Impact of oral dexamethasone versus placebo after ED treatment of migraine with phenothiazines on the rate of recurrent headache: a randomised controlled trial

OBJECTIVE: Evidence suggests that the rate of recurrent headache after treatment of migraine in the emergency department (ED) is high. The mechanisms for this are unclear, but neurogenic inflammation may play a role. There is conflicting evidence about whether adjuvant dexamethasone reduces the rate of recurrent headache. The aim of this study was to compare the rate of recurrent headache in patients with migraine randomised to receive a single dose of oral dexamethasone or placebo at discharge after treatment in the ED with intravenous phenothiazine.

METHODS: A double-blind, randomised, placebo-controlled trial was conducted in the ED of three community teaching hospitals. Adult patients with physician-diagnosed migraine were treated with intravenous phenothiazine and at discharge were randomised to receive either 8 mg oral dexamethasone or placebo as a single dose. Follow-up was by telephone at 48-72 h and the proportion of patients with recurrent headache overall and in the subgroup with headache duration <24 h was recorded.

RESULTS: 63 patients (76% women) of median age 39 years were enrolled, 61 of whom (97%) completed follow-up. The pooled rate of recurrent headache was 33%. 32 were randomised to placebo and 31 to dexamethasone. The rate of recurrent headache in the dexamethasone and control groups was 27% (8/30) vs 39% (12/31) (relative risk (RR) 0.69, 95% CI 0.33 to 1.45, p = 0.47). For 40 patients with headache lasting <24 h the rate of recurrent headache in the dexamethasone and control groups was 15% (3/20) vs 45% (9/20), a reduction in absolute risk of 30% (RR 0.33, 95% CI 0.11 to 1.05, p = 0.08).

CONCLUSION: A single oral dose of dexamethasone following phenothiazine treatment for migraine in the ED did not reduce the rate of recurrent headache. There is weak evidence for a possible benefit in the subgroup who present within <24 h of symptom onset. A multicentre trial to confirm this finding is warranted.

Symptoms, ill-health and quality of life of the members of a Porton Down veterans' support group

Background There has been a Human Volunteer Programme at the British chemical weapons research facility at Porton Down since the First World War, in which some of the participants were exposed to chemical warfare agents.

Aim To identify any striking specific morbidity patterns in members of the Porton Down Veterans Support Group (PDVSG).

Methods A self-completed postal questionnaire was prepared including health immediately after the visits to Porton Down, subsequent diagnoses and hospital admissions, symptoms in, and after, the first 5 years after the visits, fatigue symptoms and current quality of life, measured using the SF-36.

Results Responses were received from 289 of 436 (66%). Results reported here relate to 269 male respondents of mean age 66.8 years. Sixty-six per cent reported their first visit to Porton Down in the 1950s. The most common diagnoses or hospital admissions reported were diseases of the circulatory system. In the first 5 years after their visits the most common symptoms were headache, irritability or outbursts of anger and feeling un-refreshed after sleep. In the later period, most common symptoms were fatigue, feeling un-refreshed after sleep and sleeping difficulties. Sixty-five per cent met the definition for a case of ‘fatigue’. Current quality of life dimensions were consistently lower than age-specific estimates from general population samples.

Conclusions Members of the PDVSG responding to this survey reported poorer quality of life than the general population. Despite there being no clear pattern of specific morbidities, we cannot rule out ill-health being potentially associated with past experience at Porton Down

Olanzapine / fluoxetine combination for treatment resistant depression : efficacy and clinical utility

Antidepressant monotherapy is a first-line treatment for depression; however, not all sufferers will adequately respond to treatment. When treating a patient with treatment-resistant depression, the clinician needs to consider all factors which may contribute to an inadequate response to an antidepressant. These include accuracy of diagnosis and medication adherence, as well as the patient’s personality, lifestyle, life events and social circumstances. If it is determined that treatment resistance is due to failure of efficacy of antidepressant monotherapy, then an augmentation strategy using an atypical antipsychotic may be considered. Treatment using olanzapine/fluoxetine combination (OFC) is one of many options. Four randomized, acute-phase trials have suggested OFC is useful for reducing Montgomery–Åsberg Depression Rating Scale scores after inadequate response to antidepressant monotherapy. OFC has been useful at doses of olanzapine/fluoxetine 6/25, 6/50, 12/25 and 12/50 mg/day, with 1/5 mg/day suggested to be an ineffective dose. Treatment with OFC has been associated with some side effects, including weight gain and the metabolic syndrome, somnolence, dry mouth, increased appetite and headache. Treatment decisions therefore need to be made to balance the risks and benefits.

Isolation of a novel Orientia species (O. chuto sp. nov.) from a patient infected in Dubai

In July 2006, an Australian tourist returning from Dubai, in the United Arab Emirates (UAE), developed acute scrub typhus. Her signs and symptoms included fever, myalgia, headache, rash, and eschar. Orientia tsutsugamushi serology demonstrated a 4-fold rise in antibody titers in paired serum collections (1:512 to 1:8,192), with the sera reacting strongest against the Gilliam strain antigen. An Orientia species was isolated by the in vitro culture of the patient's acute blood taken prior to antibiotic treatment. The gene sequencing of the 16S rRNA gene (rrs), partial 56-kDa gene, and the full open reading frame 47-kDa gene was performed, and comparisons of this new Orientia sp. isolate to previously characterized strains demonstrated significant sequence diversity. The closest homology to the rrs sequence of the new Orientia sp. isolate was with three strains of O. tsutsugamushi (Ikeda, Kato, and Karp), with a nucleotide sequence similarity of 98.5%. The closest homology to the 47-kDa gene sequence was with O. tsutsugamushi strain Gilliam, with a nucleotide similarity of 82.3%, while the closest homology to the 56-kDa gene sequence was with O. tsutsugamushi strain TA686, with a nucleotide similarity of 53.1%. The molecular divergence and geographically unique origin lead us to believe that this organism should be considered a novel species. Therefore, we have proposed the name “Orientia chuto,” and the prototype strain of this species is strain Dubai, named after the location in which the patient was infected.

Efficacy and adverse effects of venlafaxine in children and adolescents with ADHD : a systematic review of non-controlled and controlled trials

Attention deficit hyperactivity disorder (ADHD) is a common psychiatric disorder in children and adolescents. Stimulants are commonly prescribed for ADHD management. There is clinical trial evidence that some medications with noradrenergic properties such as atomoxetine are effective. It is of theoretical and practical importance if other agents with noradrenergic properties display a comparable pattern of efficacy.
This paper is a systematic review of the efficacy and safety of venlafaxine for treating children and adolescents with ADHD. MEDLINE, Google scholar, Scopus, and Web of science (ISI) databases were electronically searched in July 2012, updated on November 2012. Time and language of publication were not exclusion criteria. Efficacy outcomes were assessed by a valid and reliable parent- and/or teacher-reported instrument to evaluate clinical symptoms. Adverse effects were also evaluated.

There were three uncontrolled trials and only two double blind controlled clinical trials. Venlafaxine appeared effective for treating ADHD. The rates of some adverse effects of venlafaxine were less than those documented for methylphenidate.

While one of the two small controlled trials did not find difference between venlafaxine ad methylphenidate, the other trial reported lower efficacy for venlafaxine. Headache, insomnia, and nausea were among the most common adverse effects.

This systematic review provides preliminary support that venlafaxine may have short term utility in treating ADHD in children and adolescents. However, before recommending venlafaxine for treatment, more robust and larger clinical trials, in particular providing evidence of its long-term efficacy, safety and tolerability are required.

N-acetylcysteine versus placebo for treating nail biting, a double blind randomized placebo controlled clinical trial

Nail biting is a common behavioral problem. While there are established behavioral interventions for management, they are of modest efficacy, and there is minimal evidence for effective pharmacotherapy. This study investigated the role of N-acetylcysteine (NAC) a potent glutathione and glutamate modulator for the treatment of pathological nail biting in children and adolescents. This pilot randomized, double-blind, placebo-controlled clinical trial of NAC (800mg/day) or placebo enrolled 42 children and adolescents with chronic nail biting. Nail length was the objective outcome. Evaluations were carried out three times; before treatment, one month after enrollment in the study, and two months after enrollment. The duration (chronicity) of nail biting in the NAC and placebo groups was 3.63(2.45) and 5.09(3.74) years (P=0.14). The mean nail length gradually increased in both the NAC and placebo groups during this trial. There was a statistically significant difference between the two groups regarding increased nail length after the first month of trial [(5.21(5.75) and 1.18(3.02) millimeters], however no difference after two months was observed. Two patients in the NAC group discontinued medication due to adverse events. One patient experienced headache, agitation, and social withdrawal, and another patient expressed severe aggression after taking medication and was withdrawn from the study. This study supports the hypothesis that NAC decreases nail biting behavior in children and adolescents over the short term. NAC is relatively well tolerated and severe adverse effects are rare. However, there was a high rate of dropout. Further studies with longer durations that build on these preliminary data are recommended.

Determining criteria to assess patient readiness for discharge from postanaesthetic care: an international Delphi study

Aims and objectives
To obtain expert consensus on essential criteria required to assess patient readiness for discharge from the postanaesthetic care unit.

Background
A patient's condition can deteriorate after surgery, and the immediate postoperative period is recognised internationally as a time of increased risk to patient safety. A recent systematic review identified evidence-based assessment criteria for the safe discharge of patients from the postanaesthetic care unit and identified gaps in the evidence.

Design
Descriptive consensus study using the Delphi method.

Methods
Members of international clinical specialist groups with expertise in anaesthesia or postanaesthetic care participated in three consultation rounds. Online surveys were used to determine expert consensus with regard to aspects of postanaesthetic care and specific criteria for assessing patient readiness for discharge. Three rounds of surveys were conducted from May 2011–September 2012.

Results
Twenty-three experts contributed to the panel. Consensus, that is, at least 75% agreement, was reached in regard to 24 criteria considered essential (e.g. respiratory rate 100%; pain 100%; heart rate 95%; temperature 91%). Consensus was also reached for 15 criteria not considered essential (e.g. appetite 96%; headache 76%). Consensus was not obtained for a further 10 criteria. Participants (95%) agreed that a discharge tool was important to ensure safe patient discharge.

Conclusion
Consensus was achieved by a panel of international experts on the use of a tool to assess patient readiness for discharge from postanaesthesia care unit and specific variables to be included or excluded from the tool. Further work is required to develop a tool and test its reliability and validity.

Relevance to clinical practice
The findings of this study have informed the development of an evidence-based tool to be piloted in a subsequent funded study of nursing assessment of patient readiness for discharge from the postanaesthetic care unit.

Determining criteria to assess patient readiness for discharge from postanaesthetic care: An international Delphi study

Aims and objectives: To obtain expert consensus on essential criteria required to assess patient readiness for discharge from the postanaesthetic care unit. Background: A patient's condition can deteriorate after surgery, and the immediate postoperative period is recognised internationally as a time of increased risk to patient safety. A recent systematic review identified evidence-based assessment criteria for the safe discharge of patients from the postanaesthetic care unit and identified gaps in the evidence. Design: Descriptive consensus study using the Delphi method. Methods: Members of international clinical specialist groups with expertise in anaesthesia or postanaesthetic care participated in three consultation rounds. Online surveys were used to determine expert consensus with regard to aspects of postanaesthetic care and specific criteria for assessing patient readiness for discharge. Three rounds of surveys were conducted from May 2011-September 2012. Results: Twenty-three experts contributed to the panel. Consensus, that is, at least 75% agreement, was reached in regard to 24 criteria considered essential (e.g. respiratory rate 100%; pain 100%; heart rate 95%; temperature 91%). Consensus was also reached for 15 criteria not considered essential (e.g. appetite 96%; headache 76%). Consensus was not obtained for a further 10 criteria. Participants (95%) agreed that a discharge tool was important to ensure safe patient discharge. Conclusion: Consensus was achieved by a panel of international experts on the use of a tool to assess patient readiness for discharge from postanaesthesia care unit and specific variables to be included or excluded from the tool. Further work is required to develop a tool and test its reliability and validity. Relevance to clinical practice: The findings of this study have informed the development of an evidence-based tool to be piloted in a subsequent funded study of nursing assessment of patient readiness for discharge from the postanaesthetic care unit.

Poor tolerance of motor cortex rTMS in chronic migraine

Background:
Two small studies had evaluated the efficacy of rTMS in migraine. One tested high frequency rTMS over the dorsolateral prefrontal cortex while the other evaluated 1 Hz rTMS over the vertex.
Aim:
To test the feasibility of 10 Hz rTMS of motor cortex as an adjunctive therapy in patients with chronic migraine.
Materials and Methods:
We randomized (2:1 ratio) chronic migraine patients on medical preventive treatment to receive either rTMS or sham therapy for 10 sessions. rTMS (80% resting motor threshold, 10Hz, 20 trains, 5 secs/train, inter-train interval 1 min, total 1000 stimuli/session) was applied over the right motor cortex.
Result:
Nine patients were randomized. Six received rTMS
and three had sham therapy. Three patients in the rTMS arm withdrew from the study due to increased headache frequency and discomfort from the treatment. The remaining six cases (3 rTMS, 3 sham) completed the study. The study was prematurely stopped due to the significant worsening of headache from rTMS. No significant differences in outcome measures were found between real and sham rTMS.
Conclusion:
Although the study was terminated prematurely, the high dropout rate (50%) due to worsening headaches suggested that rTMS over the motor cortex is poorly tolerated in chronic migraine.

Evaluation of neck muscle size: long-term reliability and comparison of methods

Although it is important for prospective studies, the reliability of quantitative measures of cervical muscle size on magnetic resonance imaging is not well established. The aim of the current work was to assess the long-term reliability of measurements of cervical muscle size. In addition, we examined the utility of selecting specific sub-regions of muscles at each vertebral level, averaging between sides of the body, and pooling muscles into larger groups. Axial scans from the base of skull to the third thoracic vertebra were performed in 20 healthy male subjects at baseline and 1.5 years later. We evaluated the semi-spinalis capitis, splenius capitis, spinalis cervicis, longus capitis, longus colli, levator scapulae, sternocleidomastoid, anterior scalenes and middle with posterior scalenes. Bland-Altman analysis showed all measurements to be repeatable between testing-days. Reliability was typically best when entire muscle volume was measured (co-efficients of variation (CVs): 3.3-8.1% depending on muscle). However, when the size of the muscle was assessed at specific vertebral levels, similar measurement precision was achieved (CVs: 2.7-7.6%). A median of 4-6 images were measured at the specific vertebral levels versus 18-37 images for entire muscle volume. This would represent considerable time saving. Based on the findings we also recommend measuring both sides of the body and calculating an average value. Pooling specific muscles into the deep neck flexors (CV: 3.5%) and neck extensors (CV: 2.7%) can serve to reduce variability further. The results of the current study help to establish outcome measures for interventional studies and for sample size estimation.

An update on the clinical pharmacology of the dipeptidyl peptidase 4 inhibitor alogliptin used for the treatment of type 2 diabetes mellitus.

Alogliptin, a dipeptidyl peptidase-4 (DPP-4) inhibitor that is a class of relatively new oral hypoglycaemic drugs used in patients with type 2 diabetes (T2DM), can be used as monotherapy or in combination with other anti-diabetic agents, including metformin, pioglitazone, sulfonylureas and insulin with a considerable therapeutic effect. Alogliptin exhibits favorable pharmacokinetic and pharmacodynamic profiles in humans. Alogliptin is mainly metabolized by cytochrome P450 (CYP2D6) and CYP3A4. Dose reduction is recommended for patients with moderate or worse renal impairment. Side effects of alogliptin include nasopharyngitis, upper-respiratory tract infections and headache. Hypoglycaemia is seen in about 1.5% of the T2DM patients. Rare but severe adverse reactions such as acute pancreatitis, serious hypersensitivity including anaphylaxis, angioedema and severe cutaneous reactions such as Stevens-Johnson syndrome have been reported from post-marketing monitoring. Pharmacokinetic interactions have not been observed between alogliptin and other drugs including glyburide, metformin, pioglitazone, insulin and warfarin. The present review aimed to update the clinical information on pharmacodynamics, pharmacokinetics, adverse effects and drug interactions, and to discuss the future directions of alogliptin.