Clinical variation in the treatment of trigger finger: An international survey of orthopaedic and plastic surgeons.

Trigger finger is a common condition affecting the hand. Therapeutic variability surrounds the management of trigger finger, especially in the mild cases. The aim of this study was to survey secondary care surgeons to describe the current management of trigger fingers. The steering group developed a survey for hand surgeons. Following piloting, the survey was distributed to hand surgeons in the United Kingdom and The Netherlands. A total of 713 plastic surgeons and orthopaedic surgeons were invited to participate in the online survey and 440 (62%) surgeons completed the survey. In both mild and moderate cases of trigger finger, steroid injection was the preferred treatment option. Open surgery was the treatment of choice for severe cases. However, there was variation in delivery of care, including type and dosage of steroid, site of injection, interval between injections, maximum number of injections, type of incision and treatment of patients with diabetes or rheumatoid arthritis. This highlights the need for a better evidence base for the treatment of trigger fingers.

Tenosynovial giant cell tumours of the hand: A multicentre case-control study.

Many factors have been proposed to contribute to the risk of recurrent tenosynovial giant cell tumours (TSGCT); however, we remain unable to predict those at risk, which formed the rationale for this multicentre retrospective case-control study of 28 patients with recurrence. We included cases of recurrence in a 1:1 ratio matched for age and sex with controls over 10 years. Using Cox regression, we present hazard ratios (HRs) for recurrence with 95% confidence intervals (CIs). Out of 285 cases, 28 individuals developed recurrence after a median of 2.4 years. Recurrent TSGCT had a higher mitotic count/mm2 in the primary tumour (median increase of 3 [IQR 1, 7]). Mitotic count in the primary tumour was associated with the risk of recurrence (adjusted HR 1.1 [95% CI 1.1, 1.2]) meaning that for every additional mitosis, the risk of recurrence increased by 10% per annum. We recommend a prospective cohort study to validate our findings.

Randomized feasibility trial of replacing or discarding the nail plate after nail-bed repair in children.

BACKGROUND: Nail-bed injuries are the most common hand injury in children. Surgical dogma is to replace the nail plate after repairing the nail bed. Recent evidence suggests this might increase infection rates and returns to clinic. The aim of this feasibility trial was to inform the design and conduct of a definitive trial comparing replacing or discarding the nail plate after nail-bed repair. METHODS: This study recruited participants from four hand units in the UK between April and July 2015. Participants were children under the age of 16 years with a nail-bed injury requiring surgery. They were randomized to either having the nail plate replaced or discarded after nail-bed repair. The follow-up method was also allocated randomly (postal versus clinic). Information was collected on complications at 2 weeks and 30 days, and on nail-plate appearance at 4 months using the Zook classification. Two possible approaches to follow-up were also piloted and compared. RESULTS: During the recruitment phase, there were 156 potentially eligible children. Sixty were randomized in just over 3 months using remote web-based allocation. By 2 weeks, there were two infections, both in children with replaced nail plates. The nail-replaced group also experienced more complications. There was no evidence of a difference in return rates between postal and clinic follow-up. CONCLUSION: Recruitment was rapid and nail-bed repair appeared to have low complication and infection rates in this pilot trial. The findings have led to revision of the definitive trial protocol, including the mode and timing of follow-up, and modification of the Zook classification.

Long term study into surgical re-exploration of the 'free flap in difficulty'.

BACKGROUND: Free tissue transfers must survive in order to achieve their surgical goals. There is little consensus about managing the 'failing' free flap, and practice is often guided by anecdote. MATERIAL AND METHODS: We have prospectively collected data about all free flaps performed within our department between 1985 and 2008 (2569 flaps). We identified 327 flaps which were re-explored a total of 369 times. We analysed these flaps with regard to indication for re-exploration, operative findings and outcome. RESULTS: Thirteen percent (327) of free flaps were re-explored. Of these, 291 (83%) had a successful outcome. Successful re-explorations took place at a mean 19h post-op and unsuccessful re-explorations at a mean 56h post-op. Clinical diagnosis prior to re-exploration was confirmed operatively in 91% of cases. CONCLUSION: We have considered the factors that allowed us to achieve the salvage rates described over a prolonged period, and identified two key areas. Firstly, we favour a model for free flap monitoring with clinical judgement at its core. Secondly, we feel the facility to recover patients post-operatively in a specialised, warmed environment, and return them to theatre quickly should the need arise, is essential. These two simple, yet institutionally determined factors are vital for maintaining excellent success rates.

Free tissue transfers in the first 2 years of life--a successful cost effective and humane option.

Experience shows that young children are favourable candidates for microsurgical reconstruction, having few of the established risk factors for flap failure. In children's reconstructive surgery free tissue transfer (FTT) permits reconstruction whilst retaining growth potential, and reduces the overall number and duration of care episodes, and their related distress to the child and family. We present one centre's experience of free tissue transfer in children less than 2 years of age, over a 15-year period, demonstrating that free tissue transfer can be successfully employed in children under 2 years old. Salient aspects of patient selection, pre-operative counselling, and per-operative management are presented. Data from all free flaps in children under 2 years of age at the time of surgery were collected prospectively. Forty-seven flaps were performed as 37 separate procedures, in 32 children under 2 years of age. In ten patients, double transfers were performed in single procedures. Free tissue transfers were performed for reconstruction of congenital defects, following trauma and meningococcal septicaemia. All but one flap survived. In our series operative and ischaemia times, re-exploration, complication and flap failure rates were not higher than in comparable adult or older paediatric series from this unit, suggesting that there is no microvascular, or other, factor inherent to the infant that should preclude the use of free tissue transfer. Individual microsurgeons with appropriate facilities should not be inhibited from performing free tissue transfers which are humane and cost effective when compared with alternatives for very young children.

Alcohol, wine and mental health: focus on dementia and stroke.

The relative risks of coronary heart disease (CHD) and overall mortality are reduced by moderate consumption of alcoholic beverages, particularly wine, which has major implications for public health. It appears likely that this beneficial effect of alcohol will soon be extended to some mental disorders. Although data on psychosis and mood and anxiety disorders are currently lacking, it appears that the relative risks of developing ischaemic stroke and Alzheimer's or vascular dementia are also lowered by moderate alcohol consumption. Such findings are still tentative because of the inherent methodological problems involved in population-based epidemiological studies, and it is unclear whether the benefit can be ascribed to alcohol itself or to other constituents specific to wine such as polyphenols. Plausible biological mechanisms have been advanced for the protective effect of alcohol and wine against CHD, many of which will also play roles in their protective actions against cerebrovascular disease and dementia. The specific antioxidant properties of wine polyphenols may be particularly important in preventing Alzheimer's disease. Because of the substantially unpredictable risk of progression to problem drinking and alcohol abuse, the most sensible advice to the general public is that heavy drinkers should drink less or not at all, that abstainers should not be indiscriminately encouraged to begin drinking for health reasons, and that light to moderate drinkers need not change their drinking habits for health reasons, except in exceptional circumstances.

Mirtazapine enhances the effect of haloperidol on apomorphine-induced climbing behaviour in mice and attenuates haloperidol-induced catalepsy in rats.

Activation of 5-HT1A receptors has been shown to attenuate catalepsy induced by typical antipsychotic compounds. Since mirtazapine (Remeron; Org 3770) has indirect 5-HT1A receptor stimulating properties as well as antagonist properties at alpha2-adrenoceptors and 5-HT2 receptors, it was of interest to investigate how the compound could modulate the effect of haloperidol on apomorphine-induced climbing behaviour in mice and haloperidol-induced catalepsy in rats. In the apomorphine climbing test, it was found that mirtazapine (2.2-22 mg/kg) did not change the climbing behaviour of mice induced by 1 mg/kg of apomorphine. However, when given as a co-treatment with haloperidol, mirtazapine (1 and 10 mg/kg) dose-dependently augmented the inhibiting effect of haloperidol on this climbing behaviour. Co-treatment with the 5-HT1A receptor agonist 8-OH-DPAT (0.1 mg/kg) also augmented the effect of haloperidol. Catalepsy induced by haloperidol (4.6 mg/kg) was attenuated by mirtazapine (2.2-22 mg/kg). The strongest effect was seen at 90 min after haloperidol treatment. The results obtained in these experiments suggest that co-treatment with mirtazapine may enhance the antipsychotic effect of haloperidol and reduce its extrapyramidal side effects, thereby widening its therapeutic window.

Designing a new generation of antidepressant drugs.

Although longer-term adaptive changes in receptor sensitivity may better explain the delayed onset of action of antidepressants, the mechanism based on acutely elevated noradrenaline (NA) and serotonin (5-HT) synaptic levels remains the basis for new drug design. The dual action concept, which postulates that effects on both NA and 5-HT are more advantageous than a selective action on serotonin reuptake (SSRI), has been used to design new antidepressants such as venlafaxine and mirtazapine. Both drugs enhance NA and 5-HT neurotransmission with little affinity for receptors mediating tricyclic-like side effects. Mirtazapine, the prototype noradrenergic and specific serotonergic antidepressant (NaSSA), specifically enhances 5-HT1 neurotransmission and blocks 5-HT2 and 5-HT3 receptors, and in contrast to venlafaxine lacks SSRI-like and adverse cardiovascular side effects. The unique pharmacological action of mirtazapine is a result of implementation of two concepts: dual action as a basis of efficacy combined with receptor-specific action as a basis of tolerability.

OS benefìcios e os riscos das drogas antidepressivas / The benefts and risks of antidepressent drugs

As drogas antidepressivas alteram de forma inequìvoca a evoluçäo a curto prazo da doença depressiva, tendo reduzido consideravelmente os riscos de morbidade. Sua influência sobre a evoluçäo crônica da depressäo ou sobre o aumento da mortalidade associada à doença depressiva näo é täo fácil de se quantificar. Todavia, os benefìcios de um tratamento eficaz da depressäo ultrapassäo muito os consideráveis riscos de se tratar os pacientes deprimidos inadequadamente ou de näo tratá-los. A maioria dos antidepressivos atualmente disponìveis apresenta uma eficácia semelhante, apesar de alguns serem mais apropriados em certos tipos de pacientes, quando säo proeminentes cerpos sintomas ou quando um efeito colateral, em particular, é indesejável. Os antidepressivos variam quanto a seus efeitos colaterais, e as drogas näo-tricìclicas mais recentes parecem proporcionar riscos menores de efeitos anticolinérgicos e cardiovasculares. Todas essas novas drogas apresentam, no entanto, outros efeitos adversos, tendo levado, nos casos da zimeldina e da nomifensina, a sua retirada do mercado e, no da mianserina, ao controle da prescriçäo. A análise dos dados de superdosagem indica que o maior risco dos antidepressivos é o óbito por dose excessiva, sendo que o número destes eventos ultrapassa, de longe, o dos óbitos por efeitos adversos. Sugere-se que quaisquer avaliaçöes dos benefìcios e dos riscos globais de drogas antidepressivas devem incluir näo apenas os riscos com doses terapêuticas, mas também os perigos decorrentes da superdosagem

Os beneficios e os riscos das drogas antidepressivas

As drogas antidepressivas alternaram de forma inequivoca a evolucao a curto prazo da doenca depressiva, tendo reduzido consideravelmente os riscos de morbidade. Sua influencia sobre a evolucao cronica da depressao ou sobre o aumento da mortalidade associada a doenca depressiva nao e tao facil de se quantificar. Todavia, os beneficios de um tratamento eficaz da depressao ultrapassam muito os consideraveis riscos de se tratar os pacientes deprimidos inadequadamente ou de nao trata-los. A maioria dos antidepressivos atualmente disponiveis apresenta uma eficacia semelhante, apesar de alguns serem mais apropriados em certos tipos de pacientes, quando sao proeminentes certos sintomas ou quando um efeito colateral, em particular, e indesejavel. Os antidepressivos variam quanto a seus efeitos colaterais, e as drogas nao-triciclicas mais recentes parecem proporcionar riscos menores de efeitos anticolinergicos e cardiovasculares. Todas essas novas drogas apresentam, no entanto, outros efeitos adversos, tendo levado, nos casos da zimeldina e da nomifensina, a sua retirada do mercado e, no da mianserina, ao controle da prescricao. a analise dos dados de superdosagem indica que o maior risco dos antidepressivos e o obito por dose excessiva, sendo que o numero destes eventos ultrapassa, de longe, o dos obitos por efeitos adversos. Sugere-se que quaisquer avaliacoes dos beneficios e dos riscos globais de drogas antidepressivas devem incluir nao apenas os riscos com doses terapeuticas, mas tambem os perigos decorrentes da superdosagem.

Why do fatal overdose rates vary between antidepressants?

Age specific death rates for poisoning with different antidepressant drugs, based on mortality statistics and the numbers of prescriptions dispensed, were calculated for England and Wales 1979-1985. There are marked variations in mortality associated with different drugs; the highest rates are found with amitriptyline and dothiepin whereas the lowest were associated with mianserin and clomipramine. For all drugs considered, the calculated mortality rates for the over 65 year olds, though still substantial, were lower than those in patients under 65 years of age, probably because of a diminished detection rate of poisoning in this older age group. A high proportion of the fatal overdoses implicating amitriptyline and dothiepin involved more than one substance. The rank order of mortality rates from antidepressants was identical in the different age groups. The implications of these findings are discussed. It is concluded that the variations in mortality rates are mostly due to variations in the inherent toxicity of the drugs (particularly their cardiovascular effects) and only in part due to possible differences in compliance. It is suggested that when antidepressant drugs are prescribed, the risk of death from overdose should be taken into account. Tricyclic drugs, particularly amitriptyline, dothiepin, doxepin, trimipramine and maprotiline, should be avoided in patients at risk of suicide, whatever the age of the patient.

Neurochemical and autonomic pharmacological profiles of the 6-aza-analogue of mianserin, Org 3770 and its enantiomers.

The neurochemical and autonomic pharmacological profile of 1,2,3,4,10, 14b-hexahydro-2-methyl-pyrazino[2,1-a]pyrido[2,3-c]pyrido[2, 3-c] [2] benzazepine [+/-)Org 3770) and the related antidepressant drug, mianserin, have been compared. The uptake of [3H]noradrenaline ([3H]NA) in vitro was weakly affected by (+/-)Org 3770 (pKi = 5.6) in contrast to mianserin (pKi = 7.4). Both (+/-)Org 3770 and mianserin facilitated the release of [3H]NA in slices of cortex. The effects of NA mediated by alpha 2-adrenoceptors on the release of both [3H]NA or [3H]serotonin ([3H]5-HT) were antagonized by (+)Org 3770 with pKi values of 8.4 and 8.1, respectively. However, (-)Org 3770 only antagonized the effect of NA on the release of [3H]5-HT (pA2 = 7.7). The binding of [3H]rauwolscine to alpha 2-adrenoceptors was inhibited by (+/-)Org 3770 and mianserin with identical affinity (pKi = 7.0), whereas the binding of [3H]prazosin to alpha 1-adrenoceptors was less potently affected by (+/-)Org 3770 (pKi = 6.4) than by mianserin (pKi = 7.1). A similar difference was found for alpha 1- and alpha 2-adrenoceptors in vas deferens of the rat. The binding of [3H]mianserin to 5-HT2 receptors was less potently blocked by (+/-)Org 3770 (pKi = 8.1) than by mianserin (pKi = 9.4) while the binding of [3H]mepyramine to histamine-1 receptors was more potently affected by (+/-)Org 3770 (pKi = 9.3) than by mianserin (pKi = 8.75). The binding of [3H]quinuclidinylbenzilate to muscarinic cholinergic receptors was blocked equally by (+/-)Org 3770 (pKi = 6.1) and mianserin (pKi = 6.3). Similar data on tryptamine-D, histamine-1 and muscarinic cholinergic receptors in isolated organs were obtained. A prominent role for the blockade of alpha 2-adrenoceptors in the therapeutic effects of mianserin and (+/-)Org 3770 in depression is suggested, probably excluding a role of inhibition of the uptake of NA.