Relevant Safety Data Research Articles

Comparative Evaluation of Three Different Doses of Spinal Isobaric Ropivacaine in Patients Undergoing Day Care Perineal Surgeries: A Randomized Double-blind Study.

Background and objective:Ropivacaine owing to its propensity of causing motor blockade of reduced duration, is preferred for ambulatory day care surgery. Intrathecal ropivacaine has shown effective analgesia for lower limb surgery. Our study plans to evaluate spinal ropivacaine in three different doses in patients undergoing day care perineal surgery.Methodolgy:90 ASA-I patients scheduled to undergo day care perineal surgery were randomized to receive intrathecal ropivacaine. Group I (n=30) received 15mg of intrathecal ropivacaine, Group II (n=30) received 18.75 mg of intrathecal ropivacaine and Group III (n=30) received 22.5 mg of intrathecal ropivacaine. Onset of sensory block at T 10, peak sensory block level, duration of sensory block, onset and duration of motor block and relevant safety data were recorded.Result:Onset of analgesia was significantly shorter in Group III (3.5 min ; P <0.0001). However, time taken for peak sensory blockade was comparable in group II and III (12.76 and 11.93 mins). Duration of analgesia was longer and statistically significant in Group III (201.6 mins: P <0.0001) when compared to Group I and II. Onset of motor block was observed to be shortest in Group III (6.7 mins) and duration of motor block was longest in Group III (153.73 mins). These two parameters were statistically significant than Group I and II (P <0.0001).Conclusion:Intrathecal ropivacaine in a dose of 18.75 and 22.5 mg were observed to be equally effective in providing satisfactory analgesia. However, higher dose was associated with profound sensory and motor block.

Long-term safety of growth hormone-A combined registry analysis.

Preliminary data from the French cohort of the Safety and Appropriateness of Growth hormone treatments in Europe (SAGhE) study raised concerns regarding the safety of recombinant human GH, suggesting that GH may increase mortality and incidence of stroke in patients treated during childhood for GH deficiency or short stature. We evaluated published safety data, focusing on mortality, neoplasms, cerebrovascular events and diabetes across a number of large-scale pharmaceutical company GH registries. A literature review was conducted using PubMed, EMBASE and Google Scholar to identify all relevant safety data from manufacturers' GH registries published between 1988 and April 2016. Results were hand-sorted to exclude nonrelevant publications; bibliographic references from retrieved articles were evaluated for any additional references. The published data do not support an increased risk of mortality in children or adults treated with GH. There was no evidence of an increased risk of stroke, new malignancy, leukaemia, nonleukaemic extracranial tumours or recurrence of intracranial malignancy in patients without risk factors. The risk of a second neoplasm is increased, particularly if patients have received radiation therapy for a central nervous system tumour. There may be an increased risk of type 2 diabetes in GH-treated patients, but this appears to be confined to those with pre-existing risk factors. Patients with risk factors for malignancy or type 2 diabetes should be treated with caution and monitored during follow-up, but current published data provide reassurance on the long-term safety profile of GH in patients receiving GH treatment.

Informationsgehalt von Medikationsplänen vor dem Hintergrund der Einführung des einheitlichen patientenbezogenen Medikationsplans

BackgroundPolypharmacy and complex medication regimens are challenging in patient care. Written information like a medication schedule is the main component in this context. To exchange these data the federal medication plan is an adequate medium. However there is insufficient knowledge of whether structures for implementation exist and which categories are already used in daily practice. It is also unknown how often an update for these schedules is necessary. MethodsDuring a medication review including a brown-bag analysis the current medication from 500 patients was assessed and compared to the medication schedule available. In this way we established both the categories of the federal medication plan that are already in use and the age of the plan. Age and frequency of data within the different categories were compared to the number of deviations. In addition, these data were analyzed for different authorships. ResultsNone of the 399 medication schedules fully complied with the draft. The brand name was listed in only 33.8 %, but with large deviations (41 %) from the currently used brand. Brand names and the name of the active component were used in a mixed manner. Dosage was missing in 34.6 % of the medications, and in 80.2 % the formulations were not provided. Indication was lacking in 95.2 % of the medications and intake recommendations in 96.7 %. Large differences were seen with different authors. The average age of the plans was 4.5 months [range 0–12 months]. The number of discrepancies increased by 50 % after two months, statistical significance was reached after 4.5 months (p=0.039). ConclusionThe complete categories of the federal medication plan are not commonly used in everday practice. Essential information such as the correct brand name, dosages and intake recommendations as well as medication relevant safety data concerning galenic form and indication is not fully provided. To achieve implementation and completeness of medication plans, interprofessional collaboration of all healthcare professions with the involvement of patients is reasonable. Updating is necessary after each change in medication but should also be routinely conducted every 3 months.

Safety and Efficacy of Methotrexate in Psoriasis: A Meta-Analysis of Published Trials.

BackgroundMethotrexate (MTX) has been used to treat psoriasis for over half a century. Even so, clinical data characterising its efficacy and safety are sparse.ObjectiveIn order to enhance the available evidence, we conducted two meta-analyses, one for efficacy and one for safety outcomes, respectively, according to PRISMA checklist. (Data sources, study criteria, and study synthesis methods are detailed in Methods).ResultsIn terms of efficacy, only eleven studies met criteria for study design and passed a Cochrane risk of bias analysis. Based on this limited dataset, 45.2% [95% confidence interval 34.1–60.0] of patients achieve PASI75 at primary endpoint (12 or 16 weeks, respectively, n = 705 patients across all studies), compared to a calculated PASI75 of 4.4 [3.5–5.6] for placebo, yielding a relative risk of 10.2 [95% C.I. 7.1–14.7]. For safety outcomes, we extended the meta-analysis to include studies employing the same dose range of MTX for other chronic inflammatory conditions, e.g. rheumatoid arthritis, in order not to maximise capture of relevant safety data. Based on 2763 patient safety years, adverse events (AEs) were found treatment limiting in 6.9 ± 1.4% (mean ± s.e.) of patients treated for six months, with an adverse effect profile largely in line with that encountered in clinical practice. Finally, in order to facilitate prospective clinical audit and to help generate long-term treatment outcomes under real world conditions, we also developed an easy to use documentation form to be completed by patients without requirement for additional staff time.LimitationsMeta-analyses for efficacy and safety, respectively, employed non-identical selection criteria.ConclusionsThese meta-analyses summarise currently available evidence on MTX in psoriasis and should be of use to gauge whether local results broadly fall within outcomes.

Pain management in the acute care setting: Update and debates.

Pain management in the paediatric acute care setting is underutilised and can be improved. An awareness of the analgesic options available and their limitations is an important starting point. This article describes the evolving understanding of relevant pharmacogenomics and safety data of the various analgesic agents with a focus on agents available in Australia and New Zealand. It highlights the concerns with the use of codeine in children and discusses alternative oral opioids. Key features of oral, parenteral, inhaled and intranasal analgesic agents are discussed, as well as evidence supported use of sweet tasting solutions and non-pharmacological interventions. One of the biggest changes in acute care pain management has been the advent of intranasal fentanyl providing reliable potent analgesia without the need for intravenous access. The article will also address the issue of multimodal analgesia where a single agent is insufficient.

Occupational Asthma: An Overview

Occupational asthma is a form of asthma that is often under-diagnosed and under-reported. Unrecognized occupational asthma can lead to progression of disease and increased morbidity. The medical history is a critical element for establishing a diagnosis of OA. The history should include a detailed assessment of the workplace environment, the work process, changes in symptoms in and away from the workplace, and a review of relevant material safety data sheets that may provide clues regarding exposure(s) and the potential cause(s). Objective testing including spirometry pre- and post-bronchodilators, peak expiratory flow rate monitoring in and out of the workplace, provocation testing (i.e., methacholine challenge) to assess for airway hyperresponsiveness, and, if feasible, specific provocation by experienced personnel in a controlled setting to a suspected inciting agent are necessary for confirming a diagnosis. Skin or serologic testing for specific IgE to aeroallergens to assess the worker's atopic status is useful especially when considering certain forms of OA where atopy is a risk factor. Specialized laboratory testing may be useful for specific OA causes. It is important to correctly make the diagnosis of OA as the impact on the worker's future employment and earning power can be significantly affected.

Scientific Opinion on application (EFSA‐GMO‐NL‐2010‐87) for the placing on the market of genetically modified herbicide tolerant oilseed rape GT73 for food containing or consisting of, and food produced from or containing ingredients produced from, oilseed rape GT73 (with the exception of refined oil and food additives) under Regulation (EC) No 1829/2003 from Monsanto

This scientific opinion is a risk assessment for the placing on the market of the genetically modified (GM) herbicide-tolerant oilseed rape (OSR) GT73 for food containing or consisting of, and food produced from or containing ingredients produced from, OSR-GT73. OSR-GT73 contains a single insert consisting of the goxv247 and CP4 epsps expression cassettes. Both proteins confer tolerance against glyphosate-based-herbicides. Bioinformatic analyses of inserted DNA and flanking regions did not raise safety concerns. Levels of CP4 EPSPS and GOXv247 proteins in OSR-GT73 were analysed and the stability of the genetic modification was demonstrated. No biologically relevant differences were identified in the compositional/agronomic/phenotypic characteristics of OSR-GT73 compared with its conventional counterpart, except for the newly expressed proteins. No indication of potential concerns over the safety of the newly expressed CP4-EPSPS and GOXv247 proteins or the occurrence of unintended effects were identified in either OSR-GT73 pollen/pollen-containing dietary supplements or the adventitious presence of trace levels of seeds in human foods. An equivalent assessment with isolated seed protein could not be made because of the lack of availability of relevant consumption and safety data. There are no indications of increased establishment and spread of feral OSR-GT73 plants, or of hybridising wild relatives, unless exposed to glyphosate-based-herbicides. Potential interactions of feral plants with the biotic/abiotic environment do not raise concerns. Environmental risks of horizontal gene transfer into bacteria were not identified. The monitoring plan and reporting intervals are in line with the intended uses. The environmental risk assessment of OSR-GT73 did not identify any safety concerns, in the context of its intended uses. While the Panel is not in a position to conclude on the safety of OSR pollen as such, it concludes that the genetic modification in OSR-GT73 does not constitute an additional health risk if OSR-GT73 pollen were to replace non-GM OSR pollen.

Drug safety evaluation of defibrotide

Introduction: Hepatic veno-occlusive disease (VOD), also known as sinusoidal obstruction syndrome (SOS), is a potentially life-threatening complication of chemotherapeutic conditioning used in preparation for hematopoietic stem-cell transplantation (SCT). Defibrotide (DF) has been shown in Phase II and III trials to improve complete response in patients with severe VOD (sVOD). None of the articles, to date, provide a comprehensive review of the safety of DF in VOD and/or a range of other conditions.Areas covered: This article reviews current clinical findings on DF, primarily in terms of safety for use in treatment and prophylaxis of VOD, and relevant safety data for its use in other diseases. The literature review was conducted using a PubMed search with the fixed term ‘defibrotide' in combination with ≥ 1 of ‘safety', ‘veno-occlusive disease' (with and without ‘treatment', ‘prevention'), ‘oncology', ‘myeloma', ‘microangiopathy', ‘anti-thrombotic' and ‘peripheral vascular disorder'. Related articles from the EBMT and ASH conference websites were also included.Expert opinion: DF was well tolerated in majority of the studies. The safety profile of DF is largely favourable with toxicities comparable to control populations in the setting of SCT complicated by sVOD.

Holistic Approach to Airport Surface Safety

Airport surface safety is acknowledged worldwide as a key area to aviation safety. However, current methods for analyzing and mitigating surface safety occurrences are piecemeal in their approach and limited in scope and perspective. This paper emphasizes the need for a holistic approach to surface safety and introduces a new methodology for the development of a holistic taxonomy for critical factors underlying airport surface safety occurrences. The taxonomy incorporates findings from the relevant literature, safety data, airport surveys, and interviews with subject matter experts. It benefits from the viewpoints of all the relevant aviation stakeholders (regulators, air navigation service providers, airport authorities, airlines, ground handling companies, accident investigation boards) and derives its robustness from the combination of a number of research methods. The application of the taxonomy to support the safety risk management function within the context of safety management systems is proposed. Application of the taxonomy to a multinational data set (North America, Europe, Oceania) verifies that the databases complement each other and that a holistic picture can only be achieved through their combined use. In addition, the analysis indicates that differences in the data sets are a function of the national air traffic system and airport infrastructure, underlying regulations, reporting system and safety culture, and the viewpoint of the aviation stakeholder that is represented. Finally, the holistic approach proposed in this paper is shown to be transferable to other areas of aviation safety.

Quality parenteral nutrition: an ideal mixed bag

Professor Pennington was an advocate for quality in all aspects of nutrition support and its delivery, ensuring that the patient remained at the centre of all decisions, and that specialist artificial nutrition support was best managed by the multidisciplinary nutrition team and the education of the wider healthcare community. Within the conference theme of 'Quality', this commentary aims to outline drivers for and risks to aspects of quality in parenteral nutrition (PN) services. Quality is defined as a particular property or attribute associated with excellence; in the context of the provision of PN this can be translated to quality processes and standards in the assessment, prescription, preparation, administration and monitoring of PN. Quality products and services are delivered through the timely application of knowledge, competence, procedures and standards. Quality can be so easily compromised; inattention, ignorance and arrogance all play their part. PN is a high-risk therapy; the quality of its delivery should not be entirely dependent on the skills, knowledge and competence of those delivering this care but on accepted standards, procedures, communication, resource and infrastructure. Identification of key steps in the provision of PN and a review of the relevant patient safety data reveal points where safeguards can be put in place to ensure quality is not compromised. Full evaluation of standardisation, computerisation and competency-based training as risk-reduction strategies is required.

Ocular Safety of Infliximab

Dear Editor: We read with interest the recent paper by Giansanti et al. on the intraocular safety of infliximab (Remicade ) in animal and cell culture models. Infliximab safety is an important factor as intraocular use of anti-Tumor Necrosis Factor (TNF)-a agents have been proposed as a potential therapeutic approach for patients with ocular inflammation. However, we feel that the intraocular safety data presented in this paper using infliximab in rabbits is misleading, as the manufacturer has published that infliximab does not bind rabbit TNF-a. The authors stated that the aim of the study ‘‘was to confirm the retinal safety of intravitreal infliximab at 2 mg in a rabbit model and to undertake safety testing of different doses of infliximab using a cell culture model [retinal ganglion (RGC-5) and retinal pigment epithelial (RPE) cell lines].’’ The rabbits were given intraocular injections of either infliximab or sterile saline solution. The authors found ‘‘slit-lamp biomicroscopy, indirect funduscopy, and electroretinogram (ERG) evidenced no significant difference between control and infliximab-injected eyes.’’ Histological results also showed no difference between the eyes injected with infliximab and those injected with sterile saline solution. The authors concluded that this result ‘‘suggests that infliximab has no direct retinal toxicity using rabbit [model].’’ However, to demonstrate safety of the antibody they assumed that infliximab (anti-human TNF-a) cross reacts with rabbit TNF-a, which they did not establish or discuss. In support of their work we also found that intravitreal infliximab showed no apparent toxicity in 6 New Zealand albino rabbits when analyzed by clinical examination, ERG, and histologic evaluation (unpublished data). However, we also discovered that according to the Remicade package insert, infliximab does not cross react with TNF-a in species other than humans and chimpanzees. This was confirmed by personal communication with the manufacturer (Centocor) stating that they tested ‘‘neutralization of rabbit TNF-a by infliximab using a bioassay, and it was negative.’’ Therefore, this issue of binding the host TNF-a is critical when assessing the safety of a therapeutic agent in another species, which the authors do not bring up in their discussion. They do state in their discussion that infliximab has been reported in an Association for Research in Vision and Ophthalmology (ARVO) abstract to reduce uveitis. This report has not been substantiated in the peer review literature and further classification of mechanism of action would be necessary. The data do demonstrate the absence of nonspecific ocular toxicity of the carrier vehicle in infliximab, but do not demonstrate in vivo safety for the anti-TNF-a antibody. The in vitro results of Giansanti et al. showed no effect of infliximab on two cell lines: ARPE-19 (human RPE cell line) and RGC-5 (Sprague-Dawley rat ganglion cell line). The data using the ARPE-19 cell line do suggest in vivo safety as this cell line is human and can express TNF-a; however, infliximab does not cross-react with the rat TNF-a. Without binding of the target tissue TNF-a, the safety of the infliximab drug carrier can be concluded only from the RGC-5 data. When testing biologics such as anti-TNF-a in animals or cell culture, it is essential to establish that the agent binds the target tissue before relevant safety data can be inferred. This study (and our unpublished work) does demonstrate safety of the drug carrier in rabbits and cell culture. However, additional testing would be needed to infer intraocular safety. For example, either testing of another anti-TNF-a antibody that binds the animal used for the toxicity study, or using a different species that does have cross-reactivity with the agent. In this case, chimpanzees could be used for toxicity studies of infliximab. Cross-reactivity has been a common assumption in many toxicity studies, but it is essential to establish especially when future patient care may be affected.

Unknown Exposures: Gaps in Basic Characterization Addressed with Person-Portable Gas Chromatography-Mass Spectrometry Instrumentation

A newly developed person-portable gas chromatography-mass spectrometry (GC-MS) system was used to analyze several solvent standards, contact cement, paint thinner, and polychlorinated biphenyl samples. Passive solid phase microextraction sampling and fast chromatography with a resistively heated low thermal mass GC column were used. Results (combined sampling and analysis) were obtained in <2 min for solvent, contact cement, and paint thinner samples, and in <13 min for the polychlorinated biphenyl sample. Mass spectra produced by the small toroidal ion trap detector used were similar to those produced with heavily used transmission quadrupole mass spectrometers for polychlorinated biphenyl compounds, simple alkanes, and cycloalknes, while mass spectra for benzene and the ketone compounds analyzed showed evidence for ion/molecule reactions in the ion trap. For one of the contact cement samples analyzed, no evidence was found to indicate the presence of n-hexane, although the relevant material safety data sheet listed this ingredient. Specific chemical constituents corresponding to a potentially wide range of petroleum distillate compounds were identifiable from GC-MS analyses. The possibility for an improved basic characterization step in the exposure assessment process exists with the availability of fast, person-portable GC-MS, although work is needed to further refine this tool and understand the best ways it may be used.

Ongoing under-reporting of clinically relevant safety data in phase II studies of tyrosine kinase inhibitors

Ongoing under-reporting of clinically relevant safety data in phase II studies of tyrosine kinase inhibitors

Reply: Ongoing under-reporting of clinically relevant safety data in phase II studies of tyrosine kinase inhibitors

Reply: Ongoing under-reporting of clinically relevant safety data in phase II studies of tyrosine kinase inhibitors

Precautionary Governance and the Limits of Scientific Knowledge: A Democratic Framework for Regulating Nanotechnology

I. INTRODUCTION II. A PRINCIPLE IN SEARCH OF MEANING: THE NORMATIVE FLUIDITY OF THE PRECAUTIONARY PRINCIPLE A. Introduction: On the Pragmatic Nature of the Precautionary Principle B. The Normative Fluidity of the Precautionary Principle: A Close Look 1. The Hazard Condition 2. The Knowledge Condition 3. The Prescriptive Dimension III. FROM AMBIVALENCE TO POLITICS: THE PRECAUTIONARY PRINCIPLE AS A POLITICAL FRAMEWORK FOR REGULATING RISKS A. Why Politics: Legitimacy, Reflexivity and Creativity B. The Politics of Precaution: Generic Building Blocks 1. The Hazard Condition 2. The Knowledge Condition 3. The Prescriptive Dimension IV. RE-POLITICIZING THE GOVERNANCE OF RISK: FIVE CHALLENGES IN THE DEMOCRATIZATION OF RISK REGULATION IN THE CONTEXT OF NANOTECHNOLOGY A. Extending the Horizon of Civic Participation: From the Regulation of Risks to the Governance of Innovation and Scientific Policy B. Changing the Institutional Framework of Doing Nanoscience: Science Shops Mediating Agents C. E-deliberation 1. Multi-layered Participation--Confronting the Attraction Problem 2. Using Computer Supported Argumentation and Collaborative Decisionmaking Systems D. Risk Visualization E. De-Biasing the Decisionmaking Process V. BRINGING DEMOCRACY INTO THE PRECAUTIONARY PRINCIPLE: CONCLUDING REMARKS I. INTRODUCTION Nanotechnology presents regulators with a difficult challenge. Nanomaterials and nanoprocesses involve deep uncertainties regarding their potential benefits and health and environmental risks, reflecting the embryonic state of the underlying science. These uncertainties are exacerbated by the fact that nanotechnology is not a uniform domain, but encompasses a broad range of technologies and products, including bionanotechnology, supramolecular chemistry, nanostructured materials, and self-assembly nanoprocesses. (1) Given these uncertainties, there have been various calls to use the precautionary principle (PP) a governing principle in the regulation of nanotechnology. Thus, for example, the Intergovernmental Forum on Chemical Safety (IFCS) recommended in September 2008 that the precautionary principle be used as one of the general principles of risk management throughout the life cycle of manufactured (2) A recent joint statement by several environmental NGOs notes similarly that It]he Precautionary Principle must be applied to nanotechnologies because scientific research to-date suggests that exposure to at least some nanomaterials, nanodevices, or the products of nanobiotechnology is likely to result in serious harm to human health and the environment. (3) Drawing on the PP, many environmental groups have called for a moratorium on the sale (and even research) of products containing nanomaterials, arguing that the research to date is insufficient to guarantee the safety of nanoproducts, and that whatever safety research has been conducted has not been properly disseminated to the public. (4) The need to apply a precautionary strategy in the regulation of nanotechnology has also been recognized by legal scholars, (5) advisory bodies (6) and 'regulators. (7) These calls rest on several assumptions: * There is plausible support for the claim that nanotechnology is possibly risky, and is risky in novel and non-uniform ways. (8) * There is an expanding gap between the pace at which new products containing nanomaterials are being developed and the generation of relevant environmental, health and safety data. This gap also reflects the fact that current methods of risk assessment are not necessarily appropriate for the evaluation of nanomaterials. …

Clinical pharmacology, efficacy and safety of atazanavir: a review

Background: Atazanavir (ATV) is a potent and safe protease inhibitor (PI) initially approved in adult HIV-1 infected patients in combination with other antiretroviral drugs with once daily administration. In combination with nucleoside reverse transcriptase inhibitors (NRTIs) and boosted with ritonavir, it has been established as the preferred initial regimen in published guidelines. Objective: This article reviews relevant pharmacodynamic, pharmacokinetic, efficacy and safety data of ATV, administered boosted with ritonavir or unboosted, in comparison with other PIs and/or non-NRTIs, with special focus on recent studies. Methods: Review articles, recent primary literature and scientific meeting reports were analyzed. Results: Compared to most PIs with similar efficacy, the advantages of ATV are a once daily administration with only 100 mg ritonavir when boosted, a good gastrointestinal tolerance with limited diarrhea, a neutral effect on cholesterol and triglycerides, and a favorable resistance profile. However, highly frequent hyperbilirubinemia is observed resulting in some cases in clinical jaundice. Unboosted ATV must be cautiously used because increased resistances have been described. Conclusion: The combination of a similar efficacy, a better tolerance and a low pill burden, as compared to other PIs, makes boosted ATV one of the best options, in combination with NRTIs, in PI-naive HIV-1 infected patients.

Efavirenz – Still First-line King?

Background: Efavirenz is a potent, safe and tolerable non-nucleoside reverse transcriptase inhibitor (NNRTI) recommended as initial therapy. Recently, several new antiretroviral drugs, including second generation NNRTIs, protease-inhibitors, an integrase-inhibitor and a CCR5 inhibitor, have become or will be shortly available. Objective: This article will review relevant efficacy and safety data of efavirenz compared to these novel agents or certain common alternate drugs currently used as initial therapy in treatment-naive patients. Methods: Published articles and conference presentations pertaining to efavirenz and/or the newer antiretroviral agents were evaluated. Results/conclusions: Efavirenz will continue to be preferred initial therapy for now. If longer-term studies of integrase inhibitors and second-generation NNRTIs confirm initial findings, they will eventually supplant efavirenz as preferred first-line agents.

Intravitreal bevacizumab (Avastin) treatment is safe in terms of intraocular and blood pressure: authors' reply

Editor, W e thank Ziemssen et al. (2007) for their interest and valuable comments on our recent article (Kernt et al. 2007). We agree completely that when using intravitreal anti-vascular endothelial growth factor drugs (VEGF) – especially ‘off-label’– one needs to be aware of possible systemic side-effects. In late 2005, when we started collecting data for our study, few reports on treatment by intravitreal bevacizumab existed and no evidence on safety or possible side-effects with regard to intraocular (IOP) or blood pressure (BP) was available. In order to improve patient safety in this situation, our study was designed to collect relevant safety data in a consecutive small patient group. We apologize for the limited design in terms of patient numbers but do believe, because of the completed follow-up, that our data offer a valuable contribution to the safety of intravitreal bevacizumab. We wish to emphasize our complete agreement on the need for sufficient BP management. This is especially true for patients such as those in our reported patient group who suffer from neovascular age-related macular degeneration (AMD) or from diabetic retinopathy (DR), both usually with significant comorbidity. Systemic hypertension is without doubt one of the major causes for morbidity and mortality in the Western world (Ramsay et al. 1999). Therefore, in our inand out-patients we emphasize tight BP control. Being an ophthalmological referral centre this means frequent referrals to internal medicine or the general practitioner treating the patient. The data shown in our study as ‘baseline’ prove that in many patients BP control remains unsatisfactory, although most patients were on at least one form of BP medication. No changes in BP medication occurred during follow-up, data that were not presented because of space limitations and the focus on IOP in an ophthalmological publication. A question was also raised about whether intraindividual BP variability and diurnal oscillations were considered. (The same is also true for IOP.) Baseline measurements of BP and IOP were always taken at hospitalization (approximately 10:00 hr); the intravitreal bevacizumab injection was performed between 14:00 hr and 15:00 hr. Therefore, a similar diurnal cycle-phase can be assumed for all patients. The BP data were indeed distributed normally; intraindividual information was used by anova analysis. Posthoc paired testing was corrected for multiple testing. In the first 6 hr after injection, BP measurements were meant to accompany IOP measurements and to accustom patients with the procedure rather than to detect any change. All patients were hospitalized for at least 1 day at the time of the study, making any return visits unnecessary for the first 24 hr. From our point of view, the out-patient followup data at 2, 6 and 12 weeks are more relevant because a significant increase in BP after systemic bevacizumab treatment is known to occur after several weeks (Michels et al. 2005; Hurwitz & Saini 2006). We agree with Ziemssen et al. (2007) that the ‘baseline’ measurement may be influenced by stress and several other factors such as diurnal changes. However, the first BP measurement was taken several hours before the surgical treatment. In most single BP measurements – including those taken at home – the physician or hospital has to cope with a similar bias. Moreover, the variance analysis can detect any changes over time and is not dependent on only one baseline. On multiple posthoc paired testing, any changes occurring after several weeks would be clinically relevant, while the observed early decreases in BP may represent some of the effects already discussed. In summary, patient safety is a major concern, especially when the treatment is ‘off-label’ and must include all possible side-effects. Therefore, we thank Ziemssen et al. (2007) for their comments regarding BP and the opportunity to further illustrate some previously unaddressed points. We believe that the limited number of patients included is the main limitation of our study and therefore relatively rare effects cannot be assessed. Nevertheless, we believe that our data show validly that a significant increase in IOP or BP does not occur with intraocular bevacizumab. Still further investigations with larger patient numbers are needed to investigate any relatively rare complications and to assess patient safety completely.

Efavirenz/emtricitabine/tenofovir disoproxil fumarate fixed-dose combination: first-line therapy for all?

ATRIPLA™ (Bristol-Myers Squibb and Gilead Sciences) is a complete regimen in a single, fixed-dose combination tablet that contains: efavirenz 600 mg, emtricitabine 200 mg and tenofovir disoproxil fumarate 300 mg. Current treatment guidelines recommend this triple combination for initial therapy because of its excellent potency, tolerability and favorable safety profile. Individually, these agents have long half-lifes that allow for once-daily dosing and may provide a pharmacologic bridge for the occasional missed dose. Although several options for once-daily regimens are available, comparative clinical trials are still in progress. This article reviews relevant efficacy and safety data of efavirenz, emtricitabine and tenofovir disoproxil fumarate, compared with other once-daily agents or certain common alternate drugs presently used as initial therapy in treatment-naive patients.

Infliximab in the treatment of psoriasis

Psoriasis is one of the most common chronic inflammatory diseases with a prevalence of 2–3%. Traditional treatment options in patients with moderate-to-severe disease include ultraviolet light irradiation and systemic agents such as methotrexate and cyclosporine. In a substantial subgroup of patients, these treatments are not effective, associated with intolerable side effects or contraindicated due to comorbidities. Increased production of tumor necrosis factor-α has been identified as an important disease pathomechanism in psoriasis. Infliximab (Remicade®) is a chimeric monoclonal antibody directed against tumor necrosis factor-α that has recently been approved for the treatment of moderate-to-severe plaque psoriasis in Europe. This article reviews the relevant clinical and safety data of infliximab in psoriasis with emphasis on its practical use in this indication.