A Retrospective Service- Evaluation of Implant Success, Survival, Periimplant Health and Prosthetic Complications in a Cohort of Head and Neck Cancer Patients.

OBJECTIVES: To determine the success, survival, peri-implant health and prosthetic complications in head and neck cancer patients receiving oral rehabilitation utilising dental implants between 2008 and the present day. MATERIALS AND METHODS: Service evaluation. Survival Group: Retrospective review of records to determine implant survival and prosthetic complications. Success Group: Examination to determine implant success and health. RESULTS: Survival Group: 260 implants in 81 individuals, median follow up 49.2 months. 89.3% implant survival at 96 months, no further failures up to 133 months. 40.9% individuals required repair or remake of prosthesis by 72 months - mostly denture re-lines. Success group: 164 implants in 48 individuals, median follow up 56 months. Peri-implant mucositis detected in 22% of fixtures (37.5% individuals); peri-implantitis in 12.8% (25% individuals); 33.3% fixtures exhibiting periimplantitis at 120 months. Previous smoking significantly associated with development of peri-implantitis (HR 2.372, p=0.032, 95CI:1.232, 93.317). Compromised survival (e.g. peri-implantitis), absolute (not in mouth) or clinical failure estimated to occur in 28.1% fixtures at 101 months, mostly due to peri-implantitis. CONCLUSIONS: There is a large burden of ongoing care in this cohort, requiring interventions to improve peri-implant health and maintain complex prostheses. Oral rehabilitation and ongoing maintenance in this cohort is complex and multi-disciplinary.

WHO guide to good prescribing is 25 years old: quo vadis?

INTRODUCTION: Twenty-five years ago, the World Health Organization (WHO) published the Guide to Good Prescribing (GGP), followed by the accompanying Teacher's Guide to Good Prescribing (TGGP). The GGP is based on a normative 6-step model for therapeutic reasoning and prescribing, and provides a six-step guide for students to the process of rational prescribing. METHOD: We reviewed the need to update both WHO publications by evaluating their use and impact, including new (theoretical) insights and demands. Based on information from literature, Internet, and other (personal) sources, we draw the following conclusions. RESULTS: 1. An update of the GGP and TGGP, both in terms of content and form, is necessary because of the current need for these tools (irrational medicine use and unavailability of medicines), the lack of similar documents, and the lack of connection with recent developments, such as Internet and modern education; 2. The basic (6-step) model of the GGP is effective in terms of rational prescribing in the undergraduate situation and is still consistent with current theories about (context) learning, clinical decision-making, and clinical practice; 3. The dissemination and introduction of the GGP and TGGP in education has been successful so far, but is still not optimal because of lack of support and cooperation. CONCLUSIONS: On the basis of the evaluation results, a plan for the revision of the GGP and TGGP is presented.

Stacked volume holographic gratings for extending the operational wavelength range in LED and solar applications.

A novel stacking procedure is presented for volume phase holographic gratings (VPHGs) recorded in photopolymer material using Corning Willow Glass as a flexible substrate in order to achieve broader angular and spectral selectivity in a diffractive device with high efficiency for solar and LED applications. For the first time to our knowledge, we have shown a device designed for use with a white LED that has the same input and output angles and high efficiency when illuminated by different wavelengths. In this paper, two VPHGs were designed, experimentally recorded, and tested when illuminated at normal incidence. The experimental approach is based on stacking two individual gratings in which the spatial frequency and slant have been tailored to the target wavelength and using real-time on-Bragg monitoring of the gratings in order to control the recorded refractive index modulation, thereby optimizing each grating efficiency for its design wavelength. Lamination of the two gratings together was enabled by using a flexible glass substrate (Corning Willow Glass). Recording conditions were studied in order to minimize the change in diffraction efficiency and peak diffraction angle during lamination and bleaching. The final fabricated stacked device was illuminated by a white light source, and its output was spectrally analyzed. Compared to a single grating, the stacked device demonstrated a twofold increase in angular and wavelength range. The angular and wavelength selectivity curves are in good agreement with the theoretical prediction for this design. This approach could be used to fabricate stacked lenses for white light LED or solar applications.

Effectiveness of an mHealth application to improve hypertension health literacy in India.

AIM: The purpose of this research was to determine the effectiveness of a mobile health or mHealth application to improve hypertension health literacy among vulnerable populations in India. Additionally, we sought to estimate relationships between participant knowledge on hypertension and sociodemographic variables. BACKGROUND: The World Health Organization advocates for the use of mobile technology to improve public health outcomes. INTRODUCTION: The incidence of hypertension is on the rise in India, and effective and sustainable interventions are needed. METHODS: A quantitative single arm pre-test post-test interventional and correlational design was used to test the hypertension mHealth application among participants in a limited resource setting. A paired t-test was performed to compare pre- and post-test results after participant use of the mHealth application. A regression model was used to estimate relationships between participant hypertension health literacy and sociodemographic variables. RESULTS: A statistically significant improvement in test scores among participants after use of the mHealth app was found. Sociodemographic characteristics such as living in an urban environment, married, increased number of people living in household and alcohol use were determined to have a statistically significant effect on improvement of test score. DISCUSSION: Results indicated the application was effective among participants with varied literacy and health literacy levels. These findings contribute to the potential widespread scalability of the app among populations with varied demographics. CONCLUSION: This application provides an effective and valuable culturally tailored educational resource for nurses and other health providers to use to improve hypertension health literacy among vulnerable populations in India. IMPLICATIONS FOR NURSING PRACTICE AND HEALTH POLICY: This study contributes to nursing and health policy by answering a call from the World Health Organization to implement and research mHealth interventions to improve health outcomes, particularly in a low and middle income country where preventive health access is limited.

The impact of simulation education on self-efficacy towards teaching for nurse educators.

AIM: The objective of this study was to assess the impact of a simulation workshop on self-efficacy towards teaching for nurse educators in India. Additionally, we sought to revise and validate a tool to measure self-efficacy in teaching for use with a global audience. BACKGROUND: Simulation is an evidence-based teaching and learning method and is increasingly used in nursing education globally. INTRODUCTION: As new technology and teaching methods such as simulation continue to evolve, it is important for new as well as experienced nurse educators globally to have confidence in their teaching skills and abilities. METHODS: The study included (1) instrument revision, and measures of reliability and validation, (2) an 8-h faculty development workshop intervention on simulation, (3) pre- and post-survey of self-efficacy among nurse educators, and (4) investigation of relationship between faculty socio-demographics and degree of self-efficacy. RESULTS: The modified tool showed internal consistency (r = 0.98) and was validated by international faculty experts. There were significant improvements in total self-efficacy (P < 0.001) and subscale scores among nurse educators after the simulation workshop intervention when compared to pre-survey results. No significant relationships were found between socio-demographic variables and degree of self-efficacy. DISCUSSION: Strong self-efficacy in teaching among nurse educators is crucial for effective learning to occur. CONCLUSIONS AND IMPLICATIONS FOR NURSING: Results indicated the simulation workshop was effective in significantly improving self-efficacy towards teaching for nurse educators using an internationally validated tool. IMPLICATIONS FOR NURSING POLICY: The Minister of Health in India recently called for improvements in nursing education. Introducing nursing education on simulation as a teaching method in India and globally to improve self-efficacy among teachers is an example of a strategy towards meeting this call.

Platelet responses to agonists in a cohort of highly characterised platelet donors are consistent over time.

BACKGROUND AND OBJECTIVES: Platelet function shows significant inheritance that is at least partially genetically controlled. There is also evidence that the platelet response is stable over time, but there are few studies that have assessed consistency of platelet function over months and years. We aimed to measure platelet function in platelet donors over time in individuals selected from a cohort of 956 donors whose platelet function had been previously characterised. MATERIALS AND METHODS: Platelet function was assessed by flow cytometry, measuring fibrinogen binding and P-selectin expression after stimulation with either cross-linked collagen-related peptide or adenosine 5'-diphosphate. Eighty-nine donors from the Cambridge Platelet Function Cohort whose platelet responses were initially within the lower or upper decile of reactivity were retested between 4 months and five and a half years later. RESULTS: There was moderate-to-high correlation between the initial and repeat platelet function results for all assays (P ≤ 0·007, r2 0·2961-0·7625); furthermore, the range of results observed in the initial low and high responder groups remained significantly different at the time of the second test (P ≤ 0·0005). CONCLUSION: Platelet function remains consistent over time. This implies that this potential influence on quality of donated platelet concentrates will remain essentially constant for a given donor.

A model for upscaling global partnerships and building nurse and midwifery capacity.

AIM: To provide a unique model for use in guiding global collaboration and policy to upscale nursing and midwifery partnerships. BACKGROUND AND INTRODUCTION: Nurses and midwives across nations need skills reaching beyond the bedside and unit level in today's complex, global, multifaceted healthcare milieu. Thoughtful consideration, research and concomitant development of models to guide appropriate upscaling of nurse and midwifery capacity within and between nations are needed. DISCUSSION: This article explores an integrated global approach to upscaling nurse and midwifery capacity using examples of partnerships between nursing and midwifery programmes across multiple continents. CONCLUSION AND IMPLICATIONS FOR NURSING: Global nurse and midwifery capacity is effectively being developed using a myriad of approaches. A new model is presented to illustrate supports, strategies and activities to achieve intermediate and long-term goals for capacity building through strong and sustainable global partnerships. IMPLICATION FOR NURSING POLICY: Development of global skills can focus the nurse and midwife to influence policy-level decisions. Human resource planning that can impact countrywide provision of health care begins in the preservice setting for both nurses and midwives. A global experience can be a value-added component to the well-rounded education of future nurses. Education during preparation for entry into practice is a strategic way to develop a worldview. Incorporating reflective practice can build skills and shape attitudes to prepare the new nurse to be comfortable as a global healthcare provider. An expanded world view is the springboard to more robust and informed involvement and inclusion in policy-level discussions.

Assortative mating but no evidence of genetic divergence in a species characterized by a trophic polymorphism.

Disruptive selection is a process that can result in multiple subgroups within a population, which is referred to as diversification. Foraging-related diversification has been described in many taxa, but many questions remain about the contribution of such diversification to reproductive isolation and potentially sympatric speciation. Here, we use stable isotope analysis of diet and morphological analysis of body shape to examine phenotypic divergence between littoral and pelagic foraging ecomorphs in a population of pumpkinseed sunfish (Lepomis gibbosus). We then examine reproductive isolation between ecomorphs by comparing the isotopic compositions of nesting males to eggs from their nests (a proxy for maternal diet) and use nine microsatellite loci to examine genetic divergence between ecomorphs. Our data support the presence of distinct foraging ecomorphs in this population and indicate that there is significant positive assortative mating based on diet. We did not find evidence of genetic divergence between ecomorphs, however, indicating that isolation is either relatively recent or is not strong enough to result in genetic divergence at the microsatellite loci. Based on our findings, pumpkinseed sunfish represent a system in which to further explore the mechanisms by which natural and sexual selection contribute to diversification, prior to the occurrence of sympatric speciation.

Interventions for hidradenitis suppurativa: a Cochrane systematic review incorporating GRADE assessment of evidence quality.

More than 50 interventions have been used to treat hidradenitis suppurativa (HS), and so therapy decisions can be challenging. Our objective was to summarize and appraise randomized controlled trial (RCT) evidence for HS interventions in adults. Searches were conducted in Medline, Embase, CENTRAL, LILACS, five trials registers and abstracts from eight dermatology conferences until 13 August 2015. Two review authors independently assessed study eligibility, extracted data and assessed methodological quality. Primary outcomes were quality of life and adverse effects of the interventions. Twelve trials, from 1983 to 2015, investigating 15 different interventions met our inclusion criteria. The median trial duration was 16 weeks and the median number of participants was 27. Adalimumab 40 mg weekly improved the Dermatology Life Quality Index (DLQI) by 4·0 points, which equates to the minimal clinically important difference for the scale, compared with placebo (95% confidence interval -6·5 to -1·5 points). Evidence quality was reduced to 'moderate' because the results are based on only a single study. Adalimumab 40 mg every other week was ineffective in a meta-analysis of two studies comprising 124 participants. Infliximab 5 mg kg(-1) improved the DLQI score by 8·4 points after 8 weeks in a moderate-quality study completed by 33 of 38 participants. Etanercept 50 mg twice weekly was ineffective. Inclusion of a gentamicin sponge prior to primary closure did not improve outcomes. Other interventions, including topical and oral antibiotics, were investigated by relatively small studies, preventing treatment recommendations due to imprecision. More, larger RCTs are required to investigate most HS interventions, particularly oral treatments and surgical therapy. Moderate-quality evidence suggests that adalimumab given weekly and infliximab are effective, whereas adalimumab every other week is ineffective.

Nanoparticles for controlled delivery and sustained release of chlorhexidine in the oral environment.

OBJECTIVES: Chlorhexidine (CHX) is in widespread use as a topical antimicrobial agent. Within the field of oral medicine, it is used in the prevention of ventilator-associated pneumonia as well as in the treatment of oral candidosis and microbial-associated lichenoid reactions. The objective of this study was to develop a strategy for controlled, sustained topical delivery of CHX using nanoparticle technology. METHODS: Chlorhexidine was applied to hydroxyapatite, selected as a tooth analogue, as conventional CHX digluconate solutions and as aqueous suspensions of CHX hexametaphosphate nanoparticles with total CHX concentrations of 1, 2.2 and 5 mM. Soluble CHX release from the treated hydroxyapatite was monitored over a period of 7 days. RESULTS: A repeated-measures ANOVA with post hoc LSD test indicated that CHX release was 2-3× greater, and sustained for longer, when CHX was delivered as CHX hexametaphosphate nanoparticles than in aqueous solution with 2.2 and 5 mM CHX (P = 0.020 and 0.013, respectively), but there was no statistically significant difference at 1 mM CHX (P = 0.172). CONCLUSIONS: Chlorhexidine hexametaphosphate nanoparticles increased both the local dose and duration of soluble CHX delivery when applied to hydroxyapatite surfaces. This may provide a means to deliver a sustained dose of CHX with less frequent interventions.

Student nurses' perceived challenges of nursing in India.

BACKGROUND: A profound nursing shortage exists in India. Increasingly nursing students in India are opting to migrate to practise nursing abroad upon graduation. Perceptions and attitudes about nursing are shaped during student experiences. PURPOSE: The purpose in conducting this research was to illuminate student nurses' perceived challenges of nursing in India. SETTING AND SAMPLE: This study took place at a hospital-based, private mission non-profit school of nursing in Bengaluru, India. Purposive sampling of nursing students yielded 14 participants. METHODS: Photovoice, a qualitative participatory action research methodology, was used. Data were collected between August 2013 and January 2014. A strong international collaboration between researchers resulted in qualitative thematic interpretation of photographs, critical group dialogue transcripts, individual journal entries and detailed field notes. RESULTS: Two main themes were identified including the perceived challenges of a hierarchal system and challenges related to limited nursing workforce capacity. Subcategories of a hierarchal system included challenges related to image, safety, salary and balance. Subcategories of limited workforce capacity were migration, work overload, physical demand, incongruence between theory and practice, and knowledge. DISCUSSION: Nursing as a profession in India is still in its infancy when measured against standard criteria. IMPLICATIONS FOR HEALTH POLICY: Change in health policy is needed to improve salary, safety for nurses, and nurse to patient ratios to address hierarchal and workforce capacity challenges in India.

Barriers and enablers to implementing police mental health co-responder programs: A qualitative study using the consolidated framework for implementation research.

Background: Police and mental health co-responder programs operate internationally and can be effective in providing timely and appropriate assessment, brief intervention, and referral services for people experiencing mental health crises. However, these models vary greatly, and little is known about how the design and implementation of these programs impacts their effectiveness. Method: This study was a qualitative, post hoc implementation determinant evaluation of mental health co-responder units in Brisbane, Australia, comprising of verbal or written interviews with police and mental health staff with an on-road role in the co-responder units, and their managers. The Consolidated Framework for Implementation Research was used to identify barriers and enablers to the program's implementation and effectiveness. Results: Participants (n = 30) from all groups felt strongly that the co-responder units are a substantial improvement over the usual police management of mental health crisis cases, and lead to better outcomes for consumers and the service. Enablers included an information-sharing agreement; the Mental Health Co-Responder (MHCORE) program's compatibility with existing police and mental health services; and the learning opportunity for both organizations. Barriers included cultural differences between the organizations, particularly risk-aversion to suicidality for police and a focus on least-restrictive practices for health; extensive documentation requirements for health; and a lack of specific mental health training for police. Conclusions: Using an evidence-based implementation science framework enabled identification of a broad range of contextual barriers and enablers to implementation of police mental health co-responder programs. Adapting the program to address these barriers and enablers during the planning, implementation, monitoring, and evaluation phases increases the likelihood of the service's effectiveness. These findings will inform the spread and scale of the co-responder program across Queensland, and will be relevant to police districts internationally considering implementing a co-responder program.

A large and rising proportion of calls to police relate to mental health crises, however police lack the resources, knowledge, training and supports to effectively address these crises. In Brisbane, Australia people in mental health crisis who are attended by police are routinely transported under an Emergency Examination Authority to a hospital emergency department. This is time-consuming for both the consumer and police, may be stressful or distressing for the consumer, and can put pressure on emergency departments. Co-responder programs team a senior mental health clinician with a senior police officer. There is evidence that a qualified and experienced mental health clinician providing people in mental health crisis with a timely assessment and brief intervention in the field, and where appropriate, referral to support services, leads to better outcomes for the consumer, reduced hospital transport, reduced time per case, and reduced overall service costs. Although many papers have been written evaluating the outcomes of these programs, few have considered factors that impact the implementation, effectiveness, and sustainment of co-responder teams. We used an implementation science approach based on the Consolidated Framework for Implementation Research to identify barriers to and enablers of mental health co-responder program implementation within an Australian metropolitan setting. Understanding these barriers and enablers allows a more streamlined, better-informed roll-out of future programs, and adaptation of existing models to improve effectiveness. The results will be relevant for any police district considering implementing a mental health co-responder program. They will also be used to inform the ongoing program.

Novel optical fiber design for low-cost optical interconnects in consumer applications.

We propose a novel fiber design optimized for short-reach interconnects in consumer applications. A detailed analysis of the optical and mechanical properties of this fiber design is presented. Results are presented demonstrating (i) low bend loss and enhanced mechanical reliability in bends as small as 3 mm diameter; (ii) high power budget margin to enable relaxed mechanical tolerances on transmitter, receiver, and expanded-beam connectors for low-cost connectivity; and (iii) high bandwidth capability and system testing results at 10 Gb/s.

Dietary carotenoid levels affect carotenoid and retinoid allocation in female Chinook salmon Oncorhynchus tshawytscha.

This study examined the effect of dietary carotenoid availability on carotenoid and retinoid concentrations in the flesh, plasma, skin and eggs of female Chinook salmon Oncorhynchus tshawytscha. Carotenoid concentrations in all tissues were closely related to dietary availability. Early in the breeding season, carotenoids were stored primarily in the muscle, with a flesh carotenoid concentration of 9.9 microg g(-1) in fish fed a high carotenoid diet compared with 1.9 microg g(-1) in fish fed a low carotenoid diet. During the breeding season, carotenoid reserves were mobilized predominantly to the eggs and also to the skin. By the end of the breeding season, carotenoid concentrations in the eggs were 17.9 microg g(-1) in fish fed a high carotenoid diet and 3.9 microg g(-1) in fish fed a low carotenoid diet. Conversely, egg retinoid concentrations were only c. 20% lower in fish fed a low v. high carotenoid diet, which suggests that retinoid concentrations were not limited by the availability of carotenoid precursors. Egg carotenoid concentrations were not correlated with either skin carotenoid concentration or colouration, which suggests that female carotenoid displays are not a reliable signal that males can use to evaluate egg carotenoid resources.

Prevalence of HIV indicator conditions in late presenting patients with HIV: a missed opportunity for diagnosis?

AIM: To evaluate prior prevalence of HIV indicator conditions in late-presenters with HIV infection. DESIGN: Retrospective cohort study between 2000 and 2014 in a healthcare network in Melbourne, Australia comparing patients presenting with late diagnosis of HIV infection (CD4 < 350 cells/ml) to those patients who had a CD greater than or equal to 350 cells/ml at presentation. METHOD: The European AIDS Clinical Society guidelines on HIV indicator guided testing were used to assess for any indicator conditions in their prior medical history which may have represented a missed opportunity for earlier diagnosis. Main outcome measures: Descriptive statistics and prevalence of HIV indicator conditions. RESULTS: Of 436 patients with HIV infection, 82 were late presenters. Late presenters were more commonly male (83% vs. 75%, P = 0.11), older (mean age 45 vs. 39 years), born overseas (61% vs. 58%, P = 0.68) and report heterosexual transmission as their exposure risk (51% vs. 31%, P < 0.001). Of 80 patients with late presentation of HIV infection, 54 (55%) had at least one, 29 (36%) at least 2, 12 (15%) at least 3 and 5 (6%) had 4 or more previous HIV indicator conditions which would have triggered HIV testing according to guidelines. The most common indicator conditions were: unexplained loss of weight (31%), herpes zoster (10%), thrombocytopenia or leukopenia (10%), oral or oesophageal candidiasis (10%) and community acquired pneumonia (9%). Twenty patients (25%) had HIV indicator conditions diagnosed at least 12 months before the eventual diagnosis of HIV infection. DISCUSSION/ CONCLUSION: Patients diagnosed with late-presenting HIV often had an HIV indicator condition prior to presentation, presenting a missed opportunity for earlier diagnosis.

The MHC and non-random mating in a captive population of Chinook salmon.

Detailed analysis of variation in reproductive success can provide an understanding of the selective pressures that drive the evolution of adaptations. Here, we use experimental spawning channels to assess phenotypic and genotypic correlates of reproductive success in Chinook salmon (Oncorhynchus tshawytscha). Groups of 36 fish in three different sex ratios (1:2, 1:1 and 2:1) were allowed to spawn and the offspring were collected after emergence from the gravel. Microsatellite genetic markers were used to assign parentage of each offspring, and the parents were also typed at the major histocompatibility class IIB locus (MHC). We found that large males, and males with brighter coloration and a more green/blue hue on their lateral integument sired more offspring, albeit only body size and brightness had independent effects. There was no similar relationship between these variables and female reproductive success. Furthermore, there was no effect of sex ratio on the strength or significance of any of the correlations. Females mated non-randomly at the MHC, appearing to select mates that produced offspring with greater genetic diversity as measured by amino-acid divergence. Females mated randomly with respect to male genetic relatedness and males mated randomly with respect to both MHC and genetic relatedness. These results indicate that sexual selection favours increased body size and perhaps integument coloration in males as well as increases genetic diversity at the MHC by female mate choice.

Nitric oxide production and perivascular nitration in brain after carbon monoxide poisoning in the rat.

Nitric oxide is a short-lived free radical and physiological mediator which has the potential to cause cytotoxicity. Studies were conducted to investigate whether nitric oxide, and the potent oxidant peroxynitrite, were generated in brain during experimental carbon monoxide (CO) poisoning in the rat. Nitric oxide production was documented by electron paramagnetic resonance spectroscopy, and found to be increased by ninefold immediately after CO poisoning. Evidence that peroxynitrite was generated was sought by looking for nitrotyrosine in the brains of CO-poisoned rats. Nitrotyrosine was found deposited in vascular walls, and also diffusely throughout the parenchyma in inummocytochemical studies. The affinity and specificity of an anti-nitrotyrosine antibody was investigated and a solid phase immunoradiochemical assay was developed to quantity nitrotyrosine in brain homogenates. A 10-fold increase in nitrotyrosine was found in the brains of CO-poisoned rats. Platelets were involved with production of nitrotyrosine in the early phase of exposure to CO. However, nitrotyrosine formation and leukocyte sequestration were not decreased in thrombocytopenic rats poisoned with CO according to the standard model. When rats were pre-treated with the nitric oxide synthase inhibitor, L-nitroarginine methyl ester, formation of both nitric oxide and nitrotyrosine in response to CO poisoning were abolished, as well as leukocyte sequestration in the microvasculature, endothelial xanthine dehydrogenase conversion to xanthine oxidase, and brain lipid peroxidation. We conclude that perivascular reactions mediated by peroxynitrite are important in the cascade of events which lead to brain oxidative stress in CO poisoning.

Mapping the platelet profile for functional genomic studies and demonstration of the effect size of the GP6 locus.

BACKGROUND: Evidence suggests the wide variation in platelet response within the population is genetically controlled. Unraveling the complex relationship between sequence variation and platelet phenotype requires accurate and reproducible measurement of platelet response. OBJECTIVE: To develop a methodology suitable for measuring signaling pathway-specific platelet phenotype, to use this to measure platelet response in a large cohort, and to demonstrate the effect size of sequence variation in a relevant model gene. METHODS: Three established platelet assays were evaluated: mobilization of [Ca(2+)](i), aggregometry and flow cytometry, each in response to adenosine 5'-diphosphate (ADP) or the glycoprotein (GP) VI-specific crosslinked collagen-related peptide (CRP). Flow cytometric measurement of fibrinogen binding and P-selectin expression in response to a single, intermediate dose of each agonist gave the best combination of reproducibility and inter-individual variability and was used to measure the platelet response in 506 healthy volunteers. Pathway specificity was ensured by blocking the main subsidiary signaling pathways. RESULTS: Individuals were identified who were hypo- or hyper-responders for both pathways, or who had differential responses to the two agonists, or between outcomes. 89 individuals, retested three months later using the same methodology, showed high concordance between the two visits in all four assays (r(2) = 0.872, 0.868, 0.766 and 0.549); all subjects retaining their phenotype at recall. The effect of sequence variation at the GP6 locus accounted for approximately 35% of the variation in the CRP-XL response. CONCLUSION: Genotyping-phenotype association studies in a well-characterized, large cohort provides a powerful strategy to measure the effect of sequence variation in genes regulating the platelet response.

Combined oral contraceptive pills for treatment of acne.

BACKGROUND: Acne is a common skin disorder among women. Although no uniform approach to the management of acne exists, combination oral contraceptives (COCs), which contain an estrogen and a progestin, often are prescribed for women. OBJECTIVES: To determine the effectiveness of combined oral contraceptives (COCs) for the treatment of facial acne compared to placebo or other active therapies. SEARCH STRATEGY: We searched the computerized databases of the Cochrane Central Register of Controlled Trials (CENTRAL), MEDLINE, EMBASE, POPLINE, Biological Abstracts and LILACS for randomized controlled trials of COCs and acne. We wrote to authors of identified trials to seek any unpublished or published trials that we might have missed. SELECTION CRITERIA: All randomized controlled trials reported in any language that compared the effectiveness of a COC containing an estrogen and a progestin to placebo or another active therapy for acne in women were eligible. DATA COLLECTION AND ANALYSIS: We extracted data on total and specific (i.e., open or closed comedones, papules, pustules and nodules) facial lesion counts; acne severity grades; global assessments by the clinician or the participant and discontinuation due to adverse events. Data were entered and analyzed in RevMan. MAIN RESULTS: The search yielded 23 trials: 5 placebo-controlled trials made 3 different comparisons, 17 trials made 13 comparisons between 2 different COC regimens, and 1 additional trial compared a COC to an antibiotic. COCs reduced acne lesion counts, severity grades and self-assessed acne compared to placebo. Differences in the comparative effectiveness of COCs containing varying progestin types and dosages, though, were less clear. COCs that contained chlormadinone acetate or cyproterone acetate improved acne better than levonorgestrel, although this apparent advantage was based on limited data. A COC with cyproterone acetate might result in better acne outcomes than one with desogestrel; however, the three studies comparing these COCs produced conflicting results. Likewise, levonorgestrel showed a slight improvement over desogestrel in acne outcomes in one trial, but a second trial found no difference between the COCs. AUTHORS' CONCLUSIONS: The three COCs evaluated in placebo-controlled trials are effective in reducing inflammatory and non-inflammatory facial acne lesions. Few differences were found between COC types in their effectiveness for treating acne. How COCs compare to alternative acne treatments is unknown since limited data were available regarding this question.

Interventions for pityriasis rosea.

BACKGROUND: Pityriasis rosea is a scaly rash that mainly affects young adults. It can be very itchy but most people recover within 2 to 12 weeks. OBJECTIVES: To assess the effects of interventions for pityriasis rosea. SEARCH STRATEGY: We searched the Cochrane Skin Group Specialised Register (December 2004), the Cochrane Central Register of Controlled Clinical Trials in The Cochrane Library (Issue 4, 2004), MEDLINE (1966 to January 2005), EMBASE (1976 to January 2005), LILACS (1982 to January 2005), BIOSIS Preview (1980 to June 2002), and ongoing trials databases. We scanned bibliographies of published studies, abstracts from dermatology conference proceedings, corresponded with trialists and contacted the pharmaceutical industry. SELECTION CRITERIA: Randomised controlled trials evaluating interventions for pityriasis rosea. DATA COLLECTION AND ANALYSIS: Two authors independently assessed trial quality and extracted data. We contacted study authors to retrieve missing data. MAIN RESULTS: Three trials involving 148 people were included. One poor quality trial (23 people), compared intravenous glycyrrhizin and intravenous procaine. It found no significant difference between the two interventions for treating symptoms and rash. One fair quality trial (85 people), compared the oral antihistamine dexchlorpheniramine (4 mg), the oral steroid betamethasone (500 mcg), and a combination of betamethasone (250 mcg) and dexchlorpheniramine (2 mg). It found no significant difference in itch resolution at two weeks, as rated by the participants, between dexchlorpheniramine and betamethasone, and the combination of dexchlorpheniramine and betamethasone. However, both dexchlorpheniramine and betamethasone alone seem to be better at clearing rash than the combination of dexchlorpheniramine and betamethasone. These interventions were not compared with placebo. The small good quality trial (40 people) that compared oral erythromycin and placebo found that erythromycin was more effective than placebo in terms of rash improvement, as rated by the trialists, after two weeks (RR 13.00; 95% CI 1.91 to 88.64). It was also more effective in decreasing the itch score (difference of 3.95 points, 95% CI 3.37 to 4.53). No serious adverse effects were reported for the interventions. Two out of 17 people on oral erythromycin and 1 out of 17 on placebo reported minor gastrointestinal upset. AUTHORS' CONCLUSIONS: We found inadequate evidence for efficacy for most treatments for pityriasis rosea. Oral erythromycin may be effective in treating the rash and decreasing the itch. However, this result should be treated with caution since it comes from only one small RCT. More research is necessary to evaluate the efficacy of erythromycin and other treatments.