data on the optimum dose success rates, duration of effect, complications and medium-term outcomes are limited. This study aims to analyse the authors' experience to provide medium-term results of BtA in symptomatic refractory patients. MATERIALS AND METHODS: Patients with refractory IOAB who were treated with BtA (Botox®) were retrospectively analysed. All patients had urodynamic study before treating with BtA. Group A had low-dose BtA (LDBtA) at 5 units/kg (maximum 150 units), and Group B had high-dose BtA (HDBtA) at 10 units/kg (maximum 300 Units). Post-BtA clinical response, functional bladder capacity (FBC) and postvoid residual (PVR) were assessed in addition to the duration of response. RESULTS: Thirty-nine patients, 11 male and 28 female, were analysed. Forty-six percentage had symptom improvement (73% of males and 36% of females [P = 0.072, ns]). The difference in response rates between LDBtA and HDBtA was not statistically significant (P = 0.684). Increase in total bladder capacity (TBC) was greater in those given HDBtA (P ≤ 0.001), but the increase in FBC was not different between the groups, due to greater PVRs in the HDBtA group. Nine patients (23%) developed UTI; however, six of these patients suffered with UTI pre-BtA as well. Only three were asymptomatic after a single treatment with BtA. The remainder required further BtA or oral anticholinergic therapy. At a median follow-up of 35.4 months (interquartile range [IQR] 25.2-46.6), 12 (31%) were asymptomatic and off all therapy, 18 (46%) were still symptomatic despite therapy and 9 (23%) had their symptoms controlled on continuing treatment. DISCUSSION AND CONCLUSIONS: Botulinum toxin-A improves symptoms in 46% of children after the first injection in refractory IOAB. Although HDBtA resulted in greater increase in bladder capacity, it conferred no advantage in terms of success rate or duration of response. Five units/kg may be an optimum dose to use as a first treatment with the understanding that some patients will require a higher dose. And, there will be a cohort of patients who need a dose lower than 5 units/kg. A higher dose is more likely to lead to PVR leading to urine stasis and UTIs. The success of BtA only lasts until its effect wears off, and the majority of this cohort (36/39) required continuing treatment with repeat BtA or anticholinergic agents. However, it remains a useful option in patients who are intolerant or unresponsive to anticholinergic medication with symptomatic resolution in 30% at medium-term follow-up.

Guideline for the diagnosis and management of vitiligo.

This detailed and user-friendly guideline for the diagnosis and management of vitiligo in children and adults aims to give high quality clinical advice, based on the best available evidence and expert consensus, taking into account patient choice and clinical expertise. The guideline was devised by a structured process and is intended for use by dermatologists and as a resource for interested parties including patients. Recommendations and levels of evidence have been graded according to the method developed by the Scottish Inter-Collegiate Guidelines Network. Where evidence was lacking, research recommendations were made. The types of vitiligo, process of diagnosis in primary and secondary care, and investigation of vitiligo were assessed. Treatments considered include offering no treatment other than camouflage cosmetics and sunscreens, the use of topical potent or highly potent corticosteroids, of vitamin D analogues, and of topical calcineurin inhibitors, and depigmentation with p-(benzyloxy)phenol. The use of systemic treatment, e.g. corticosteroids, ciclosporin and other immunosuppressive agents was analyzed. Phototherapy was considered, including narrowband ultraviolet B (UVB), psoralen with ultraviolet A (UVA), and khellin with UVA or UVB, along with combinations of topical preparations and various forms of UV. Surgical treatments that were assessed include full-thickness and split skin grafting, mini (punch) grafts, autologous epidermal cell suspensions, and autologous skin equivalents. The effectiveness of cognitive therapy and psychological treatments was considered. Therapeutic algorithms using grades of recommendation and levels of evidence have been produced for children and for adults with vitiligo.

Review of outcomes of 500 consecutive cases of non-melanoma skin cancer of the head and neck managed in an oral and maxillofacial surgical unit in a District General Hospital.

We provide a non-melanoma skin cancer (NMSC) service for skin cancers of the head and neck in the south-west of England. We hypothesised that certain anatomical sites such as the nose and eyelid would have a higher incidence of close or involved margins than others, and that the choice of repair might influence the excised margins. We therefore retrospectively analysed the data of 500 consecutive NMSC that were operated on in the oral and maxillofacial surgery unit of Taunton and Somerset NHS Trust. The database reports were crosschecked against the Trust's own pathology reporting system to ensure that they were accurate. Data collected included clinical and personal details of patients, anatomical sites, type of reconstruction, histopathological diagnosis, excision margins, and complications. Of the 500 patients reviewed 362 (72%) were basal cell carcinomas (BCC) and 138 (28%) squamous cell carcinomas (SCC). The outcomes of 243 patients treated by primary closure, 134 treated by reconstruction with local flaps, and 123 treated by skin grafts, were reviewed with particular attention paid to the anatomical site and excision margins. There was an overall incomplete excision rate of 10.8% (n=54) and 29 patients developed complications (5.8%). We confirmed that rates of close or incomplete margins are more likely in certain anatomical sites such as the nose, forehead, and ear. The rate of involved margins was unaffected by choice of surgical technique.

Oral transmucosal fentanyl citrate (OTFC) for the treatment of breakthrough pain in cancer patients: a controlled dose titration study.

Oral transmucosal fentanyl citrate (OTFC) is a novel opioid formulation in which the potent synthetic mu-agonist fentanyl is embedded in a sweetened matrix that is dissolved in the mouth. It is undergoing investigation as a treatment for cancer-related breakthrough pain, a prevalent phenomenon defined as a transitory flare of moderate to severe pain that interrupts otherwise controlled persistent pain. There have been no controlled trials of other treatments for this condition. To evaluate the safety and efficacy of ascending doses of OTFC, a novel controlled dose titration methodology was developed that applied blinding and randomization procedures to the evaluation of recurrent pains in the home environment. The study was a multicenter, randomized, double-blind dose titration study in ambulatory cancer patients. The sample comprised adult patients receiving a scheduled oral opioid regimen equivalent to 60-1000 mg oral morphine per day, who were experiencing at least one episode per day of breakthrough pain and had achieved at least partial relief of this pain by use of an oral opioid rescue dose. After collection of 2 days of baseline data concerning the efficacy of the usual rescue drug, patients were randomly treated with either 200 or 400 microg OTFC unit doses in double-blind fashion. Up to two breakthrough pains each day could be treated with up to four OTFC unit doses per pain. OTFC in unit doses containing 200, 400, 600, 800, 1200 or 1600 microg of fentanyl citrate were available for the study. The unit dose was titrated upward in steps until the patient had 2 consecutive days on which breakthrough pain could be treated with the single unit dose, titration was ineffective at a 1600 microg unit dose, or 20 days elapsed. To maintain the double-blind, orders to titrate up were ignored one-third of the time according to a pre-defined randomization schedule accessible only to an unblinded study pharmacist. Main outcome measures included, numeric or categorical measures of pain intensity, pain relief, and global assessment of drug performance. Dose response relationships were found suggesting that the methodology was sensitive to opioid effects. Seventy-four percent of patients were successfully titrated. There was no relationship between the total daily dose of the fixed schedule opioid regimen and the dose of OTFC required to manage the breakthrough pain. Although the study was not designed to provide a definitive comparison between OTFC and the usual rescue drug, exploratory analyses found that OTFC provided significantly greater analgesic effect at 15, 30 and 60 min, and a more rapid onset of effect, than the usual rescue drug. Adverse effects of the OTFC were typically opioid-related, specifically somnolence, nausea and dizziness. Very few adverse events were severe or serious. This study demonstrated the feasibility of controlled trial methodology in studies of breakthrough pain. OTFC appears to be a safe and effective therapy for breakthrough pain, and dose titration can usually identify a unit dose capable of providing adequate analgesia. If the lack of a relationship between the effective OTFC dose and fixed schedule opioid regimen is confirmed, dose titration may be needed in the clinical use of this formulation. Further investigation of OTFC as a specific treatment for breakthrough pain is warranted.

Imaging human intra-cerebral connectivity by PET during TMS.

Non-invasive imaging of human inter-regional neural connectivity by positron emission tomography (PET) during transcranial magnetic stimulation (TMS) was performed. The hand area of primary motor cortex (M1) in the left cerebral hemisphere was stimulated with TMS while local and remote effects were recorded with PET. At the stimulated site, TMS increased blood flow (12-20%) in a highly focal manner, without an inhibitory surround. Remote covariances, an index of connectivity with M1, were also focal. Connectivity patterns established in non-human species were generally confirmed. Excitatory connectivity (positive covariance) was observed in ipsilateral primary and secondary somatosensory areas (S1 and S2), in ipsilateral ventral, lateral premotor cortex (M2) and in contralateral supplementary motor area (SMA). Inhibitory connectivity (negative covariance) was observed in contralateral M1.

Symptom assessment.

Medical intervention aims to eliminate disease, to mitigate disease effect, and maximize quality of life. Throughout the course of illness, accurate symptom assessment is imperative if these goals are to be achieved. Symptom scales may facilitate this process in the clinical setting. Many valid scales are available for research, and investigators must be familiar with a methodology that can quantify the impact of therapies on symptoms, symptom distress, and overall QOL.

A British Cardiac Society survey of the potential for the secondary prevention of coronary disease: ASPIRE (Action on Secondary Prevention through Intervention to Reduce Events).

OBJECTIVE: To measure the potential for secondary prevention of coronary disease in the United Kingdom. DESIGN: Cross sectional survey of a representative sample of coronary patients from a retrospective review of hospital medical records and patient interview and examination. SETTING: Stratified random sample of 12 specialist cardiac centres and 12 district general hospitals drawn from 34 specialist cardiac centres and 261 district general hospitals in 12 geographic areas in the United Kingdom. SUBJECTS: 2583 patients < or = 70 yr; 25 consecutive males and 25 consecutive females identified retrospectively in each of four diagnostic categories: coronary artery bypass grafting, percutaneous transluminal coronary angioplasty, acute myocardial infarction, and acute myocardial ischaemia without evidence of infarction. MAIN OUTCOME MEASURES: Risk factor recording and management in medical records; the prevalence and control of risk factors at interview six months after the procedure or event. RESULTS: Recording of coronary risk factors in patient's records was incomplete and this varied by risk factor. Smoking habit and blood pressure were most completely recorded, whereas a history of hyperlipidaemia and blood cholesterol concentrations were least complete. Risk factor records were more likely to be complete in cardiac centres than in district hospitals. At interview 10% to 27% of patients were still smoking cigarettes and 75% remained overweight, females more severely so. Up to a quarter of patients remained hypertensive, males more severely so than females. Over three quarters had a total cholesterol > 5.2 mmol/l. In patients on medication for blood pressure, cholesterol or glucose, risk factor profiles were little better than in those who were not. Only about one patient in three was taking a beta blocker after infarction. Up to a fifth of patients who had had acute myocardial ischaemia were not taking aspirin at follow up. CONCLUSIONS: There is considerable potential to reduce the risk of a further major ischaemic event in patients with established coronary disease. This can be achieved by effective lifestyle intervention, the rigorous management of blood pressure and cholesterol, and the appropriate use of prophylactic drugs.

Prenylated flavonoids in the roots of yellow lupin.

A further investigation of the methanol-soluble compounds in yellow lupin roots has revealed a new diprenylchromone, a new coumaronochromone (lupinalbin H), a new isoflavone 5,7,4'-trihydroxy-8,3'-di-(3,3-dimethylally)isoflavone (isolupalbigenin), and some complex flavanones. The latter compounds have been identified as two known diprenylated flavanones (lonchocarpol A and euchrestaflavanone A), two diasteroisomeric pairs of dihydrofuranoflavanones (lonchocarpols C1 and C2, and lonchocarpols D1 and D2, the structures formerly proposed for lonchocarpols C and D were also reinvestigated), a new furanoflavanone (lupinenol), and three 8-prenylflavanones with an additional (2RS)-hydroxy-3-methyl-3-butenyl side chain. The structures of the latter flavanones were unambiguously identified by spectroscopic (1H NMR) comparison with 6-, 8- and 3'-prenylnaringenins chemically prepared from (2S)-naringenin. The antifungal activity of the prenylated naringenins, and of the various yellow lupin flavanones, was determined by TLC place bioassays using Cladosporium herbarum as the test fungus.

Cardiovascular autonomic insufficiency in a patient with metastatic malignancy.

A case of cardiovascular autonomic insufficiency is described in a cachectic 70-year-old man with widely metastatic small-cell tumor. The patient experienced disabling syncopal episodes in association with severe postural hypotension. Tests of cardiovascular autonomic insufficiency were abnormal. The introduction of fludrocortisone and the use of elastic stockings produced palliation of the symptomatology, but his condition deteriorated and he died. Autopsy demonstrated unexpectedly extensive tumor invasion of autonomic nervous tissue. Although cardiovascular autonomic insufficiency (CAI) has been described in association with malignancy and malnutrition, local tumor invasion of autonomic nervous tissue and radiation injury may have been other possible, albeit unusual, etiologic factors. This case illustrates the differential diagnosis of hypotension and CAI in patients with advanced metastatic malignancy and also emphasizes the need for autopsy studies when speculating as to the cause of CAI in this group of patients.

The management of spinal cord compression in patients with advanced malignancy.

We retrospectively evaluated the medical records of 17 hospice patients who developed spinal cord or cauda equina compression due to metastatic epidural tumor to ascertain the nature and outcome of the disorder in this setting. Epidural compression occurred following admission to the hospice in five cases and prior to admission in 12 cases. Six patients were ambulatory following treatment, and this favorable outcome occurred only in those who were ambulatory at diagnosis. In the group of patients who were paraplegic after treatment, problems related to pain, decubitus ulcers, and constipation were most challenging. This experience highlights the need for a more vigilant approach to back pain in patients at risk of epidural compression in the hospice setting. Further studies are necessary to establish the appropriate management of these patients.

Self-esteem, life stress and psychiatric disorder.

Using a special subsample from a survey of women in Edinburgh investigations were carried out into (a) which types of life event are associated with lowered self-esteem; (b) the role of life events and self-esteem in onset of psychiatric disorder; and (c) the additional significance of prior psychiatric consultation in determining onset. Stressors involving impaired relationships with others were the only ones clearly associated with lowered self-esteem. Minor psychiatric illness was predicted by stress of uncertain outcome, and, to a lesser extent, by impaired relationship stress. Onset of major depression was best predicted by an interaction between total stress experienced and low self-esteem. There was evidence that such onset involves a pre-existing low level of self-esteem on which life stress impinges, rather than life stress generating low self-esteem and then onset. A small group of subjects characterised by low self-esteem, prior psychiatric consultation and maladaptive coping seemed to be fluctuating in and out of psychiatric illness irrespective of stress.

Life events and other factors implicated in onset and in remission of psychiatric illness in women.

Life stressors for 574 Edinburgh women were assessed for uncertain outcome, impaired relationships and other characteristics. Thirteen weeks were covered either with no illness present or before a transient episode of Research Diagnostic Criteria (RDC)-defined anxiety/depression (duration less than 13 weeks) or before a longer episode or before illness remission or during continuing illness. Exploratory analysis suggested that stressors of uncertain outcome preceded longer illness onset. Impaired relationships went with continuing illness. Stressors with neither of these, and with fewer than two other characteristics, preceded transient illness. Remaining stressors predicted remission, as did ending of long-term difficulties. Self-esteem, support, coping, previous illness and marital status also discriminated between the groups.

Life events and the onset of affective disorder. A longitudinal general population study.

This paper examines the relationship between life events (ascertained by the Bedford College method) and the onset of affective disorder (defined according to the RDC scheme) in a longitudinal general population survey of women. Fall-off in the reporting of minor events is examined and discussed. Event rates, proportions of women challenged by events, and measures of the risk of RDC disorder associated with the experience of particular events are reported. The results based upon data from an initial interview were largely consistent with those based upon follow-up data, and underpinned earlier work. For both data sets, major difficulties were associated with illness onset. Severe dependent events showed stronger effects than severe independent events but both categories were rare. New substantive findings arising from short-term general population event research are unlikely.