Optimizing surgery of metaphyseal-diaphyseal fractures of the fifth metatarsal: a cadaveric study on implications of intramedullary screw position, screw parameters and surrounding anatomic structures.

AIMS: Many advocate screw fixation of fractures to the metaphyseal-diaphyseal junction of the fifth metatarsal base, better known as Jones fractures (JF), to facilitate quicker ambulation and return to sport. Maximizing screw parameters based on fifth metatarsal (MT5) anatomy, alongside understanding the anatomic structures compromised by screw insertion, may optimize surgical outcomes. This study aims to (1) correlate the proximity of JF to the peroneus brevis (PB) and plantar fascia (PF) footprints and (2) quantify optimal screw parameters given MT5 anatomy. MATERIALS AND METHODS: 3D CT-scan reconstructions were made of 21 cadaveric MT5s, followed by meticulous mapping of the PB and PF onto the reconstructions. Based on bone length, shape, narrowest intramedullary canal (IMC) diameter, and surrounding anatomy, two traditional debated screw positions were modeled for each reconstruction: (1) an anatomically positioned screw (AP), predicated on maximizing screw length by following the IMC for as long as possible, and (2) a clinically achievable screw (CA), predicated on maximizing screw length without violating the fifth tarso-metatarsal joint or adjacent cuboid bone. Fixation parameters were calculated for all models. RESULTS: The PB and PF extended into the JF site in 29% and 43%, respectively. AP's did not affect PB and PF footprint but required screw entry through the cuboid and fifth tarso-metatarsal joint in all specimens. CA screw entry sites, avoiding the cuboid and fifth tarso-metatarsal joint, partially compromised the PB and PF insertions in 33% and 62% with a median surface loss of 1.6%%(range 0.2-3.2%) and 0.81%%(range 0.05-1.6%), respectively. Mean AP screw length was 64±3.6mm and thread length 49±4.2mm. Mean CA screw length was 48±5.8mm and thread length 28±6.9mm. CONCLUSION: This study underscores the challenges associated with surrounding MT5 anatomy as they relate to optimal JF treatment. Both the extent of JF as well as a clinically achievable positioned screw violate the PB and PF footprints - although the degree to which even partial disruption of these footprints has on outcome remains unclear. To minimize damage to surrounding structures, including the PB and PF footprint, while allowing a screw length approximately two thirds of the metatarsal length, the CA screw position is recommended. This position balances the desire to maximize pull out strength while avoiding cortical penetration or inadvertent fracture site distraction.

An empowerment model of workplace support following disclosure, for people with MS.

BACKGROUND: Vocational interventions aimed at increasing job retention for people with multiple sclerosis (MS) are reliant upon a partnership with a supportive work environment. A better understanding of the types of psychosocial support that are most conducive to retaining employees' sense of work-efficacy will enhance the success of interventions aimed at reducing workplace barriers to job maintenance. OBJECTIVE: The objective of this study is to identify the types of psychosocial support that people with MS require post-disclosure, in order to maintain their employment status. In particular, we examined the roles of psychological safety and work-efficacy. METHODS: We interviewed 40 employees with MS either individually (n = 25) or within three focus groups (n = 15). These interviews were audio-taped and the content analysed, using an inductive thematic approach. RESULTS: Themes to emerge in organisational responses to disclosure were: a focus on ability (leading to enhanced perceptions of psychological safety and higher work-efficacy) and on disability (leading to diminished psychological safety and reduced perceptions of work-efficacy). CONCLUSION: Organisational responses to disclosure demonstrating trust and inclusive decision making, and focussing on employee abilities, enhance perceptions of psychological safety at work. This increases the likelihood that employees with MS will retain their sense of work-efficacy and reduce their intentions to leave.

Disclosure of diagnosis of multiple sclerosis in the workplace positively affects employment status and job tenure.

BACKGROUND: For many employees with multiple sclerosis (MS), disclosure of their diagnosis at work is seen as a high-risk strategy that might lead to diminished perceptions of their capabilities by supervisors and colleagues, if not outright discrimination. The consequence of this mistrust surrounding the disclosure process is that employees with MS may leave it until too late to effectively manage symptoms at work. OBJECTIVE: The objective of this paper is to statistically evaluate the relationship between disclosure of diagnosis at work and maintenance of employment. METHODS: Three annual, large-sample self-report surveys of MS patients prospectively examined the relationship between disclosure of diagnosis at work and employment status. A total of 1438 people responded to all three surveys. Of employed persons in 2010 (n = 946), 673 also responded to the 2012 survey. Of these 673 respondents 564 were still employed. RESULTS: People who had disclosed their MS status to an employer were more likely to remain in employment in Year 3. The effect of disclosure in predicting employment status remained after controlling for age, gender, hours worked and level of disability. CONCLUSION: This study provides the first empirical support for the positive role of disclosure in maintaining employment status, measured both as job retention and tenure in current employment.

Analysis of variation in plasma concentrations of nelfinavir and its active metabolite M8 in HIV-positive patients.

OBJECTIVE: To characterize sources of variation in plasma concentrations of nelfinavir and its active metabolite M8 and to evaluate the use of therapeutic drug monitoring for nelfinavir treatment. METHODS: Plasma samples and patient's characteristics were obtained from outpatient clinic. Differences between groups of patients were studied by comparing the observed plasma concentrations with the corresponding concentration on a pharmacokinetic population curve based on median plasma levels. RESULTS: Plasma samples (618) were available from 355 patients taking 1250 mg nelfinavir twice daily. The median ratio between M8 and nelfinavir concentrations was 0.29. This ratio appeared to be independent of the time after ingestion. Statistically significantly lower M8 concentrations were found in Black and Asian patients, or when comedication with CYP3A4 inducers was used. Coadministration of CYP2C19 inhibitors, such as omeprazole, decreased the median M8/nelfinavir ratio. Nevertheless, nelfinavir concentrations and summed concentrations of nelfinavir and M8 were only marginally affected in these patients. Diarrhoea was identified as a cause for lower nelfinavir concentrations, without changing the M8/nelfinavir ratio. In a number of patients with suspected therapy failure or intoxication, abnormal nelfinavir plasma concentrations were found. Dose adjustments based on nelfinavir plasma levels were helpful in a number of patients. CONCLUSION: This study shows that the total concentration of nelfinavir and M8 together is not significantly influenced when variation in M8 levels occurs. Consequently, measuring M8 concentrations in addition to nelfinavir concentrations is not required for the purpose of therapeutic drug monitoring for this drug.

[Drug interactions of Hypericum perforatum (St. John's wort) are potentially hazardous]. / Combinaties van Hypericum perforatum (sint-janskruid) met andere geneesmiddelen risicovol.

Hypericum can lower the plasma levels of simultaneously administered drugs by induction of metabolism. Combinations of hypericum products with warfarin, cyclosporin, oral contraceptives, theophylline, fenprocoumon, digoxin and indinavir have led to reported interactions and reduced therapeutic activity. It is therefore not advisable to combine hypericum products with other drugs, especially CYP3A4 and p-glycoprotein substrates. Discontinuing hypericum after protracted use may lead to higher plasma levels of the drugs used simultaneously, with the risk of adverse effects. Registered homeopathic preparations with a dilution of 1 in 10,000 or weaker may be regarded as safe.

[Role of cytochrome P450 enzymes in pharmaceutical preparations]. / De rol van cytochroom-P450-enzymen bij geneesmiddeleninteracties.

Cytochrome P450 enzymes are responsible for pharmacokinetic interactions with sometimes serious adverse effects. If a drug is known to be a substrate, inhibitor or inducer of one of the cytochrome P450 isoenzymes, it can be estimated with which other drugs it will interact. The interaction profile of a new drug plays an increasing role in the assessment of the benefit/risk ratio by regulatory authorities. Interactions in practical situation can, however, never be ruled out without proper precautions of both pharmacists and physicians. More attention for the possible occurrence of interactions and searching for a good alternative for one of the drugs to be used should lead to a reduction in the number of adverse events related to interactions.

Rat liver microsomal cytochrome P450-dependent oxidation of 3,5-disubstituted analogues of paracetamol.

1. The cytochrome P450-dependent binding of paracetamol and a series of 3,5-disubstituted paracetamol analogues (R = -F, -Cl, -Br, -I, -CH3, -C2H5, -iC3H7) have been determined with beta-naphthoflavone (beta NF)-induced rat liver microsomes and produced reverse type I spectral changes. Ks,app varied from 0.14 mM for 3,5-diiC3H7-paracetamol to 2.8 mM for paracetamol. 2. All seven analogues underwent rat liver microsomal cytochrome P450-dependent oxidation, as reflected by the formation of GSSG in the presence of GSH. The GSSG-formation was increased in all cases upon pretreatment of rats by beta-naphthoflavone (beta NF) and was generally decreased upon pretreatment by phenobarbital (PB). 3. Rat liver microsomal cytochrome P450 as well as horseradish peroxidase catalysed the formation of 3,5-disubstituted NAPQI analogues from the corresponding parent compounds, as identified by UV-spectrophotometry of the NAPQI analogues and by GC/MS detection of the following GSH-conjugates: 2-glutathione-S-yl-3,5-dimethyl-1,4-dihydroxybenzene, 2-glutathione-S-yl-3,5-dichloro-paracetamol, and 2-glutathione-S-yl-3,5-dibromo-paracetamol. 4. In liver microsomal (beta NF-induced) incubations, apparent K(m) values, as determined for the cytochrome P450 catalysis-dependent oxidation of GSH, for seven 3,5-disubstituted paracetamol analogues (R = -F, -Cl, -Br, -I, -CH3, -C2H5, iC3H7) varied from 0.07 to 0.64 mM. Paracetamol exhibited an apparent K(m) of 0.73 mM. Apparent Vmax values for the cytochrome P450 catalysis dependent oxidation of GSH varied from 0.66 nmol min-1 mg-1 protein for paracetamol to 3.0 nmol min-1 mg-1 protein for 3,5-dimethyl-paracetamol.