Evaluating the implementation of a hypertension program based on mHealth and community pharmacies integration to primary care centers at a municipality level in Argentina during the COVID-19 pandemic.

Introduction: While pharmacists-led interventions in hypertension have proven effective in high-income countries, their implementation and impact in low- and middle-income countries (LMIC) remain limited. This study assessed the implementation and outcomes of the hypertension program FarmaTeCuida (FTC), which integrated community pharmacies into the public primary care level using information and communication technologies. The study took place during the pandemic in General Pueyrredón, Buenos Aires, Argentina, so modifications to the implementation strategy and expected outcomes were also analyzed. Methods: A mixed-methods study was conducted using the non-adoption, abandonment, scaling-up, dissemination, and sustainability (NASSS) conceptual model. Qualitative in-depth interviews were conducted with key stakeholders using snowball sampling until thematic saturation was achieved. The quantitative approach employed a quasi-experimental, prospective, longitudinal design in a cohort of hypertensive patients enrolled in the FTC program since October 2020 to March 2022. Adoption, access, adherence to follow-up, and blood pressure levels were assessed. Clinical outcomes were compared to a cohort of hypertensive patients attending primary health care centers (PHCCs) in 2021 but not enrolled in the FTC program. Routine data from this cohort was obtained from the municipal health information system (HIS). Results: Out of 33 PHCCs, 23 adopted the FTC program, but only four collaborated with community pharmacies. A total of 440 patients were recruited, with 399 (91%) enrolled at PHCCs. Hypertension was detected in 63% (279/440) of cases at the first visit (113 were possible hypertensive patients; 26 new hypertensive patients and 140 already diagnosed). During follow-up, FTC identified 52 new hypertensive patients (12% out of 440). Reduction of systolic blood pressure (SBP) was observed in patients enrolled in both the FTC program and the comparison group over 60 days. In the multivariate analysis that included all hypertensive patient (FTC and HIS) we found strong evidence that for each month of follow up, SBP was reduced by 1.12 mmHg; however, we did not find any significant effect of the FTC program on SBP trend (interaction FTC*months has a p-value = 0.23). The pandemic was identified as the main reason for the program's underperformance; in addition we identified barriers related to technology, patient suitability, implementation team characteristics, and organizational factors. Discussion: Our study, grounded in the NASSS model, highlights the profound complexity of introducing innovative strategies in low- and middle-income settings. Despite substantial challenges posed by the pandemic, these obstacles provided valuable insights, identified areas for improvement, and informed strategies essential for reshaping the care paradigm for conditions like hypertension in resource-constrained environments.

Effectiveness of dinoprostone gel, misoprostol vaginal insert and dinoprostone vaginal insert for induction of labour in twin pregnancies.

OBJECTIVES: To compare the effectiveness and safety of Dinoprostone Gel (DG), Misoprostol Vaginal Insert (MVI) and Dinoprostone Vaginal Insert (DVI) for induction of labour (IOL) in twin pregnancies. STUDY DESIGN: Retrospective cohort study of twin pregnancies > 34 + 0 weeks gestation that underwent induction of labour (IOL) with DG, MVI or DVI between December 2016 and November 2019 in a Tertiary NHS hospital, North West England, UK. Delivery characteristics, maternal complications and neonatal outcomes were compared between the three groups. RESULTS: A total of 87 twin pregnancies were included for analysis. 27 women received DG, 34 received MVI and 26 DVI. The MVI cohort had a higher proportion of nulliparous women (55.9%) compared to the DG and DVI cohorts, 29.6% and 38.5% respectively. No other differences amongst demographic characteristics were considered clinically significant. DG demonstrated a significantly quicker time to delivery (minutes) compared to DVI (1021 ± 556 versus 1649 ± 852; P = 0.0026). Significantly fewer women required terbutaline for hyperstimulation/tachysystole in the DG group compared to MVI (0% vs 32%; RR 0.05; 95% CI 0.003-0.88). Both DG and MVI groups required significantly less oxytocin following artificial rupture of membranes compared to DVI (33% vs 65%; RR 0.51; 95% CI 0.28-0.93) and (29% vs 65%; RR 0.45; 95% CI 0.25-0.81). There were no significant differences in mode of delivery, maternal complications and neonatal outcomes. CONCLUSION: Our data suggests that for women with a twin pregnancy considering a planned labour that induction with DG, MVI and DVI appear to be equally safe and effective IOL methods. These results should be interpreted with caution due to the study being underpowered to detect significant adverse outcomes. In order to determine the optimal method of IOL in twins, direct randomised comparison is needed.

Jaguar (Panthera onca) density and tenure in a critical biological corridor.

We estimated jaguar density and tenure, and investigated ranging behavior, using camera traps across the Maya Forest Corridor, a human-influenced landscape in central Belize that forms the only remaining connection for jaguar populations inhabiting two regional forest blocks: the Selva Maya and the Maya Mountain Massif. Jaguars were ubiquitous across the study area. Similar to the neighboring Selva Maya, mean density ranged from 1.5 to 3.1 jaguars per 100 km2, estimated by spatial capture-recapture models. Cameras detected almost twice as many males as females, probably reflecting detection bias, and males ranged more widely than females within the camera grid. Both sexes crossed two major rivers, while highway crossings were rare and male-biased, raising concern that the highway could prevent female movement if traffic increases. Jaguars were more transient where the landscape was fragmented with settlements and agriculture than in contiguous forest. Compared with jaguars in the protected forests of the Maya Mountains, jaguars in central Belize displayed a lower potential for investment in intraspecific communication, indicative of a lower quality landscape; however, we did detect mating behavior and juveniles. Tenure of individuals was shorter than in the protected forests, with a higher turnover rate for males than females. At least three-quarters of reported jaguar deaths caused by people were male jaguars, and the majority was retaliation for livestock predation. Jaguars seem relatively tolerant to the human-influenced landscape of central Belize. However, intensification of game hunting and lethal control of predators would threaten population persistence, while increased highway traffic and clear-cutting riparian forest would severely limit the corridor function. Our results show that the viability of the corridor, and thus the long-term survival of jaguar populations in this region, will depend on appropriate land-use planning, nonlethal control of livestock predators, enforcement of game hunting regulations, and wildlife-friendly features in future road developments.

Utilizando trampas-cámara, se estimó la densidad, permanencia y desplazamiento de jaguares a través del Corredor del Bosque Maya, un paisaje dominado por humanos en la zona central de Belice y que actualmente representa la única posibilidad de conectividad para las poblaciones de jaguares que habitan en dos grandes bloques boscosos regionales: La Selva Maya y El Macizo de las Montañas Mayas. Los jaguares estuvieron presentes en toda el área de estudio. De igual forma que en la vecina Selva Maya, la densidad media varió de 1.5 a 3.1 jaguares por cada 100 km2, estimada con modelos espaciales de captura-recaptura. Las cámaras detectaron casi el doble de machos que hembras, probablemente reflejando un sesgo de detección; y los machos se desplazaron más ampliamente que las hembras a lo largo de la cuadrícula de las cámaras. Jaguares de ambos sexos cruzaron dos ríos principales, mientras que el cruce de carreteras no fue común y estuvo sesgado hacia los machos, generando la preocupación de que las carreteras puedan impedir el movimiento de hembras si el tráfico vehicular aumenta. Los jaguares fueron más transitorios en paisajes fragmentados por asentamientos humanos y agricultura que en áreas de bosque continuo. Comparando con los jaguares de los bosques protegidos de las Montañas Mayas, los jaguares de la zona central de Belice mostraron menor potencial para invertir en comunicación intraespecífica, indicador de un paisaje de menor calidad; sin embargo, se detectó comportamiento de apareamientos y la presencia de juveniles. La permanencia de individuos fue más corta que en los bosques protegidos, con una tasa de recambio más alta para machos que para hembras. Al menos las tres cuartas partes de las muertes reportadas de jaguares causadas por humanos correspondieron a jaguares machos, la mayoría como retaliación por la muerte de ganado. Los jaguares parecen relativamente tolerantes del paisaje dominado por humanos en la zona central de Belice. Sin embargo, el aumento de la cacería de especies presa y el control letal de predadores amenazaría la persistencia de la población, mientras que el aumento del tráfico vehicular y la deforestación de bosques de galería reducirían severamente la funcionalidad del corredor. Nuestros resultados muestran que la viabilidad del corredor y por lo tanto la sobrevivencia de jaguares a largo plazo en esta región dependerá de la planificación apropiada del uso del suelo, de un control no letal de predadores de ganado, una mejor regulación de la cacería, y de una infraestructura amigable con la vida silvestre en las futuras carreteras.

Assessing the role of regulatory bodies in managing health professional issues and errors in Europe.

OBJECTIVE: This paper explores how medical regulatory bodies in nine European countries manage professional issues involving quality and patient safety, to build on limited existing information on procedures for regulating medical professionals in Europe. DESIGN: Twelve vignettes describing scenarios of concerns about standards of physicians were developed, covering clinical, criminal and administrative matters. Medical regulatory bodies in nine European countries were asked what action they would normally take in each situation. Their responses were related to their regulatory mandate. RESULTS: Responses varied greatly across participating countries. Regulators are always involved where patients are at risk or where a criminal offence is committed within the clinical setting. Non-criminal medical issues were generally handled by the employer, if any, at their discretion. Countries varied in the use of punitive measures, the extent to which they took an interest in issues arising outside professional activities, and whether they dealt with issues themselves or referred cases to another regulatory authority or took no action at all. CONCLUSIONS: There is little consistency across Europe on the regulation of medical professionals. There is considerable diversity in the range of topics that regulatory bodies oversee, with almost all covering health care quality and safety and others encompassing issues related to reputation, respect and trust. These inconsistencies have significant implications for professional mobility, patient safety and quality of care.

The number of people with glaucoma worldwide in 2010 and 2020.

AIM: To estimate the number of people with open angle (OAG) and angle closure glaucoma (ACG) in 2010 and 2020. METHODS: A review of published data with use of prevalence models. Data from population based studies of age specific prevalence of OAG and ACG that satisfied standard definitions were used to construct prevalence models for OAG and ACG by age, sex, and ethnicity, weighting data proportional to sample size of each study. Models were combined with UN world population projections for 2010 and 2020 to derive the estimated number with glaucoma. RESULTS: There will be 60.5 million people with OAG and ACG in 2010, increasing to 79.6 million by 2020, and of these, 74% will have OAG. Women will comprise 55% of OAG, 70% of ACG, and 59% of all glaucoma in 2010. Asians will represent 47% of those with glaucoma and 87% of those with ACG. Bilateral blindness will be present in 4.5 million people with OAG and 3.9 million people with ACG in 2010, rising to 5.9 and 5.3 million people in 2020, respectively. CONCLUSIONS: Glaucoma is the second leading cause of blindness worldwide, disproportionately affecting women and Asians.

New paradigms in the mechanisms and management of glaucoma.

During the last 30 years, the definition of glaucoma as been revised to eliminate the inclusion of intraocular pressure. Open angle glaucoma is the second leading cause of blindness in the world, but the proportion of those with the disease who become blind is low. Diagnostic methods for glaucoma need improvement. The pathogenetic steps to loss of neurons in glaucoma are increasingly understood and non-pressure lowering therapies are on the horizon.

Gene therapy for optic nerve disease.

PURPOSE: There has been recent interest in the potential use of gene therapy techniques to treat ocular disease. In this article, we consider the optic nerve diseases that are potentially most amenable to gene therapy. METHODS: We discuss the recent success of gene transfer experiments in animal models of glaucoma, optic neuritis, Leber's hereditary optic neuropathy (LHON), and optic nerve transection, and we assess the possibility of using similar techniques to treat human disease in the future. RESULTS: We have achieved highly efficient transfection of retinal ganglion cells in a rat model of glaucoma following a single intravitreal injection of adeno-associated virus (AAV). In our model, we have found that AAV-mediated gene therapy with brain-derived neurotrophic factor has a significant neuroprotective effect compared to saline or control virus injections. Guy and co-workers have successfully used AAV-mediated gene therapy to replace the defective mitochondrial enzyme subunit in cells derived from human patients with LHON. Gene therapy techniques have also shown promise in animal models of optic neuritis and optic nerve trauma. CONCLUSIONS: Human diseases with single-gene defects such as LHON may soon be treated successfully by gene therapy, assuming that vectors continue to improve and are well tolerated in the human eye. Other optic nerve diseases such as glaucoma that do not have a single-gene defect may also benefit from gene therapy to enhance RGC survival. In all cases, the risks of treatment will need to be balanced against the potential benefits.

Stem cells to replace the optic nerve.

Methods that exist now and that might be developed are suggested to replace retinal ganglion cells and their axons in the optic nerve, ultimately to re-establish functional vision in eyes blind from glaucoma.

Conservation genetics of the Far Eastern leopard (Panthera pardus orientalis).

The Far Eastern or Amur leopard (Panthera pardus orientalis) survives today as a tiny relict population of 25-40 individuals in the Russian Far East. The population descends from a 19th-century northeastern Asian subspecies whose range extended over southeastern Russia, the Korean peninsula, and northeastern China. A molecular genetic survey of nuclear microsatellite and mitochondrial DNA (mtDNA) sequence variation validates subspecies distinctiveness but also reveals a markedly reduced level of genetic variation. The amount of genetic diversity measured is the lowest among leopard subspecies and is comparable to the genetically depleted Florida panther and Asiatic lion populations. When considered in the context of nonphysiological perils that threaten small populations (e.g., chance mortality, poaching, climatic extremes, and infectious disease), the genetic and demographic data indicate a critically diminished wild population under severe threat of extinction. An established captive population of P. p. orientalis displays much higher diversity than the wild population sample, but nearly all captive individuals are derived from a history of genetic admixture with the adjacent Chinese subspecies, P. p. japonensis. The conservation management implications of potential restoration/augmentation of the wild population with immigrants from the captive population are discussed.

The prevalence of glaucoma in a population-based study of Hispanic subjects: Proyecto VER.

OBJECTIVE: To determine the prevalence of glaucoma in a population-based sample of Hispanic adults older than 40 years. METHODS: Using 1990 census data for Arizona, groups of persons living in sections of the city in Nogales and Tucson were randomly selected with a probability proportional to the Hispanic population older than 40 years. We tried to recruit all eligible adults in homes with 1 self-described Hispanic adult. Detailed ocular examinations at a local clinic included visual acuity testing, applanation tonometry, gonioscopy, an optic disc evaluation, and a threshold visual field test. Open-angle glaucoma (OAG) was defined using a proposed international system for prevalence surveys, including threshold visual field defect and optic disc damage. Angle-closure glaucoma was defined as bilateral appositional angle closure, combined with optic nerve damage (judged by field and disc as for OAG). RESULTS: Examinations were conducted in 72% (4774/6658) of eligible persons, with a 1.97% prevalence (95% confidence interval, 1.58%-2.36%) of OAG (94 persons). The age-specific OAG prevalence increased nonlinearly from 0.50% in those aged 41 to 49 years to 12.63% in those 80 years and older. Angle-closure glaucoma was detected in 5 persons (0.10%). Sex, blood pressure, and cigarette smoking were not significant OAG risk factors. Only 36 (38%) of the 94 persons with OAG were aware of their OAG before the study. Screening results with an intraocular pressure higher than 22 mm Hg (in the eye with a higher pressure) would miss 80% of the OAG cases. CONCLUSIONS: The prevalence of OAG in Hispanic persons was intermediate between reported values for white and black persons. The prevalence increased more quickly with increasing age than in other ethnic groups. Glaucoma was the leading cause of bilateral blindness.

Quantification of optic nerve axon loss associated with a relative afferent pupillary defect in the monkey.

OBJECTIVE: To quantify the amount of optic nerve axonal loss associated with the presence of a mild relative afferent pupillary defect (RAPD) in an experimental monkey model. METHODS: The right macula of 5 rhesus monkeys (Macaca mulatta) was treated with concentrically enlarging diode laser burns until an RAPD was detected using a transilluminator light and measured with neutral density filters. Intervals between treatments were 3 to 7 days over a period of 2 months. Pupillary responses to light stimulation were recorded with a monocular infrared television pupillometer. Two months after detection of an RAPD, 5 treated and 4 control monkeys underwent euthanasia and enucleation. Histopathologic analysis and quantification of optic nerve axon counts using an image analysis system were performed. RESULTS: No RAPD was observed despite an estimated ganglion cell loss of up to 26%. A 0.6 log unit RAPD was present in 5 monkeys when the laser scar incorporated the entire macula within the temporal vascular arcades. One eye had progressive vitreomacular traction with worsening of the RAPD to 1.8 log units without further laser treatment. Histopathologic evaluation disclosed complete loss of the normal retinal architecture within the macula. The average fiber loss for the 4 treated eyes with 0.6 log unit RAPDs compared with fellow eyes was 53.3% (95% confidence interval [CI], 45.0%-61.6%). The average difference in axon counts between untreated pairs of optic nerves was 12.8% (95% CI, 10.0%-15.6%). Optic nerve axon loss between pairs of experimental and control eyes was statistically significant (P<.001). CONCLUSION: In rhesus monkeys, an RAPD develops after an approximate unilateral loss between 25% and 50% of retinal ganglion cells. CLINICAL RELEVANCE: Owing to redundancy in the anterior visual pathways, unilateral retinal ganglion cell loss may occur prior to the observation of an RAPD. The presence of an RAPD measuring 0.6 log units implies that significant retinal ganglion cell injury has occurred.

The catalytic site of the pectin biosynthetic enzyme alpha-1,4-galacturonosyltransferase is located in the lumen of the Golgi.

Alpha-1,4-galacturonosyltransferase (GalAT) is an enzyme required for the biosynthesis of the plant cell wall pectic polysaccharide homogalacturonan (HGA). GalAT activity in homogenates from pea (Pisum sativum L. var. Alaska) stem internodes co-localized in linear and discontinuous sucrose gradients with latent UDPase activity, an enzyme marker specific for Golgi membranes. GalAT activity was separated from antimycin A-insensitive NADH:cytochrome c reductase and cytochrome c oxidase activities, enzyme markers for the endoplasmic reticulum and the mitochondria, respectively. GalAT and latent UDPase activities were separated from the majority (80%) of callose synthase activity, a marker for the plasma membrane, suggesting that little or no GalAT is present in the plasma membrane. GalAT activities in proteinase K-treated and untreated Golgi vesicles were similar, whereas no GalAT activity was detected after treating Golgi vesicles with proteinase K in the presence of Triton X-100. These results demonstrate that the catalytic site of GalAT resides within the lumen of the Golgi. The products generated by Golgi-localized GalAT were converted by endopolygalacturonase treatment to mono- and di-galacturonic acid, thereby showing that GalAT synthesizes 1-->4-linked alpha-D-galacturonan. Our data provide the first enzymatic evidence that a glycosyltransferase involved in HGA synthesis is present in the Golgi apparatus. Together with prior results of in vivo labeling and immunocytochemical studies, these results show that pectin biosynthesis occurs in the Golgi. A model for the biosynthesis of the pectic polysaccharide HGA is proposed.

Risk factors for late-onset infection following glaucoma filtration surgery.

OBJECTIVE: To determine the risk factors for late-onset infection following glaucoma filtration surgery. METHODS: We performed a case-control study comparing 131 cases of late-onset infection collected from 27 surgeons at 10 centers with 500 controls matched for date of surgery and surgeon. The criterion for the presence of infection was severe anterior chamber reaction occurring later than 4 weeks after surgery. An opaque bleb and positive culture results were not required for diagnosis. Risk factors were identified by univariate and multivariate logistic regression analyses. RESULTS: Some of the risk factors that were statistically significant in the multivariate model after adjusting for age, race, and sex were (1) performance of a full-thickness rather than a guarded procedure (risk ratio [RR], 13.1; 95% confidence interval [CI], 2.12-80.9), (2) filtration surgery performed without concurrent cataract surgery (RR, 2.25; 95% CI, 1.24-4.08), (3) use of mitomycin (RR, 2.48; 95% CI, 1.06-5.83), (4) intermittent use of antibiotics after surgery (RR, 2.10; 95% CI, 1.09-4.02), and (5) continuous use of antibiotics after surgery (RR, 5.94; 95% CI, 2.09-16.9). CONCLUSIONS: Eyes undergoing full-thickness procedures or filtration surgery without cataract extraction are at increased risk for late infection. Intraoperative mitomycin and episodic or continuous antibiotic use after the postoperative period are associated with an increased risk of infection.

Optic nerve transection in monkeys may result in secondary degeneration of retinal ganglion cells.

PURPOSE: Interest in neuroprotection for optic neuropathies is, in part, based on the assumption that retinal ganglion cells (RGCs) die, not only as a result of direct (primary) injury, but also indirectly as a result of negative effects from neighboring dying RGCs (secondary degeneration). This experiment was designed to test whether secondary RGC degeneration occurs after orbital optic nerve injury in monkeys. METHODS: The superior one third of the orbital optic nerve on one side was transected in eight cynomolgus monkeys (Macaca fascicularis). Twelve weeks after the partial transection, the number of RGC bodies in the superior and inferior halves of the retina of the experimental and control eyes and the number and diameter of axons in the optic nerve were compared by detailed histomorphometry. Vitreous was obtained for amino acid analysis. A sham operation was performed in three additional monkeys. RESULTS: Transection caused loss of 55% +/- 13% of RGC bodies in the superior retina of experimental compared with fellow control eyes (mean +/- SD, t-test, P < 0.00,001, n = 7). Inferior RGCs, not directly injured by transection, decreased by 22% +/- 10% (P = 0.002). The loss of superior optic nerve axons was 83% +/- 12% (mean +/- SD, t-test, P = 0.0008, n = 5) whereas, the inferior loss was 34% +/- 20% (P = 0.02, n = 5). Intravitreal levels of glutamate and other amino acids in eyes with transected nerves were not different from levels in control eyes 12 weeks after injury. Fundus examination, fluorescein angiography, and histologic evaluation confirmed that there was no vascular compromise to retinal tissues by the transection procedure. CONCLUSIONS: This experiment suggests that primary RGC death due to optic nerve injury is associated with secondary death of surrounding RGCs that are not directly injured.

Diagnostic capabilities of frequency-doubling technology, scanning laser polarimetry, and nerve fiber layer photographs to distinguish glaucomatous damage.

PURPOSE: To investigate the ability of three diagnostic tests: frequency-doubling technology (FDT), scanning laser polarimetry (GDx), and nerve fiber layer (NFL) photographs to distinguish normal from glaucomatous eyes. METHODS: Data were obtained in a cross-sectional, hospital clinic-based study, including one eye from each of 253 persons older than 40 years (68 normal, 94 glaucoma suspects and 91 glaucoma patients). We performed a comprehensive ocular examination, as well as static automated perimetry (Humphrey 24-2), screening FDT, GDx, optic nerve stereoscopic photographs and high-contrast NFL photographs. RESULTS: The following were significantly different for glaucomatous patients compared with suspects and normals: mean values of mean deviation (MD, Humphrey 24-2) and corrected pattern standard deviation (CPSD), 11 GDx indices, mean FDT testing time and missed points, and NFL graded defects (ANOVA, Mantel-Haenszel test; p = 0.0001). Using Humphrey 24-2 test results and clinical assessment as the defining features of glaucoma, we found that the optimal mix of sensitivity and specificity values were 84% and 100% for FDT (presence of any defect); 62% and 96% for GDx (The Number, cut-off value of 27); and, 95% and 82% for NFL photographs (presence of any abnormality). FDT testing took the least time to be administered. CONCLUSIONS: The FDT had the best diagnostic performance. Neural network analysis of GDx data outperformed other elements of its software.

Phylogenetics, genome diversity and origin of modern leopard, Panthera pardus.

Leopards, Panthera pardus, are widely distributed across southern Asia and sub-Saharan Africa. The extent and phylogeographic patterns of molecular genetic diversity were addressed in a survey of 77 leopards from known geographical locales representing 13 of the 27 classical trinomial subspecies. Phylogenetic analysis of mitochondrial DNA sequences (727 bp of NADH5 and control region) and 25 polymorphic microsatellite loci revealed abundant diversity that could be partitioned into a minimum of nine discrete populations, tentatively named here as revised subspecies: P. pardus pardus, P. p. nimr, P. p. saxicolor, P. p. fusca, P. p. kotiya, P. p. delacouri, P. p. japonensis, P. p. orientalis and P. p. melas. However, because of limited sampling of African populations, this may be an underestimate of modern phylogeographic population structure. Combined phylogeographic and population diversity estimates support an origin for modern leopard lineages 470,000-825,000 years ago in Africa followed by their migration into and across Asia more recently (170,000-300,000 years ago). Recent demographic reductions likely have led to genetic impoverishment in P. p. orientalis and in the island subspecies P. p. kotiya.