Survivorship and Radiological Analysis of a Monoblock, Hydroxyapatite-Coated Titanium Stem in Revision Hip Arthroplasty.

BACKGROUND: We evaluated the survivorship, incidence of complications, radiological subsidence, proximal stress shielding, and patient-reported outcomes of a conservative, monoblock, hydroxyapatite-coated femoral stem. METHODS: This retrospective cohort study reports on 254 revision hip arthroplasties between January 2006 and June 2016. The mean age of patients was 71 years. The mean length of follow-up was 62 months (range 12-152). RESULTS: There were 13 stem re-revisions: infection (4), periprosthetic fracture (4), aseptic stem loosening (3), stem fracture (1), and extended trochanteric osteotomy nonunion (1). Kaplan-Meier aseptic stem survivorship was 97.33% (confidence interval 94-100) at 6 years. There were 29 intraoperative fractures. There were 6 cases of subsidence greater than 10 mm; however, none required revision. Ninety-six percent of cases showed no proximal stress shielding. Thigh pain was reported in 3% of cases. CONCLUSION: This study confirms that this stem provides good survivorship at 6 years, acceptable complication rates, adequate proximal bone loading, low incidences of thigh pain, and reliable clinical performance in revision hip arthroplasty. KEY MESSAGE: A monoblock, fully hydroxyapatite-coated titanium stem is reliable in revision arthroplasty with mild-moderate femur deficiencies.

Hip offset and leg-length restoration in revision hip arthroplasty with a monoblock, hydroxyapatite-coated stem.

AIMS: Restoration of normal hip biomechanics in arthroplasty surgery is important in order to achieve good muscle function and joint stability. METHODS: In this retrospective cohort study, we examined the postoperative radiographs of 131 femoral revision arthroplasty procedures using a monoblock, fully hydroxyapatite (HA)-coated titanium stem. Femoral offset, modified-global offset and leg length were measured of the operated and contralateral hips. RESULTS: Femoral offset was restored to ±10 mm in 108 cases (82%), modified-global offset was restored ±10 mm in 93 cases (71%) and leg length was restored to ±10 mm in 102 cases (81%). There were 4 dislocations with a mean follow-up period of 38 months. CONCLUSIONS: Restoration of hip biomechanics is achievable with a monoblock stem and thus is a viable option in revision hip arthroplasty.

Risk Factors of 120-Day Mortality Among Hip Fractures With Concomitant COVID-19 Infection.

Background Hip fractures cause substantial morbidity and mortality worldwide, and the coronavirus disease 2019 (COVID-19) pandemic has only worsened the global burden. Increased 120-day mortality is well established in the literature among hip fractures with COVID-19. However, the risk factors associated with mortality have been poorly understood. We aimed to determine the risk factors associated with increased 120-day mortality among hip fractures with COVID-19. Methods Seventy patients with hip fractures with confirmed COVID-19 infection between March 2020 and December 2021 were included. Thirty-three patients who died within 120 days of admission were allotted to the non-survivor group and the rest 37 patients were allotted to the survivor group. Various parameters such as demographic variables, Nottingham Hip Fracture Score (NHFS), Charlson Comorbidity Index (CCI), American Society of Anesthesiologists (ASA), Abbreviated Mental Score Test (AMTS), National Early Warning Score (NEWS), fracture type, operation type, and delay in surgery were compared between the groups to determine the risk factors for increased mortality. Multivariate regression analysis was performed to know the independent association with increased mortality. Results A total of 33 patients died within 120 days giving the 120-day mortality rate of 47.1%. Baseline parameters such as ASA, AMTS on admission, NEWS on admission, and type of residence did not significantly affect mortality. The mean NHFS was significantly high in non-survivors (5.38 ± 1.52) compared to survivors (4.40 ± 1.75) (p < 0.001). Similarly, mean CCI was also significantly high in non-survivors (5.58 ± 1.74) compared to survivors (4.76 ± 2.29) (p < 0.001). A total of 70% (seven out of 10) of patients with delayed surgery of more than 36 hours from the admission died within 120 days of admission (p < 0.001). Mortality was significantly higher in patients who underwent internal fixation of fractures like a dynamic hip screw (DHS) or intramedullary (IM) nailing than in those who underwent hemiarthroplasty or total hip arthroplasty (THA). Post-operative parameters such as early mobilization and the multidisciplinary approach to review these patients made no difference to the mortality. Multivariate regression analysis of the parameters that made a significant difference in the mortality showed that delay in surgery and type of surgery (internal fixation) independently increased the mortality among these patients (p < 0.001). However, NHFS and CCI were not independently affecting the mortality among hip fractures with concomitant COVID-19. Conclusion The 120-day mortality rate among patients with hip fractures with concomitant COVID-19 was 47.1%. Delay in surgery of more than 36 hours and patients who underwent internal fixation were independent risk factors associated with increased mortality among these patients.

COVID-19 Vaccination: Does It Alter Postoperative Mortality and Morbidity in Hip Fractures?

Introduction The primary aim of our study was to evaluate the impact of coronavirus disease 2019 (COVID-19) vaccination on mortality in patients with hip fractures by comparing it to those who are unvaccinated. Our secondary objective was to compare the impact on postoperative morbidity parameters like length of hospital stay and complications. Methods A total of 619 hip fractures were divided into the 'Vaccinated group' consisting of 300 patients who had COVID-19 vaccination and the 'Unvaccinated group' consisting of 319 patients who were not vaccinated. Patient demographic variables, Nottingham hip fracture score, American Society of Anesthesiologists (ASA) grade, type of anaesthesia used, and Charlson Comorbidity Index were collected. Our primary outcome measures were 30- and 90-day mortality. Secondary outcome measures included postoperative complications like thromboembolic complications, cardiac, and respiratory complications, etc. Mortality among the COVID-positive patients was also compared between the groups. Results Thirty-day postoperative mortality was higher in the unvaccinated group at 13.2% than in the vaccinated group at 5.3%. A similar increase in 90-day mortality was also observed in the unvaccinated group at 24.8% when compared to 14.7% in the vaccinated group(p<0.001). Despite having a higher baseline prevalence of cardiac comorbidities, the Vaccinated group had fewer post-operative cardiac, thromboembolic, and neurological complications (p>0.05). Moreover, electrolyte imbalance and AKI were also seen in fewer patients in the vaccinated group compared to the control group (p<0.05). Furthermore, it was found that among the vaccinated patients who did have perioperative COVID-19 infection, the 30-day mortality was significantly lower (10%) compared to the control group (31.2%) (p<0.001). Similarly, 90-day mortality was significantly lower (25%) compared to the control group (43.75%) (p<0.001). Conclusion Vaccination against COVID-19 independently reduced mortality and morbidity among patients with hip fractures when compared to those who are not vaccinated. Furthermore, it decreased the risk of acquiring COVID-19, and subsequent postoperative complications. Among those who are infected with COVID-19 despite vaccination, the mortality was significantly lesser.

COVID-19 Infection Increases Mortality and Complications in Patients With Neck of Femur Fracture.

Hip fractures commonly occur in elderly patients with multiple comorbidities. Contracting coronavirus disease 2019 (COVID-19) when healing from hip fractures places the patients at a higher risk of respiratory compromise and death. This study aimed to compare the 30- and 90-day mortality rates of patients with hip fracture with and without COVID-19. The secondary aim was to determine the impact of COVID-19 on the parameters of morbidity such as health complications and length of hospital stay. All patients with hip fractures who presented to our hospital between March and December 2020 were classified into one of two subgroups: those with a clinical and/or laboratory diagnosis of COVID-19 and those without. Patient demographics, American Society of Anesthesiologists score, Nottingham Hip Fracture Score, Charlson Comorbidity Index, complications, length of stay, and 30- and 90-day mortality rates were measured in patients with hip fractures with and without a clinical diagnosis of COVID-19. We found that COVID-19 infection independently increased the 30- and 90-day mortality rates, respiratory complications, and length of hospital stay in patients with hip fractures. This is the first study to report the 90-day mortality of COVID-19 infection in such patients.

Randomised controlled trial of an innovative hypoglycaemia pathway for self-care at home and admission avoidance: a partnership approach with a regional ambulance trust.

Background: Hypoglycaemia is a common and potentially life-threatening condition in people with diabetes, commonly caused by medications such as insulin. Hypoglycaemic events often require in-patient treatment and/or follow-up with a diabetes specialist nurse (DSN) or GP to make adjustments to medication. This referral pathway commonly relies on patient self-referral to primary care, and as a result many patients are not actively followed up and go on to experience repeat hypoglycaemic events. Methods: Randomised controlled trial in partnership with East Midlands Ambulance Service NHS Trust. People with diabetes calling out an ambulance for a severe hypoglycaemic episode and meeting the eligibility criteria were randomised to either a novel DSN-led pathway or to their general practice for routine follow-up. Primary outcome was proportion of participants with a documented consultation with a healthcare professional to discuss the management of their diabetes within 28 days of call-out. Results: 162 people were randomised to one of the pathways (73 DSN arm, 89 GP arm) with 81 (50%, 35 DSN, 46 GP) providing full consent to be followed up. Due to lower than anticipated randomisation and consent rates, the recruitment target was not met. In the 81 participants who provided full consent, there were higher rates of consultation following the call-out when referred to a DSN compared to primary care (90% vs. 65%). Of the 81 participants, 26 (32%) had a second call-out within 12 months. Conclusions: Consultation rates following the call-out were high in the DSN-led arm, but there was insufficient power to complete the planned comparative analysis. The study highlighted the difficulty in recruitment and delivery of research in pre-hospital emergency care. Further work is needed to provide more feasible study designs and consent procedures balancing demands on ambulance staff time with the need for robust well-designed evaluation of referral pathways.

Ambulance attendance for substance and/or alcohol use in a pandemic: Interrupted time series analysis of incidents.

INTRODUCTION: The ambulance attendance for substance and/or alcohol use in a pandemic (ASAP) study explores incidents during the COVID-19 lockdown in the East Midlands region of the United Kingdom (23 March-4 July 2020). METHOD: Retrospective cross-sectional count per day of ambulance attendances from the East Midlands Ambulance Service Trust. Ambulance attendances relating to alcohol or other drug use in the year prior, during lockdown and weeks following, were examined using interrupted time series analysis by patient demographics and geographical location. RESULTS: A total of 36 104 records were identified (53.7% male, 84.5% ethnicity classified as White, mean age 38.4 years). A significant drop in the number of attendances per day at the start of lockdown (-25.24, confidence interval - 38.16, -12.32) was observed, followed by a gradual increase during the ongoing lockdown period (0.36, confidence interval 0.23, 0.46). Similar patterns were found across genders, age groups 16-64 and urban/rural locations. DISCUSSION AND CONCLUSION: The pattern of ambulance attendances for alcohol or other drug use changed during the COVID-19 lockdown period. Lockdown significantly affected the use of ambulances for incidents involving alcohol or other drug use, impacting on health-care services. Further research into hazardous use of alcohol or other drugs during the lockdown periods is needed to inform policy, planning and public health initiatives.

Early Functional Outcomes After Evolutionary Total Knee Arthroplasty: A Randomized Controlled Trial. Is New Always Better?

Total knee replacement (TKR) designs continue to evolve with the aim of improving patient outcomes; however, there remains a significant patient dissatisfaction rate. We report the early functional outcomes of an evolutionary knee design in the context of a single-blinded, noninferiority, randomized controlled trial. METHODS: Patients were randomized to receive either the P.F.C. SIGMA or ATTUNE knee implant systems (DePuy Synthes). All implants were fixed-bearing, cruciate-retaining, and cemented constructs. Patients were assessed at baseline and 6 weeks, 3 months, and 1 year postoperatively using clinical and functional outcome measures, including range of motion, Oxford Knee Score (OKS), Oxford Knee Score-Activity and Participation Questionnaire (OKS-APQ), Patient Knee Implant Performance (PKIP) score, 5-Level EuroQol 5 Dimensions (EQ-5D-5L), and Short Form-36 outcome measures. RESULTS: There were 150 patients who underwent a surgical procedure (76 with the ATTUNE implant and 74 with the P.F.C. SIGMA implant), with 147 patients remaining at the final review. No differences were observed in any of the outcome measures between the groups at any time point. Tourniquet time was significantly shorter in the P.F.C. SIGMA arm (p = 0.001); however, this had no clinical impact on the OKS (analysis of covariance [ANCOVA] test) at the final review (p = 0.825). There was no difference in the numbers of patients achieving the minimal clinically important difference for the OKS between the groups (p = 0.817). CONCLUSIONS: This trial did not show inferiority of the ATTUNE implant when compared with the P.F.C. SIGMA implant. The authors believe that implant innovation should continue and that modern implants should be introduced into the market following randomized controlled trials. Further work should assess the effect of non-implant-related factors on patient outcomes. LEVEL OF EVIDENCE: Therapeutic Level I. See Instructions for Authors for a complete description of levels of evidence.

Toxicological risks of Chinese herbs.

As traditional Chinese medicine (TCM) has become more popular there have been increasing concerns about safety and potential toxicity of the Chinese materia medica (CMM) comprising plants, animal parts and minerals. The potential toxicity of many CMM is well recognised in TCM and to reduce risks use of some herbs is restricted whilst specific processing methods have been developed to modify the activities/toxicity of others. However adverse reactions have been reported, many of these are due misuse or abuse of Chinese medicine. The main problem remains products adulterated with pharmaceuticals for weight loss or erectile dysfunction. But some herbs have narrow therapeutic ranges (e.g., Aconitum species) so toxic effects are frequently reported. Toxic effects from chronic or cumulative dosing are difficult to detect in the traditional setting and recent reports have demonstrated the health problems from Aristolochia species. Despite safety concerns, Chinese medicine appears to be relatively safe with comparatively few reports of adverse reactions compared with overall drug reports. The wealth of information in the Chinese literature needs to be more widely available. As TCM is widely used by patients, improved pharmacovigilance and pharmacoepidemiology can contribute valuable safety information, relevant to clinical use.

Functional outcome of total hip arthroplasty after a previous hip arthroscopy: a retrospective comparative cohort study.

BACKGROUND: Despite patients demonstrating significant short-term clinical improvement from a hip arthroscopy (HA), a number of patients progress to significant osteoarthritis of the hip requiring total hip arthroplasty (THA). This study aims to evaluate if there is any difference in the functional outcome of patients undergoing THA after a previous hip arthroscopy compared to patients undergoing THA for primary osteoarthritis of the hip. METHODS: Between 2010 and 2013, in a group of 414 patients who underwent hip arthroscopy, we identified 18 patients who underwent a subsequent uncemented THA. These formed the study group. During the same period, 625 patients underwent an uncemented THA performed for primary OA, of which 63 patients were matched to the study group for age, follow-up and implants used. These formed the control group. Pre-op and post-op Oxford Hip Scores (OHS) were recorded for all patients. RESULTS: A mean follow-up of 26.5 and 26.3 months was observed in the study and control groups respectively. The median (interquartile ranges) preoperative OHS were 14 (8.25, 17.0) and 18.5 (13.25, 24.75) in the 2 groups. Corresponding postoperative scores were 40 (31.25, 45) and 46 (43, 48). Median difference between the preoperative and postoperative OHS was 27 (19, 31) and 25 (18.25, 31). Adjusting for the pre-treatment scores, the postoperative scores in the study arm were significantly lower than for the control arm with an estimate (SE) of -0.464 (p = 0.012). Post-hoc power analysis showed that the study was sufficiently powered to detect a meaningful difference in scores. CONCLUSION: Total hip arthroplasty after hip arthroscopy leads to satisfactory functional outcomes. However, the functional outcome in this group is significantly worse than in a matched cohort of patients undergoing THA for osteoarthritis. There was no difference in the rate of complications between the 2 groups.

Characteristics and practices of Traditional Chinese Medicine retail shops in London, UK: A cross-sectional study using an observational approach.

ETHNOPHARMACOLOGICAL RELEVANCE: Traditional Chinese Medicine (TCM) is a popular form of ethnomedicine in the UK, and is accessed by Western, Chinese and other ethnic groups. The current regulatory regime does not effectively protect the public against poor-quality and unsafe TCMs. Understanding ethnopharmacological information on how TCM is promoted and practiced may help to inform initiatives aimed at ensuring the safe use of TCMs in the UK, and put laboratory-based ethnopharmacological investigations of TCMs in a broader context. AIM OF THE STUDY: This study aimed to examine the characteristics and practices of TCM retail outlets in London, UK, and to identify factors relevant to the safe use of TCM in the UK. MATERIALS AND METHODS: TCM retail outlets ('shops') in London, UK, were identified using a systematic approach. A structured questionnaire including questions on shop business type was used to recruit participant shops. Shops consenting to participate were visited within six weeks of providing consent. A piloted semi-structured questionnaire on shop characteristics was used for data collection following observation. The British National Formulary 53 was used to classify medical conditions/uses for TCMs promoted in the shops. Data were stored and analysed using MS Access 2003, MS Excel 2003 and SPSS 13. RESULTS: In total, 54 TCM shops in London were identified, of which 94% offered TCM consultations with a TCM practitioner. Detailed characteristics were described within 35/50 shops that gave consent to observing their premises. Most shops labelled and displayed over 150 Chinese Materia Medica (CMMs; crude materials, particularly herbs) for dispensing after consultations with a TCM practitioner. Medical conditions/uses and Patent Chinese Medicines (PCMs) were commonly promoted. In total, 794 occurrences of 205 different medical conditions/uses (median=32, QL=19, QU=48) were identified. These conditions/uses most commonly related to the following therapeutic systems: central nervous system (160/794, 20.2%); musculoskeletal and joint disease (133/794, 16.8%); obstetrics, gynaecology, and urinary-tract disorders (122/794, 15.4%); skin (102/794, 12.9%); gastrointestinal system (62/794, 7.8%). Specific conditions/uses that were frequently promoted included eczema (19/23 shops, 82.6%), arthritis (18/23, 78.3%), acne (17/23, 73.9%), obesity/weight loss/slimming (17/23, 73.9%) and psoriasis (17/23, 73.9%). Claimed conditions/uses included some serious medical conditions (e.g. diabetes, cancer and hypertension) and those focusing on vulnerable groups (e.g. children's diseases and pregnancy treatments). CONCLUSIONS: TCM shops in London, UK, typically displayed names of a wide range of medical conditions/uses for TCMs using readily understandable medical terms, implying TCM can be used to prevent or treat these conditions. However, many of these advertisements did not comply with UK regulations on medical claims for herbal medicines. Future studies should explore how these advertisements influence consumers' decisions to access TCM in the UK, practices of TCM shop staff towards the supply of TCMs in the UK, and what are the health implications at the individual and population levels.

Patient satisfaction with tourniquet application and local anaesthesia infiltration in carpal tunnel decompression and the relationship with overall satisfaction.

This was a prospective study designed to determine what effect poor tolerance to tourniquet application and local anaesthesia infiltration in open carpal tunnel decompression has on overall patient satisfaction with the surgical procedure. Fifty patients were recruited into the study. Visual analogue scores (VAS) were recorded postoperatively for pain related to tourniquet application, local anaesthesia infiltration and the surgical procedure overall. In terms of the procedure, poor tolerance to the tourniquet and local anaesthetic showed no significant relationship to the overall patient satisfaction (Student t-test). The factors, which are related to satisfaction with carpal tunnel decompression, are discussed.

Pharmacovigilance of herbal medicine.

Pharmacovigilance is essential for developing reliable information on the safety of herbal medicines as used in Europe and the US. The existing systems were developed for synthetic medicines and require some modification to address the specific differences of medicinal herbs. Traditional medicine from many different cultures is used in Europe and the US which adds to the complexities and difficulties of even basic questions such as herb naming systems and chemical variability. Allied to this also is the perception that a 'natural' or herbal product must be safe simply because it is not synthetic which means that the safety element of monitoring for such medicines can be overlooked because of the tag associated with such products. Cooperation between orthodox physicians and traditional practitioners is needed to bring together the full case details. Independent scientific assistance on toxicological investigation, botanical verification can be invaluable for full evaluation of any case report. Systematic pharmacovigilance is essential to build up reliable information on the safety of herbal medicines for the development of appropriate guidelines for safe effective use.

Pharmacovigilance practice and risk control of Traditional Chinese Medicine drugs in China: current status and future perspective.

ETHNOPHARMACOLOGICAL RELEVANCE: Traditional Chinese Medicine (TCM), including Traditional Chinese Medicine drugs (TCM drugs), has been playing a very important role in health protection and disease control for thousands of years in China. Relying on natural products, mainly of herbal origin, used either as raw materials for decoction, as prepared herbal medicines or as formulated traditional medicines, TCM is still widely accepted by Chinese people, especially for chronic diseases treatment. This extensive use warrants safety measures and so TCM drug safety monitoring and risk management are becoming increasingly important tasks for the Chinese State Food and Drug Administration (SFDA). METHODS: The Adverse Drug Reaction (ADR) monitoring system in China was established both for western and TCM drugs in 1989 as a voluntary reporting system with a National Center collecting and compiling reports. Serious or multi-case reports on individual TCM drug or formulated products are detailed in the Chinese ADR Information Bulletin to inform the public and Drug Administrative authorities for risk management. RESULTS: About 10-15% of the ADR reports received by the National Center are related to TCM drugs and mainly pertaining to the formulated products. In certain cases, the suspension of a particular TCM preparation is decided by SFDA China. CONCLUSION: The model of safety monitoring and risk management of TCM drugs is still under exploration. Indeed, the characteristics and risk factors associated with these drugs require both proper understanding and control of the risk by strengthening standardization of clinical applications, basic science research, quality control in manufacturing, exploration of the actives monitoring methodology and enhancement of international communication and cooperation.

Good practice in reviewing and publishing studies on herbal medicine, with special emphasis on traditional Chinese medicine and Chinese materia medica.

ETHNOPHARMACOLOGICAL RELEVANCE: Studies on traditional Chinese medicine (TCM), like those of other systems of traditional medicine (TM), are very variable in their quality, content and focus, resulting in issues around their acceptability to the global scientific community. In an attempt to address these issues, an European Union funded FP7 consortium, composed of both Chinese and European scientists and named "Good practice in traditional Chinese medicine" (GP-TCM), has devised a series of guidelines and technical notes to facilitate good practice in collecting, assessing and publishing TCM literature as well as highlighting the scope of information that should be in future publications on TMs. This paper summarises these guidelines, together with what has been learned through GP-TCM collaborations, focusing on some common problems and proposing solutions. The recommendations also provide a template for the evaluation of other types of traditional medicine such as Ayurveda, Kampo and Unani. MATERIALS AND METHODS: GP-TCM provided a means by which experts in different areas relating to TCM were able to collaborate in forming a literature review good practice panel which operated through e-mail exchanges, teleconferences and focused discussions at annual meetings. The panel involved coordinators and representatives of each GP-TCM work package (WP) with the latter managing the testing and refining of such guidelines within the context of their respective WPs and providing feedback. RESULTS: A Good Practice Handbook for Scientific Publications on TCM was drafted during the three years of the consortium, showing the value of such networks. A "deliverable - central questions - labour division" model had been established to guide the literature evaluation studies of each WP. The model investigated various scoring systems and their ability to provide consistent and reliable semi-quantitative assessments of the literature, notably in respect of the botanical ingredients involved and the scientific quality of the work described. This resulted in the compilation of (i) a robust scoring system and (ii) a set of minimum standards for publishing in the herbal medicines field, based on an analysis of the main problems identified in published TCM literature. CONCLUSION: Good quality, peer-reviewed literature is crucial in maintaining the integrity and the reputation of the herbal scientific community and promoting good research in TCM. These guidelines provide a clear starting point for this important endeavour. They also provide a platform for adaptation, as appropriate, to other systems of traditional medicine.

Review of current and "omics" methods for assessing the toxicity (genotoxicity, teratogenicity and nephrotoxicity) of herbal medicines and mushrooms.

ETHNOPHARMACOLOGICAL RELEVANCE: The increasing use of traditional herbal medicines around the world requires more scientific evidence for their putative harmlessness. To this end, a plethora of methods exist, more or less satisfying. In this post-genome era, recent reviews are however scarce, not only on the use of new "omics" methods (transcriptomics, proteomics, metabonomics) for genotoxicity, teratogenicity, and nephrotoxicity assessment, but also on conventional ones. METHODS: The present work aims (i) to review conventional methods used to assess genotoxicity, teratogenicity and nephrotoxicity of medicinal plants and mushrooms; (ii) to report recent progress in the use of "omics" technologies in this field; (iii) to underline advantages and limitations of promising methods; and lastly (iv) to suggest ways whereby the genotoxicity, teratogenicity, and nephrotoxicity assessment of traditional herbal medicines could be more predictive. RESULTS: Literature and safety reports show that structural alerts, in silico and classical in vitro and in vivo predictive methods are often used. The current trend to develop "omics" technologies to assess genotoxicity, teratogenicity and nephrotoxicity is promising but most often relies on methods that are still not standardized and validated. CONCLUSION: Hence, it is critical that toxicologists in industry, regulatory agencies and academic institutions develop a consensus, based on rigorous methods, about the reliability and interpretation of endpoints. It will also be important to regulate the integration of conventional methods for toxicity assessments with new "omics" technologies.