Practice patterns in the care of acute Achilles tendon ruptures : is there an association with level I evidence?

AIMS: To determine whether the findings from a landmark Canadian trial assessing the optimal management of acute rupture of the Achilles tendon influenced the practice patterns of orthopaedic surgeons in Ontario, Canada. MATERIALS AND METHODS: Health administrative databases were used to identify Ontario residents ≥ 18 years of age with an Achilles tendon rupture from April 2002 to March 2014. The rate of surgical repair (per 100 cases) was calculated for each calendar quarter. A time-series analysis was used to determine whether changes in the rate were chronologically related to the dissemination of results from a landmark trial published in February 2009. Non-linear spline regression was then used independently to identify critical time-points of change in the surgical repair rate to confirm the findings. RESULTS: A total of 29 531 patients sustained an Achilles tendon rupture during the study period. Consistently, around 21 out of every 100 cases underwent surgical repair up to the first quarter of 2010. However, by the first quarter of 2014, only 6.5 cases per 100 had surgery. A statistically significant decrease in the rate of surgical repair was observed within one year of the presentation of landmark trial results in 2009 (p < 0.001). July 2009 was independently identified as a critical time at which the surgical repair rate began to significantly decline (p < 0.001). The dissemination of trial results was associated with a significant drop in the rate of surgical repair at non-teaching hospitals (p = 0.001). CONCLUSION: The current study demonstrates that large, well-designed randomised trials, have the potential to encourage significant changes in the practice patterns of orthopaedic surgeons. Cite this article: Bone Joint J 2017;99-B:1629-36.

The epidemiology and trends in management of acute Achilles tendon ruptures in Ontario, Canada: a population-based study of 27 607 patients.

AIMS: The aims of this study were to establish the incidence of acute Achilles tendon rupture (AATR) in a North American population, to select demographic subgroups and to examine trends in the management of this injury in the province of Ontario, Canada. PATIENTS AND METHODS: Patients ≥ 18 years of age who presented with an AATR to an emergency department in Ontario, Canada between 1 January 2003 and 31 December 2013 were identified using administrative databases. The overall and annual incidence density rate (IDR) of AATR were calculated for all demographic subgroups. The annual rate of surgical repair was also calculated and compared between demographic subgroups. RESULTS: A total of 27 607 patients (median age, 44 years; interquartile range 26 to 62; 66.5% male) sustained an AATR. The annual IDR increased from 18.0 to 29.3 per 100 000 person-years between 2003 and 2013. The mean IDR was highest among men between the ages of 40 and 49 years (46.0/100 000 person-years). The annual rate of surgical repair dropped from 20.1 in 2003 to 9.2 per 100 AATRs in 2013. There was a noticeable decline after 2009. CONCLUSION: The incidence of AATR is increasing in Ontario, while the annual rate of surgical repair is decreasing. A sharp decline in the rate of surgical repair was noted after 2009. This coincided with the publication of several high-quality RCTs which showed similar outcomes for the 'functional' non-operative management and surgical repair. Cite this article: Bone Joint J 2017;99-B:78-86.

Involvement of gamma-amino butyric acid (GABA) in the anticonvulsant action of methaqualone.

The effects of methaqualone on isonicotinic acid hydrazide, 6-mercapto propionic acid, picrotoxin, and strychnine-induced convulsion were studied in mice and the results compared with diazepam. Methaqualone, like diazepam, was found to be a selective antagonist of isoniazid-induced convulsion and a much less effective inhibitor of strychnine convulsion. Methaqualone elicits muscle-relaxant, sedative, and anticonvulsant effects at different dose levels. At low, nonsedative doses the drug produces anticonvulsant effects, and at higher doses, muscle-relaxant and sedative effects. It appears that the mechanism(s) of action of methaqualone in on GABA deficiency or receptor blockade, rather than on glycine receptors.

Attenuation of stereotyped behaviour by sex steroids.

Effects of sex steroids, testosterone, progesterone, and estradiol on PEA-induced stereotyped behaviour (SB) has been studied in normal, castrated, and ovariectomised mice. Effects of sex steroids on amphetamine-induced sterotypy and hyperactivity are also described. In castrated and ovariectomised mice B-phenylethylamine (PEA) increased SB. Pretreatment with sex steroids attenuated PEA-induced stereotypy in normal, castrated, and ovarietomised mice. Sex steroid pretreatment significantly inhibited PEA- and amphetamine-induced SB, but failed to alter increased motor activity due to amphetamine or PEA. The possible effect of sec steroids on SB through changes in central neurotransmitters are discussed.

Possible involvement of 5-hydroxytryptamine and cyclic-AMP in tolerance to tremorine analgesia in mice.

The phenomenon of tolerance to the analgesic action of tremorine in mice was studied by the hot-plate and tail-clip methods. Reduction in 5-HT levels in brain by parachlorophenylalamine pretreatment decreased the ED50 of tremorine analgesia in tremorine tolerant mice. 5-Hydroxyptophan, L-Dopa or alpha-methyl-para-tyrosine did not influence the analgesic response to tremorine in tremorine tolerant animals. However, theophylline was found to enhance the tolerance to tremorine analgesia. Brain 5-HT and cAMP are probably involved in tremorine tolerance, whereas neither noradrenaline nor dopamine is involved in the phenomenon.

Effect of muscimol, a central GABA receptor agonist, on the catalepsy, striatal homovanillic acid increase, and analgesia induced by pilocarpine in rats.

Muscimol, a structural analog of GABA, significantly potentiated pilocarpine-induced analgesia in rats, but failed to alter pilocarpine-induced catalepsy. It also failed to affect pilocarpine-elicited increase in homovanillic acid levels in the striatum. These findings suggest that the potentiation of pilocarpine-induced analgesia by muscimol is unrelated to an interaction of the GABAergic system with the striatal cholinergic or dopaminergic systems.

Measurement of antipyretic activity of ibuprofen and paracetamol in children.

The antipyretic activity of ibuprofen (Brufen) and paracetamol (Crocin) was compared in 22 children with pyrexia who received either ibuprofen or paracetamol in syrup form. Both axillary and rectal temperatures were recorded prior to drug administration and 1/2, 1, 2, 3, 4, 5, 6, 8, and 12 hours after dosing. Analysis of the results in terms of rate of temperature decrease and degree and duration of decrease in temperature indicated that both drugs produced significant reduction in temperature and in the rate of temperature decrease. The maximum effect of the two drugs was similar. However, ibuprofen was more effective than paracetamol at 6 and 8 hours after administration, and its duration of action was longer. The associated antipyretic and antiinflammatory features of ibuprofen could provide an advantage in the control of exudative forms of upper respiratory tract infections.

A study of interaction of low-dose combination oral contraceptive with Ampicillin and Metronidazole.

Plasma levels of norethisterone (NET), ethinyl estradiol (EE), Ampicillin or Metronidazole were estimated in 16 women, who were taking low-dose oral combination contraceptive pills (containing norethisterone acetate 1 mg and ethinyl estradiol 30 microgram) and in whom concurrently, either Ampicillin (6 women) or Metronidazole therapy (10 women) was given. Neither Ampicillin nor Metronidazole therapy altered the 'peak' or 24-hour plasma levels and area under the curve, for NET and EE. Furthermore, oral contraceptive treatment did not alter the 'peak' levels of Ampicillin or Metronidazole. Progesterone (P) levels were in the anovulatory range in all Ampicillin treated cycles. However, in Metronidazole treated group, two out of 10 women showed a P rise of more than 4 ng/ml. The study was expanded to include another group of 15 women treated with Metronidazole, where only one women showed a P rise of more than 4 ng/ml. The occurrence of 'escape ovulation' as suggested by P rise of more than 4 ng/ml in three out of 25 Metronidazole treated women is either a chance incidence due to a different pharmacological response in them, or most probably due to the default in the regular intake of pills in these women. This is supported by the observation that one out of three women showing a P rise (greater than 4 ng/ml( during concurrent Metronidazole therapy, also showed ovulatory P values in oral contraceptive-only treated cycles. Furthermore, in the control group also, one out of 10 women had ovulatory P levels (greater than 4 ng/ml) in oral contraceptive-only treated cycles.

PIP: Plasma levels of (NET) norethisterone, (EE) ethinyl estradiol, Ampicillin, or Metronidazole were estimated in 16 women who were taking low-dose (OC) oral contraceptives (containing norethisterone acetate, 1 mg, and ethinyl estradiol, 30 mcg) and in whom concurrently, either Ampicillin (6 women) or Metronidazole therapy (10 women) was given. Neither drug altered the peak or 24-hour plasma levels and area under the curve for NET and EE. Furthermore, OC treatment did not alter the peak levels of either Ampicillin or Metronidazole. (P) Progresterone levels were in the anovulatory range in all Ampicillin-treated cycles. However, in Metronidazole-treated group, 2 of 10 women showed a P rise of more than 4 ng/ml. The study was expanded to include another group of 15 women treated with Metronidazole and only 1 woman showed a P rise of more than 4 ng/ml. The occurrence of 'escape ovulation' as suggested by a P rise of more than 4 ng/ml in 3 of 25 Metronidazole-treated women is either a chance incidence due to a different pharmacological response in them, or most probably due to the default in the regular intake of pills in these women. This is supported by the observation that 1 out of 3 women showing a P rise ( 4 ng/ml) during concurrent Metronidazole therapy also showed ovulatory P values in OC-only treated cycles. Furthermore, in the control group, 1 out of 10 women had ovulatory P levels ( 4 ng/ml) in OC-only treated cycles.

A study of interaction of a low-dose combination oral contraceptive with anti-tubercular drugs.

Low-dose combination contraceptive (containing norethisterone acetate 1 mg and ethinyl estradiol 30 micrograms) was administered to women receiving concurrent therapy with either Rifampicin or "triple" antitubercular treatment consisting of paraaminosalicylic acid (PAS), isonicotinic acid hydrazide (INH) and streptomycin. Plasma levels of norethisterone (NET) and ethinyl estradiol (EE), PAS and INH were measured and the area under curve (AUC) was calculated for NET and EE. Rifampicin treatment (9 women) caused a statistically significant reduction of the plasma NET levels as well as the AUC of NET. In this group of women, though a trend for reduction in EE levels was observed in individual subjects, it was not statistically significant. Out of 7 regularly menstruating women on Rifampicin therapy, 2 showed a premenstrual rise of plasma progesterone (P) levels (> 4 ng/ml) suggesting an ovulatory cycle and 3 experienced menstrual irregularities. In contrast, plasma levels of NET and EE as well as their AUCs were not altered in 8 women receiving "triple" antitubercular therapy. Only one woman out of 8, had menstrual irregularity and all women had P levels in the anovulatory range. Furthermore, oral contraceptive treatment did not alter the plasma levels of PAS and INH.

Pharmacokinetics of ethynyloestradiol in women for different populations.

The pharmacokinetics of a dose of 50 microgram ethynyloestradiol administered orally was studied in fourteen centres. Absorption was rapid and the highest serum concentrations of total ethynyloestradiol were found in most subjects at 1 h and by 24 h concentrations were less than 250 pg/ml. Calculation of the half-lives for absorption, distribution and elimination showed wide variations between subjects, the half-life of elimination varying from 2.5 h to more than 30 h. Bioavailability as measured by the area under the serum ethynyloestradiol concentration-time curve also showed more than a ten-fold variation. Intra-centre differences in the various parameters measured were as large as the inter-centre differences.

Rate of metabolism of norethisterone in women from different populations.

The rate of metabolism of orally administered norethisterone was compared in fourteen centres by measuring plasma levels of the steroid by radioimmunoassay at varying times after oral administration of a 1 mg dose. The inter-centre differences were of the same order as the intra-centre differences. Variations in metabolism appeared not to be due to variations in body size.

Pharmacokinetics of mefloquine in children aged 6 to 24 months.

The study was carried out in 12 children aged 6 months to 2 years, with uncomplicated falciparum malaria admitted to the Hospital for Tropical Diseases, Bangkok. They were treated with mefloquine in the form of MSP (mefloquine 250 mg+sulfadoxine 500 mg+pyrimethamine 25 mg) at a single dose of 25 mg mefloquine base/kg body weight. All of them were cured (28 days follow-up) with minimal side effects. Pharmacokinetic parameter determination was carried out in 9 cases. The results revealed that MRT, t1/2 and tmax in this study (children 6-24 months old) are comparable to the values in children aged 5-12 years, but shorter than in adult patients. Cmax and AUC in children 6-24 months old are comparable to those in children of 5-12 years, but much higher than in adult patients. Vz/f values in this study are comparable to those in children 5-12 years old, but lower than in adult patients.

Perceptions of risk and optimistic bias for acute gastrointestinal illness: a population survey.

Optimistic bias refers to the tendency of individuals to believe that they are less likely to experience negative events compared with other people. Individuals who perceive their risk of an adverse health event to be low may not be as receptive to informational messages aimed at disease prevention. Our objective was to estimate the magnitude of optimistic bias for acute gastrointestinal illness, and to describe demographic associations with, and reasons for, individuals' perception of personal risk. Data were obtained by a retrospective, cross-sectional telephone survey of 2057 randomly selected English-speaking residents of Ontario, Canada conducted between May 2005 and April 2006. Data were collected on the occurrence of acute gastrointestinal illness during the 28 days prior to the survey, demographics, respondents' perception of their personal risk of acute gastrointestinal illness compared with the average person, and the reasons for this perception. Associations with perception of illness were evaluated using ordinal logistic regression and reasons for perception of risk were explored qualitatively. Optimistic bias was present among all respondents, but was not statistically significant within the group that had experienced acute gastrointestinal illness in the previous 28 days. Rural residency and not having experienced acute gastrointestinal illness in the previous 28 days were associated with a lower perception of risk compared with the average person. Proportionally fewer individuals who had not completed secondary education saw themselves as at less than average risk. The most common reason given for the perception of lower risk was that the respondent was healthier than the average person, although personal lifestyle choices also were provided as reasons. The presence of optimistic bias may negatively impact compliance with public health initiatives to reduce acute gastrointestinal illness. Therefore, recognizing the demographic characteristics associated with a perception of lower risk and understanding the reasons for this perception may help with targeting effective preventive messaging.