Bimatoprost Implant Biodegradation in the Phase 3, Randomized, 20-Month ARTEMIS Studies.

Purpose: To evaluate the time course of biodegradation of an intracameral, biodegradable, sustained-release bimatoprost implant that lowers intraocular pressure without the need for daily eye drops. Methods: In 2 identically designed, randomized, phase 3 clinical trials, adults with open-angle glaucoma or ocular hypertension and open iridocorneal angles inferiorly in the study eye were administered 10- or 15-µg bimatoprost implant (day 1 and weeks 16 and 32) or twice-daily topical timolol 0.5%. Implants were assessed on gonioscopy throughout the studies. Investigators reported whether implants were visible, estimated the size of visible implants relative to their initial size at implantation, and reported the implant location. Data for 10-µg implant placed on day 1 were pooled from both studies for analysis. Results: A total of 372 patients received the 10-µg bimatoprost implant. The degree of implant biodegradation at each follow-up time point was variable among patients. The implant frequently swelled during the initial phase of biodegradation from 6 to 28 weeks. Accelerated biodegradation occurred between 31 and 52 weeks, resulting in 82% of implants absent or ≤25% of initial size by 52 weeks. By month 20, 95% of implants had biodegraded to absent or ≤25% of initial size. The implant was predominantly located inferiorly in the iridocorneal angle. Conclusions: Bimatoprost implant biodegradation in phase 3 studies showed some degree of variability among patients. Clinically significant implant biodegradation was observed in the majority of patients by 12 months. Clinical studies are in progress to further understand implant biodegradation and the ideal timing for implant re-administration. ClinicalTrials.gov NCT02247804; ClinicalTrials.gov NCT02250651.

Progesterone, progestins, and the heart.

All combination hormone replacement regimens contain estrogen and a progestational agent. The Women's Health Initiative trial demonstrated that taking the combination of conjugated estrogen and medroxyprogesterone resulted in a higher risk of myocardial infarction and stroke in the study population. However, not all progestational agents are alike in their cardiovascular properties. This article reviews what is known about the most commonly prescribed agents: progesterone, medroxyprogesterone, norethindrone, and norethindrone acetate. We compare data on markers of lipid metabolism, inflammation, and clotting function, and review studies that measure their direct effects on cardiac vessels.

Progesterone, progestins, and the heart.

All combination hormone replacement regimens contain estrogen and a progestational agent. The Women's Health Initiative trial demonstrated that taking the combination of conjugated estrogen and medroxyprogesterone resulted in a higher risk of myocardial infarction and stroke in the study population. However, not all progestational agents are alike in their cardiovascular properties. This article reviews what is known about the most commonly prescribed agents: progesterone, medroxyprogesterone, norethindrone, and norethindrone acetate. We compare data on markers of lipid metabolism, inflammation, and clotting function, and review studies that measure their direct effects on cardiac vessels.

The Clinical Utility of Food Addiction: Characteristics and Psychosocial Impairments in a Treatment-Seeking Sample.

Little is known about the characteristics of individuals seeking treatment for food addiction (FA), and the clinical utility of FA has yet to be established. To address these gaps, we examined (i) the demographic, eating pathology, and psychiatric conditions associated with FA and (ii) whether FA is associated with psychosocial impairments when accounting for eating-related and other psychopathology. Forty-six patients seeking treatment for FA completed self-report questionnaires and semi-structured clinical interviews. The majority of the sample were women and self-identified as White, with a mean age of 43 years. Most participants (83.3%) presented with a comorbid psychiatric condition, most commonly anxiety and mood disorders, with a mean of 2.31 comorbid conditions. FA was associated with binge eating severity and anxiety symptoms, as well as psychological, physical, and social impairment. In regression analyses controlling for binge eating severity, food cravings, depression, and anxiety, FA remained a significant predictor only of social impairment. Taken together, the results suggest that individuals seeking treatment for FA are likely to present with significant comorbid conditions, in particular anxiety disorders. The results of the present research provide evidence for the clinical utility of FA, particularly in explaining social impairment.

A comparison of long-term intraocular pressure fluctuation in patients treated with bimatoprost or latanoprost.

PURPOSE: To evaluate long-term intraocular pressure (IOP) fluctuation in patients with glaucoma or ocular hypertension treated with bimatoprost or latanoprost. DESIGN: Post hoc analysis of prospectively collected data from a previously reported multicenter, investigator-masked, randomized clinical trial of bimatoprost and latanoprost. METHODS: Patients were treated bilaterally with bimatoprost (n = 133) or latanoprost (n = 136) for six months. IOP measurements were taken at 8 am, 12 pm, and 4 pm at baseline, week 1, and months 1, 3, and 6. Long-term IOP fluctuation during treatment was determined as the standard deviation (SD) of all 12 follow-up measurements. RESULTS: There was no significant between-group difference in short-term daily IOP fluctuation at baseline. Long-term IOP fluctuation over six months of treatment [mean SD (range SD)] was 1.9 (0.5 to 6.3) mm Hg with latanoprost vs 1.7 (0.5 to 3.9) mm Hg with bimatoprost (P = .050). Latanoprost-treated eyes were more likely than bimatoprost-treated eyes to have long-term IOP fluctuation of > or =3 mm Hg (7.8% vs 2.5% of eyes; P = .009). CONCLUSIONS: Bimatoprost-treated eyes demonstrated less long-term fluctuation in IOP compared with latanoprost-treated eyes in this six-month study. Additional studies are needed to confirm these findings and to determine their impact on glaucomatous progression.

A Masked, Randomized, Phase 3 Comparison of Triple Fixed-Combination Bimatoprost/Brimonidine/Timolol versus Fixed-Combination Brimonidine/Timolol for Lowering Intraocular Pressure.

OBJECTIVE: To evaluate the efficacy and safety of triple fixed-combination bimatoprost 0.01%/brimonidine 0.15%/timolol 0.5% (TFC) versus dual fixed-combination brimonidine 0.2%/timolol 0.5% (DFC) in primary open-angle glaucoma and ocular hypertension. METHODS: Patients with intraocular pressure (IOP) ≥23 and ≤34 mmHg were randomized to twice-daily TFC or DFC. The primary variable is the change in worse eye mean IOP from baseline at week 12 (modified intent-to-treat (mITT) population). Secondary endpoints are mean IOP and mean change from baseline at weeks 1, 2, 4, 8, and 12 (mITT population). TFC superiority was demonstrated if the primary variable favored TFC (p ≤ 0.05). Sensitivity analyses were conducted, and safety was assessed at all visits. RESULTS: TFC (n = 93) provided greater IOP reductions from baseline than DFC (n = 97) at week 12 (treatment difference, 0.85 mmHg; p = 0.028) and all other visits. TFC was also superior to DFC in patients with high baseline IOP (i.e., IOP ≥ 25 mmHg; p ≤ 0.011). Conjunctival hyperemia, ocular irritation, and dry eye were reported more often with TFC (p ≤ 0.016); however, discontinuations for ocular adverse events were similar between treatments. CONCLUSIONS: TFC demonstrated IOP-lowering benefits that outweigh the risk of predominantly mild ocular side effects, which may be particularly relevant in patients who require greater IOP lowering to prevent/delay disease progression. This trial is registered with ClinicalTrials.gov registry number: NCT01241240.

A randomized, investigator- masked clinical trial comparing the efficacy and safety of gatifloxacin 0.3% administered BID versus QID for the treatment BID versus QID for the treatment of acute bacterial conjunctivitis of acute bacterial conjunctivitis.

PURPOSE: To compare the efficacy and safety of To compare the efficacy and safety of gatifloxacin ophthalmic solution 0.3% (Zymar) administered BID versus QID in patients with acute bacterial conjunctivitis. METHODS: In a randomized, investigator-masked clinical trial, patients diagnosed with bacterial conjunctivitis (based on signs and symptoms) received gatifloxacin either BID or QID for 5 days. Visits were scheduled at day 0, day 3, and day 5. Conjunctival cultures were taken at each visit. The clinical cure rate at day 5 was determined for the entire patient population (primary endpoint). Additionally, clinical cure at day 5 was evaluated for a population of patients defined a priori (per protocol) as being culture positive at baseline and with no substantial protocol deviations. Safety was determined through recording of adverse events. Minimal inhibitory concentrations (MIC) and susceptibility of isolates to gatifloxacin were determined using a broth dilution method. RESULTS: Patient characteristics in both the BID and QID groups (N = 104) were similar in terms NN of baseline demographics and disposition. The clinical cure rate on day 5 in the entire, intentto-treat (ITT) population was 86.5% (45/52) in the gatifloxacin BID group and 71.2% (37/52) in the gatifloxacin QID group (95% CI: [-0.03, 30.80]; p = 0.096). In both treatment groups, 5/52 patients (9.6%) reported adverse events. The most common adverse event was conjunctivitis. No serious adverse events were reported. In the a priori-defined per-protocol (PP) population, the clinical cure rate on day 5 was 95.5% (21/22) in the gatifloxacin BID group and 85.7% (18/21) in the gatifloxacin QID group (95% CI: [-7.57, 21.05]; p = 0.294). At baseline, 96.1% (98/102) of the isolates were susceptible to gatifloxacin. The overall MIC(90) (mean +/- standard error of the mean) was 0.5 +/- 1.3 microg/mL. CONCLUSION: In this study, gatifloxacin 0.3% administered BID was as effective and as safe as gatifloxacin 0.3% administered QID for 5 days for the treatment of bacterial conjunctivitis.

Efficacy of a preservative-free formulation of fixed-combination bimatoprost and timolol (Ganfort PF) in treatment-naïve patients vs previously treated patients.

PURPOSE: To evaluate, using subgroup analysis, the effect of treatment status on the intraocular pressure (IOP)-lowering efficacy of a preservative-free formulation of fixed-combination bimatoprost 0.03%/timolol 0.5% (FCBT PF). METHODS: A primary, multicenter, randomized, double-masked, 12-week study compared the efficacy and safety of FCBT PF with preserved FCBT (Ganfort(®)) in 561 patients diagnosed with glaucoma or ocular hypertension. For this analysis, eligible patients were treatment-naïve or had inadequate IOP lowering and underwent a washout of previous treatment. IOP (8 am, 10 am, and 4 pm) was measured at baseline and weeks 2, 6, and 12. Subgroup analysis of the FCBT PF arm assessed changes in average eye IOP from baseline in treatment-naïve vs previously treated patients. To evaluate the effect of treatment status at baseline (treatment-naïve vs previously treated) on IOP reduction in the FCBT PF treatment group, an analysis of covariance model was used with treatment status and investigator as fixed effects, and baseline average eye IOP, age, glaucoma diagnosis, and baseline average eye corneal thickness as covariates. P-values and the 95% confidence intervals were determined using the model. RESULTS: In the FCBT PF arm, IOP mean changes from baseline ranged from -8.7 mmHg to -9.8 mmHg in treatment-naïve patients (N=50), compared with -7.3 mmHg to -8.5 mmHg in previously treated patients (N=228). Baseline IOP, age, glaucoma diagnosis, and corneal thickness significantly affected IOP reduction in the FCBT PF group. Adjusting for these covariates, FCBT PF had a greater IOP-lowering effect (0.8-1.7 mmHg) in treatment-naïve patients than previously treated patients, which was statistically significant (P≤0.05) at seven of nine time points. CONCLUSION: In this subgroup analysis, FCBT PF reduced IOP more effectively in treatment-naïve than in previously treated patients possibly due, in part, to altered responsiveness or tachyphylaxis that has been associated with prior ocular hypotensive agent treatment.

A randomized, investigator-masked comparison of diurnal responder rates with bimatoprost and latanoprost in the lowering of intraocular pressure.

In glaucoma and ocular hypertension, clinically relevant intraocular pressure lowering due to a new medication is frequently defined as at least a 15% or 20% reduction from baseline intraocular pressure. This report compares the percentages of treated patients achieving such reductions in intraocular pressure after 6 months of treatment with bimatoprost or latanoprost. In the previously published study (Noecker et al: A six-month randomized clinical trial comparing the intraocular pressure-lowering efficacy of bimatoprost and latanoprost in patients with ocular hypertension or glaucoma. Am J Ophthalmol 135:55-63, 2003), patients with glaucoma or ocular hypertension were randomly assigned to once-daily treatment with bimatoprost 0.03% (n=133) or latanoprost 0.005% (n=136), after washout of any previous glaucoma medications. The primary outcome measure of that study was mean change from baseline intraocular pressure. The secondary, post hoc analysis presented here compares the diurnal and long-term responder rates observed with bimatoprost and latanoprost patients. Diurnal responders were defined as patients who achieved at least a 15% or 20% reduction from baseline intraocular pressure at each of the three timepoints (8 am, 12 pm, and 4 pm) on a given visit. At week 1 and months 1, 3, and 6, in the bimatoprost group, 70.7-81.2% of patients achieved at least a 15% reduction in IOP at each timepoint, and 57.9-68.4% achieved at least a 20% reduction. Significantly fewer patients receiving latanoprost achieved a 15% or a 20% decrease in IOP at each timepoint: 48.5-61.8% of patients achieved at least a 15% decrease and 36.0-47.1% achieved at least a 20% decrease. (P< or =.007). The data presented here suggest that patients using bimatoprost are more likely than patients using latanoprost to achieve intraocular pressure reductions of at least 15% or 20% from baseline throughout the day.

Two-year double-masked comparison of bimatoprost with timolol in patients with glaucoma or ocular hypertension.

The object of this study was to compare the long term efficacy and safety of bimatoprost with timolol in patients with glaucoma or ocular hypertension. In a 12-month extension of two identically designed 1-year, multicenter, randomized, double-masked clinical trials, patients were treated topically with bimatoprost 0.03% QD (n=167), bimatoprost 0.03% BID (n=131), or timolol 0.5% BID (n=81). Main outcome measures were IOP at 8 am and 10 am and safety parameters. Bimatoprost QD provided significantly greater mean reduction from baseline IOP than did timolol at both measurements at each study visit (P< or =.001). At 10 am (peak timolol effect) at month 24, the mean reduction from baseline IOP was 7.8 mm Hg with bimatoprost QD and 4.6 mm Hg with timolol (P<.001). Patients treated with bimatoprost QD also sustained significantly lower mean IOP than timolol-treated patients at every follow-up visit throughout the 2-year study period (P< or =.006). At 10 am at month 24, a significantly greater proportion of bimatoprost QD than timolol patients achieved target pressures of < or =13-18 mm Hg (P< or =.010). Bimatoprost sustained an excellent safety profile during the second year of treatment. Most adverse events were mild, and there were no reports of increased iris pigmentation, uveitis, or CME. The incidence of hyperemia was significantly higher with bimatoprost QD (13.8%) than with timolol (2.5%) (P=.006). Mean reduction from baseline IOP with bimatoprost BID was not significantly different from that with timolol at month 24 at 10 am (P=.474). We conclude that bimatoprost QD provides superior IOP lowering to timolol, and is safe and well tolerated over 24 months of treatment.

A six-month randomized clinical trial comparing the intraocular pressure-lowering efficacy of bimatoprost and latanoprost in patients with ocular hypertension or glaucoma.

PURPOSE: To compare the intraocular pressure (IOP)-lowering efficacy and safety of topical bimatoprost 0.03% with latanoprost 0.005%. DESIGN: Multicenter, randomized, investigator-masked clinical trial. METHODS: After washout of glaucoma medications, ocular hypertension or glaucoma patients were randomly assigned to once-daily bimatoprost 0.03% (n = 133) or latanoprost 0.005% (n = 136) for 6 months. The primary outcome measure was mean change from baseline IOP (8 AM, 12 PM, 4 PM). Secondary measures included mean IOP, ophthalmologic examination, adverse events, and the percentage of patients reaching specific target IOPs. RESULTS: Mean change from baseline IOP was significantly greater for bimatoprost patients than for latanoprost patients at all measurements on each study visit; 1.5 mm Hg greater at 8 AM (P <.001), 2.2 mm Hg greater at 12 PM (P <.001), and 1.2 mm Hg greater at 4 PM (P =.004) at month 6. At the end of the study, the percentage of patients achieving a > or = 20% IOP decrease was 69% to 82% with bimatoprost and 50% to 62% with latanoprost (P < or = .003). In addition, the distribution of patients achieving target pressures in each range (< or = 13 to < or = 15 mm Hg, >15 to < or = 18 mm Hg, and > 18 mm Hg) showed that bimatoprost produced lower target pressures compared with latanoprost at all times measured (P < or = .026). Few patients were discontinued for adverse events (6 on bimatoprost; 5 on latanoprost). On ophthalmologic examination, conjunctival hyperemia (P <.001) and eyelash growth (P =.064) were more common in bimatoprost patients. CONCLUSIONS: Bimatoprost is more effective than latanoprost in lowering IOP. Both drugs were well tolerated, with few discontinuations for adverse events.

Expectativas sobre vias de parto entre acadêmicas de psicologia / Expectations regarding the types of delivery among psychology students

Introdução: vários fatores interferem de maneira significativa na escolha da via de parto. No início da gravidez a maioria das mulheres indica preferência pelo parto normal, entretanto, a maior parte termina por fazer a cesárea. No Brasil, 55% dos partos realizados são cesáreas e há um predomínio deste tipo de parto, especialmente no sistema privado de saúde. Objetivo: compreender as expectativas de acadêmicas de Psicologia que nunca passaram pela experiência de parto, sobre as vias de parto. Metodologia: foi utilizado como instrumento de coleta de dados um questionário semiestruturado de autoaplicação individual com questões abertas referentes a expectativas em relação ao parto. A pesquisa configura-se como um estudo qualitativo e para análise de dados foi utilizada a análise de conteúdo. Resultados: participaram da pesquisa 109 mulheres, com média de idade de 22,7 anos, desvio padrão de 4,6, que nunca passaram pela experiência de parto. Estas mulheres demonstraram esperar, principalmente, uma assistência médica de qualidade, desejavam o parto normal por este possibilitar uma recuperação melhor e mais rápida, afirmaram sentirem medo que haja complicações e sofrimento no parto e tinham medo da dor. Conclusão: é necessário fornecer à mulher mais informações, apoio e suporte no momento da escolha da via de parto.

Introduction: various factors significantly interfere in the type of delivery choice. At the start of a pregnancy, the majority of women indicate a preference for a normal delivery, however, a greater part end up having a caesarean delivery. In Brazil, 55% of deliveries performed are Caesarean, and there is a predominance of this type of delivery especially in the private health care system. Objective: to understand the expectations of Psychology students who have never gone through the experience of delivery regarding the types of delivery. Methodology: a self-administrated semi-structured questionnaire with open questions regarding expectations relating to delivery was utilized as a data collection instrument. The research was configured as a qualitative study, and for the data analysis, content analysis was utilized. Results: the participants were 109 women, averaging 22.7 years old with a standard error of 4.6, who never passed through the childbirth experience. These women hoped, principally, for quality medical assistance, and wished for this to enable a better and faster recovery from normal delivery. They stated that they feared that there would be complications and pain during the delivery, and that they were afraid of the pain. Conclusion: it´s necessary to provide more information and support to the woman when choosing the type of delivery.

Control of intraocular pressure and fluctuation with fixed-combination brimonidine-timolol versus brimonidine or timolol monotherapy.

PURPOSE: To evaluate control of intraocular pressure (IOP) and IOP fluctuation in patients with ocular hypertension or glaucoma treated with fixed-combination brimonidine-timolol compared with brimonidine or timolol monotherapy. DESIGN: Post hoc analysis of data from 2 identical, 12-month, randomized, double-masked, multicenter trials. METHODS: Patients were treated bilaterally with fixed brimonidine-timolol twice a day (n = 385), brimonidine tartrate 0.2% 3 times a day (n = 382), or timolol 0.5% twice a day (n = 392). Diurnal IOP was measured at follow-up visits at weeks 2 and 6 and months 3, 6, 9, and 12. IOP fluctuation was defined as the standard deviation of IOP measurements. RESULTS: The percentage of patients with mean diurnal IOP <18 mm Hg and short-term (daily) IOP fluctuation ≤2 mm Hg was statistically significantly higher in the brimonidine-timolol group than in the brimonidine or timolol group at each follow-up visit (at month 12, brimonidine-timolol 43.0%; brimonidine 18.9%, timolol 33.5%, P ≤ .017). At each hour (8 AM, 10 AM, 3 PM, and 5 PM), the percentage of patients with mean IOP <18 mm Hg and long-term (intervisit) IOP fluctuation ≤2 mm Hg was statistically significantly higher with brimonidine-timolol than with brimonidine or timolol alone (at 8 AM, brimonidine-timolol 41.0%, brimonidine 11.3%, timolol 23.7%, P < .001). CONCLUSIONS: Patients treated with fixed-combination brimonidine-timolol were more likely than patients treated with either brimonidine or timolol alone to achieve a combination of low mean IOP and low short-term (daily) or long-term (intervisit) IOP fluctuation.

A 3-month randomized controlled trial of bimatoprost (LUMIGAN) versus combined timolol and dorzolamide (Cosopt) in patients with glaucoma or ocular hypertension.

PURPOSE: To compare the efficacy and safety of topical bimatoprost (LUMIGAN; Allergan, Inc., Irvine, CA) once daily with that of topical combined timolol and dorzolamide (Cosopt; Merck and Co, Inc., Whitehouse Station, NJ) twice daily. DESIGN: Prospective, randomized, double-masked, multicenter clinical trial. PARTICIPANTS: One hundred seventy-seven patients with a diagnosis of glaucoma or ocular hypertension and inadequate control of intraocular pressure (IOP) after at least 2 weeks of topical timolol maleate 0.5% monotherapy. METHODS: Patients were randomized to receive bimatoprost 0.03% once daily (n = 90) or combined timolol 0.5% and dorzolamide 2% twice daily (n = 87) over a 3-month period. MAIN OUTCOME MEASURES: Intraocular pressure, the primary end point, was measured at 8 AM and 10 AM at baseline, week 1, and months 1, 2, and 3, and also at 4 PM and 8 PM at baseline and month 3. RESULTS: Bimatoprost provided significantly greater IOP lowering compared with combined timolol and dorzolamide. At the 8 AM measurements, bimatoprost lowered mean IOP 6.8 mmHg to 7.6 mmHg from baseline, whereas combined timolol and dorzolamide lowered mean IOP 4.4 to 5.0 mmHg from baseline (P<0.001). At the last follow-up, patients had better diurnal IOP control with bimatoprost than combined timolol and dorzolamide. At 8 AM at the 3-month visit, the percentages of patients achieving IOPs of