Netarsudil as an Adjunctive Therapy: Efficacy and Factors Contributing to a Favorable IOP-Lowering Effect.

Purpose: The aim of the study is to assess netarsudil's intraocular pressure (IOP)-lowering potential when prescribed as an adjunctive agent, to examine the effect of baseline IOP on patients' response to netarsudil, and to explore patients' characteristics predictive of pronounced responses to netarsudil. Methods: This is a single-center, multiprovider retrospective cohort study set at Massachusetts Eye and Ear. Patients with a diagnosis of glaucoma or ocular hypertension on netarsudil and at least one other hypotensive agent for glaucoma who had at least one month of follow-up were included. Patients with additional procedures or glaucoma medication changes were excluded. The main outcome measures were IOP reduction, Kaplan-Meier survival analyses, netarsudil responder type, and complication rates. Results: 236 eyes of 236 patients were included. The mean baseline IOP was 19.06 ± 4.6 mmHg on an average of 4 ocular hypotensive medications. 196 (83.1%) patients experienced IOP reduction at the first follow-up visit of 2.84 ± 0.30 mmHg at 55.66 ± 51.89 days. IOP reduction at the second visit among these patients was 3.01 ± 0.44 mmHg at 133.24 ± 77.63 days. After starting netarsudil, 59% had a sustained response (median duration of 315 days), 25% had a robust response (>20% IOP reduction for at least 80% of visits), and 10% had a super response (>20% and >10 mmHg IOP reduction). Netarsudil was effective as an adjunctive therapy across all baseline IOP categories with greater relative IOP reduction in higher baseline IOP groups. Conclusions: Netarsudil is an effective adjunctive glaucoma therapy. IOP reductions between 2 and 3 mmHg are typical, but a minority had more pronounced and sustained effects (>10 mmHg). Further analysis is needed to assess specific demographic and clinical factors predictive of these robust responses.

Effectiveness of Selective Laser Trabeculoplasty Applied to 360° vs. 180° of the Angle.

PURPOSE: To compare the effectiveness and safety of 360° and 180° of Selective Laser Trabeculoplasty (SLT) for the treatment of elevated intraocular pressure (IOP). METHODS: Retrospective cohort study. The main outcome measure was the Kaplan-Meier analysis comparing the cumulative probabilities of survival between the 360° and 180° SLT groups in terms of IOP reduction. Success was defined as ≥20% IOP reduction from baseline with an IOP between 5-18 mmHg and ≤1 glaucoma medication added postoperatively. Additional outcome measures included changes in average IOP, number of glaucoma medications, and the incidence of postoperative IOP spikes. Measurements were obtained at 6 weeks, 1 year, and 2 years postoperatively. RESULTS: Two hundred and fifty-eight eyes of 258 patients were included in the 360° group, and 196 eyes of 196 patients were included in the 180° group. The mean IOP reductions at 2 years were 2.21 ± 2.02 mmHg and 2.43 ± 1.81 mmHg (p=0.33) in the 180° and 360° groups, respectively. There were no significant differences in the incidence of postoperative IOP spikes between the two groups. There was a significant difference in the survival curves of the two groups (p=0.035). The Cox proportional-hazard model indicated that 360° of SLT application was a significant predictor of long-term success (p=0.030). CONCLUSIONS: 360° of SLT application seems to provide for greater long-term IOP control than 180° of application without putting patients at an elevated risk for postoperative IOP spikes.

Exploring discrimination towards pharmacists in practice settings

BACKGROUND: Discrimination towards pharmacists, as a public-facing health professional group, is reported but not well-studied. OBJECTIVES: The aims of this study were to identify accounts of discrimination in pharmacy practice and to explore the nature and impacts of and discrimination experienced by pharmacists. METHODS: A cross-sectional survey was emailed to practice-based preceptors associated with the School of Pharmacy at the University of Otago. The survey included demographic questions, in addition to questions asking about the frequency and sources of different types of discrimination and abuse encountered in practice. Survey respondents could also provide their contact information for follow-up interviews. Interviews occurred after completion of the survey to better understand the nature of discrimination in pharmacy practice. A thematic analysis of interview transcripts was conducted to identify pertinent themes. RESULTS: A total of 43 participants completed the survey. A total of 29 (67.4%) respondents reported experiencing discrimination in pharmacy practice. The most common types of discrimination experienced included discrimination based on gender, appearance, or past, present, or expected pregnancy. Verbal abuse and sexual harassment were also frequently reported. Most discrimination was sourced from patients, colleagues, or supervisors/leaders. Discrimination specific to pregnancy was largely sourced from supervisors/leaders. Verbal abuse was sources primarily from patients, patient's family, supervisors/leaders, and other healthcare professionals. Patients were the primary source of sexual harassment. Three themes were identified from the interview phase: Discrimination occurs for a variety of reasons from different sources with different behaviors, the impact on a person is individualized/personal, and preventative strategies can be broad and encompass multiple layers of society. CONCLUSIONS: Findings of this study support the notion that training programs must adjust to adequately train pharmacists with effective coping strategies, prevention mechanisms, and resilience building strategies. Pharmacist employers should also be accountable to creating zero tolerance workplaces and providing route maps for how pharmacists report and navigate situations when faced with discrimination. Doing so may result in a better equipped workforce that is able to navigate the pressures encountered through discrimination in practice

No disponible

Exploring discrimination towards pharmacists in practice settings.

BACKGROUND: Discrimination towards pharmacists, as a public-facing health professional group, is reported but not well-studied. OBJECTIVES: The aims of this study were to identify accounts of discrimination in pharmacy practice and to explore the nature and impacts of and discrimination experienced by pharmacists. METHODS: A cross-sectional survey was emailed to practice-based preceptors associated with the School of Pharmacy at the University of Otago. The survey included demographic questions, in addition to questions asking about the frequency and sources of different types of discrimination and abuse encountered in practice. Survey respondents could also provide their contact information for follow-up interviews. Interviews occurred after completion of the survey to better understand the nature of discrimination in pharmacy practice. A thematic analysis of interview transcripts was conducted to identify pertinent themes. RESULTS: A total of 43 participants completed the survey. A total of 29 (67.4%) respondents reported experiencing discrimination in pharmacy practice. The most common types of discrimination experienced included discrimination based on gender, appearance, or past, present, or expected pregnancy. Verbal abuse and sexual harassment were also frequently reported. Most discrimination was sourced from patients, colleagues, or supervisors/leaders. Discrimination specific to pregnancy was largely sourced from supervisors/leaders. Verbal abuse was sources primarily from patients, patient's family, supervisors/leaders, and other healthcare professionals. Patients were the primary source of sexual harassment. Three themes were identified from the interview phase: Discrimination occurs for a variety of reasons from different sources with different behaviors, the impact on a person is individualized/personal, and preventative strategies can be broad and encompass multiple layers of society. CONCLUSIONS: Findings of this study support the notion that training programs must adjust to adequately train pharmacists with effective coping strategies, prevention mechanisms, and resilience building strategies. Pharmacist employers should also be accountable to creating zero tolerance workplaces and providing route maps for how pharmacists report and navigate situations when faced with discrimination. Doing so may result in a better equipped workforce that is able to navigate the pressures encountered through discrimination in practice.

Immune Signatures Associated With Clonal Isotype Switch After Autologous Stem Cell Transplantation for Multiple Myeloma.

BACKGROUND: High-dose chemotherapy and autologous stem cell transplantation (ASCT) are integral components of the overall treatment for patients with multiple myeloma (MM) aged ≤ 65 years. The emergence of oligoclonal immunoglobulin bands (ie, immunoglobulins differing from those originally identified at diagnosis [termed clonal isotype switch (CIS)]) has been reported in patients with MM after high-dose chemotherapy followed by autologous stem cell transplantation. However, the clinical relevance and the correlation with immune reconstitution remains unclear. PATIENTS AND METHODS: Patients with MM who had undergone ASCT from 2007 to 2016 were included in the present study. The percentage of natural killer cells, B-cells, and T-cells was measured using flow cytometry in pre- and post-ASCT bone marrow samples. CIS was defined as the appearance of a new serum monoclonal spike on serum protein electrophoresis and immunofixation that differed from original heavy or light chain detected at diagnosis. RESULTS: A retrospective analysis of 177 patients with MM who had undergone ASCT detected CIS in 39 (22%). CIS after ASCT correlated with improved progression-free survival (52.2 vs. 36.6 months; P = .21) and overall survival (75.1 vs. 65.4 months; P = .021). Patients with a relapse had an isotype that differed from a CIS, confirming the benign nature of this phenomenon. CIS was also associated with lower CD8 T-cell percentages and a greater CD4/CD8 ratio (2.8 vs. 0.2; P = .001) compared with patients who did not demonstrate a CIS, suggestive of more profound T-cell immune reconstitution in this group. CONCLUSION: Taken together, our data have demonstrated that a CIS is a benign phenomenon and correlates with a reduced disease burden and enriched immune repertoire beyond the B-cell compartment.

Timing Embryo Preservation for a Patient with High-Risk Newly Diagnosed Acute Myeloid Leukemia.

Great strides have been made in the treatment of acute myeloid leukemia (AML) resulting in increased number of survivors over all age groups, but especially in patients of reproductive age. Given the gonadotoxicity of high-dose induction chemotherapy and subsequent allogeneic stem cell transplant, it is paramount that fertility preservation options are discussed and explored at the time of diagnosis as fertility preservation has been associated with greater quality of life in survivors. Starting the conversation early is especially important for female patients given the time needed for all currently available fertility preservation techniques. Furthermore, due to a lack of current guidelines for the optimal timing of treatment, patients often encounter difficulties trying to balance life-saving treatment and fertility preservation. We present a case of female patient of reproductive age diagnosed with AML who opted for ovarian stimulation, oocyte retrieval, and subsequent IVF following a cycle of induction chemotherapy with satisfactory results for both embryo generation and disease treatment.

Predicting Successful Phase Advancement and Regulatory Approval in Multiple Myeloma From Phase I Overall Response Rates.

PURPOSE: Drug development in oncology is resource intensive, time consuming, and frequently unsuccessful. Here, we hypothesized that therapeutic benefit of published phase I studies of antimyeloma investigational agents was associated with advancement to phase II and future regulatory approval. PATIENTS AND METHODS: Seventy four phase I trials that treated patients with multiple myeloma (n = 2,408) conducted from 2004 to 2015 were analyzed to assess drug safety, efficacy, phase advancement, and regulatory approval. RESULTS: The median overall response rate (ORR) for all single-agent trials evaluated was 13.2%. However, the ORR in trials that advanced to phase II was 19%, whereas it was only 4% in trials that failed to advance. The median ORR was 23% for trials testing agents that were ultimately approved by the US Food and Drug Administration compared with only 8% for trials testing agents that were not approved (hazard ratio, 2.21; 95% CI, 2.01 to 2.61; P = .012). Importantly, the absolute number of phase I trials in multiple myeloma, but not the success rate, significantly increased over the period studied. The proportion of industry-sponsored trials also steadily increased over that same period. The ratio of initial dose to maximum tolerated dose was 0.29, suggesting that many patients were undertreated. CONCLUSION: Investigational agents with higher ORRs in phase I trials were more likely to advance to phase II trials and achieve US Food and Drug Administration approval. Our results suggest that designing phase I trials to maximize the antimyeloma efficacy of a given compound may lead to more successful and cost-effective drug development.

A piezoelectric immunosensor for specific capture and enrichment of viable pathogens by quartz crystal microbalance sensor, followed by detection with antibody-functionalized gold nanoparticles.

A sensitive bacteria enrichment and detection system for viable Escherichia coli O157:H7 was developed using a piezoelectric biosensor-quartz crystal microbalance (QCM) with antibody-functionalized gold nanoparticles (AuNPs) used as detection verifiers and amplifiers. In the circulating-flow QCM system, capture antibodies for E. coli O157:H7 were first immobilized onto the QCM chip. The sample containing E. coli O157:H7 was circulated through the system in the presence of 10 ml of brain heart infusion (BHI) broth for 18 h. The cells of E. coli O157:H7 specifically captured and enriched on the chip surface of the QCM were identified by QCM frequency changes. Listeria monocytogenes and Salmonella Typhimurium were used as negative controls. After bacterial enrichment, detection antibody-functionalized AuNPs were added to enhance the changes in detection signal. The use of BHI enrichment further enhanced the sensitivity of the developed system, achieving a detection limit of 0-1 log CFU/ml or g. The real-time monitoring method for viable E. coli O157:H7 developed in this study can be used to enrich and detect viable cells simultaneously within 24h. The unique advantages of the system developed offer great potential in the microbial analysis of food samples in routine settings.