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1.
Int J Biol Sci ; 16(3): 435-446, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32015680

RESUMO

Purpose: Drug-induced nephrotoxicity can occur in patients with pre-existing renal dysfunction or renal ischemia, potentially leading to chronic kidney disease (CKD) and end-stage renal disease (ESRD). Prompt treatment of CKD and the related side effects is critical in preventing progression to ESRD. The goal of this study was to demonstrate the therapeutic potential of urine-derived stem cells (USC) to treat chronic kidney disease-induced by nephrotoxic drugs and renal ischemia. Materials and methods: Human USC were collected, expanded and characterized by flow cytometry. A CKD model was induced by creating an ischemia-reperfusion injury and gentamicin administration. Twenty-eight adult immunodeficient rats were divided into three groups: PBS-treated group (n=9), USC-treated group (n=9), and sham group with age-matched control animals (n=10). Cell suspension of USC (5 x 106 / 100µl / kidney) or PBS was injected bilaterally into the renal parenchyma 9 weeks after CKD model creation. Renal function was evaluated by collection blood and urine samples to measure serum creatinine and glomerulus filtration rate. The kidneys were harvested 12 weeks after cell injection. Histologically, the extent of glomerulosclerosis and tubular atrophy, the amount of collagen deposition, interstitial fibrosis, inflammatory monocyte infiltration, and expression of transforming growth factor beta 1 (TGF-ß1), and superoxide dismutase 1 (SOD-1) were examined. Results: USC expressed renal parietal epithelial cells (CD24, CD29 and CD44). Renal function, measured by GFR and serum Cr in USC-treated group were significantly improved compared to PBS-treated animals (p<0.05). The degree of glomerular sclerosis and atrophic renal tubules, the amount of fibrosis, and monocyte infiltration significantly decreased in USC-treated group compared to the PBS group (p<0.05). The level of TGF-ß1 expression in renal tissues was also significantly lower in the PBS group, while the level of SOD-1 expression was significantly elevated in the USC group, compared to PBS group (p<0.05). Conclusions: The present study demonstrates the nephron-protective effect of USC on renal function via anti-inflammatory, anti-oxidative stress, and anti-fibrotic activity in a dual-injury CKD rat model. This provides an alternative treatment for CKD in certain clinical situations, such as instances where CKD is due to drug-induced nephrotoxicity and renal ischemia.

2.
J Sex Med ; 2020 Jan 27.
Artigo em Inglês | MEDLINE | ID: mdl-32001204

RESUMO

INTRODUCTION: The human placenta provides a bountiful and noncontroversial source of stem cells which have the potential for regeneration of injured tissue. These cells may restore erectile function after neurovascular tissue injury such as that seen in radical pelvic surgeries and pelvic trauma. AIM: To determine the effect of human placenta-derived stem cells on erectile function recovery and histological changes at various time points in a cavernous nerve injury rat model and to study the fate of injected stem cells throughout the regenerative process. METHODS: Human placental stem cells (PSCs) were dual labeled with monomeric Katushka far red fluorescent protein (mKATE)-renLUC using a lentivirus vector. A pelvic neurovascular injury-induced erectile dysfunction model was established in male, athymic rats by crushing the cavernous nerves and ligating the internal pudendal neurovascular bundles, bilaterally. At the time of defect creation, nonlabeled PSCs were injected into the corpus cavernosum at a concentration of 2.5 × 106 cells/0.2 mL. The phosphate-buffered saline-treated group served as the negative control group, and age-matched rats (age-matched controls) were used as the control group. Erectile function, histomorphological analyses, and Western blot were assessed at 1, 6, and 12 weeks after model creation. The distribution of implanted, dual-labeled PSCs was monitored using an in vivo imaging system (IVIS). Implanted cells were further tracked by detection of mKATE fluorescence in histological sections. MAIN OUTCOME MEASURE: The main outcome measure includes intracavernous pressure/mean arterial pressure ratio, neural, endothelial, smooth muscle cell regeneration, mKATE fluorescence, and IVIS imaging. RESULTS: The ratio of intracavernous pressure to mean arterial pressure significantly increased in PSC-injected rats compared with phosphate-buffered saline controls (P < 0.05) at the 6- and 12-week time points, reaching 72% and 68% of the age-matched control group, respectively. Immunofluorescence staining and Western blot analysis showed significant increases in markers of neurons (84.3%), endothelial cells (70.2%), and smooth muscle cells (70.3%) by 6 weeks in treatment groups compared with negative controls. These results were maintained through 12 weeks. IVIS analysis showed luminescence of implanted PSCs in the injected corpora immediately after injection and migration of cells to the sites of injury, including the incision site and periprostatic vasculature by day 1. mKATE fluorescence data revealed the presence of PSCs in the penile corpora and major pelvic ganglion at 1 and 3 days postoperatively. At 7 days, immunofluorescence of penile PSCs had disappeared and was diminished in the major pelvic ganglion. CLINICAL IMPLICATIONS: Placenta-derived stem cells may represent a future "off-the-shelf" treatment to mitigate against development of erectile dysfunction after radical prostatectomy or other forms of pelvic injury. STRENGTH & LIMITATIONS: Single dose injection of PSCs after injury resulted in maximal functional recovery and tissue regeneration at 6 weeks, and the results were maintained through 12 weeks. Strategies to optimize adult stem cell therapy might achieve more effective outcomes for human clinical trials. CONCLUSION: Human PSC therapy effectively restores the erectile tissue and function in this animal model. Thus, PSC therapy may provide an attractive modality to lessen the incidence of erectile dysfunction after pelvic neurovascular injury. Further improvement in tissue regeneration and functional recovery may be possible using multiple injections or systemic introduction of stem cells. Gu X, Thakker PU, Matz EL, et al. Dynamic Changes in Erectile Function and Histological Architecture After Intracorporal Injection of Human Placental Stem Cells in a Pelvic Neurovascular Injury Rat Model. J Sex Med 2019; XX:XXX-XXX.

3.
J Palliat Care ; : 825859719892083, 2020 Jan 23.
Artigo em Inglês | MEDLINE | ID: mdl-31973645

RESUMO

BACKGROUND: Palliative care has been developed in recent years in many sub-Saharan countries in Africa due to activities of African Association for Palliative Care. Palliative care units have been established also in most hospitals in Tanzania. Yet very little is known about their functions. Long-term studies about the sustainability of palliative care have not been carried out. METHODS: The attitudes of 101 members of hospital staff and persons in charge of palliative care services of Ilembula District Designated Hospital (IDDH), Tanzania, were assessed using a modified and prevalidated questionnaire annually in 2014 to 2017. The inquiries were executed on randomly allocated days. Also, the patient and economy registries were analyzed. Additional qualitative data were obtained in personal interviews and during observational visits twice a year at the IDDH. RESULTS: Ilembula District Designated Hospital has a true multiprofessional palliative care team, which provides services in the hospital, in the villages, and at homes. The activities are based on careful 5-year planning and budgeting. Up to 17 villages have been included in the services. Ninety-five percent of the patients were HIV infected. Short-acting morphine oral solution was the only available strong opioid. The hospital staff evaluated palliative care as good or excellent; 50% of the staff would need more support in the end-of-life care. CONCLUSIONS: A sustainable palliative care service can be built in a Tanzanian rural hospital if an advanced planning and budgeting are made. In Tanzania, the biggest group of palliative care patients are still HIV-infected individuals. There is a lack of opioids in the country.

4.
Pharm Res ; 37(3): 36, 2020 Jan 21.
Artigo em Inglês | MEDLINE | ID: mdl-31965346

RESUMO

PURPOSE: We describe the preparation of injectable polymeric paste (IPP) formulations for local and sustained release of drugs. Furthermore, we include the characterization and possible applications of such pastes. Particular attention is paid to characteristics relevant to the successful clinical formulation development, such as viscosity, injectability, degradation, drug release, sterilization, stability performance and pharmacokinetics. METHODS: Paste injectability was characterized using measured viscosity and the Hagen-Poiseuille equation to determine injection forces. Drug degradation, release and formulation stability experiments were performed in vitro and drug levels were quantified using HPLC-UV methods. Pharmacokinetic evaluation of sustained-release lidocaine IPPs used five groups of six rats receiving increasing doses subcutaneously. An anti-cancer formulation was evaluated in a subcutaneous tumor xenograft mouse model. RESULTS: The viscosity and injectability of IPPs could be controlled by changing the polymeric composition. IPPs demonstrated good long-term stability and tunable drug-release with low systemic exposure in vivo in rats. Preliminary data in a subcutaneous tumor model points to a sustained anticancer effect. CONCLUSIONS: These IPPs are tunable platforms for local and sustained delivery of drugs and have potential for further clinical development to treat a number of diseases.

5.
Res Dev Disabil ; 97: 103545, 2020 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-31811993

RESUMO

BACKGROUND: Research suggests that autistic individuals may be more likely to come into contact with police and have more negative experiences in police custody. However, limited information about the difficulties they experience during the custody process is available. AIMS: This study explores the experiences of autistic individuals and officers during a walkthrough of the custody process to identify specific difficulties in these encounters and what support is needed to overcome these. METHODS AND PROCEDURES: A participative walkthrough method was developed to provide autistic individuals and officers an interactive opportunity to identify areas where further support in the custody process was needed. Two autistic participants and three officers took part in the study. OUTCOMES AND RESULTS: Autistic participants reported negative experiences due to: i) the emotional impact of the physical setting and custody process ii) communication barriers leading to increased anxiety and iii) exposure to sensory demands. Officers highlighted three factors which limit their ability to support autistic individuals effectively: i) the custody context ii) barriers to communication and iii) knowledge and understanding of autism. CONCLUSIONS AND IMPLICATIONS: Adjustments are needed to the custody process and environment to support interactions between autistic individuals and officers and improve the overall wellbeing of autistic individuals.

6.
Stem Cells Transl Med ; 9(1): 80-92, 2020 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-31328435

RESUMO

There is a need for effective wound treatments that retain the bioactivity of a cellular treatment, but without the high costs and complexities associated with manufacturing, storing, and applying living biological products. Previously, we developed an amnion membrane-derived hydrogel and evaluated its wound healing properties using a mouse wound model. In this study, we used a full thickness porcine skin wound model to evaluate the wound-healing efficacy of the amnion hydrogel and a less-processed amnion product comprising a lyophilized amnion membrane powder. These products were compared with commercially available amnion and nonamnion wound healing products. We found that the amnion hydrogel and amnion powder treatments demonstrated significant and rapid wound healing, driven primarily by new epithelialization versus closure by contraction. Histological analysis demonstrated that these treatments promote the formation of a mature epidermis and dermis with similar composition to healthy skin. The positive skin regenerative outcomes using amnion hydrogel and amnion powder treatments in a large animal model further demonstrate their potential translational value for human wound treatments.

7.
Ultrasonics ; 101: 106033, 2020 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-31561207

RESUMO

The objective of this study was to use ultrasound in combination with nanoparticulate formulations of taxane drugs for an additive approach to overcome multidrug resistance (MDR). Polymeric nanoparticulate formulations containing both chemotherapeutic taxane drugs and a polymeric inhibitor (MePEG17-b-PCL5) of drug resistant proteins have been previously developed in an attempt to overcome MDR in cells. High frequency (>1 MHz) ultrasound has been shown to increase the uptake of cytotoxic drugs in MDR proliferating cells and has been suggested as a different way to overcome MDR, resensitize drug resistant cancer cells and allow for chemotherapeutic efficacy. MDCK-MDR cells were incubated with docetaxel (DTX) or paclitaxel (PTX) loaded, solid core, nanoparticles made from a 50:50 ratio of two diblock copolymers, MePEG114-b-PCL200 and MePEG17-b-PCL5 (PCL200/PCL5). The accumulation of drug in MDCK-MDR cells was measured using radiolabeled drug and the viability of cells was determined using an MTS cell proliferation assay. The effect of ultrasound (4 MHz, 32 W/cm2, 10 s, 25% duty cycle) on drug uptake and cell viability was studied. Using free DTX or PTX, MDCK-MDR cells were killed at sublethal doses of drug with the P-gp inhibitor (MePEG17-b-PCL5) present at a concentration of just 0.006% (m/v) and cell death began after just 3 h of incubation. Using sublethal incubation doses of PTX or DTX in PCL200/PCL5 nanoparticles for 90 min, followed by a second exposure to blank PCL200/PCL5 nanoparticles, cell viability dropped by approximately 60% at 24 h. Drug accumulation increased by 1.43-1.9 fold following five bursts of ultrasound applied at 90 min. Both, increased ultrasound exposure and increased concentrations of blank nanoparticles during the second incubation allowed for increased levels of cell death. The combined use of ultrasound with taxane and P-gp inhibitor loaded polymeric nanoparticles may allow for increased accumulation of drug and inhibitor which may then release both agents inside cells in a controlled manner to overcome drug resistance in MDR cells.


Assuntos
Membro 1 da Subfamília B de Cassetes de Ligação de ATP/antagonistas & inibidores , Antineoplásicos Fitogênicos/farmacologia , Docetaxel/farmacologia , Nanopartículas/química , Paclitaxel/farmacologia , Polietilenoglicóis/farmacologia , Ondas Ultrassônicas , Animais , Antineoplásicos Fitogênicos/química , Proliferação de Células/efeitos dos fármacos , Sobrevivência Celular/efeitos dos fármacos , Docetaxel/química , Cães , Sistemas de Liberação de Medicamentos , Resistência a Múltiplos Medicamentos , Resistencia a Medicamentos Antineoplásicos , Paclitaxel/química , Polietilenoglicóis/química , Polímeros/química , Polímeros/farmacologia , Células Tumorais Cultivadas
8.
Artigo em Inglês | MEDLINE | ID: mdl-31767941

RESUMO

OBJECTIVE: Focal therapy has emerged as a treatment option for low- to intermediate-risk localized prostate cancer (PCa) patients, to balance the risks for urinary and sexual morbidity of radical treatment with the psychological burden of active surveillance. In this context, we developed ST-4PC, an injectable, polymeric paste formulation containing docetaxel (dtx) and bicalutamide (bic) for image-guided focal therapy of PCa. The objective of this work was to evaluate the in vitro characteristics and in vivo toxicity and efficacy of ST-4PC. MATERIAL AND METHODS: In vitro drug release was evaluated using high-performance liquid chromatography. In vivo toxicity of blank- and drug-loaded ST-4PC was assessed in mice and rats. Tumor growth inhibition was evaluated in LNCaP subcutaneous (s.c.) and LNCaP-luc orthotopic xenograft models. Using the s.c. model, mice were monitored weekly for weight loss, tumor volume (TV) and serum PSA. For the orthotopic model, mice were additionally monitored for bioluminescence as measure of tumor growth. RESULTS: ST-4PC demonstrated a sustained and steady release of incorporated drugs with 50% dtx and 20% bic being released after 14 days. While no systemic toxicity was observed, dose-dependent local side effects from dtx developed in the s.c. but not in the orthotopic model, illustrating the limitations of s.c. models for evaluating local cytotoxic therapy. In the s.c. model, 0.1%/4% and 0.25%/4% dtx/bic ST-4PC paste significantly reduced PSA progression, but did not have a significant inhibitory effect on TV. ST-4PC loaded with 1%/4% dtx/bic significantly reduced TV, serum PSA, and bioluminescence in the orthotopic xenograft model. Compared with drugs dissolved in DMSO, ST-4PC significantly delayed tumor growth. CONCLUSION: Image-guided focal therapy using ST-4PC demonstrated promising inhibition of PSA progression and orthotopic tumor growth in vivo without significant toxicity, and warrants further clinical evaluation.

9.
Cell Transplant ; 28(12): 1542-1551, 2019 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-31684762

RESUMO

This study investigated the safety of a novel cell-labeling technology with mKATE and Renilla reniformis luciferase (mKATE-renLUC) and assessed the efficacy on tracking implanted human placental stromal cells (PSC) in an erectile dysfunction (ED) animal model. Human PSC were labeled with mKATE-renLUC using a lentivirus. Cell viability, apoptosis, proliferation, migration, surface marker expression and differentiation potential of the labeled PSC were evaluated and compared with non-labeled PSC. The paracrine profile of labeled cells was examined using an angiogenesis protein array. The brightness and duration of labeled cells with different densities were evaluated. An ED rat model was established and labeled PSC were injected into cavernosal tissue of the penis. The migration and distribution of transplanted PSC were monitored using an IVIS imaging system in real time. Implanted PSC were identified in isolated tissues via detection of mKATE fluorescence. The cell viability, morphology, proliferation, migration, surface marker expression and differentiation potential of mKATE-renLUC-labeled PSC were similar to those of non-labeled cells in vitro (no statistical difference p>0.05). Similar expressions of trophic factors were found between labeled and non-labeled PSC. The migration and distribution of PSC expressing renLUC were tracked in vivo using IVIS imaging system. mKATE-positive PSC were detected in penile, kidney, prostate and hepatic tissues using histological methods. This labeling technology provides a safe and effective cell-tracking approach with a brighter fluorophore and codon-optimized luciferase.

10.
J Couns Psychol ; 2019 Oct 14.
Artigo em Inglês | MEDLINE | ID: mdl-31613128

RESUMO

Therapists and clients often have different perspectives about what is helpful and what they wish for in therapy, but it is unclear how their perspectives differ and whether their agreement have implications for therapy outcome. In a mixed-method study, 18 therapists and clients were interviewed separately after termination about their experiences and what they wished had been different about their psychotherapy. Transcripts were analyzed using consensual qualitative research. Therapists and clients agreed moderately that exploration of the therapeutic relationship, therapists' use of challenges, and therapist validation and support were helpful. In contrast, there was low agreement on wishes. Whereas clients wished that therapists had provided more structure and direction, therapists did not mention any typical wishes. Using multilevel modeling, a high level of agreement on what was helpful was associated with reductions in psychological symptoms and interpersonal problems, although no relationship was found between agreement on wishes and outcome. The findings underscore the importance of therapist-client agreement about helpful aspects of therapy for successful therapy. (PsycINFO Database Record (c) 2019 APA, all rights reserved).

11.
Proc Biol Sci ; 286(1912): 20191584, 2019 Oct 09.
Artigo em Inglês | MEDLINE | ID: mdl-31594514

RESUMO

Capturing wild animals is common for conservation, economic or research purposes. Understanding how capture itself affects lifetime fitness measures is often difficult because wild and captive populations live in very different environments and there is a need for long-term life-history data. Here, we show how wild capture influences reproduction in 2685 female Asian elephants (Elephas maximus) used in the timber industry in Myanmar. Wild-caught females demonstrated a consistent reduction in breeding success relative to captive-born females, with significantly lower lifetime reproduction probabilities, lower breeding probabilities at peak reproductive ages and a later age of first reproduction. Furthermore, these negative effects lasted for over a decade, and there was a significant influence on the next generation: wild-caught females had calves with reduced survival to age 5. Our results suggest that wild capture has long-term consequences for reproduction, which is important not only for elephants, but also for other species in captivity.

12.
J Appl Oral Sci ; 27: e20180663, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31596368

RESUMO

OBJECTIVE: To investigate the use of polymethyl methacrylate (PMMA) electrospun fiber mats containing different amounts of polyethylene oxide (PEO) as a doxycycline delivery system and to test antibacterial activity against an oral pathogen. METHODOLOGY: PMMA powders or PEO (mol wt 200 Kd) (10,20,30% w/w/) were dissolved in N, N-dimethylformamide (DMF) to obtain a final polymer concentration of 15% in DMF (w/v). 2% Doxycycline monohydrate was added to the solutions and submitted to vortex mixing. The solution was transferred to a plastic syringe and fit into a nanofiber electrospinning unit. The parameters applied were: voltage at 17.2 kV; distance of 20 cm between the needle tip and the collector plate; target speed at 2 m/min; and transverse speed at 1cm/min. Syringe pump speed was 0.15 mm/min. The drug release analysis was performed by removing aliquots of the drug-containing solution (in PBS) at specific periods. Doxycycline release was quantified using RP-HPLC. Fiber mats from all groups had their antibacterial action tested against S. mutans based on inhibition halos formed around the specimens. The experiments were performed in triplicate. Gravimetric analysis at specific periods was performed to determine any polymer loss. Morphological characterization of the electrospun fibers was completed under an optical microscope followed by SEM analysis. RESULTS: The addition of PEO to the PMMA fibers did not affect the appearance and diameter of fibers. However, increasing the %PEO caused higher doxycycline release in the first 24 h. Fibers containing 30% PEO showed statistically significant higher release when compared with the other groups. Doxycycline released from the fibers containing 20% or 30% of PEO showed effective against S. mutans. CONCLUSION: The incorporation of PEO at 20% and 30% into PMMA fiber mat resulted in effective drug release systems, with detected antibacterial activity against S. mutans.


Assuntos
Antibacterianos/farmacocinética , Doxiciclina/farmacocinética , Nanofibras/química , Polietilenoglicóis/farmacocinética , Polimetil Metacrilato/farmacocinética , Análise de Variância , Antibacterianos/química , Cromatografia Líquida de Alta Pressão/métodos , Doxiciclina/química , Imersão , Microscopia Eletrônica de Varredura , Peso Molecular , Polietilenoglicóis/química , Polimetil Metacrilato/química , Reprodutibilidade dos Testes , Streptococcus mutans/efeitos dos fármacos , Fatores de Tempo , Água/química
13.
Mayo Clin Proc ; 94(11): 2220-2229, 2019 11.
Artigo em Inglês | MEDLINE | ID: mdl-31619367

RESUMO

OBJECTIVE: To assess the patterns of angiotensin converting enzyme inhibitors and angiotensin receptor blockers (ACE-I/ARB) discontinuation in the setting of chronic kidney disease (CKD) progression in real-world clinical practice. PATIENTS AND METHODS: We identified incident ACE-I/ARB users with a baseline estimated glomerular filtration rate (eGFR) ≥15 mL/min/1.73 m2 and without end-stage renal disease in the Geisinger Health System between January 1, 2004, and December 31, 2015. We investigated the associations of CKD stage, hospitalizations with and without acute kidney injury (AKI), serum potassium, bicarbonate level, thiazide, and loop diuretic use with ACE-I/ARB discontinuation. RESULTS: Among the 53,912 ACE-I/ARB users, the mean age was 59.9 years, and 50.6% were female. More than half of users discontinued ACE-I/ARB within 5 years of therapy initiation. The risk of ACE-I/ARB discontinuation increased with more advanced CKD stage. For example, patients who initiated ACE-I/ARB with CKD stage G4 (eGFR: 15-29 mL/min/1.73 m2) were 2.09-fold (95% CI, 1.87-2.34) more likely to discontinue therapy than those with eGFR ≥ 90 mL/min/1.73 m2. Potassium level greater than 5.3 mEq/L, systolic blood pressure ≤ 90 mm Hg, bicarbonate level < 22 mmol/L, and intervening hospitalization-particularly AKI-related-were also strong risk factors for ACE-I/ARB discontinuation. Thiazide diuretic use was associated with lower risk, whereas loop diuretic use was associated with higher risk of discontinuation. CONCLUSION: In a real-world cohort, discontinuation of ACE-I/ARB was common, particularly in patients with lower eGFR. Hyperkalemia, hypotension, low bicarbonate level, and hospitalization (AKI-related, in particular) were associated with a higher risk of ACE-I/ARB discontinuation. Additional studies are needed to evaluate the risk-benefit balance of discontinuing ACE-I/ARB in the setting of CKD progression.


Assuntos
Antagonistas de Receptores de Angiotensina/uso terapêutico , Inibidores da Enzima Conversora de Angiotensina/uso terapêutico , Adesão à Medicação , Insuficiência Renal Crônica/tratamento farmacológico , Idoso , Antagonistas de Receptores de Angiotensina/efeitos adversos , Inibidores da Enzima Conversora de Angiotensina/efeitos adversos , Progressão da Doença , Feminino , Taxa de Filtração Glomerular , Humanos , Masculino , Pessoa de Meia-Idade , Insuficiência Renal Crônica/sangue , Insuficiência Renal Crônica/fisiopatologia , Fatores de Risco
14.
Am J Epidemiol ; 2019 Oct 01.
Artigo em Inglês | MEDLINE | ID: mdl-31573030

RESUMO

A society's social structure and the interactions of its members determine when key drivers of health occur, for how long they last, and how they operate. Yet, it has been unclear whether causal inference methods can help us find meaningful interventions on these fundamental social drivers of health. Galea and Hernán propose that we place hypothetical interventions on a spectrum and estimate their effects by emulating trials, either through individual-level data analysis or systems science modeling (Galea & Hernán. Am J Epidemiol. 2019;XX(XX):XXXX-XXXX)). In this commentary, by way of example in health disparities research, we probe this "closer engagement of social epidemiology with formal causal inference approaches." The formidable, but not insurmountable, tensions call for causal reasoning and effect estimation in social epidemiology that should always be enveloped by a thorough understanding of how systems and the social exposome shape risk factor and health distributions. We argue that one way towards progress is a true partnership of social epidemiology and causal inference with bilateral feedback aimed at integrating social epidemiologic theory, causal identification and modeling methods, systems thinking, and improved study design and data. To produce consequential work, we must make social epidemiology more causal and causal inference more social.

15.
BMC Evol Biol ; 19(1): 193, 2019 10 21.
Artigo em Inglês | MEDLINE | ID: mdl-31638893

RESUMO

BACKGROUND: The existence of extended post-reproductive lifespan is an evolutionary puzzle, and its taxonomic prevalence is debated. One way of measuring post-reproductive life is with post-reproductive representation, the proportion of adult years lived by females after cessation of reproduction. Analyses of post-reproductive representation in mammals have claimed that only humans and some toothed whale species exhibit extended post-reproductive life, but there are suggestions of a post-reproductive stage for false killer whales and Asian elephants. Here, we investigate the presence of post-reproductive lifespan in Asian elephants using an extended demographic dataset collected from semi-captive timber elephants in Myanmar. Furthermore, we investigate the sensitivity of post-reproductive representation values to availability of long-term data over 50 years. RESULTS: We find support for the presence of an extended post-reproductive stage in Asian elephants, and that post-reproductive representation and its underlying demographic rates depend on the length of study period in a long-lived animal. CONCLUSIONS: The extended post-reproductive lifespan is unlikely due to physiological reproductive cessation, and may instead be driven by mating preferences or condition-dependent fertility. Our results also show that it is crucial to revisit such population measures in long-lived species as more data is collected, and if the typical lifespan of the species exceeds the initial study period.


Assuntos
Elefantes/fisiologia , Longevidade/fisiologia , Reprodução/fisiologia , Animais , Feminino , Masculino , Mianmar , Fatores de Tempo
16.
Int J Pharm Pract ; 2019 Oct 30.
Artigo em Inglês | MEDLINE | ID: mdl-31663215

RESUMO

OBJECTIVES: The Western Pacific Pharmaceutical Forum aims to foster Good Pharmacy Practice (GPP) in the Western Pacific Region (WPR). Our objective in this work was to develop and implement a process that equitably and constructively engaged pharmacy associations from the diverse cultures, languages and models of pharmacy practice in the WPR to identify common issues influencing the implementation of GPP. METHODS: The World Café concept was incorporated into a modified Tuckman's model for group development to conduct a workshop of leaders from the major pharmacy associations of the WPR. Facilitated discussion groups and collaborative decision-making were used to gather opinions and achieve agreement between the regional leaders. KEY FINDINGS: Participants reported the method to be open, systematic and enabled full contribution. Two major issues were identified in relation to each of the four key pharmacist roles associated with GPP. The regional pharmacy leaders agreed the common priority issue for implementing GPP as: 'National competency standards should be established to enable the formulation of professional development framework that lead to enhanced pharmacy practice and patient care' and developed a strategy and work plan to address this issue. CONCLUSIONS: Identification of GPP issues and the common major priority occurred with shared knowledge of the current state of practice across the WPR. The adopted methodology overcame cultural and practice differences to ensure full and equal participation of all delegates. The approach ensured ownership by all participants of the strategy and work plan developed to address competency and professional development in the WPR.

17.
Aust Health Rev ; 2019 Sep 11.
Artigo em Inglês | MEDLINE | ID: mdl-31505158

RESUMO

In response to rising healthcare costs, healthcare payers across the globe have been experimenting with performance-based payment models that link payments to providers with the quality of care that they provide. Community pharmacy in Australia has yet to be significantly affected by these changes. Initial steps have been taken to fund quality-linked interventions by pharmacists, such as the provision of medicines in dose administration aids, but funding for dispensing prescriptions remains solely based on a fee-for-service model. At the foundation of any performance-based payment model are measures that, in aggregate, reflect the quality of care that is provided. Patient adherence to prescription regimens can be correlated with the counselling provided by pharmacists and, as such, can serve as the measure on which a performance-based payment model for dispensing can be constructed. Experience in the US suggests per-prescription payments to a pharmacy can be increased or decreased by a small, yet meaningful, amount based on a measure of the level of adherence of patients of the pharmacy. The current dispensing payment model in the Australian Pharmaceutical Benefits Scheme may be able to be modified in a similar manner to support provision by pharmacists of improved quality of care.What is known about the topic?Dispensing in community pharmacy in Australia is currently remunerated on a fee-for-service basis that carries no incentive to deliver an enhanced performance that could lead to improved quality of care.What does this paper add?Several countries have introduced alternative payment models that link the level of funding to the quality of services provided by healthcare practitioners, and potentially to patient outcomes. Counselling is an integral aspect of pharmacists' dispensing and, based on the principle that counselling improves adherence, which improves outcomes, remuneration paid to a pharmacy for dispensing could be adjusted in relation to the level of adherence demonstrated by patients of the pharmacy.What are the implications for practitioners?Pharmacists would be incentivised through quality-linked dispensing remuneration to provide enhanced counselling and other inputs that lead to improved patient outcomes and health system benefits.

18.
J Anim Ecol ; 2019 Jun 21.
Artigo em Inglês | MEDLINE | ID: mdl-31222736

RESUMO

Advanced maternal age at birth can have pronounced consequences for offspring health, survival and reproduction. If carried over to the next generation, such fitness effects could have important implications for population dynamics and the evolution of ageing, but these remain poorly understood. While many laboratory studies have investigated maternal age effects, relatively few studies have been conducted in natural populations, and they usually only present a "snapshot" of an offspring's lifetime. In the present study, we focus on how maternal age influences offspring life-history trajectories and performance in a long-lived mammal. We use a multigenerational demographic dataset of semi-captive Asian elephants to investigate maternal age effects on several offspring life-history traits: condition, reproductive success and overall survival. We show that offspring born to older mothers display reduced overall survival but higher reproductive success, and reduced survival of their own progeny. Our results show evidence of a persistent effect of maternal age on fitness across generations in a long-lived mammal. By highlighting transgenerational effects on the fitness of the next generation associated with maternal age, the present study helps increase our understanding of factors contributing to individual variation in ageing rates and fitness.

19.
Am J Epidemiol ; 2019 May 30.
Artigo em Inglês | MEDLINE | ID: mdl-31145432

RESUMO

Covariate balance is a central concept in the potential outcomes literature. With selected populations or missing data, balance across treatment groups can be insufficient for estimating marginal treatment effects. Recently, a framework for using covariate balance to describe measured confounding and selection-bias for time-varying and other multivariate exposures in the presence of right-censoring has been proposed. Here, we revisit this framework to consider balance across levels of right-censoring over time in more depth. Specifically, we develop measures of covariate balance that can describe what is known as 'dependent censoring' in the literature, along with its associated selection-bias, under multiple mechanisms for right censoring. Such measures are interesting because they substantively describe the evolution of dependent censoring mechanism(s). Furthermore, we provide weighted versions that can depict how well such dependent censoring has been eliminated when inverse probability of censoring weights are applied. These results provide a conceptually grounded way to inspect covariate balance across levels of right-censoring as a validity check. As a motivating example, we apply these measures to a study of hypothetical 'static' and 'dynamic' treatment protocols in a sequential multiple assignment randomized trial of antipsychotics with high dropout rates.

20.
JAMA Netw Open ; 2(4): e192606, 2019 04 05.
Artigo em Inglês | MEDLINE | ID: mdl-31002324

RESUMO

Importance: It is unknown whether and how pharmacy closures alter medication adherence. Objective: To examine the association between pharmacy closures and adherence to statins, ß-blockers, and oral anticoagulants among adults 50 years or older in the United States. Design, Setting, and Participants: In this retrospective cohort study, comparative interrupted time series analyses were performed using a nationally representative 5% random sample of anonymized, longitudinal, individual-level pharmacy claims from IQVIA LRx LifeLink. Analyses included all prescription claims for individuals followed up between January 1, 2011, and December 31, 2016. Separate cohorts were derived for users of statins, ß-blockers, and oral anticoagulants. The differential association of pharmacy closure was examined as a function of baseline adherence, pharmacy, and individual characteristics. Main Outcomes and Measures: Difference in monthly adherence, measured as proportion of days covered, during 12-month baseline and follow-up periods among patients using a pharmacy that subsequently closed (closure cohort) compared with their counterparts (control cohort). Results: Among 3 089 803 individuals filling at least 1 statin prescription between January 1, 2011, and December 31, 2016 (mean [SD] age, 66.3 [9.3] years; 52.0% female), 3.0% (n = 92 287) filled at a pharmacy that subsequently closed. Before closure, monthly adherence was similar in the closure and control cohorts (mean [SD], 70.5% [26.7%] vs 70.7% [26.5%]). In multivariable models, individuals filling at pharmacies that closed experienced an immediate and significant decline (on average, an absolute change of -5.90%; 95% CI, -6.12% to -5.69%) in statin adherence during the first 3 months after closure compared with their counterparts. This difference persisted over 12 months of follow-up. A similar decline in adherence was observed when examining cohorts using ß-blockers (-5.71%; 95% CI, -5.96% to -5.46%) or oral anticoagulants (-5.63%; 95% CI, -6.24% to -5.01%). The mean association of pharmacy closure with adherence was greater among individuals using independent pharmacies (-7.89%; 95% CI, -8.32% to -7.47%) or living in neighborhoods with fewer pharmacies (-7.98%; 95% CI, -8.50% to -7.47%) compared with their counterparts. Conclusions and Relevance: Pharmacy closures are associated with persistent, clinically significant declines in adherence to cardiovascular medications among older adults in the United States. Efforts to reduce nonadherence to prescription medications should consider the role of pharmacy closures, especially among patients at highest risk.

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