Randomised controlled trial to compare GP-run orthopaedic clinics based in hospital outpatient departments and general practices

BACKGROUND: To reduce outpatient waiting times, a growing number of outpatient clinics for selected groups of patients are being provided by GPs with special interests (GPwSIs). AIM: To determine whether there are differences in patient satisfaction or clinical outcome among patients attending orthopaedic clinics provided by GPwSIs in hospital or community settings. DESIGN OF STUDY: Randomised controlled trial. SETTING: Hospital outpatient departments or general practices. METHOD: Three hundred and twenty-one patients with minor orthopaedic problems were referred by GPs to the orthopaedic surgery department of the University Hospitals of Leicester NHS Trust; 168 patients were randomised to care by GPwSIs in practices, and 153 were randomised to care by the same GPwSIs in clinics held at hospital outpatient departments. Patients completed the SF-36v2 and satisfaction questionnaires at their first appointment, and again 3 months later. RESULTS: There was no significant difference between the sites in changes in health. After the first clinic attendance, patients attending practice-based clinics were more satisfied with access to appointments and information received. CONCLUSION: For selected orthopaedic referrals seen by GPwSIs, there were no significant differences in clinical outcomes between practice-based and hospital-based clinics, but some features of practice-based clinics tend to be preferred by patients.     

New-generation azaindole-adamantyl-derived synthetic cannabinoids

Purpose

This work reports the synthesis and pharmacological and analytical data for a new series of recently identified azaindole-adamantyl-derived synthetic cannabinoids (SCs).

Methods

Each SC was synthesised using an efficient and divergent synthesis, and assessed by electron ionisation mass spectrometry (EIMS). The cannabimimetic activity of each compound was conducted using a fluorometric imaging plate reader (FLIPR) assay.

Results

The described EIMS method and retention time by gas chromatography were able to effectively differentiate each of the analogues regardless of the bicyclic core. For the first time in these SC structures, the bicyclic ring system was shown to have an impact on the cannabimimetic activities in the fluorometric assay of membrane potential. Analogues ranged from moderately potent at both CB₁ and CB₂ (e.g., AP4AIC EC₅₀?=?160 nM and EC₅₀?=?64 nM, respectively) to not active at either cannabinoid receptor (AP4AICA, AP5AICA, and APIC).

Conclusions

Further investigation into receptor selectivity surrounding these bicyclic cores could prove useful for future therapeutic applications.

     

The chemistry and pharmacology of synthetic cannabinoid SDB‐006 and its regioisomeric fluorinated and methoxylated analogs

Synthetic cannabinoids are the largest and most structurally diverse class of new psychoactive substances, with manufacturers often using isomerism to evade detection and circumvent legal restriction. The regioisomeric methoxy‐ and fluorine‐substituted analogs of SDB‐006 (N‐benzyl‐1‐pentyl‐1H‐indole‐3‐carboxamide) were synthesized and could not be differentiated by gas chromatography–mass spectrometry (GC–MS), but were distinguishable by liquid chromatography–quadrupole time‐of‐flight–MS (LC–QTOF–MS). In a fluorescence‐based plate reader membrane potential assay, SDB‐006 acted as a potent agonist at human cannabinoid receptors (CB₁ EC₅₀ = 19 nM). All methoxy‐ and fluorine‐substituted analogs showed reduced potency compared to SDB‐006, although the 2‐fluorinated analog (EC₅₀ = 166 nM) was comparable to known synthetic cannabinoid RCS‐4 (EC₅₀ = 146 nM). Using biotelemetry in rats, SDB‐006 and RCS‐4 evoked comparable reduction in body temperature (~0.7°C at a dose of 10 mg/kg), suggesting lower potency than the recent synthetic cannabinoid AB‐CHMINACA (>2°C, 3 mg/kg).     

A STUDY OF THE SPINAL CORD BY NISSL'S METHOD IN TYPHOID FEVER AND IN EXPERIMENTAL INFECTION WITH THE TYPHOID BACILLUS

(1) The application of the Nissl method to the study of the motor cells of the spinal cord, and the nerve cells of the dorsal root ganglia in typhoid fever, shows that these cells regularly suffer pathological changes in the course of the infection. (2) The alterations in the motor cells are more constant and of a severer grade than are those in the cells of the sensory ganglia. The more characteristic changes consist of disintegration, solution and destruction of the chromatic substance of the cell starting from the axone hillock and proceeding toward the nucleus. Coincidently the nuclei of the affected cells seek the periphery. Alterations are also suffered by the nucleus and nucleolus. (3) While this central form of ehromatolysis is the prevailing type of pathological change, disintegration, etc., of the Nissl bodies situated in the periphery of the cell and in the dendrites is also observed (peripheral chromatolysis). (4) In experimental infection with typhoid bacilli in rabbits a similar series of lesions in the corresponding nerve cells in the spinal cord and ganglia is encountered. (5) The main or central type of lesions discovered is identical with that found in man and animals after section, destruction, or even slight injury of the peripheral nerves. (6) The examination of the peripheral nerves arising from the lumbar segment of the cord (the site in man and rabbit of the most profound changes) in rabbits inoculated with typhoid bacilli showed well-marked evidences of parenchymatous degeneration. (7> It is probable that lesions of the peripheral nerves in typhoid fever in human beings are common and that the post-typhoid hyper sthesias and paralyses are due to this cause. (8) Restitution of the chromatic granules may take place in the affected nerve cells, the new formation beginning about the nucleus and extending through the protoplasm.     

Avidity maturation following vaccination with a meningococcal recombinant hexavalent PorA OMV vaccine in UK infants

To date, there are no data assessing the utility of avidity indices as a surrogate marker for the induction of immunological memory following meningococcal serogroup B outer membrane vesicle (OMV) vaccination. We studied infants who had been immunized with three doses of a recombinant hexavalent PorA OMV vaccine at ages 2-4 months, together with a fourth dose at age 12-18 months. A control group had received a single dose of the same vaccine at age 12-18 months. As previously reported, serum bactericidal antibody (SBA) titres increased after each of the first three doses, with a significant increase observed from 6 months post third dose to 1 month post fourth dose. The geometric mean avidity indices (GMAI), against strain H44/76 OMVs, increased from 1 month post first dose to 1 month post third dose. Significant increases in GMAI were observed at 6 months post third dose and again following the fourth dose. At 32-42 months of age, though the SBA titres had returned to post first dose levels, the GMAI remained elevated. No increase in avidity was observed in the control group. Antibody avidity indices are useful laboratory markers for the priming of immunological memory following vaccination with meningococcal serogroup B OMV vaccines.     

Infections of intracardiac devices

Intracardiac devices are increasingly used to correct hemodynamically dysfunctional valves and electrophysiologic abnormalities. These devices become infected at relatively low rates. Nevertheless, when these low rates are applied to widely used devices, significant numbers of infections result. Additionally, these infections have been associated with high degrees of morbidity and high mortality rates. This article reviews the epidemiology, microbiology, clinical presentation, and medical as well as surgical therapy of intracardiac device infections.     

Getting to the meaning of the regular past tense: evidence from neuropsychology

Neuropsychological impairments of English past tense processing inform a key debate in cognitive neuroscience concerning the nature of mental mechanisms. Dual-route accounts claim that regular past tense comprehension deficits reflect a specific impairment of morphological decomposition (e.g., jump + ed), disrupting the automatic comprehension of word meaning accessed via the verb stem (e.g., jump). Single-mechanism accounts claim that the deficits reflect a general phonological impairment that affects perception of regular past tense offsets but which might preserve normal activation of verb semantics. We tested four patients with regular past tense deficits and matched controls, using a paired auditory semantic priming/lexical decision task with three conditions: uninflected verbs (hope/wish), regular past tense primes (blamed/accuse), and irregular past tense primes (shook/tremble). Both groups showed significant priming for verbs with simple morphophonology (uninflected verbs and irregular past tenses) but the patients showed no priming for verbs with complex morphophonology (regular past tenses) in contrast to controls. The findings suggest that the patients are delayed in activating the meaning of verbs if a regular past tense affix is appended, consistent with a dual-route account of their deficit.     

Women and health care professionals' preferences for Down's Syndrome screening tests: a conjoint analysis study

OBJECTIVE: To describe and compare women and health care professionals' preferences for Down's Syndrome screening tests with different test characteristics. DESIGN: Cross sectional questionnaire based conjoint analysis study. SETTING: London teaching hospital. SAMPLE: 291/383 women in their first or second trimester of pregnancy and 98/122 health care professionals (41 obstetricians, senior house officers and above and 57 qualified midwives) providing care at the same hospital. METHODS: Women completed a questionnaire while attending a clinic visit for a dating scan or a routine 20-week anomaly scan. Health care professionals completed a postal questionnaire. MAIN OUTCOME MEASURES: The relative values participants attach to Down's Syndrome screening test attributes: time of test, detection rate and risk of miscarriage of a baby unaffected by Down's Syndrome as a result of subsequent diagnostic tests. RESULTS: Pregnant women and health care professionals shared broadly similar relative values regarding the importance of safe tests, conducted early and with high detection rates. When asked to choose between different Down's Syndrome screening tests, health care professionals valued earlier tests more highly than did women. CONCLUSIONS: While pregnant women and health care professionals share similar relative values regarding optimal prenatal tests, health care professionals place a higher value on earlier tests. This may result in screening policies that overweight timing in the selection of a test to the relative neglect of tests associated with lower miscarriage rates and higher detection rates but conducted later in pregnancy.