Increased prevalence of oral potentially malignant lesions among Croatian War invalids, a cross-sectional study.

Background: The main objective of this study was to investigate the frequency and type of oral pathological changes, oral subjective symptoms and the knowledge about oral cancer in the population of Croatian military invalids from the Homeland War. Material and Methods: A total of 102 Croatian military invalids from the Homeland War participated in the study. Data were collected on the presence of subjective symptoms in the oral cavity, and a detailed clinical examination of the oral mucosa was performed. Results: Almost half of the participants, 46 (45.1%), reported being smokers, and 64 (62.7%) consumed alcohol daily. Subjective symptoms in the oral cavity were reported by 25 (24.5%) of them. Pathological changes were found in 35 (34.3%) participants, of whom 14 (13.7%) had potentially malignant changes. Pathohistological findings confirmed the diagnosis of a potentially malignant lesion in 10 subjects and indicated the presence of moderate dysplasia in two, carcinoma in situ in one, and invasive carcinoma in one. Conclusions: Participants didn't show adequate knowledge of risk factors. Forty-one changes in the oral cavity were found in 35 subjects, and as many as 14 were potentially malignant. According to the participants, most dentists and family physicians don't thoroughly and regularly examine their patients' oral mucosa. Key words:Oral cancer, oral lichen planus, leukoplakia, erythroplakia, actinic cheilitis, Croatian Homeland War invalids.

Effect of Denosumab Therapy on Pain Level in Diffuse Sclerosing Osteomyelitis of the Mandible: a Case Report.

This is the first case report where two patients were under uniform denosumab administration protocol in diffuse sclerosing osteomyelitis (DSO) treatment and were closely monitored for 18 months. Objectives: This study aimed to describe the beneficial effects of denosumab in DSO treatment as well as pain relief and the significant lack of long-term use due to poorer outcomes after repeated use. DSO of the jaw is a poorly understood rare chronic disease the treatment of which is still very challenging despite a rapid development of medicine. Different medical treatments have been proposed without any significant long-lasting success. Bisphosphonates have offered substantial clinical benefit in DSO therapy, but due to harmful pharmacodynamic properties, denosumab therapy has been used to replace bisphosphonate therapy. Patients had a reduction in pain intensity with each subsequent application of denosumab but with less success than the first administration of denosumab. This case report has shown that denosumab could be a promising conservative treatment option for pain treatment in patients suffering from DSO.

Intramammary Ethno-Veterinary Formulation in Bovine Mastitis Treatment for Optimization of Antibiotic Use.

Increasing pressure on animal and human health as well as food security, due to antimicrobial resistance, is leading to increased demand for natural-product-derived antibiotics worldwide. Considering the importance of bovine mastitis as well as the huge challenge posed by mastitis therapy in cattle production, the main goal of this research was to evaluate the effectiveness of the essential oil-based pharmaceutical (Phyto-Bomat), as an alternative to the existing treatment with antibiotics. The therapeutic response of the cows was monitored using clinical and bacteriological cure of the proposed formulation. Among 550 dairy cows, 75 were diagnosed with a clinical or subclinical form of mastitis and divided into three experimental groups: treated with antibiotic; Phyto-Bomat; antibiotic and Phyto-Bomat. Indicators of bacteriological cure were somatic cell count (SCC), total bacterial count, and causative agent isolation, while the clinical cure was accessed by observing physical udder conditions. All mentioned indicators were assessed before and after the treatment (1st and 7th day post-treatment), with all of the three therapeutic protocols. After Phyto-Bomat treatment, no visible signs of irritation were noticed, while no significant effect in reducing SCC and total bacterial count was observed. Phyto-Bomat has shown promising results in the treatment of mastitis, without the risk of udder irritation, alone or in combination with antibiotics as part of a mastitis control program during lactation.

Possible influence of styloid process length on isolated vertigo of unknown aetiology.

OBJECTIVE: Eagle syndrome or styloid process syndrome is a clinical condition of complex aetiology. Since, as a consequence of vascular compression,due to the length of the styloid process and its nearness to the internal carotid artery,it can lead to vertigo. Vertigo may be the only symptom of stylocarotid syndrome and it is extremely challenging diagnose.To the best of our knowledge, this is the first study that measures the lengths of styloid process on the Croatian population's,and possible influence of styloid process length on isolated vertigo of unknown aetiology. METHODS: This study included 829 subjects who were divided into two groups.The first group was the control group, consisting of 800 subjects.The second group, study group, consisted of 29 subjects who suffered from the vertigo of unknown aetiology. RESULTS: The statistically significant difference between the study and the control group was observed in the length of the styloid process, and in the closest distance of the styloid process from the carotid artery. CONCLUSIONS: The prolonged styloid process and its close association with the internal carotid artery may affect vertigo of unknown aetiology and should be clinically and radiographically investigated in cases of unexplained vertigo as an isolated and only symptom within stylocarotid syndrome.

Third molar maturity index (I3M) assessment according to different geographical zones: a large multi-ethnic study sample.

Identification of living undocumented individuals highlights the need for accurate, precise, and reproducible age estimation methods, especially in those cases involving minors. However, when their country of origin is unknown, or it can be only roughly estimated, it is extremely difficult to apply assessment policies, procedures, and practices that are accurate and child-sensitive. The main aim of this research is to optimize the correct classification of adults and minors by establishing new cut-off values for four different continents (Africa, America, Asia, and Europe). For this purpose, a vast sample of 10,701 orthopantomographs (OPTs) from four continents was evaluated. For determination and subsequent validation of the new third molar maturity index (I3M) cut-off values by world regions, a cross-validation by holdout method was used and contingency tables (confusion matrices) were generated. The lower third molar maturity indexes, from both left and right side (I3ML and I3MR) and the combination of both sides (I3ML_I3MR) were calculated. The new cut-off values, that aim to differentiate between a minor and an adult, with more than 74.00% accuracy for all populations were as follows (I3ML; I3MR; I3ML_I3MR, respectively): Africa = (0.10; 0.10; 0.10), America = (0.10; 0.09; 0.09), Asia = (0.15; 0.17; 0.14), and Europe = (0.09; 0.09; 0.09). The higher sensitivity (Se) was detected for the I3ML for male African people (91%) and the higher specificity (Sp) of all the parameters (I3ML; I3MR; I3ML_I3MR) for Europeans both male and female (> 91%). The original cut-off value (0.08) is still useful, especially in discriminating individuals younger than 18 years old which is the goal of the forensic methods used for justice.

Treatment of Inflammatory Dentigerous Cyst Using a Surgical T Drain in a Child.

Dentigerous cysts are rarely reported in young children. They are usually asymptomatic and only identified when becoming significantly large. Treatment by enucleation may damage structures like the inferior alveolar nerve, maxillary sinus, or permanent teeth, thus reducing the child's quality of life. Therefore, conservative surgical treatment such as decompression is indicated. This case report describes the treatment and subsequent complete regression of an inflammatory dentigerous cyst based on the decompression method using a customized surgical tube in a 10-year-old girl. The innervation was preserved, and permanent teeth erupted.

Chemical Composition, Antimicrobial Activity, and Withdrawal Period of Essential Oil-Based Pharmaceutical Formulation in Bovine Mastitis Treatment.

Due to the emergence of antibiotic-resistant bacteria, the risk it represents to public health, and the possible consequences for animal health and welfare, there is an increasing focus on reducing antimicrobial usage (AMU) in animal husbandry. Therefore, a great interest in developing alternatives to AMU in livestock production is present worldwide. Recently, essential oils (EOs) have gained great attention as promising possibilities for the replacement of antibiotics. The current study aimed to test the potential of using a novel EO-based pharmaceutical formulation (Phyto-Bomat) in bovine mastitis treatment. The antibacterial activity was performed using the microdilution technique. Lactating dairy cows were treated with 15 mL of Phyto-Bomat in the inflamed quarter for 5 consecutive days in order to analyze blood and milk samples for thymol and carvacrol residues using gas chromatography and mass spectrometry (GC-MS). Antimicrobial activity expressed as the minimum inhibitory concentration (MIC) and minimal bactericidal concentration (MBC) indicates that this formulation has the highest activity against Gram-positive strains. The dominant compounds in Phyto-Bomat were thymol and carvacrol, at 12.58 ± 1.23 mg/mL and 23.11 ± 2.31 mg/mL, respectively. The quantification of these two compounds in evaluated biological samples showed that 24 h after administration the concentration of thymol and carvacrol in milk samples was at the same level as before application. On the other hand, thymol and carvacrol were detectable in plasma samples even after 24 h post-treatment, with values ranging from 0.15-0.38 and 0.21-0.66 µg/mL, respectively. The tested formulation showed encouraging results of antibacterial activity against bovine mastitis pathogens, as well as the withdrawal period of dominant compounds, which implies that further testing regarding the bacteriological and clinical cure rates in clinical settings is needed.

The Cameriere, Haavikko, Demirjian, and Willems methods for the assessment of dental age in Croatian children.

AIM: This study aimed to evaluate the accuracy and precision of the Cameriere European formula, Demirjian, Haavikko, and Willems methods for estimating dental age in a sample of children with permanent dentition in Croatia. MATERIAL AND METHODS: The study consisted of a sample of 1576 panoramic radiographs; a sub-sample of 84 OPGs, in which all first seven mandibular teeth were maturated, was excluded from the study. A final sample of 1492 (704 males and 788 females) aged 6.0 to 13.9 years was evaluated. Seven mandibular teeth from the left side of the mandible were analyzed, and dental age (DA) was determined by the Cameriere European formula, Demirjian method from 1976, Haavikko, and Willems methods and compared to chronological age (CA). In addition, the mean age difference (DA-CA), the mean absolute error (MAE) between dental and chronological age, the percentage of the individuals of dental age within ± 0.25 to ± 2 years of chronological age, and intra-observer and inter-observer statistics were calculated. RESULTS: The Cameriere European formula estimated the best dental age compared to the chronological age; the mean underestimation was - 0.4 years for both sexes, Haavikko underestimated by - 0.17 years, while Demirjian and Willems overestimated by 1.02 years and 0.48 years, respectively. The most significant difference showed the Demirjian method in 11-year-old and 12-year-old females. The MAE were 0.50 years, 1.01 years, 0.61 years, and 0.78 years in males and 0.51 years, 1.18 years, 0.61 years, and 0.70 years in females for the Cameriere European formula, Haavikko, Willems, and Demirjian methods, respectively. Furthermore, the Cameriere European formula showed the highest proportions of individuals with DA within ± 0.5 year difference of the CA, 61.5% in males and 59.6% in females. In addition, the Cameriere method showed the best intra-observer and inter-observer agreements. CONCLUSIONS: Although the Demirjian method was used previously in Croatian children for legal, medical, and clinical purposes, the Cameriere European formula, Haavikko, and Willems were more accurate in the tested sample. According to our findings, the Cameriere European formula showed the best accuracy and precision in dental age assessment in Croatian children following Haavikko, and we recommend it as the method of the first choice in forensic and clinical analyses.

Veterinary Practitioners' Standpoints and Comprehension towards Antimicrobial Use-Are There Opportunities for Antimicrobial Stewardship Improvement?

The main subject of the research is the assessment of the knowledge, attitudes and behaviors of veterinarians regarding the use of antibiotics (AMU) and antimicrobial resistance (AMR) through a questionnaire conducted among veterinarians in the northern region of Serbia. A total of 62 respondents completed the questionnaire, which represents a response rate of 44.3%. Male veterinarians are less likely to be in the group of veterinarians with insufficient knowledge (p < 0.05). Veterinarians engaged in mixed practice (small and large animals) (p < 0.001) and veterinarians who have over 100 patients per month (p < 0.005) are also less likely to be in the group with insufficient knowledge of antimicrobial resistance. The proportion of those with insufficient knowledge is growing among veterinarians whose source is the Internet (p < 0.01), while the proportion of those with insufficient knowledge about antimicrobial resistance is declining among veterinarians whose source of information is continuous education (p < 0.05). The majority of the respondents (n = 59, 95.2%) completely agreed that AMR is a very big issue in the global health sector right now. Unfortunately, there are crucial gaps in the knowledge and attitudes of the surveyed participants. They do not appear to be aware of the importance of AMU in veterinary medicine and its influence on overall AMR, or the crucial part that non-prescribed antibiotics have in all of it. Positively, many veterinarians use good practice AMU guidelines in their everyday practice and in line with the global trend of AMU reduction, respondents have also decreased their AMU compared to the previous year.

Validation of the Italian, European, North German, Malaysian, and South African black formulas on Cameriere method using panoramic radiographs in Kenyan children.

This study aimed to validate the accuracy of five different formulas based on the Cameriere method for age estimation in Kenyan children. We analyzed panoramic radiographs of 350 Kenyan children (184 males and 166 females) aged between 6 and 13 years. The dental development of each child was estimated by the analysis of the first seven left permanent teeth in the left mandible. Dental age was calculated by the Italian, European, North German, Malaysian, and South African black formulas previously published in peer-review journals. The children's mean chronological age (CA) was 9.34 ± 2.02 years and 9.26 ± 2.01 years for males and females. In males, the South-African formula overestimated CA least, by 0.12 years, followed by the Italian formula by 0.22 years, the European formula by 0.37 years, the Malaysian formula by 0.48 years, and the North-German formula overestimated the most, by 0.57 years. In females, the South-African formula underestimated CA by - 0.12 years. The Italian overestimated by 0.12 years, followed by the North-German formula by 0.29 years, the European formula by 0.31 years, and the Malaysian formula by 0.40 years. The Italian formula provided the best accuracy in the absolute difference within ± 1 year, by 75.72% and 75%, following the North-German formula by 66.47% and 70.27% for males and females, respectively. Therefore, the findings suggest that the Italian formula best estimates dental age in Kenyan children.

Effect of an Antioxidant Supplement Combination on Boar Sperm.

The study was conducted on a commercial pig farm located in Serbia. Thirty Duroc or Landrace breed boars were randomly selected for this study. The experimental group was fed a compound feed with added organic selenium and Oxynat 3D. The antioxidant status parameters of boar seminal plasma were evaluated using a biochemical analyzer and commercial Randox kits. The sperm chromatin structure assay (SCSA) using flow cytometry (FC) provided information about spermatozoa's DNA status. Additionally, the total number of motile spermatozoa and spermatozoa kinematic parameters were measured using the computer-assisted sperm analysis (CASA) system. The aim of this study was to improve the parameters of semen by combining two preparations that have a potential antioxidant effect, but also to establish the level of various antioxidant enzymes in native sperm. There was no statistically significant difference in total antioxidant capacity and glutathione peroxidase activity in the seminal plasma obtained from the experimental and control groups of boars. Regarding the superoxide dismutase activity, the research results showed a difference in the control group compared to the experimental one. Moreover, spermatozoa DNA fragmentation and the total number of motile spermatozoa showed statistically significant lower and higher values, respectively, in experimental compared to the control groups. The combination of these two preparations shows significantly enhanced vital parameters of semen. To the best of our knowledge, this study is the first in which the ejaculate parameters were examined after the application of a combination of these two antioxidant supplements.

Human Amniotic Membrane Plug for Chronic or Persistent Macular Holes.

PURPOSE: To report on the use of human amniotic membrane for macular holes at 2 Canadian tertiary care centers. DESIGN: Retrospective cohort study. SUBJECTS: Twenty-two patients with persistent or chronic macular holes. METHODS: Macular hole surgery was performed by 3 vitreoretinal surgeons. MAIN OUTCOME MEASURES: Macular hole closure with complete plugging by human amniotic membrane on spectral-domain OCT. RESULTS: The closure rate was 91% (20 of 22; median follow-up, 7 months), with no statistically significant visual acuity change overall. Complications included subretinal silicone oil (5%), choroidal neovascularization (5%), atrophy (5%), and cystoid macular edema (9%). CONCLUSIONS: Anatomical success with limited visual recovery was observed.

Long-Term Efficacy of a Treat-and-Extend Regimen with Ranibizumab in Patients with Neovascular Age-Related Macular Disease: An Open-Label 12-Month Extension to the CANTREAT Study.

INTRODUCTION: The objective of this study is to assess the long-term effectiveness of a treat-and-extend (T&E) anti-vascular endothelial growth factor regimen in patients with neovascular age-related macular degeneration who remain on T&E and those switched from once-monthly (OM) dosing to T&E (OM-T&E). METHODS: In this 12-month extension of the 2-year CANTREAT study, patients received intravitreal ranibizumab 0.5 mg in a T&E regimen. Main outcome measures included mean change in best-corrected visual acuity (BCVA) from baseline and from month 24 to month 36; percentages of patients who gained ≥5, ≥10, or ≥15 Early Treatment of Diabetic Retinopathy Study (ETDRS) letters or lost ≥5, ≥10, or ≥15 letters from baseline and from month 24 to month 36; and number of injections administered from baseline and from month 24 to month 36 for both groups. RESULTS: Of the 139 patients (73 T&E, 66 OM-T&E) in the extension, 121 (68 T&E, 53 OM-T&E) completed 36 months. Mean (standard deviation [SD]) BCVA changes from baseline to the extension last visit (month 33-36) were +6.6 (11.4) letters in the T&E group and +4.8 (14.3) letters in the OM-T&E group, representing maintenance of 24-month gains. The mean (SD) numbers of injections during the extension were 7.3 (2.7) for T&E and 7.1 (2.8) for OM-T&E. DISCUSSION/CONCLUSION: These findings suggest that after 36 months of treatment, the mean BCVA improvement achieved at 24 months is maintained for both the patients exclusively treated with the T&E regimen and those that switched to T&E after 24 months in the OM regimen.

DELAYED-ONSET STREPTOCOCCUS INTERMEDIUS ENDOPHTHALMITIS FOLLOWING ANTI-VASCULAR ENDOTHELIAL GROWTH FACTOR INTRAVITREAL INJECTION.

PURPOSE: Endophthalmitis following intravitreal anti-vascular endothelial growth factor injections is frequently caused by Streptococcus viridans organisms and tends to be aggressive. Herein, we present a case of postinjection Streptococcus viridans endophthalmitis presenting in an atypically delayed fashion with good visual outcome. METHODS: Single clinical case report. RESULTS: A 91-year-old woman treated with aflibercept for exudative age-related macular degeneration of the left eye presented to the emergency department with mild pain and visual acuity decline to counting fingers, pigmented anterior chamber cells and vitreous haze 7 weeks after her most recent intravitreal injection. She had no symptoms of systemic infection. The presumptive diagnosis initially was vitreous hemorrhage. Over 10 days of observation, she developed worsening pain and vitritis suggestive of endophthalmitis, leading us to perform vitrectomy with intravitreal vancomycin and ceftazidime. Vitreous biopsy was culture positive for Streptococcus intermedius , a type of viridans streptococcus typically associated with head and neck abscesses. The infection resolved and the patient's visual acuity returned to her baseline of 20/100, with no recurrence of infection after 4 months of follow-up. CONCLUSSION: The virulence of viridans streptococci capable of producing postinjection endophthalmitis may vary widely. Infection ought to be suspected even in cases of delayed-onset intraocular inflammation.

ASSESSMENT OF CYTOGENETIC DAMAGE TO EXFOLIATED GINGIVAL CELLS IN PATIENTS WITH CHRONIC GENERALIZED PERIODONTITIS.

The aim of this cross-sectional study was to investigate the occurrence of chromosomal abnormalities through the frequency of micronuclei and other genomic damage markers in patients with chronic generalized periodontitis and without periodontal disease. Micronucleus assay was performed in exfoliated gingival epithelial cells of 35 patients with generalized chronic periodontitis and 30 control subjects with healthy periodontium. Full mouth clinical examination was performed to define periodontal condition. The mean number of cells with micronuclei observed in chronic periodontitis and control groups was 1.8 (±1.49) and 2.0 (±1.34), respectively. Differences between the groups were not significant (p=0.574). Compared to control subjects, patients with chronic periodontitis showed a significant increase in the number of binucleated cells (p≤0.001) and number of cells with nucleoplasmic bridges (p=0.042). Study results indicated that chronic periodontitis was not associated with higher occurrence of chromosomal damage in gingival cells compared to individuals with healthy periodontium.

Measurement of the open apices of mandibular first and second premolars to test the chronological age over 14 years: Study on a sample of south Indian children.

Age estimation is an integral part of forensic medical and dental practice. In many countries, the age threshold of 14 years is set to determine the minimum age for criminal responsibility. In the present study, the authors studied the final maturation of the first (IPM1) and second mandibular premolars (IPM2) by Cameriere maturity index and determined cut-offs at the age threshold of 14 years, and validate on the test sample. Orthopantomograms of 960 healthy south Indian children and sub-adults (480 boys and 480 girls) aged between 10 and 18 were analysed, 640 as training sample and 320 as a test sample. The results of logistic regression analysis with age (

Above or below 14 years? An orthopantomographic study based on chronological course of eruption of mandibular premolars and second molars in a sample of south Indian children.

In the context of dental age assessment, two significant factors can be studied; tooth mineralisation and tooth emergence. Little is known about the role of a second molar eruption in forensic age estimation. This paper aims to contribute to forensic age estimation using an age threshold of 14 years, studying the eruption stages of permanent mandibular premolars and second molars. Totally 640 orthopantomograms (OPGs) of south Indian children, aged between 10 and 18 years, were evaluated using Olze et al. staging of tooth eruption stages (A-D). Spearman's rho correlation showed a strong, positive, and statistically significant correlation between the chronological age and the eruption stages of both sexes' teeth. Accuracy, sensitivity, specificity, likelihood ratios, and post-test probability values were calculated for all tested teeth. The best performance to discriminate individuals above or below 14 years showed stage D in second molars. The sensitivity varied between 89% and 94% and specificity between 75% and 84%, respectively. Receiver operating characteristic curve analysis revealed high diagnostic performance for stage D, with area under the ROC curve (AUC) values of 84% and 85% for tooth 37 and 85% and 83% for tooth 47 in males and females, respectively. In conclusion, it is possible to predict age over 14 years in south Indian children using tooth emergence stages from OPGs with a relatively high interobserver agreement and good diagnostic accuracy. However, there are some limitations and, therefore, must be used in conjunction with other methods.

Knowledge and attitudes of water polo coaches about sports-related dental injuries and dental emergency procedures.

BACKGROUND/AIMS: With the growing popularity of water polo across the world, there has been rising awareness of the risks for orofacial injures in water polo. The aim of this study was to evaluate knowledge and attitudes of water polo coaches regarding dental trauma, dental emergency procedures and awareness about prevention of such injuries. MATERIALS AND METHODS: A specific questionnaire comprising 25 questions regarding knowledge, experiences, and behaviors following dental trauma was distributed to 62 water polo coaches during the license renewal seminar held by the Croatian Water Polo Federation, in February 2018 in Split, Croatia. Chi-square with Yates correction when necessary, and Fisher's exact tests were used in statistical analysis, and the results were considered statistically significant when P < .05. RESULTS: There were 51 water polo coaches who participated in this study. Their ages ranged from 19 to 60 years. Most of the coaches (90.2%) have seen a dental injury in their players during their coaching careers. Concerning the procedure with handling an avulsed tooth, there were 68.6% coaches who would maintain the avulsed tooth in a handkerchief or gauze along with four coaches (7.8%) who would rinse the avulsed tooth under water and wrap it in a handkerchief or gauze afterward. Only one participant (2%) would maintain the avulsed tooth in saline solution before its replantation. None of the coaches would use milk for maintaining the avulsed tooth. Only seven coaches (13.7%) have previously had education about sports-related dental injuries, dental emergency procedures, and prevention of such injuries. CONCLUSIONS: The results of this study demonstrated poor level of knowledge of water polo coaches about dental injuries and dental emergency procedures. Their knowledge and attitudes could be improved by educational programs on dental injuries and dental emergency procedures, as well as sports-related dental injuries management.

Age estimation in Turkish children and young adolescents using fourth cervical vertebra.

This study aimed to test radiographic projections of the posterior and anterior sides of the C4 vertebral body for age estimation in a cross-sectional sample of Turkish children and adolescents from the Baskent University Faculty of Dentistry. A sample of 232 x-rays from individuals aged between 5 and 15 years (101 boys and 131 girls) was analysed to investigate the correlation of age and changes in the projection ratio of the anterior and posterior sides of the body of the fourth cervical vertebra (Vba) in lateral cephalograms. The Normal Bayesian Calibration (NBC) model for age estimation was used to assess the relationship between Vba and age. The intra-observer repeatability and inter-observer agreement were 0.95 and 0.94, respectively. Age distribution gradually increased as Vba increased up to 14 years in both sexes. The difference between chronological and estimated ages did not increase with the increase in age. Calibration distributions of the dataset by the evaluation of Vba suggested mean absolute errors (MAEs) of 0.879 years and 0.906 years (mean interquartile ranges (MIQRs) 1.290 and 1.435 years)) in boys and girls, respectively. The biases of the estimates (ßERR) were 0.013 and 0.027 for boys and girls, respectively. In conclusion, the NBC method on Vba variable appears to be suitable for age estimation in Turkish children and adolescents.

Efficacy of a Treat-and-Extend Regimen With Ranibizumab in Patients With Neovascular Age-Related Macular Disease: A Randomized Clinical Trial.

Importance: Although the Canadian Treat-and-Extend Analysis Trial With Ranibizumab in Patients With Neovascular Age-Related Macular Disease (CANTREAT) reported herein and the Treat and Extend study provided data to show noninferiority of treat-and-extend (T&E) at 12 months, to date there are few data on 24-month T&E trials compared with monthly dosing. Objective: To compare the efficacy of ranibizumab using a T&E regimen to monthly dosing in treatment-naive patients with neovascular age-related macular degeneration (nAMD) after 24 months. Design, Setting, and Participants: A randomized, open-label, multicenter, noninferiority intention-to-treat trial with a margin of -5 letters in best-corrected visual acuity (BCVA) from baseline to 12 months between groups was conducted at 27 treatment centers in Canada. Participants included 580 patients with treatment-naive choroidal neovascularization secondary to AMD. The study was conducted from May 8, 2013, to August 28, 2018, and data analysis was performed between August 29 and September 12, 2018. Interventions: Patients with nAMD were randomized 1:1 to receive intravitreal ranibizumab, 0.5 mg, in either a T&E or monthly dosing regimen. Main Outcomes and Measures: Mean change in BCVA in Early Treatment of Diabetic Retinopathy Study letters from baseline to month 24. Results: Of the 580 randomized patients, 350 were women (60.3%) and 547 were white (94.3%). Mean (SD) age was 78.8 (7.8) years. By the end of month 24, 466 of the 580 randomized patients (80.3%) had completed the study and participants in the T&E arm received a mean of 17.6 injections compared with 23.5 injections for the monthly arm, for a difference of 5.9 injections and visits over 2 years (95% CI, 5.4-6.5; P < .001). The mean (SD) BCVA improvement was not worse with the T&E arm, 6.8 (14.1) letters vs 6.0 (12.6) letters, compared with the monthly arm (difference, 0.9; 95% CI, -1.6 to 3.3; P = .21). There was a gain of 15 or more letters in 25.5% of the T&E group and 23.1% of the monthly treatment group (difference, 2.4%; 95% CI, -6.8% to 11.6%; P = .59) and a loss of 15 or more letters in 6.5% of the T&E group and 5.8% of the monthly treatment group (difference, -0.7%; 95% CI, -9.9% to 8.5%; P = .85). Conclusions and Relevance: These findings suggest that change in vision from baseline is not worse with a T&E compared with a monthly regimen of ranibizumab for nAMD through 24 months, achieving clinically meaningful improvements in BCVA despite fewer injections and visits. Trial Registration: ClinicalTrials.gov identifier: NCT02103738.