Polycystic ovary syndrome influences the level of serum amyloid A and activity of phospholipid transfer protein in HDL2 and HDL3.

STUDY QUESTION: Is polycystic ovary syndrome (PCOS) associated with altered levels of pro-inflammatory high-density lipoproteins (HDL) and activity of HDL-associated enzymes? SUMMARY ANSWER: In PCOS, HDL contained increased levels of the inflammatory marker serum amyloid A (SAA) and altered functioning of HDL-associated phospholipid transfer protein (PLTP), with these changes being independent of BMI, body fat and insulin resistance (IR). WHAT IS KNOWN ALREADY: PCOS is associated with adipocyte-derived inflammation, which potentially increases the risk of cardiovascular disease and diabetes. SAA is an inflammatory marker that is released from hypertrophic adipocytes and interacts with HDL, reducing their anti-atherogenic properties. No studies have previously investigated if SAA-associated HDL influences the HDL-associated enzymes namely, PLTP and cholesterol ester transfer protein (CETP) in women with PCOS. PARTICIPANTS/MATERIALS, SETTINGS, METHODS: Obese women with PCOS were matched with controls for BMI and percentage body fat (n = 100/group; cohort-1); a subset of these women (n = 64/group; cohort-2) were further matched for IR. HDL in blood samples was subfractionated into HDL2 and HDL3 by rapid ultracentrifugation. SAA was measured in serum, HDL2 and HDL3 by an enzyme-linked immunosorbent assay and the activities of PLTP and CETP were measured in HDL2 and HDL3 by fluorimetric assays. MAIN RESULTS AND THE ROLE OF CHANCE: In the PCOS women from cohort-1, SAA was increased in serum, HDL2 and HDL3 (P = 0.038, 0.008 and 0.001 versus control, respectively), as was the activity of PLTP in HDL2 and HDL3 (P = 0.006 and 0.009 versus controls, respectively). In the PCOS women from cohort-2, SAA was increased in serum, HDL2 and HDL3, although only significantly in HDL3 (P = 0.083, 0.120 and 0.034 versus controls, respectively), as was the activity of PLTP in HDL2 and HDL3, although this was only significant in HDL2 (P = 0.045 and 0.070 versus controls, respectively). LIMITATIONS, REASONS FOR CAUTION: First, insulin sensitivity was not determined by the euglycaemic-hyperinsulinaemic clamp. Secondly, the method used to estimate body fat was not able to discriminate between visceral and peripheral fat. Thirdly, larger study groups would be required to confirm if PCOS independently contributed to SAA-related HDL and functional changes to this lipoprotein, independent of BMI, percentage body fat and IR. WIDER IMPLICATIONS OF THE FINDINGS: This is the first study to highlight the usefulness of HDL-associated SAA as a marker to identify increased inflammation in women with PCOS. This study also identified that the functioning of HDL was altered in women with PCOS. These findings illustrate a mechanism through which cardiovascular disease may increase in PCOS. STUDY FUNDING/COMPETING INTERESTS: Funded by the Irish Endocrinology Society. No competing interests. CLINICAL TRIAL REGISTRATION NUMBER: NCT001195168.

Routine HIV testing in the emergency department: tough lessons in sustainability.

OBJECTIVES: Routine HIV testing in nonspecialist settings has been shown to be acceptable to patients and staff in pilot studies. The question of how to embed routine HIV testing, and make it sustainable, remains to be answered. METHODS: We established a service of routine HIV testing in an emergency department (ED) in London, delivered by ED staff as part of routine clinical care. All patients aged 16 to 65 years were offered an HIV test (latterly the upper age limit was removed). Meetings were held weekly and two outcome measures examined: test offer rate (coverage) and test uptake. Sustainability methodology (process mapping; plan-do-study-act (PDSA) cycles) was applied to maximize these outcome measures. RESULTS: Over 30 months, 44,582 eligible patients attended the ED. The mean proportion offered an HIV test was 14%, varying from 6% to 54% per month over the testing period. The mean proportion accepting a test was 63% (range 33-100%). A total of 4327 HIV tests have been performed. Thirteen patients have been diagnosed with HIV infection (0.30%). PDSA cycles having the most positive and sustained effects on the outcome measures include the expansion to offer blood-based HIV tests in addition to the original oral fluid tests, and the engagement of ED nursing staff in the programme. CONCLUSIONS: HIV testing can be delivered in the ED, but constant innovation and attention have been required to maintain it over 30 months. Patient uptake remains high, suggesting acceptability, but time will be required before true embedding in routine clinical practice is achieved.

Clinical and cost implications of using immediate MRI in the management of patients with a suspected scaphoid fracture and negative radiographs results from the SMaRT trial.

AIMS: The aim of the Scaphoid Magnetic Resonance Imaging in Trauma (SMaRT) trial was to evaluate the clinical and cost implications of using immediate MRI in the acute management of patients with a suspected fracture of the scaphoid with negative radiographs. PATIENTS AND METHODS: Patients who presented to the emergency department (ED) with a suspected fracture of the scaphoid and negative radiographs were randomized to a control group, who did not undergo further imaging in the ED, or an intervention group, who had an MRI of the wrist as an additional test during the initial ED attendance. Most participants were male (52% control, 61% intervention), with a mean age of 36.2 years (18 to 73) in the control group and 38.2 years (20 to 71) in the intervention group. The primary outcome was total cost impact at three months post-recruitment. Secondary outcomes included total costs at six months, the assessment of clinical findings, diagnostic accuracy, and the participants' self-reported level of satisfaction. Differences in cost were estimated using generalized linear models with gamma errors. RESULTS: The mean cost up to three months post-recruitment per participant was £542.40 (sd £855.20, n = 65) for the control group and £368.40 (sd £338.60, n = 67) for the intervention group, leading to an estimated cost difference of £174 (95% confidence interval (CI) -£30 to £378; p = 0.094). The cost difference per participant increased to £266 (95% CI £3.30 to £528; p = 0.047) at six months. Overall, 6.2% of participants (4/65, control group) and 10.4% of participants (7/67, intervention group) had sustained a fracture of the scaphoid (p = 0.37). In addition, 7.7% of participants (5/65, control group) and 22.4% of participants (15/67, intervention group) had other fractures diagnosed (p = 0.019). The use of MRI was associated with higher diagnostic accuracy both in the diagnosis of a fracture of the scaphoid (100.0% vs 93.8%) and of any other fracture (98.5% vs 84.6%). CONCLUSION: The use of immediate MRI in the management of participants with a suspected fracture of the scaphoid and negative radiographs led to cost savings while improving the pathway's diagnostic accuracy and patient satisfaction. Cite this article: Bone Joint J 2019;101-B:984-994.

Dapoxetine, a novel treatment for premature ejaculation, does not have pharmacokinetic interactions with phosphodiesterase-5 inhibitors.

Potential pharmacokinetic interactions between dapoxetine, a serotonin transporter inhibitor developed for the treatment of premature ejaculation (PE), and the phosphodiesterase-5 inhibitors tadalafil and sildenafil, agents used in the treatment of erectile dysfunction (ED), were investigated in an open-label, randomized, crossover study (n=24 men) comparing dapoxetine 60 mg, dapoxetine 60 mg+tadalafil 20 mg, and dapoxetine 60 mg+sildenafil 100 mg. Plasma concentrations of dapoxetine, tadalafil, and sildenafil were determined by liquid chromatography-tandem mass spectrometry. Tadalafil did not affect the pharmacokinetics of dapoxetine, whereas sildenafil increased the dapoxetine AUCinf by 22%; these effects were deemed not clinically important. Dapoxetine did not appear to affect the pharmacokinetics of tadalafil or sildenafil. Most adverse events were mild in nature. Thus, dapoxetine has no clinically important pharmacokinetic interactions with tadalafil or sildenafil, and the combinations are well tolerated.

Recurrent dislocation of a posterior-stabilized prosthesis: a series of three cases.

We report three cases of recurrent posterior dislocation of primary posterior-stabilized total knee replacements. In all of the cases, reduction was not possible under sedation alone, and general anaesthesia was needed to allow disengagement of the components and reduction of the dislocation. In addition, it was noted in all cases that the ability of the patients to flex their knee replacement excessively contributed to the instability. The design of the prosthesis, and issues of operative technique are discussed with reference to this serious complication.

Management of paediatric clavicle fractures--is follow-up necessary? An audit of 346 cases.

We investigated the incidence of complications following childhood clavicle fractures and the necessity for follow-up in fracture clinic after the first orthopaedic consultation. We found that review in fracture clinic has no impact upon the outcome of clavicle fractures and complications such as non-union, mal-union or neurovascular problems are exceptionally rare. We concluded that there is no need for follow-up of children with isolated, uncomplicated clavicle fractures. These patients should be discharged after their first assessment in fracture clinic.

Socio-cultural factors affecting breast feeding and other infant feeding practices in an urban community.

PIP: A study of infant feeding practices was carried out as part of a larger longitudinal study of an urban birth cohort in an area of South Delhi, India. 802 mothers of children over 1 year of age were selected randomly for interview. The study group is considered to be a representative sampling of the economic, cultural, and ethnic groups within the population of all of Delhi. Breast feeding was almost universal but for varying durations. 5.5%, 11.7%, and 22.8% of the children were breast fed for less than 1 month, 2 months, and 6 months respectively. Literate and older mothers tended to breast feed for shorter periods of time. Illiterate mothers, on the other hand, tended to prolong breast feeding unduly. The sex of the infant and the duration of the urban stay of the mother did not seem to affect the duration of breast feeding. Supplementation with liquid feeds, 50% diluted buffalo milk in the majority of cases, was begun rather early but the introduction of semisolids and solids was very often unduly delayed. This was particularly true among illiterate mothers. Thus, it is felt that a concerted effort to educate mothers, especially illiterate and underprivileged mothers, regarding the role of breast feeding and the benefits of supplementation feeding would improve infant nutritional status.^ieng

Enhancement of transdermal penetration and bioavailability of poorly soluble acyclovir using solid lipid nanoparticles incorporated in gel cream.

The objective of this work was to increase the amount of acyclovir in the basal epidermis, site of herpes virus simplex infection, using the solid lipid nanoparticles loaded gel cream as carriers. Solid lipid nanoparticles were prepared by high pressure homogenisation method and incorporated in a semisolid submicron gel cream. Acyclovir distribution into rat skin after topical application of solid lipid nanoparticles loaded gel cream was determined by fabricated Franz diffusion cell. The results showed that, the quantity of the acyclovir in the basal epidermis with the solid lipid nanoparticles loaded submicron gel cream was two folds times more than marketed acyclovir gel cream. This type of carrier can improve acyclovir loaded therapy since it increases drug retention in the basal epidermis.

Preventing recurrence of radioulnar synostosis with pedicled adipofascial flaps.

The surgical treatment of post-traumatic radioulnar synostosis is difficult. Recurrence after resection alone is a concern with poor long-term maintenance of forearm rotation. We report on the use of pedicled adipofascial flaps to prevent recurrence and facilitate maintenance of movement in six adult patients with radioulnar synostosis. Five involved the proximal radioulnar joint and one the distal radioulnar joint. In four the flap was based on the radial artery and in two on the posterior interosseous artery. Mean intraoperative supination was 78° and pronation was 76°. Mean follow up was 32 months. At follow-up, mean supination was 71° and pronation was 70°. No patient had radiological recurrence of synostosis. The only complication was a transient posterior interosseous nerve palsy. Pedicled adipofascial flaps are a safe addition to resection alone which may prevent recurrence and maintain the range of forearm rotation achieved at operation.

Medical negligence in orthopaedic surgery: a review of 130 consecutive medical negligence reports.

Payments by the NHS Litigation Authority continue to rise each year, and reflect an increase in successful claims for negligence against NHS Trusts. Information about the reasons for which Trusts are sued in the field of trauma and orthopaedic surgery is scarce. We analysed 130 consecutive cases of alleged clinical negligence in which the senior author had been requested to act as an expert witness between 2004 and 2006, and received information on the outcome of 97 concluded cases from the relevant solicitors. None of the 97 cases proceeded to a court hearing. Overall, 55% of cases were abandoned by the claimants' solicitors, and the remaining 45% were settled out of court. The cases were settled for sums ranging from pound 4500 to pound 2.7 million, the median settlement being pound 45,000. The cases that were settled out of court were usually the result of delay in treatment or diagnosis, or because of substandard surgical technique.

Formulation and evaluation of pharmaceutically equivalent parenteral depot suspension of methyl prednisolone acetate.

The aim of the present study was to formulate and evaluate pharmaceutically equivalent injectable aqueous suspension for parenteral depot of methyl prednisolone acetate. Various aqueous suspensions were prepared by rapid stirring and colloid milling method. The prepared aqueous suspensions were subjected to particle size determination, sedimentation study, in vitro release studies (pH dependent dissolution study), and stability studies. The optimized formulation consisted of 4% w/w of methyl prednisolone acetate, 2.91% w/w of PEG-3350, 0.19% w/v of injection grade Tween-80, 0.68% w/w of monobasic sodium phosphate, 0.15% w/w of di-basic sodium phosphate, 0.91% w/v of benzyl alcohol, 0.32% w/w sodium meta bisulphate. The f(2) value was calculated for innovator (DepoMedrol( ((R)) ), Batch No. MPH-0254) and optimized formulation at pH 6.8 and pH 7.4 phosphate buffers. The f(2) values of 62.94 and 54.37 were obtained at pH 6.8 and pH 7.4 phosphate buffers respectively. The particle size ranged 23-27 mum at D value of 0.9 for both test and innovator product.

Evaluation of hydrophobic nanoparticulate delivery system for insulin.

Insulin loaded hydrophobic nanoparticles were prepared by solvent diffusion followed by lyophilization. Nanoparticles were characterized for mean size by dynamic laser scattering and for shape by scanning electron microscopy. Insulin encapsulation efficiency, in vitro stability of nanoparticles in presence of proteolytic enzymes and in vitro release were determined by high pressure liquid chromatography analysis. The biological activity insulin from the nanopraticles was estimated by enzyme-linked immunosorbant assay and in vivo using Wister diabetic rats. Nanoparticles ranged 0.526±0.071 µm in diameter. Insulin encapsulation efficiency was 95.7±1.2%. Insulin hydrophobic nanoparticles suppressed insulin release promoted sustained release in pH 7.4 phosphate buffer and shown to protect insulin from enzymatic degradation in vitro in presence of chymotripsin. Nanoencapsulated insulin was bioactive, demonstrated through both in vivo and in vitro.

Insulin-egg yolk dispersions in self microemulsifying system.

Formulation of insulin into a microemulsion very often presents a physicochemical instability during their preparation and storage. In order to overcome this lack of stability and facilitate the handling of these colloidal systems, stabilization of insulin in presence of hydrophobic components of a microemulsion appears as the most promising strategy. The present paper reports the use of egg yolk for stabilization of insulin in self microemulsifying dispersions. Insulin loaded egg yolk self microemulsifying dispersions were prepared by lyophilization followed by dispersion into self microemulsifying vehicle. The physicochemical characterization of selfmicroemulsifying dispersions includes such as insulin encapsulation efficiency, in vitro stability of insulin in presence of proteolytic enzymes and in vitro release. The biological activity of insulin from the dispersion was estimated by enzyme-linked immunosorbant assay and in vivo using Wistar diabetic rats. The particle size ranged 1.023±0.316 µm in diameter and insulin encapsulation efficiency was 98.2±0.9 %. Insulin hydrophobic self microemulsifying dispersions suppressed insulin release in pH 7.4 phosphate buffer and shown to protect insulin from enzymatic degradation in vitro in presence of chymotripsin. Egg yolk encapsulated insulin was bioactive, demonstrated through both in vivo and in vitro.

The detection of patients with 'fragility fractures' in fracture clinic - an audit of practice with reference to recent British Orthopaedic Association guidelines.

INTRODUCTION: The British Orthopaedic Association published guidelines on the care of fragility fracture patients in 2003. A section of these guidelines relates to the secondary prevention of osteoporotic fractures. The objective of this audit was to compare practice in our fracture clinic to these guidelines, and take steps to improve our practice if required. PATIENTS AND METHODS: We retrospectively audited the treatment of all 462 new patients seen in January and February 2004. Using case note analysis, 38 patients who had sustained probable fragility fractures were selected. Six months' post-injury, a telephone questionnaire was administered to confirm the nature of the injury and to find out whether the patient had been assessed, investigated or treated for osteoporosis. A second similar audit was conducted a year later after steps had been taken to improve awareness amongst the orthopaedic staff and prompt referral. RESULTS: During the first audit period, only 5 of 38 patients who should have been assessed and investigated for osteoporosis were either referred or offered referral. This improved to 23 out of 43 patients during the second audit period. CONCLUSIONS: Improvements in referral and assessment rates of patients at risk of further fragility fractures can be achieved relatively easily by taking steps to increase awareness amongst orthopaedic surgeons, although additional strategies and perhaps the use of automated referral systems may be required to achieve referral rates nearer 100%.

The effect of total hip replacement on the employment status of patients under the age of 60 years.

INTRODUCTION: A retrospective study was undertaken of a consecutive cohort of 86 patients (101 hips) under the age of 60 years operated on by a single orthopaedic team between 1993 and 2003 at a district general hospital. PATIENTS AND METHODS: Demographic and diagnostic data were collected from patients' hospital records, and a detailed questionnaire regarding occupational status was used at follow-up. RESULTS: Nearly all of the patients working prior to surgery returned to employment following surgery. Nearly half of those not working pre-operatively regained employment postoperatively; among those that did not return to work, this was for reasons unrelated to their hip. Those patients who had been out of work prior to their surgery took significantly longer to return to work. CONCLUSIONS: Our study demonstrates that total hip replacement is effective in keeping patients under the age of 60 years employed. It is also effective in allowing those already off work due to hip pain to return to work, although there is a much greater delay.

Do patients need to earn total knee arthroplasty?

Traditional orthopaedic thinking dictates that performing total knee arthroplasty (TKA) in patients with relatively early stages of osteoarthritis (OA) will lead to a poor outcome. Our goal was to test this perception, using radiologic parameters as a marker of the degree of OA. Our study involved 130 consecutive patients who underwent TKA for OA. The radiographs of each patient were graded according to the Ahlback classification. Outcome was measured prospectively using the Oxford Knee Score (OKS), which was recorded both preoperatively and 1 year after surgery. The degree of radiologic OA changes preoperatively was not found to influence the outcome of surgery at 1 year, with all patient groups improving to a similar extent. In addition, as has been seen in previous studies, no correlation was found between symptoms of OA and radiologic appearances. The results of this study would support a re-evaluation of traditional orthopaedic practice. This conclusion coincides with other recent work that suggests that TKA is underused and is performed too late in the natural history of OA of the knee.