Acute macular neuroretinopathy associated with intravitreal anti-VEGF injection: A case report.

Purpose: to report a case of acute macular neuroretinopathy occurring after intravitreal aflibercept injection for macular edema due to CRVO. Observations: Two days after Aflibercept intravitreal injection, the patient developed vision loss associated with a central scotoma. Optical coherence tomography showed a hyperreflective band at the level of the outer nuclear/outer plexiform layer corresponding to the patient's scotoma, ruling in the diagnosis of acute macular neuroretinopahty. Even though the OCT abnormalities resolved spontaneously, only partial resolution of the scotoma was observed 4 months later. Conclusions and importance: Acute macular neuroretinopathy might be associated with intravitreal anti-VEGF injection.

Cryo-EM structures of inhibitory antibodies complexed with arginase 1 provide insight into mechanism of action.

Human Arginase 1 (hArg1) is a metalloenzyme that catalyzes the hydrolysis of L-arginine to L-ornithine and urea, and modulates T-cell-mediated immune response. Arginase-targeted therapies have been pursued across several disease areas including immunology, oncology, nervous system dysfunction, and cardiovascular dysfunction and diseases. Currently, all published hArg1 inhibitors are small molecules usually less than 350 Da in size. Here we report the cryo-electron microscopy structures of potent and inhibitory anti-hArg antibodies bound to hArg1 which form distinct macromolecular complexes that are greater than 650 kDa. With local resolutions of 3.5 Å or better we unambiguously mapped epitopes and paratopes for all five antibodies and determined that the antibodies act through orthosteric and allosteric mechanisms. These hArg1:antibody complexes present an alternative mechanism to inhibit hArg1 activity and highlight the ability to utilize antibodies as probes in the discovery and development of peptide and small molecule inhibitors for enzymes in general.

A phase 1 pooled PK/PD analysis of bone resorption biomarkers for odanacatib, a Cathepsin K inhibitor.

To develop a framework for evaluating the resorption effects of Cathepsin K (CatK) inhibitors and to inform dose regimen selection, a pharmacokinetic/pharmacodynamic (PK/PD) model for odanacatib (ODN) was developed based upon data from Phase 1 studies. Pooled PK/PD data from 11 studies (N = 249) were fit reasonably to a population inhibitory sigmoid Emax model. Body weight on E0 (baseline uNTx/Cr, urinary N-terminal telopeptide normalized by creatinine) and age on Emax (fractional inhibition of the biomarker response) were significant covariates for biomarker response. Simulations of typical osteoporosis patients (by age, sex and weight) indicated minimal differences between sexes in concentration-uNTx/Cr relationship. There was no evidence that regimen (daily vs. weekly dosing) influenced the PK/PD relationship of resorption inhibition for odanacatib. PK/PD models based on data from odanacatib (ODN) Phase 1 studies demonstrated that uNTx/Cr was an appropriate bone resorption biomarker for assessment of the effects of a CatK inhibitor. The models also identified the determinants of response in the PK/PD relationship for ODN (body weight on E0 and age on Emax).

Mechanistic model of hormonal contraception.

Contraceptive drugs intended for family planning are used by the majority of married or in-union women in almost all regions of the world. The two most prevalent types of hormones associated with contraception are synthetic estrogens and progestins. Hormonal based contraceptives contain a dose of a synthetic progesterone (progestin) or a combination of a progestin and a synthetic estrogen. In this study we use mathematical modeling to understand better how these contraceptive paradigms prevent ovulation, special focus is on understanding how changes in dose impact hormonal cycling. To explain this phenomenon, we added two autocrine mechanisms essential to achieve contraception within our previous menstrual cycle models. This new model predicts mean daily blood concentrations of key hormones during a contraceptive state achieved by administering progestins, synthetic estrogens, or a combined treatment. Model outputs are compared with data from two clinical trials: one for a progestin only treatment and one for a combined hormonal treatment. Results show that contraception can be achieved with synthetic estrogen, with progestin, and by combining the two hormones. An advantage of the combined treatment is that a contraceptive state can be obtained at a lower dose of each hormone. The model studied here is qualitative in nature, but can be coupled with a pharmacokinetic/pharamacodynamic (PKPD) model providing the ability to fit exogenous inputs to specific bioavailability and affinity. A model of this type may allow insight into a specific drug's effects, which has potential to be useful in the pre-clinical trial stage identifying the lowest dose required to achieve contraception.

Assessment of workplace bullying: reliability and validity of an Arabic version of the Negative Acts Questionnaire-Revised (NAQ-R).

INTRODUCTION: Interest in workplace bullying has been steadily growing since the 1990s, focusing on understanding its driving factors, prevalence rates in different occupations and countries, its consequences, as well as the characteristics of the typical bully and victim. Currently, the Negative Acts Questionnaire-Revised (NAQ-R) is the most frequently used questionnaire to assess workplace bullying. Studies in the Arab world are scarce and to date the NAQ-R has not been validated in Arabic, the official or co-official language in around 25 countries in the Middle East and Asia. The aim of this study was therefore to develop an Arabic version of NAQ-R. MATERIALS AND METHODS: 447 participants aged 18-70 years were recruited through convenient sampling. Exclusion criteria were illiteracy and employment for less than 6 months. Participants were recruited from shops, banks, travel agencies and restaurants in an area in central Beirut around a tertiary care medical centre.A two-stage process was employed to translate the original version of NAQ-R to Arabic. This translated version along with validated Arabic versions of the Satisfaction with Life Scale and the Beck Depression Inventory II were distributed to participants. RESULTS: A 14-item two-factor NAQ-R, with subscales of person-related and work-related bullying, was supported. Reliability coefficients for total and subscale scores of the NAQ-R ranged from 0.63 to 0.90. The Arabic NAQ-R had good concurrent validity as indicated by significant correlations with depression and satisfaction with life (p < 0.05). CONCLUSION: NAQ-R was translated to Arabic and adapted. The results revealed acceptable levels of reliability and construct validity. As for the underlying factor structure, it needs to be further supported.

Phase II dose-finding study on ovulation inhibition and cycle control associated with the use of contraceptive vaginal rings containing 17ß-estradiol and the progestagens etonogestrel or nomegestrol acetate compared to NuvaRing.

PURPOSE: To identify at least one contraceptive vaginal ring that effectively inhibits ovulation and demonstrates cycle control that is non-inferior to NuvaRing® (Merck Sharp & Dohme B.V., The Netherlands) in terms of an unscheduled bleeding incidence, with a non-inferiority margin of 10%. METHODS: This was a randomised, active controlled, parallel group, multicentre, partially blinded trial in healthy women 18-35 years of age. Subjects received one of six contraceptive vaginal rings with an average daily release rate of 300 µg 17ß-estradiol (E2) and various rates of either etonogestrel (ENG; 75, 100, or 125 µg/day) or nomegestrol acetate (NOMAC; 500, 700, or 900 µg/day), or the active control NuvaRing® (ENG/ethinylestradiol 120/15 µg), for three 28-day cycles. RESULTS: Ovulation inhibition was observed in all groups as confirmed by absence of progesterone concentrations compatible with ovulation (>16 nmol/L) and absence of ultrasound evidence of ovulation. All investigational rings provided good cycle control, with the ENG-E2 125/300 µg/day group being associated with the best cycle control based on the numerically lowest incidence of unscheduled bleeding and absence of scheduled bleeding. Non-inferiority to NuvaRing® with respect to the incidence of unscheduled bleeding could not be concluded for any of the investigational ring groups. The safety profile was consistent with the known safety profile of combined estrogen/progestin contraceptives and similar across all groups. CONCLUSIONS: Contraceptive rings releasing 300 µg E2 and 75-125 µg/day of ENG or 500-900 µg/day of NOMAC provided adequate ovulation inhibition and cycle control and are generally well-tolerated. While non-inferiority to NuvaRing® was not met, among the investigational rings, the ENG-E2 125/300 ring provided the best cycle control.

Bladder Cancer in Lebanon: Incidence and Comparison to Regional and Western Countries.

Lebanon has one of the highest estimated age-standardized incidence rate (ASR(w)) of bladder cancer (BC) worldwide. The aim of this study is to analyze the incidence rates for BC in Lebanon over a period of 7 years and to compare them to the rates in other countries. Data were obtained from the Lebanese National Cancer Registry for the currently available years 2005 to 2011. The calculated ASR(w) and age-specific rates were expressed as per 100 000 population. From 2005 to 2011, BC has been ranked as the third most common cancer in Lebanon. It accounted for 9.0% of all newly diagnosed cancer cases excluding nonmelanoma skin cancer. It ranked second in males and ninth in females. The average ASR(w) over this period was 31.2 in men and 7.3 in women. These incidence rates are among the highest worldwide across all age groups in both sexes. This study shows that the incidence of BC in Lebanon is high and it is among the highest worldwide. It is important to reduce the risk of BC through tobacco control and by decreasing exposure to avoidable environmental and occupational risk factors.

Knowledge, attitude and practice of Lebanese primary care physicians in nutrition counseling: a self-reported survey.

Aim This study aims to assess the knowledge, attitude and practice of primary care physicians (PCPs) in Lebanon regarding nutrition counseling and to investigate possible related barriers. BACKGROUND: Nutrition counseling is an important aspect of patient care, especially with the increase in nutrition-related disorders. METHODS: This is a descriptive study among a convenience sample of PCPs in Lebanon at two annual conferences in 2014 using an anonymous questionnaire. Findings Response rate was 54.6%. Overall, physicians considered that they have good to very good nutritional knowledge. Although they rated their formal nutritional education poorly, they had a positive attitude towards nutritional counseling and reported practicing general nutritional counseling with their patients. Barriers to nutritional counseling were: time, perceived poor patient adherence to diet, gap in physician's nutritional knowledge and lack of insurance coverage for dietitian fees. Changes should be made to medical education curricula to include nutrition courses related to prevalent health problems.

Evaluation of Periodontal Status and Treatment Needs of Institutionalized Intellectually Disabled Individuals in Lebanon.

AIMS AND OBJECTIVES: No reported data is available on the periodontal health and treatment needs of the intellectually disabled in Lebanon. To evaluate the periodontal condition and treatment needs of institutionalized intellectually disabled individuals in Lebanon. MATERIALS AND METHODS: A total of 272 individuals (141 males and 131 females) aged 15 years and 35-44 years were examined. Periodontal health was recorded following the community periodontal index of treatment needs (CPITN), and treatment need was assigned accordingly. The IBM® SPSS® statistics 20.0 and Stata/SE 11.1 statistical packages were used to carry out all statistical analyses. Statistical analysis was performed using linear regression (P ≤ 0.05). RESULTS: Healthy periodontium was recorded in 26.1%, bleeding on probing in 27.9%, supra-/sub-gingival calculus in 31.3%, pockets of 4-5 mm in 11% and ≥6 mm in 3.7%. The largest proportion of the sample was in need for oral hygiene instruction and calculus removal (42.3%). Age, geographical location, consumption of carbohydrate-rich meals and sweets between meals were significantly associated with CPITN score severity in multivariate analysis (P < 0.05). Gender, severity of disability, frequency of tooth brushing, and caretaker characteristics were not significant predictors of CPITN (P > 0.05). CONCLUSION: The predominantly poor periodontal health and social inequalities warrant nationwide preventive oral health programs in addition to planning the provision of treatment services to meet existing treatment needs.

Oral Health Status of Institutionalized Individuals with Intellectual Disabilities in Lebanon.

OBJECTIVES: To assess the dental status of institutionalized intellectually disabled individuals in Lebanon and the role of background and behavioural determinants. MATERIAL AND METHODS: Oral health was recorded for 652 individuals (6, 12, 15 and 35 - 44 years old) using the decayed, missing and filled teeth/decayed and filled teeth (DMFT/dft) index. Data collected was statistically analysed with statistical significance set at P = 0.05. RESULTS: Overall, mean DMFT index score was 5.86 (SD 6); composed of 3.64 (SD 4.05) decayed (D) teeth; 1.71 (SD 4.38) missing (M) teeth; 0.87 (SD 2.51) filled (F) teeth. DMFT was highest in adults (12.71 [SD 7.43]) and had a large component of missing (6.24 [SD 7.02]) and filled (3.31 [SD 4.56]) teeth. DMFT scores ranged between 3.5 (SD 4.44) at 6 years and 4.8 (SD 4.52) at 15 years and the decayed component was the main contributor. In multivariate analyses, governorate of residence was statistically significantly (P ≤ 0.040 and P ≤ 0.044) associated with D and DMFT, the degree of disability and caretaker educational level were statistically significantly (P = 0.009 and P = 0.008) associated with D, oral hygiene practices were statistically significantly (P ≤ 0.017; P < 0.001; P ≤ 0.017; P < 0.001) associated with D, M, F and DMFT and sugar consumption was statistically significantly (P ≤ 0.03 and P ≤ 0.019) associated with D and DMFT. CONCLUSIONS: In Lebanon, preventive and treatment programs to improve the oral health status of institutionalized intellectually disabled subjects are needed.

A survey of Oral Health in Institutionalized Population with Intellectual Disabilities: Comparison with a National Oral Health Survey of the Normal Population.

INTRODUCTION: Compared to the general population, the intellectually-disabled (ID) experience poor health and inferior access to high quality health services. AIM: To compare the oral health of institutionalized ID Lebanese individuals to that of the normal Lebanese population (NLP). MATERIALS AND METHODS: Caries and periodontal indices were recorded in 652 ID individuals (aged 6, 12, 15, and 35-44 years) residing in the 5 major Lebanese governorates. The comparison population was derived from the National Oral Health Survey conducted in 1994. RESULTS: Six-year-old ID children had an average of 3.28 decayed primary teeth, 0.22 filled primary teeth, and an overall dft score of 3.50, whereas in the general population decayed, filled, and overall dft scores were 4.90, 0.10, and 5.4, respectively. The lowest number of permanent decayed teeth in the ID was recorded in the 35-44-year-old group (3.17) and the highest in 15-year-old group (4.01). In the NLP, the number of decayed permanent teeth gradually increased from age 12 (5.14) to age 35-44 years (7.20). Caries indices were generally better in the ID than that in the NLP, except for more missing teeth in ID adults (6.24 compared to 4.98). The ID population presented with more severe periodontal disease (pocketing) whereas the NLP presented with a greater proportion with calculus. CONCLUSION: This study highlighted important differences in oral health and treatment needs in the ID compared than that of the NLP. Policy changes are required if adequate services are to be provided for this group of the population.

Psychological distress and coping strategies in parents of children with cancer in Lebanon.

OBJECTIVES: To determine the prevalence of psychological distress (PD) among parents of Lebanese children with cancer and to investigate the associated stressors and coping strategies. METHODS: A cross-sectional study conducted at the American University of Beirut Medical Center-Children Cancer Center of Lebanon in 2012. Parents of all children with cancer admitted for treatment were eligible participants. The General Health Questionnaire (GHQ-12) was used to estimate the prevalence of PD. Coping strategies were measured via the Coping Health Inventory for Parents (CHIP). Bivariate and multiple regression analyses were conducted to evaluate the relationship between GHQ-12 (scores 0-36), stressors, family/social support, and coping strategies. RESULTS: One hundred fourteen parents (68.2%) completed the anonymous questionnaire. Based on GHQ-12, significant PD was considered among 56.0% of the parents. It was found to be significantly positively associated with the degree of family financial problems and significantly negatively associated with the child's disease duration. A significant negative relationship was also found between PD and Coping (CHIP) scale, coping pattern I (Maintaining Family Integration and an Optimistic Outlook for the Situation), pattern II (Seeking Social Support), yet not with pattern III (Seeking Information). CONCLUSIONS: PD is prevalent among parents of Lebanese children hospitalized because of cancer. Screening for PD in the latter population is feasible, would identify those who are at risk for disruptive PD, and facilitate the provision of support towards better adjustment and coping. Alleviating parental PD may facilitate the realization of optimal health outcomes.

Opportunities and barriers to enhance research capacity and outputs among academic family physicians in the Arab world.

AIM: To explore the current status of academic primary care research in Arab countries and investigate the barriers to its adequate implementation. BACKGROUND: Research is an essential building block that ensures the advancement of the discipline of Family Medicine (FM). FM research thus ought to be contributed to by all family physicians; nevertheless, its development is being hindered worldwide by several challenges. The amount of research conducted by academic academic family physicians and general practitioners is scant. This phenomenon is more pronounced in the Arab countries. METHODS: An online questionnaire was emailed to all academic family physicians practicing in member Arab countries of the World Organization of Family Doctors WONCA-East Mediterranean Region. FINDINGS: Seventy-six out of 139 academic family physicians from eight Arab countries completed the questionnaire. Around 75% reported that they are required to conduct research studies, yet only 46% contributed to at least one publication. While 75% and 52.6% disclosed their interest in participating in a research team and in leading a research team respectively, 64.5% reported being currently involved in research activities. Of all, 56% have attended a research ethics course. Lack of training in research, the unavailability of a healthcare system that is supportive of research, insufficient financial resources, and the unavailability of electronic health records were perceived as major barriers in conducting FM research. CONCLUSION: Although many physicians in Arab academic institutions expressed enthusiasm to conduct research projects, FM research infrastructure remains to be weak. This demonstrates the need for immense efforts from different parties particularly governments and academic institutions.

The effect of various types of patients' reminders on the uptake of pneumococcal vaccine in adults: A randomized controlled trial.

BACKGROUND: Invasive pneumococcal disease is one of the most important vaccine-preventable diseases threatening the adult community due to missed opportunities for vaccination. This study compares the effect of three different types of patient reminder system on adulthood Streptococcus pneumoniae immunization in a primary care setting. METHODS: The study targeted patients aged 40 and older eligible for pneumococcal vaccine, but did not receive it yet (89.5% of 3072 patients) based on their electronic medical records in a family medicine center in Beirut. The sample population was randomized using an automated computer randomization system into six equal groups, receiving short phone calls, short text messaging system (sms-text) or e-mails each with or without patient education. Each group received three identical reminders spaced by a period of four weeks. Documentation of vaccine administration was then added to the longitudinal electronic patient record. The primary outcome was the vaccine administration rate in the clinics. RESULTS: Of the eligible patients due for the pneumococcal 23-polyvalent vaccine, 1380 who had mobile phone numbers and e-mails were randomized into six equal intervention groups. The various reminders increased vaccination rate to 14.9%: 16.5% of the short phone calls group, 7.2% of the sms-text group and 5.7% of the e-mail group took the vaccine. The vaccination rate was independent of the age, associated education message and the predisposing condition. CONCLUSION: Use of electronic text reminders via e-mails and mobile phones seems to be a feasible and sustainable model to increase pneumococcal vaccination rates in a primary care center.

Diabetes quality of care at a university community in Beirut.

RATIONALE, AIMS AND OBJECTIVES: To assess the quality of diabetes mellitus (DM) care provided by a group of family doctors in Beirut. METHODS: An observational study, conducted at the American University of Beirut Medical Center-Family Medicine Clinics (AUBMC-FMC), examined the electronic health records (EHRs) of the beneficiaries of the Health Insurance Plan at the American University of Beirut (AUB-HIP) who were older than 20 years (n = 9469) in 2009. The eligible population included patients with DM (n = 701). Several provider/patient-directed interventions were introduced in the late 2000s, including a comprehensive EHRs system with point-of-care computer reminders, a provider financial incentive based on an annual performance appraisal ranked against that of the US Healthcare Effectiveness Data and Information Set (HEDIS) Comprehensive Diabetes Care indicators, as well as periodic up-to-date training. RESULTS: Optimal control for HbA1c, low-density lipoprotein cholesterol, high-density lipoprotein cholesterol, triglycerides and blood pressure were found in 58.6%, 51.0%, 22.4%, 53.3% and 60.2% of the population, respectively. 64.1% and 70.0% received screening for diabetic nephropathy and a dilated eye examination, respectively. When benchmarked against the HEDIS Comprehensive Diabetes Care indicators, the AUB-HIP's quality of care was 13% higher than the average of all plans in the United States. Screening for nephropathy, however, did not reach the above benchmark. CONCLUSIONS: Benchmarking served as an important tool in evaluating the current DM care offered and in detecting gaps, yet interventions are recommended for further improvement.

Early Clinical Development Planning via Biomarkers, Clinical Endpoints, and Simulation: A Case Study to Optimize for Phase 3 Dose Selection.

BACKGROUND: This study investigated a framework that leverages the relationship between biomarkers and a target clinical endpoint to optimize an early development plan. METHODS: Different biomarker designs were assessed for proof of concept (PoC) and dose finding (DF) to improve phase 2b (Ph2b) design as well as phase 3 (Ph3) dose choice. A case study using a Bayesian trivariate normal distribution model for 2 biomarkers and a clinically relevant endpoint was utilized with simulation to assess performance characteristics. RESULTS: We found the following: (1) at typical sample sizes for early development trials, biomarkers appear useful for PoC but not for clinical endpoint DF; and (2) even with large amounts of prior information and near perfect correlation between biomarkers and clinical endpoints, Ph2b variability is only overcome by increased Ph2b sample sizes to improve Ph3 dose choice. CONCLUSIONS: For highly variable clinical endpoints, the fastest path should be to demonstrate PoC by biomarkers and then go directly to Ph2b to measure the target clinical endpoint.

What matters in the patients' decision to revisit the same primary care physician?

OBJECTIVE: To assess the priority of various aspects of the patient-primary care physician relationship in the decision to visit again that same physician. STUDY SETTINGS: A total of 400 community residents in Ras Beirut, Lebanon. STUDY DESIGN: A cross-sectional community based study sampled by a nonrandom sex-education quota-based procedure. DATA COLLECTION: Participants were asked to fill a survey where they indicated the ranking of nine items by importance in their decision to revisit the same physician. The nine items were chosen from three categories of factors: professional expertise of the physician; characteristics of the patient-physician relationship, office organization. RESULTS: Having a physician that gives the patient adequate time for discussion prevailed as rank 1 and luxurious clinic ranked as 9th. Affordability was one of the main concerns among men, those with poor health and those of lower socioeconomic status. Accessibility of the physician's phone was considered highly important among women and those of lesser education status. CONCLUSIONS: This study emphasizes the importance of adequate time with the patient, accessibility and affordability of the physician in maintaining continuity of care and patient satisfaction, beyond mere medical expertise.

Insulin therapy attitudes and beliefs of physicians in Middle Eastern Arab countries.

BACKGROUND: Studies assessing attitudes and beliefs of physicians regarding insulin therapy in Arab countries are scant despite the high prevalence of type 2 diabetes mellitus (T2DM). OBJECTIVE: This study examines family physicians' attitudes and beliefs towards insulin therapy in T2DM patients in the East Mediterranean Region of the World Organization of National Colleges, Academies and Academic Associations of General Practitioners/Family Physicians. METHODS: This is a cross-sectional study conducted on 348 family physicians invited via email to fill an anonymous online questionnaire about their attitudes, beliefs and perceived barriers regarding insulin initiation in T2DM patients. RESULTS: One hundred and twenty-two physicians completed the questionnaire. Of the 122 physicians, 73.6% preferred to delay insulin initiation until it is absolutely essential and 59.0% initiated it themselves. The majority agreed that T2DM patients benefit from insulin prior to the development of complications (85.7%) and that patient education is important (99.1%) and uncomplicated (74.7%). Sixty-three per cent expressed reluctance to start insulin mostly because of perceived patients' reluctance. Referral to endocrinologists to initiate insulin therapy was associated with inadequate experience and concern about risks, particularly in elderly patients (backward logistic regression, P < 0.05). Physicians' reluctance to initiate insulin therapy was associated with patients' perception of insulin initiation as a personal failure and threat to the quality of life (backward logistic regression, P < 0.05). CONCLUSIONS: Although family physicians in the Arab world believe in the benefits of insulin therapy, many are reluctant to initiate it themselves. Further studies are needed per country, as well as multiple measures to minimize the physicians' barriers to insulin prescription.