Adenocarcinoma of the uterine cervix metastatic to lymph nodes

OBJECTIVE: We set out to evaluate the prognostic factors in cervical adenocarcinoma metastatic to lymph nodes. STUDY DESIGN: We performed a retrospective review of 40 patients with cervical adenocarcinoma and lymph node metastasis from 1976 to 1996. RESULTS: Thirty-four patients had adenocarcinoma, and six had adenosquamous carcinoma. Median survival was 50 months. The median survival for patients with stage I disease was 69 months. Stage at diagnosis, treatment with radical hysterectomy, and receiving adjuvant therapy were associated with prolonged survival. A trend toward improved survival was noted with the use of concurrent radiation and chemotherapy as an adjuvant therapy. CONCLUSIONS: Adenocarcinoma metastatic to the lymph nodes does not have a uniformly poor prognosis, especially with early-stage disease. Improved survival was observed with the use of adjuvant therapy, specifically the use of combined chemotherapy and radiation after radical hysterectomy. The optimal therapy in this setting is yet to be determined. (Am J Obstet Gynecol 1998;178:1131-7.)     

Recurrent laryngeal nerve in thyroid surgery: a critical appraisal

Background: Identification and preservation of the recurrent laryngeal nerve (RLN) is of major concern in surgery of the thyroid gland. The purpose of this study was to review the surgical anatomy of the nerve and to describe its relationship to other important structures. Methods: A total of 325 patients were accrued in this prospective non‐randomized study from January 1999 to December 2000. All patients who had total, subtotal and hemithyroidectomies were included in this study. Each side of the thyroid gland was considered as a separate unit in the analysis of the results. Results: Two hundred and seventy‐six patients had thyroidectomies as their primary operation, while 49 patients had them as a reoperative procedure. There were 276 women and 46 men (6:1 female to male ratio) with a mean age of 43.1 years (range: 10?84 years). The total number of dissections was 502. The RLN was clearly identified in 491 (97.8%) dissections: single trunk in 323 dissections (65.8%), two extralaryngeal branches in 164 dissections (33.4%), and three extralaryngeal branches in three dissections (0.6%). One non‐recurrent laryngeal nerve was encountered (0.2%) in the series. The proximity of the RLN to the inferior thyroid artery (ITA) was noted in 444 (90.4%) dissections: 372 (83.8%) nerves were described to be posterior and intertwined between the branches of the ITA, and in 72 (16.2%) RLNs, they were observed to be anterior to the ITA. The close association of RLN to an enlarged tubercle of Zuckerkandl was documented in 381 dissections (73.7%). A total of 231 RLNs (60.8%) was seen in the tracheoesophageal groove, 18 (4.9%) nerves were observed to be lateral to the trachea, and in 109 (28.3%), they were posterior in location. Of concern in 23 (6.0%) dissections the RLN was on the anterior surface of the thyroid gland, which is at highest risk of injury before curving down to pass behind the tubercle of Zuckerkandl. It appears that the anterior course of the RLN was seen more often in the reoperative procedures to the thyroid gland (20%). Conclusions: Although various methods of localizing the RLN have been described, surgeons should be aware of the variations and have a thorough knowledge of normal anatomy in order to achieve a high standard of care. This will ensure the integrity and safety of the RLN in thyroid surgery. The anatomical variation may be minor in degree, but is of great importance as it may affect the outcome of the surgery and the patient's quality of life.     

The use of direct oral anticoagulants for extended duration thromboprophylaxis in medically ill patients: a systematic review and meta-analysis

Journal of Thrombosis and Thrombolysis - The extended use of thromboprophylaxis with direct oral anticoagulants (DOACs) for more than 30 days has been evaluated as an alternative...     

Neonatal tumours in Malaysia: a call for heightened awareness

Purpose  

Neonatal neoplasms are rare tumours notorious for their atypical presentation and unpredictable behaviour. Their optimal treatment remains uncertain, a dilemma compounded by the deleterious effects of adjuvant chemo- or radiotherapy during this vulnerable period of growth. This paper examined the relatively high incidence of these tumours and its impact on paediatric surgery in Malaysia.     

The development of biological therapies for neurological diseases: moving on from previous failures

Introduction: Although years of research have expanded the use of biologics for several clinical conditions, such development has not yet occurred in the treatment of neurological diseases. With the advancement of biologic technologies, there is promise for these therapeutics as novel therapeutic approaches for neurological diseases.

Areas covered: In this article, the authors review the therapeutic potential of different types of biologics for the treatment of neurological diseases. Preclinical and clinical studies that investigate the efficacy and safety of biologics in the treatment of neurological diseases, namely Alzheimer’s disease, amyotrophic lateral sclerosis, Parkinson disease, multiple sclerosis, and stroke, were reviewed. Moreover, the authors describe the key challenges in the development of therapeutically safe and effective biologics for the treatment of neurological diseases.

Expert opinion: Several biologics have shown promise in the treatment of neurological diseases. However, the complexity of the CNS, as well as a limited understanding of disease progression, and restricted access of biologics to the CNS has limited successful development. Therefore, more research needs to be conducted to overcome these hurdles before developing effective and safe biologics for neurological diseases. The emergence of new technologies for the design, production and delivery of biologics will accelerate translating biologics to the clinic.     

Community pharmacists’ knowledge,behaviors and experiences about adverse drug reaction reporting in Saudi Arabia

Objective

To assess community pharmacists’ knowledge, behaviors and experiences relating to Adverse Drug Reaction (ADR) reporting in Saudi Arabia.

Methods

A cross-sectional study was conducted using a validated self-administered questionnaire. A convenience sample of 147 community pharmacists working in community pharmacies in Riyadh, Saudi Arabia.

Results

The questionnaire was distributed to 147 pharmacists, of whom 104 responded to the survey, a 70.7% response rate. The mean age of participants was 29 years. The majority (n = 101, 98.1%) had graduated with a bachelorette degree and worked in chain pharmacies (n = 68, 66.7%). Only 23 (22.1%) said they were familiar with the ADR reporting process, and only 21 (20.2%) knew that pharmacists can submit ADR reports online. The majority of the participants (n = 90, 86.5%) had never reported ADRs. Reasons for not reporting ADRs most importantly included lack of awareness about the method of reporting (n = 22, 45.9%), misconception that reporting ADRs is the duty of physician and hospital pharmacist (n = 8, 16.6%) and ADRs in community pharmacies are simple and should not be reported (n = 8, 16.6%). The most common approach perceived by community pharmacists for managing patients suffering from ADRs was to refer him/her to a physician (n = 80, 76.9%).

Conclusion

The majority of community pharmacists in Riyadh have poor knowledge of the ADR reporting process. Pharmacovigilance authorities should take necessary steps to urgently design interventional programs in order to increase the knowledge and awareness of pharmacists regarding the ADR reporting process.     

A Workflow to Investigate Exposure and Pharmacokinetic Influences on High-Throughput in Vitro Chemical Screening Based on Adverse Outcome Pathways

Background

Adverse outcome pathways (AOPs) link adverse effects in individuals or populations to a molecular initiating event (MIE) that can be quantified using in vitro methods. Practical application of AOPs in chemical-specific risk assessment requires incorporation of knowledge on exposure, along with absorption, distribution, metabolism, and excretion (ADME) properties of chemicals.

Objectives

We developed a conceptual workflow to examine exposure and ADME properties in relation to an MIE. The utility of this workflow was evaluated using a previously established AOP, acetylcholinesterase (AChE) inhibition.

Methods

Thirty chemicals found to inhibit human AChE in the ToxCast™ assay were examined with respect to their exposure, absorption potential, and ability to cross the blood–brain barrier (BBB). Structures of active chemicals were compared against structures of 1,029 inactive chemicals to detect possible parent compounds that might have active metabolites.

Results

Application of the workflow screened 10 “low-priority” chemicals of 30 active chemicals. Fifty-two of the 1,029 inactive chemicals exhibited a similarity threshold of ≥ 75% with their nearest active neighbors. Of these 52 compounds, 30 were excluded due to poor absorption or distribution. The remaining 22 compounds may inhibit AChE in vivo either directly or as a result of metabolic activation.

Conclusions

The incorporation of exposure and ADME properties into the conceptual workflow eliminated 10 “low-priority” chemicals that may otherwise have undergone additional, resource-consuming analyses. Our workflow also increased confidence in interpretation of in vitro results by identifying possible “false negatives.”

Citation

Phillips MB, Leonard JA, Grulke CM, Chang DT, Edwards SW, Brooks R, Goldsmith MR, El-Masri H, Tan YM. 2016. A workflow to investigate exposure and pharmacokinetic influences on high-throughput in vitro chemical screening based on adverse outcome pathways. Environ Health Perspect 124:53–60; http://dx.doi.org/10.1289/ehp.1409450     

Perspectives of physicians practicing in low and middle income countries towards generic medicines: A narrative review

Objectives

This review was conducted to document published literature related to physicians’ knowledge, attitudes, and perceptions of generic medicines in low- and middle-income countries (LMICs) and to compare the findings with high-income countries.

Methods

A systematic search of articles published in peer-reviewed journals from January 2001 to February 2013 was performed. The search comprised nine electronic databases. The search strategy involved using Boolean operators for combinations of the following terms: generic medicines, generic medications, generic drugs, generic, generic substitution, generic prescribing, international non-proprietary, prescribers, doctors, general practitioners, physicians, and specialists.

Results

Sixteen articles were included in this review. The majority (n = 11) were from high income countries and five from LMICs. The main difference between high income countries and LMICs is that physicians from high income countries generally have positive views whereas those from LMICs tend to have mixed views regarding generic medicines. Few similarities were identified among different country income groups namely low level of physicians’ knowledge of the basis of bioequivalence testing, cost of generic medicines as an encouraging factor for generic medicine prescribing, physicians’ concerns towards safety and quality of generic medicines and effect of pharmaceutical sales representative on generic medicine prescribing.

Conclusion

The present literature review revealed that physicians from LMICs tend to have mixed views regarding generic medicines. This may be due to differences in the health care system and pharmaceutical funding system, medicine policies, the level of educational interventions, and drug information sources in countries of different income levels.     

Health care professionals’ awareness of,knowledge about and attitude to influenza vaccination

Objectives

Influenza vaccination is recommended to all health care professionals (HCPs). However, vaccination rate among HCPs is low and may be due to uncertainty about the effectiveness of the vaccine and fear of its adverse effects. Therefore, this study aimed to investigate the awareness, knowledge, and attitude of HCPs towards influenza vaccination and we ascertain reasons for not getting vaccinated.

Method

A cross-sectional conducted in 6 major hospitals in Saudi Arabia. 245 anonymous questionnaires were distributed to a convenient sample of staff during the 2012–2013 influenza season. The validated questionnaire consists of five sections that collect information about: demographics, attitude towards influenza vaccination, knowledge about influenza virus and vaccination, current practice and awareness of published guidelines.

Results

242 completed questionnaires were received, a response rate of 98%. 38% of HCPs reported getting vaccinated. The most common reasons given by HCPs for not getting vaccinated were: fear of contracting illness (16%), belief that they are not at risk from influenza because they are young and healthy (13%) and being unaware of vaccine availability (13%). Non-availability of vaccine (43%) was the highest barrier for not providing vaccine for patients and HCPs followed by safety concerns for the patients (35%) and the respondents (33%). Almost 75% of HCPs were not aware of the influenza immunization guidelines published by the Advisory Committee on Immunization Practices and Centre for Disease Control.

Conclusion

Despite the recommendations, only low percentage of HCPs in Saudi Arabian hospitals is vaccinated against influenza. The attention of health policy makers is needed to improve compliance of HCPs with guidelines on influenza vaccination.     

Application of PBPK modeling in support of the derivation of toxicity reference values for 1,1,1-trichloroethane

PBPK modeling has been increasingly applied in chemical risk assessment for dose, route, and species extrapolation. The use of PBPK modeling was explored in deriving toxicity reference values for 1,1,1-trichloroethane (1,1,1-TCE). This effort involved a 5-step process: (i) reconstruction of several published PBPK models for 1,1,1-TCE in the rat and human; (ii) selection of appropriate pharmacokinetic datasets for model comparison; (iii) determination of the most suitable PBPK model for supporting reference value derivation; (iv) PBPK model simulation of two critical studies to estimate internal dose metrics; and (v) calculation of internal dose metrics for human exposure scenarios for reference value derivation. The published model by Reitz et al. [Reitz, R.H., McDougal, J.N., Himmelstein, M.W., Nolan, R.J., Schumann, A.M., 1988. Physiologically based pharmacokinetic modeling with methylchloroform: implications for interspecies, high dose/low dose, and dose route extrapolations. Toxicol. Appl. Pharmacol. 95, 185-199] was judged the most suitable. This model has liver, fat, and rapidly and slowly perfused compartments, contains a saturable process for 1,1,1-TCE hepatic metabolism, and accommodates multiple exposure pathways in three species. Data from a human volunteer study involving acute inhalation exposure [Mackay, C.J., Campbell, L., Samuel, A.M., Alderman, K.J., Idzikowski, C., Wilson, H.K., Gompertz, D., 1987. Behavioral changes during exposure to 1,1,1-trichloroethane: time-course and relationship to blood solvent levels. Am. J. Ind. Med. 11, 223-239] and a chronic rat inhalation study [Quast, J.F., Calhoun, L.L., Frauson, L.E., 1988. 1,1,1-Trichloroethane formulation: a chronic inhalation toxicity and oncogenicity study in Fischer 344 rats and B6C3F1 mice. Fundam. Appl. Toxicol. 11, 611-625] were selected to simulate appropriate internal dosimetry data from which to derive reference value points of departure. Duration, route, and species extrapolations were performed based on internal dose metrics.