Physical restraint: perceptions of nurse managers, registered nurses and healthcare assistants.

AIM: To examine the perceptions of nurse managers, registered nurses and healthcare assistants of physical restraint use on older people in a long-term care setting in the Republic of Ireland. BACKGROUND: The use of physical restraint, although controversial, persists in long-term care settings, despite recommendations for restraint-free environments. Perception and attitude of staff can influence use of physical restraint. METHODS: A descriptive cross-sectional design was used. A total of 250 nursing and healthcare assistant staff were recruited. A questionnaire incorporating demographics and the Perceptions of Restraint Use Questionnaire was used. Descriptive and inferential statistical analyses were conducted. RESULTS: Mean age of respondents (n = 156) was 41 years, and the majority were female. Overall, a low level of importance was attached to the use of restraint. Nurse managers and registered nurses compared favourably with healthcare assistants who attached a higher importance to use of restraint. Across all three staff groups, greatest importance was attached to the use of physical restraint for reducing falls, followed by prevention of treatment interference. Restraint was least favoured as a means of impairment management. Education was not an explanatory factor in perceived importance of physical restraint use. CONCLUSION: Nurse managers and registered nurses are unlikely to use physical restraint. However, there is concern regarding perception of healthcare assistants on use of restraint. IMPLICATIONS FOR NURSING AND HEALTH POLICY: Results from this study compare favourably with those in countries that have no policy on physical restraint use. Educational programmes alone are insufficient to address use of physical restraint. Attention to skill mix with adequate support for healthcare assistants in long-term care settings is recommended.

Scarf osteotomy without internal fixation for correction of hallux valgus: A clinical and radiographic review of 148 cases.

BACKGROUND: Hallux valgus is a common condition with in excess of 120 procedures described in the literature for its correction. Traditionally, distal metatarsal osteotomies have been employed in the treatment of mild deformities, with proximal osteotomies being reserved for more severe presentations. The Scarf osteotomy without internal fixation allows large translations which can successfully correct severe hallux valgus deformities, without limitations related to screw placement. METHODS: This is a retrospective single surgeon case series performed over a three year period. One hundred and forty-eight cases were identified, with an average follow up time of 16.5 months. Visual analogue scales were used to obtain preoperative and postoperative pain and cosmetic scores, with the Foot and Ankle Disability Index (FADI) index used to assess functional status. The hallux valgus angle (HVA) and intermetatarsal angle (IMA) were assessed on preoperative and postoperative AP weight-bearing foot X-rays. RESULTS: The mean pain score improved from 7.04/10 preoperatively to 0.29/10 postoperatively. The mean cosmetic score improved from 2.1/10 to 9.1/10 postoperatively. The mean preoperative HVA and IMA were 35.04° and 15.04°, respectively. The mean postoperative HVA and IMA were 11.54° and 4.83°, respectively. The mean postoperative FADI score was 103.4/104. We report a loss of correction in two cases. One revision surgery was performed. CONCLUSIONS: We report a large series of cases of the modified Scarf osteotomy as described by Maestro-a versatile, cost-effective, safe and reliable technique with the potential for three dimensional correction. Whilst this is a technically demanding procedure, we recommend the use of the modified Scarf osteotomy in the treatment of a wide range of hallux valgus deformities.

Medium term review of the ASR implant system: A single surgeon series.

INTRODUCTION: Both ASR hip resurfacings and stemmed ASR XL arthroplasties have failed at high rates in several published series. We assessed a single surgeon series of these arthroplasties looking to identify factors associated with their failure. METHODS: All surgeries were performed by one surgeon. Patients were evaluated clinically, radiologically and with serial cobalt and chromium ion analysis. RESULTS: 274 implants were analysed - 152 ASR resurfacings and 122 ASR XL implants. Thirty revisions were performed. CONCLUSION: The failure rate of the ASR implant in our series is unacceptably high - its use in routine hip arthroplasty cannot be supported.

A cost analysis of the establishment of a dedicated orthopaedic outpatient injection clinic at a single institution.

INTRODUCTION: Traditionally orthopaedic injections were performed in a theatre setting. A dedicated outpatient injection clinic was established at our institution to attempt to provide injections more cost effectively. Our aim was to perform a cost analysis of orthopaedic injections performed in theatre, compared to those performed in a dedicated OPD injection clinic. METHODS: Patient data for all orthopaedic injections performed at a single institution from 2013 to 2014 was obtained using HIPE data. A detailed breakdown of costings for two scenarios; those performed in theatre and those in the dedicated OPD injection clinic was obtained from the hospital finance department. A unit cost per injection for theatre and OPD was derived from this financial information. RESULTS: A total of 487 injections were performed in 2013, with 491 performed in 2014. 134 (27.5%) injections were performed in the OPD in 2013 compared to 388 (79%) in 2014. The unit cost per injection was calculated as €52.13 for theatre and €23.85 for OPD, this represented a 115% decrease in cost per injection. CONCLUSION: The creation of a dedicated orthopaedic injection clinic resulted in considerable cost savings at our institution. We propose this may be a more cost-efficient model for delivery of injections in the orthopaedic setting.

Early results of the LPS™ limb preservation system in the management of periprosthetic femoral fractures.

INTRODUCTION: Achieving skeletal fixation in the presence of progressive bone loss is a surgical challenge, especially in cases of periprosthetic fracture (PPF). Unpredictable fracture patterns and preexisting bone loss frequently combine in this patient group. Megaprosthetic arthroplasty allows for immediate mobilisation and shorter periods of rehabilitation. We describe the clinical outcomes of a cohort of LPS™ megaprostheses performed for PPF by a single surgeon at our institution. METHODS: Between July 2013 and November 2015, 23 patients underwent endoprosthetic femoral replacement of which 16 were performed for PPF or bone loss. Patient demographics, surgical indication, operative details, implant composition, blood loss, survival, and revision surgery details were recorded in a prospectively maintained database. Patients underwent serial clinical and X-ray evaluations at 6 weeks, 3 months and 6 months post surgery with yearly reviews thereafter. RESULTS: The PPF cohort consisted of 9 males and 7 females with a mean age of 75 and a mean follow up of 19.2 months. The mean Oxford score prior to fracture was 41 (range 12-48), and 39 (range 13-48, p = 0.6) post megaprosthesis insertion. Postoperative dislocation of the megaprosthesis occurred in two patients (12.5%), with no postoperative infections recorded. CONCLUSION: We report minimal postoperative changes in functional outcome scores. The results of revision arthroplasty with LPS™ proximal femur megaprosthesis were satisfactory in 15/16 patients at a mean follow-up of 19.2 months. We recommend the use of megaprostheses in patients with markedly deficient bone stock for whom other available reconstructive procedures are unavailable.

Stalled replication forks within heterochromatin require ATRX for protection.

Expansive growth of neural progenitor cells (NPCs) is a prerequisite to the temporal waves of neuronal differentiation that generate the six-layered neocortex, while also placing a heavy burden on proteins that regulate chromatin packaging and genome integrity. This problem is further reflected by the growing number of developmental disorders caused by mutations in chromatin regulators. ATRX gene mutations cause a severe intellectual disability disorder (α-thalassemia mental retardation X-linked (ATRX) syndrome; OMIM no. 301040), characterized by microcephaly, urogenital abnormalities and α-thalassemia. Although the ATRX protein is required for the maintenance of repetitive DNA within heterochromatin, how this translates to disease pathogenesis remain poorly understood and was a focus of this study. We demonstrate that Atrx(FoxG1Cre) forebrain-specific conditional knockout mice display poly(ADP-ribose) polymerase-1 (Parp-1) hyperactivation during neurogenesis and generate fewer late-born Cux1- and Brn2-positive neurons that accounts for the reduced cortical size. Moreover, DNA damage, induced Parp-1 and Atm activation is elevated in progenitor cells and contributes to their increased level of cell death. ATRX-null HeLa cells are similarly sensitive to hydroxyurea-induced replication stress, accumulate DNA damage and proliferate poorly. Impaired BRCA1-RAD51 colocalization and PARP-1 hyperactivation indicated that stalled replication forks are not efficiently protected. DNA fiber assays confirmed that MRE11 degradation of stalled replication forks was rampant in the absence of ATRX or DAXX. Indeed, fork degradation in ATRX-null cells could be attenuated by treatment with the MRE11 inhibitor mirin, or exacerbated by inhibiting PARP-1 activity. Taken together, these results suggest that ATRX is required to limit replication stress during cellular proliferation, whereas upregulation of PARP-1 activity functions as a compensatory mechanism to protect stalled forks, limiting genomic damage, and facilitating late-born neuron production.

Locally advanced rectal cancer: a cooperative surgical approach to a complex surgical procedure.

Single stage en bloc abdominoperineal resection and sacrectomy, with a myocutaneous flap closure is a relatively uncommon procedure. Our case study of a 77 year old man with a locally invasive rectal adenocarcinoma highlights the complex intraoperative management of such a patient.

Differential protein acetylation induced by novel histone deacetylase inhibitors.

Histone deacetylase (HDAC) inhibitors induce the hyperacetylation of nucleosomal histones in carcinoma cells resulting in the expression of repressed genes that cause growth arrest, terminal differentiation, and/or apoptosis. In vitro selectivity of several novel hydroxamate HDAC inhibitors including succinimide macrocyclic hydroxamates and the non-hydroxamate alpha-ketoamide inhibitors was investigated using isolated enzyme preparations and cellular assays. In vitro selectivity for the HDAC isozymes (HDAC1/2, 3, 4/3, and 6) was not observed for these HDAC inhibitors or the reference HDAC inhibitors, MS-275 and SAHA. In T24 and HCT116 cells these compounds caused the accumulation of acetylated histones H3 and H4; however, the succinimide macrocyclic hydroxamates and the alpha-ketoamides did not cause the accumulation of acetylated alpha-tubulin. These data suggest "selectivity" can be observed at the cellular level with HDAC inhibitors and that the nature of the zinc-chelating moiety is an important determinant of activity against tubulin deacetylase.

Smoking and drinking among 15-16-year-old girls: do male peers have an influence?

BACKGROUND: During adolescence, people tend to begin drinking alcohol and become involved in the culture that surrounds it. AIM: To compare the influence of peer relationships among females in mixed-sex schools versus single-sex schools on cigarette smoking and alcohol consumption. METHODS: A cross-sectional study was carried out in four schools. The information was collected by means of a questionnaire. RESULTS: Two hundred and forty-eight questionnaires were completed. Of those questioned in single-sex schools, 34% had smoked a cigarette compared with 61% in mixed-sex schools (p < 0.005). The lifetime prevalence of alcohol consumption in mixed-sex schools was 88% compared with 73% in single-sex schools (p < 0.005). CONCLUSION: This study suggests that females in mixed-sex schools have a tendency to have earlier exposure to smoking and alcohol consumption than girls of the same age in single-sex schools.

Travels in Japan.

Following his attendance at the ICMART meeting, in Myasaki in 1988, the author, a BMAS member, resolved to revisit Japan. He found that acupuncture was widely practised throughout the country; although the patients were in the main elderly. The range of techniques used ranged from TCM to western, and broadly mirrored the styles practised in the West. Most young people in Japan considered acupuncture to be rather old fashioned, and it is postulated that this contrasts with the population seeking complementary medicine in the West.

Biaryl ether retrohydroxamates as potent, long-lived, orally bioavailable MMP inhibitors.

A novel series of biaryl ether reverse hydroxamate MMP inhibitors has been developed. These compounds are potent MMP-2 inhibitors with limited activity against MMP-1. Select members of this series exhibit excellent pharmacokinetic properties with long elimination half-lives (7 h) and high oral bioavailability (100%).

Discovery and characterization of the potent, selective and orally bioavailable MMP inhibitor ABT-770.

Modification of the biphenyl portion of MMP inhibitor 2a gave analogue 2i which is greater than 1000-fold selective against MMP-2 versus MMP-1. The stereospecific synthesis of both enantiomers of 2i was achieved beginning with (S)- or (R)-benzyl glycidyl ether. The (S)-enantiomer, 11 (ABT-770), is orally bioavailable and efficacious in an in vivo model of tumor growth.

A comparison of the effects of patient-controlled analgesia with intravenous opioids versus Epidural analgesia on recovery after surgery for idiopathic scoliosis.

STUDY DESIGN: Epidural infusion was compared with standard patient-controlled analgesia (PCA) in 50 patients after surgical correction of adolescent idiopathic scoliosis with respect to certain postoperative parameters. OBJECTIVES: To compare postoperative parameters after posterior spinal instrumentation and fusion (PSIF) and to determine whether epidural infusion prolongs hospital stay or increases the risk of complications. SUMMARY OF BACKGROUND DATA: Patient-controlled analgesia and epidural infusion are both safe and effective in controlling postoperative pain after PSIF. One criticism of epidural infusion has been longer hospital stays. No study was found in the literature in which PCA was compared with epidural infusion. METHODS: The records of 50 consecutive patients who had undergone PSIF were reviewed. The epidural group consisted of 30 patients and the PCA group 20. Age, weight, degree of curve, and levels fused were evenly matched. Postoperative parameters including the day that each patient tolerated a full diet, day of independent ambulation, length of hospital stay, and pain control were compared. RESULTS: Pain control was comparable in each group. The epidural group tolerated a full diet earlier and on average were discharged 0.5 days sooner than the PCA group. Both differences are statistically significant. No significant complications were reported in either group. CONCLUSIONS: Epidural infusion of opioids with bupivacaine is safe and effective for controlling postoperative pain after PSIF without an increased complication rate when compared with PCA. In the current study, patients tolerated a full diet and were discharged from the hospital an average of 0.5 days earlier than PCA-treated patients.

Evaluation of the inhibition of other metalloproteinases by matrix metalloproteinase inhibitors.

Two series of compounds synthesized as specific matrix metalloproteinase (MMP) inhibitors have been evaluated for their inhibition of non-MMPs. In a series of substituted succinyl hydroxamic acids, some were found to be significant (IC50 < 1 microM) inhibitors of leucine (microsomal) aminopeptidase, neprilysin (3.4.24.11), and thermolysin. Macrocyclic compounds in which the alpha carbon of the succinyl hydroxamate is linked to the side chain of the P2' amino acid were found to be good inhibitors of aminopeptidase, but not of neprilysin or thermolysin. Compounds of neither series were found to be significant inhibitors of angiotensin converting enzyme or carboxypeptidase A.

Recent advances in matrix metalloproteinase inhibitors research.

Excess MMP proteolytic activity has been associated with a wide variety of pathological conditions such as arthritis, cancer and heart failure. The potential utility of MMP inhibitors as therapeutic interventions in these diverse and important disease states has led to an intense effort toward the development of such inhibitors. The first generation of compounds were peptide-like broad spectrum inhibitors, active against a broad range of MMPs. However, the induction of musculoskeletal side effects seen in clinical trials with these agents has emphasized the need for a better understanding of the role that each of the MMPs plays in normal tissue turnover and disease progression. Advances in our ability to engineer and synthesize selective inhibitors as well as the discovery of small molecule, non-peptidic inhibitors has spurred an intense effort to identify potent and bioavailable second generation compounds. There are now several such compounds targeted against various subsets of the MMPs in clinical development. This review will focus on the design and structure activity relationships of these second generation compounds.

The role of platelet-activating factor (PAF) and the efficacy of ABT-491, a highly potent and selective PAF antagonist, in experimental allergic rhinitis.

Platelet-activating factor (PAF) may be an important mediator of allergic rhinitis. In the present study we evaluated the effectiveness of a recently described PAF antagonist (ABT-491) in rat and guinea pig models of allergic rhinitis. PAF, when perfused through the nasal passages of anesthetized Brown Norway rats, provoked an acute increase, measured as dye leakage, in nasal vascular permeability evident within 15 min after exposure to PAF. ABT-491, given orally 1 hr before PAF challenge, inhibited the response in a dose-related manner (ED50 = 0.3 mg/kg). Intranasal perfusion with ovalbumin in rats sensitized to the antigen 18 to 21 days before challenge also induced an increase in vascular permeability. The antigen-induced leakage was inhibited a maximum of 74% (P < or = .001) by pretreatment with ABT-491 (3 mg/kg p.o.). An antihistamine (mepyramine, 10 mg/kg i.p.), a serotonin antagonist (methysergide) and a 5-lipoxygenase inhibitor (A-79175) also exhibited efficacy in this model (56%, 87% and 65% inhibition, respectively). Nearly complete inhibition (93%, P < or = .001) of the response was achieved by coadministration of ABT-491 and methysergide. In guinea pigs intranasal administration of PAF resulted in increased airway resistance that was inhibited in a dose-dependent manner by oral administration of ABT-491 (ED50 = 1 mg/kg). Antigen-induced nasal airway resistance, triggered by exposure of sensitized animals to aerosolized ovalbumin, was also inhibited by ABT-491 (maximum inhibition 64%, P < or = .05, 10 mg/kg p.o.). The effectiveness of the antagonist was increased to 80% protection by coadministration with either an antihistamine or a 5-lipoxygenase inhibitor, agents which were separately insignificant in blocking the response to antigen. These results suggest a therapeutic utility for ABT-491, perhaps in combination with other anti-inflammatory agents, in the treatment of allergic rhinitis.

Discovery and evaluation of a series of 3-acylindole imidazopyridine platelet-activating factor antagonists.

Studies conducted with the goal of discovering a second-generation platelet-activating factor (PAF) antagonist have identified a novel class of potent and orally active antagonists which have high aqueous solubility and long duration of action in animal models. The compounds arose from the combination of the lipophilic indole portion of Abbott's first-generation PAF antagonist ABT-299 (2) with the methylimidazopyridine heterocycle moiety of British Biotechnology's BB-882 (1) and possess the positive attributes of both of these clinical candidates. Structure-activity relationship (SAR) studies indicated that modification of the indole and benzoyl spacer of lead compound 7b gave analogues that were more potent, longer-lived, and bioavailable and resulted in the identification of 1-(N, N-dimethylcarbamoyl)-4-ethynyl-3-[3-fluoro-4-[(1H-2-methylimidazo[4,5-c] pyrid-1-yl)methyl]benzoyl]indole hydrochloride (ABT-491, 22 m.HCl) which has been evaluated extensively and is currently in clinical development.

Broad spectrum matrix metalloproteinase inhibitors: an examination of succinamide hydroxamate inhibitors with P1 C alpha gem-disubstitution.

A series of P1 C alpha gem-disubstituted succinamide hydroxamate matrix metalloproteinase inhibitors were prepared stereoselectively and evaluated in vitro for their ability to inhibit MMP-1, MMP-2, and MMP-3. It was found that while methyl/allyl substitution as in 2 and 18 provided compounds that were broad spectrum inhibitors and nearly equipotent with parent inhibitor 1, a larger group such as bis-allyl as in 13 or gem-cyclopentyl as in 14 significantly reduced enzyme inhibition.

The design, synthesis, and structure-activity relationships of a series of macrocyclic MMP inhibitors.

A series of succinate-derived hydroxamic acids incorporating a macrocyclic ring were designed, synthesized, and evaluated as inhibitors of matrix metalloproteinases. The inhibitors were designed based on the published X-ray crystal structure of batimastat (1) complexed with human neutrophil collagenase (MMP-8). The synthesized compounds were shown to inhibit selected MMPs in vitro with low nanomolar potency.