[Ethical and legal aspects of violence against women]. / Aspectos éticos y legales de la violencia sobre la mujer.

Caring for female victims of violence presents health professionals with situations that require careful consideration due to the conflicts raised between the fundamental principles of bioethics. During this process, intermediate courses of action should be adopted in which none of the affected principles is totally compromised, yet always take into account due compliance with legal and deontological regulations. Within these conflicts, the possible impact on the autonomy of the victim must be taken into consideration, conditioned by the relationship of dominance with respect to their aggressor, a fundamental characteristic of gender violence. However, the fact that there is a legal obligation to issue an injury report or to communicate a well-founded suspicion of abuse is not enough to ignore the fact that the person, in this case the victim, must be a participant in the process. As such, the doctor has the obligation to inform his or her patient about this legal requirement, dedicating all the time and attention necessary to ensure that the victim understands the purpose and benefits of complying with this. In any case, and beyond the appropriate adaptation of the professional's conduct to current precepts, the ethical principle of care must be adhered to, by which the best thing the professional can do is to provide the victim with the means to avoid the repetition of new attacks, implementing prevention measures that have their origin in the accurate diagnosis of the situation of violence and in the communication of this to the authorities.

Abundance and distribution of cigarette butts on the sand of five touristic beaches in Latin America during the COVID-19 pandemic.

Cigarette butts (CB) and cigarette butt fibers (CBF) are highly abundant and frequent residues on beach sand. Also, they are hazardous waste due to their significant toxicity and potential risk to the ecosystems' biota and the health of beach tourists. This study aimed to determine the abundance and density of CB and CBF found on the active, rest, and service zones of five pilot beaches in Argentina, Colombia, Brazil, Ecuador, and Mexico. The methodology involved collecting CB and CBF in 500 m2 transects of urban tourist beaches using a citizen science-adapted methodology between June 2021 and May 2022, during the COVID-19 pandemic. The abundance and density of CB and CBF, and the Cigarette Butt Pollution Index (CBPI) were calculated. The highest proportion of CB was found in service and rest areas. Bocagrande (CO) reported the highest generation of CB and CBF and a severe CBPI.

Real-world safety and effectiveness of maintenance niraparib for platinum-sensitive recurrent ovarian cancer: A GEICO retrospective observational study within the Spanish expanded-access programme.

AIM: To describe patient characteristics, effectiveness and safety in a real-world population treated with niraparib in the Spanish expanded-access programme. PATIENTS AND METHODS: This retrospective observational study included women with platinum-sensitive recurrent high-grade serous ovarian cancer who received maintenance niraparib within the Spanish niraparib expanded-access programme. Eligible patients had received ≥2 previous lines of platinum-containing therapy, remained platinum-sensitive after the penultimate line of platinum and had responded to the most recent platinum-containing therapy. Niraparib dosing was at the treating physician's discretion (300 mg/day fixed starting dose or individualised starting dose [ISD] according to baseline body weight and platelet count). Safety, impact of dose adjustments, patient characteristics and effectiveness were analysed using data extracted from medical records. RESULTS: Among 316 eligible patients, 80% had BRCA wild-type tumours and 66% received an ISD. Median niraparib duration was 7.8 months. The most common adverse events typically occurred within 3 months of starting niraparib. Median progression-free survival was 8.6 (95% confidence interval [CI] 7.6-10.0) months. One- and 2-year overall survival rates were 86% (95% CI 81-89%) and 65% (95% CI 59-70%), respectively. Dose interruptions, dose reductions, haematological toxicities and asthenia/fatigue were less common with ISD than fixed starting dose niraparib, but progression-free survival was similar irrespective of dosing strategy. Subsequent therapy included platinum in 71% of patients who received further treatment. CONCLUSION: Outcomes in this large real-world dataset of niraparib-treated patients are consistent with phase III trials, providing reassuring evidence of the tolerability and activity of niraparib maintenance therapy for platinum-sensitive recurrent ovarian cancer. GOV REGISTRATION: NCT04546373.

Metabolic Engineering: Methodologies and Applications.

Metabolic engineering aims to improve the production of economically valuable molecules through the genetic manipulation of microbial metabolism. While the discipline is a little over 30 years old, advancements in metabolic engineering have given way to industrial-level molecule production benefitting multiple industries such as chemical, agriculture, food, pharmaceutical, and energy industries. This review describes the design, build, test, and learn steps necessary for leading a successful metabolic engineering campaign. Moreover, we highlight major applications of metabolic engineering, including synthesizing chemicals and fuels, broadening substrate utilization, and improving host robustness with a focus on specific case studies. Finally, we conclude with a discussion on perspectives and future challenges related to metabolic engineering.

A role for the circadian transcription factor NPAS2 in the progressive loss of non-rapid eye movement sleep and increased arousal during fentanyl withdrawal in male mice.

RATIONALE: Synthetic opioids like fentanyl are contributing to the rise in rates of opioid use disorder and drug overdose deaths. Sleep dysfunction and circadian rhythm disruption may worsen during opioid withdrawal and persist during abstinence. Severe and persistent sleep and circadian alterations are putative factors in opioid craving and relapse. However, very little is known about the impact of fentanyl on sleep architecture and sleep-wake cycles, particularly opioid withdrawal. Further, circadian rhythms regulate sleep-wake cycles, and the circadian transcription factor, neuronal PAS domain 2 (NPAS2) is involved in the modulation of sleep architecture and drug reward. Here, we investigate the role of NPAS2 in fentanyl-induced sleep alterations. OBJECTIVES: To determine the effect of fentanyl administration and withdrawal on sleep architecture, and the role of NPAS2 as a factor in fentanyl-induced sleep changes. METHODS: Electroencephalography (EEG) and electromyography (EMG) was used to measure non-rapid eye movement sleep (NREMS) and rapid eye movement sleep (REMS) at baseline and following acute and chronic fentanyl administration in wild-type and NPAS2-deficient male mice. RESULTS: Acute and chronic administration of fentanyl led to increased wake and arousal in both wild-type and NPAS2-deficient mice, an effect that was more pronounced in NPAS2-deficient mice. Chronic fentanyl administration led to decreased NREMS, which persisted during withdrawal, progressively decreasing from day 1 to 4 of withdrawal. The impact of fentanyl on NREMS and arousal was more pronounced in NPAS2-deficient mice. CONCLUSIONS: Chronic fentanyl disrupts NREMS, leading to a progressive loss of NREMS during subsequent days of withdrawal. Loss of NPAS2 exacerbates the impact of fentanyl on sleep and wake, revealing a potential role for the circadian transcription factor in opioid-induced sleep changes.

PI3K-regulated Glycine N-methyltransferase is required for the development of prostate cancer.

Glycine N-Methyltransferase (GNMT) is a metabolic enzyme that integrates metabolism and epigenetic regulation. The product of GNMT, sarcosine, has been proposed as a prostate cancer biomarker. This enzyme is predominantly expressed in the liver, brain, pancreas, and prostate tissue, where it exhibits distinct regulation. Whereas genetic alterations in GNMT have been associated to prostate cancer risk, its causal contribution to the development of this disease is limited to cell line-based studies and correlative human analyses. Here we integrate human studies, genetic mouse modeling, and cellular systems to characterize the regulation and function of GNMT in prostate cancer. We report that this enzyme is repressed upon activation of the oncogenic Phosphoinositide-3-kinase (PI3K) pathway, which adds complexity to its reported dependency on androgen signaling. Importantly, we demonstrate that expression of GNMT is required for the onset of invasive prostate cancer in a genetic mouse model. Altogether, our results provide further support of the heavy oncogenic signal-dependent regulation of GNMT in prostate cancer.

Twenty-five new species of mining bees (Hymenoptera: Andrenidae: Andrena) from Israel and the Levant.

Andrena is one of the most diverse bee genera, comprising about 1,600 described species of ground-nesting solitary bees. Many Andrena species are plant specialists, and several taxa have been indicated to be important pollinators of wild and/or crop plants. The Eastern Mediterranean Basin and Israel in particular are one of the main world diversity hotspots of Andrena. Based on extensive examination of museum specimens combined with DNA barcoding, we hereby describe twenty-five Levantine species of Andrena new to science: Andrena anathema Pisanty sp. nov., A. ardentia Pisanty sp. nov., A. asluji Pisanty sp. nov., A. curviocciput Pisanty & Wood sp. nov., A. dividicincta Pisanty sp. nov., A. dorchini Pisanty sp. nov., A. euphorbiae Pisanty sp. nov., A. gageae Wood & Pisanty sp. nov., A. herodesi Pisanty & Wood sp. nov., A. hulae Pisanty sp. nov., A. igraeca Pisanty & Wood sp. nov., A. inusitata Pisanty sp. nov., A. janthinoides Pisanty sp. nov., A. longistilus Pisanty & Wood sp. nov., A. lunaris Pisanty & Wood sp. nov., A. macula Pisanty & Wood sp. nov., A. obtusa Pisanty sp. nov., A. ornithogali Pisanty & Wood sp. nov., A. petrae Wood sp. nov., A. protuber Pisanty sp. nov., A. sulfurea Wood sp. nov., A. turmalina Pisanty & Wood sp. nov., A. veronicae Pisanty & Wood sp. nov., A. veterana Pisanty sp. nov., and A. xera Pisanty sp. nov. We synonymise Andrena edentula Wood with A. tadauchii Gusenleitner syn. nov., and recognise four infraspecific names as valid species: Andrena mediterranea Pisanty & Scheuchl stat. nov., A. mizorhina Warncke stat. nov., A. noacki Alfken sp. resurr. and A. ochraceohirta Alfken sp. resurr. We additionally describe the hitherto unknown sexes of four species, provide new records for fifteen species previously unknown from Israel, and list fourteen taxa whose previously reported presence in Israel is considered erroneous or questionable.

Molecular phylogeny, historical biogeography and revised classification of andrenine bees (Hymenoptera: Andrenidae).

The mining bee subfamily Andreninae (Hymenoptera: Andrenidae) is a widely distributed and diverse group of ground-nesting solitary bees, including numerous species known to be important pollinators. Most of the species diversity of Andreninae is concentrated in the mainly Holarctic genus Andrena, comprising ca. 1550 described species. The subfamily and especially the genus have remained relatively neglected by recent molecular phylogenetic studies, with current classifications relying largely on morphological characters. We sampled ultraconserved element (UCE) sequences from 235 taxa, including all andrenine genera and 98 out of 104 currently recognized Andrena subgenera. Using 419,858 aligned nucleotide sites from 1009 UCE loci, we present a comprehensive molecular phylogenetic analysis of the subfamily. Our analysis supports the recognition of seven distinct genera in the Andreninae: Alocandrena, Ancylandrena, Andrena, Cubiandrena, Euherbstia, Megandrena, and Orphana. Within the genus Andrena, present-day subgeneric concepts revealed high degrees of paraphyly and polyphyly, due to strong homoplasy of morphological characters, necessitating a thorough, extensive revision of the higher classification of the genus. Based on our findings, we place the subgenus Calcarandrena in synonymy with Andrena (Lepidandrena); Hyperandrena, Nemandrena, Scoliandrena, Tylandrena and Zonandrena with A. (Melandrena); Distandrena, Fumandrena and Proxiandrena with A. (Micrandrena); Carandrena with A. (Notandrena); Agandrena with A. (Plastandrena); Geandrena and Xanthandrena with A. (Ptilandrena); Xiphandrena with A. (Scrapteropsis); and Platygalandrena and Poliandrena with A. (Ulandrena) (new synonymies). We additionally reestablish the groups known as Opandrena and Truncandrena as valid subgenera of Andrena. Our results also show that the MRCA of Andrena + Cubiandrena dispersed from the New World to the Palaearctic probably during the Eocene-early Oligocene, followed by 10-14 Neogene dispersal events from the Palaearctic to the Nearctic and 1-6 Neogene dispersals back into the Palaearctic, all within the genus Andrena.

Are Separated Fathers Less or More Involved in Childrearing than Partnered Fathers?

Separated fathers are generally assumed to be less involved with their children than partnered fathers. Yet, extant research on separated fathers has mainly focused on nonresident fathers without taking into consideration the existing diversity in post-separation residence arrangements. In fact, separated resident and shared residence fathers may possibly be more involved than partnered fathers, because the former likely bear primary childcare responsibilities, while the latter often act as secondary caregivers. This study extends previous research by investigating father involvement via regular care and leisure activities across a full range of separated fathers, and how it compares to that of partnered fathers, as well as whether patterns differ by father's education. Data from the New Families in the Netherlands survey (N = 1592) reveal that as compared to partnered fathers, shared residence fathers and especially resident fathers are more actively involved in the regular care of their child, whereas nonresident fathers are less involved. Results are similar for leisure, except that partnered fathers are similarly involved as shared residence fathers in this activity. Education also matters: involvement of fathers across different post-separation residence arrangements is more similar to that of partnered fathers when being highly educated. These findings suggest that including resident and shared residence fathers in the picture offers a more optimistic view of fathers' post-separation parenting role, because these separated fathers are actually more actively involved in childrearing than partnered fathers. SUPPLEMENTARY INFORMATION: The online version contains supplementary material available at 10.1007/s10680-021-09593-1.

Evaluation of the reticulorumen pH throughout the feeding period for beef feedlot steers maintained in a commercial feedlot and its association with liver abscesses.

OBJECTIVE: To evaluate the reticulorumen pH of beef feedlot steers throughout the feeding period and to assess the association between the respective durations that the reticulorumen pH was ≤ 5.6 (subacute ruminal acidosis) and ≤ 5.2 (acute ruminal acidosis) and liver abscess severity. ANIMALS: 59 feedlot steers (mean body weight, 349.5 kg). PROCEDURES: On day 0, each steer was orally administered an electronic bolus that monitored the reticulorumen pH every 10 minutes for 150 days. Steers were transitioned from a starter to intermediate ration on day 8 (transition 1) and from the intermediate to finish ration on day 19 (transition 2). The ration carbohydrate and megacalorie contents increased with each transition. During each transition, the lower megacalorie ration was fed at the 8:00 am feeding and the higher megacalorie ration was fed at the 2:00 pm feeding for 3 days before the higher megacalorie ration was fed extensively. Steers were sent to slaughter after 182 days; each carcass was assessed for liver abscesses. RESULTS: The diurnal reticulorumen pH pattern was characterized by a peak at 7:00 am and nadir at 8:00 pm. The mean percentages of time that the reticulorumen pH was ≤ 5.6 and ≤ 5.2 were more than 10-fold greater during transition 1, compared with during transition 2, and were significantly greater for steers with extensive liver abscesses than for steers without extensive liver abscesses. CONCLUSIONS AND CLINICAL RELEVANCE: Efforts to minimize the duration that the reticulorumen pH is ≤ 5.6 might mitigate liver abscess formation in feedlot cattle.

Current Practices in Home Mechanical Ventilation for Chronic Obstructive Pulmonary Disease: A Real-Life Cross-Sectional Multicentric Study.

Purpose: Home mechanical ventilation (HMV) use in chronic obstructive pulmonary disease (COPD) is becoming increasingly widespread. The aim of this study was to provide an accurate description of the current practices and clinical characteristics of COPD patients on HMV in Portugal. Methods: The study was designed as a cross-sectional, multicenter real-life study of COPD patients established on HMV for at least 30 days. Data related to clinical characteristics, adaptation and ventilatory settings were collected. Results: The study included 569 COPD patients on HMV from 15 centers. The majority were male, with a median age of 72 years and a high prevalence of obesity (43.2%) and sleep apnea (45.8%). A high treatment compliance was observed (median 8h/day), 48.7% with inspiratory positive airway pressure ≥20 cmH2O and oronasal masks were the preferred interface (91.7%). There was an equal distribution of patients starting HMV during chronic stable condition and following an exacerbation. Patients in stable condition were initiated in the outpatient setting in 92.3%. Despite the differences in criteria and setting of adaptation and a slightly lower BMI in patients starting HMV following an exacerbation, we found no significant differences regarding age, gender, ventilation pressures, time on HMV, usage, severity of airflow obstruction or current arterial blood gas analysis (ABGs) in relation to patients adapted in stable condition. Conclusion: Patients were highly compliant with the therapy. In agreement with most recent studies and recommendations, there seems to be a move towards higher ventilation pressures, increased use of oronasal masks and an intent to obtain normocapnia. This study shows that chronic hypercapnic and post exacerbation patients do not differ significantly regarding patient characteristics, physiological parameters or ventilatory settings with one exception: chronic hypercapnic patients are more often obese and, subsequently, more frequently present OSA.

Precise Regulation of Cas9-Mediated Genome Engineering by Anti-CRISPR-Based Inducible CRISPR Controllers.

CRISPR/Cas9 is a powerful genome editing tool, but its off-target cleavage activity can result in unintended adverse outcomes for therapeutic applications. Here we report the design of a simple tunable CRISPR controller in which a chemically inducible anti-CRISPR protein AcrIIA4 is engineered to disable Cas9 DNA binding upon the addition of trimethoprim. Dose-dependent control over Cas9 editing and dCas9 induction was achieved, which drastically improved the specificity and biosafety of the CRISPR/Cas9 system. We utilized the anti-CRISPR protein AcrIIA4 as a means to interfere with Cas9 DNA binding activity. By fusing AcrIIA4 to a ligand-inducible destabilization domain DHFR(DD), we show significantly reduced off-target activity in mammalian cells. Furthermore, we describe a new inducible promoter system Acr-OFF based on CRISPR controllers, which is regulated by an FDA-approved ligand trimethoprim.

Incidence of COVID-19 in patients under chronic treatment with hydroxychloroquine.

OBJECTIVE: To analyze the incidence of Covid-19 in patients who are chronic users of hydroxychloroquine. PATIENTS AND METHODS: Cross-sectional retrospective observational multicenter study in health areas and districts from Castilla La-Mancha and Andalucia. Of the 4451 participants included in the first recruitment, 3817 with valid data were selected. The main variable of the study is the presence or absence of Covid-19 infection by clinical, serological or polymerase chain reaction diagnosis. Sociodemographic and clinical variables and treatment and concomitant comorbidities were recorded. RESULTS: 169 (4,45%) patients had Covid-19 infection, of which 12 (7.1 %) died and 32 (18.9%) required hospital admission. Previous respiratory pathology was related to Covid-19 infection (P < .05). Maculopathy appears in 5.3% of patients and is significantly related to the dose of hydroxychloroquine consumed (P < .05). CONCLUSION: There is no relationship between chronic use of hydroxychloroquine and the incidence of Covid-19.

OBJETIVO: Analizar la incidencia de la enfermedad del coronavirus 19 (COVID-19) en pacientes consumidores crónicos de hidroxicloroquina. PACIENTES Y MÉTODOS: Estudio multicéntrico observacional retrospectivo transversal en Áreas de Salud de Castilla La-Mancha y distritos sanitarios de Andalucía. De los 4.451 participantes incluidos en el primer reclutamiento se seleccionaron 3.817 sujetos con datos válidos. La variable principal del estudio ha sido la presencia o ausencia de infección por la COVID-19 por diagnóstico clínico, serológico o por reacción en cadena de la polimerasa. Se registraron variables sociodemográficas, clínicas y tratamientos y comorbilidades concomitantes. RESULTADOS: Ciento sesenta y nueve (4,45%) pacientes presentaron infección por la COVID-19, de los cuales fallecieron 12 (7,1%) y 32 (18,9%) requirieron ingreso hospitalario. La enfermedad respiratoria previa se relacionó con la infección por la COVID-19 (p < 0,05). La maculopatía aparece en un 5,3% de los pacientes y está relacionada significativamente con la dosis de hidroxicloroquina consumida (p < 0,05). CONCLUSIÓN: No existe relación entre consumo crónico de hidroxicloroquina e incidencia de la COVID-19.

Cas12a-assisted precise targeted cloning using in vivo Cre-lox recombination.

Direct cloning represents the most efficient strategy to access the vast number of uncharacterized natural product biosynthetic gene clusters (BGCs) for the discovery of novel bioactive compounds. However, due to their large size, repetitive nature, or high GC-content, large-scale cloning of these BGCs remains an overwhelming challenge. Here, we report a scalable direct cloning method named Cas12a-assisted precise targeted cloning using in vivo Cre-lox recombination (CAPTURE) which consists of Cas12a digestion, a DNA assembly approach termed T4 polymerase exo + fill-in DNA assembly, and Cre-lox in vivo DNA circularization. We apply this method to clone 47 BGCs ranging from 10 to 113 kb from both Actinomycetes and Bacilli with ~100% efficiency. Heterologous expression of cloned BGCs leads to the discovery of 15 previously uncharacterized natural products including six cyclic head-to-tail heterodimers with a unique 5/6/6/6/5 pentacyclic carbon skeleton, designated as bipentaromycins A-F. Four of the bipentaromycins show strong antimicrobial activity to both Gram-positive and Gram-negative bacteria such as methicillin-resistant Staphylococcus aureus, vancomycinresistant Enterococcus faecium, and bioweapon Bacillus anthracis. Due to its robustness and efficiency, our direct cloning method coupled with heterologous expression provides an effective strategy for large-scale discovery of novel natural products.

[Incidence of COVID-19 in patients under chronic treatment with hydroxychloroquine]. / Incidencia de la COVID-19 en pacientes en tratamiento crónico con hidroxicloroquina.

OBJECTIVE: To analyze the incidence of Covid-19 in patients who are chronic users of hydroxychloroquine. PATIENTS AND METHODS: Cross-sectional retrospective observational multicenter study in health areas and districts from Castilla La-Mancha and Andalucia. Of the 4451 participants included in the first recruitment, 3817 with valid data were selected. The main variable of the study is the presence or absence of Covid-19 infection by clinical, serological or polymerase chain reaction diagnosis. Sociodemographic and clinical variables and treatment and concomitant comorbidities were recorded. RESULTS: 169 (4,45%) patients had Covid-19 infection, of which 12 (7.1%) died and 32 (18.9%) required hospital admission. Previous respiratory pathology was related to Covid-19 infection (P<.05). Maculopathy appears in 5.3% of patients and is significantly related to the dose of hydroxychloroquine consumed (P<.05). CONCLUSION: There is no relationship between chronic use of hydroxychloroquine and the incidence of Covid-19.

A mutant form of ERα associated with estrogen insensitivity affects the coupling between ligand binding and coactivator recruitment.

A homozygous missense mutation in the gene encoding the estrogen receptor α (ERα) was previously identified in a female patient with estrogen insensitivity syndrome. We investigated the molecular features underlying the impaired transcriptional response of this mutant (ERα-Q375H) and four other missense mutations at this position designed to query alternative mechanisms. The identity of residue 375 greatly affected the sensitivity of the receptor to agonists without changing the ligand binding affinity. Instead, the mutations caused changes in the affinity of coactivator binding and alterations in the balance of coactivator and corepressor recruitment. Comparisons among the transcriptional regulatory responses of these six ERα genotypes to a set of ER agonists showed that both steric and electrostatic factors contributed to the functional deficits in gene regulatory activity of the mutant ERα proteins. ERα-coregulator peptide binding in vitro and RIME (rapid immunoprecipitation mass spectrometry of endogenous) analysis in cells showed that the degree of functional impairment paralleled changes in receptor-coregulator binding interactions. These findings uncover coupling between ligand binding and coregulator recruitment that affects the potency rather than the efficacy of the receptor response without substantially altering ligand binding affinity. This highlights a molecular mechanism for estrogen insensitivity syndrome involving mutations that perturb a bidirectional allosteric coupling between ligand binding and coregulator binding that determines receptor transcriptional output.

Physiologic Effects of Exogenous Dextrose in Murine Klebsiella pneumoniae Sepsis Vary by Route of Provision.

Sepsis is characterized by a dysregulated immune response to infection. Nutrition is important in the care of septic patients, but the effects of specific nutrients on inflammation in sepsis are not well defined. Our prior work has shown benefits from early enteral dextrose infusion in a preclinical endotoxemia model of sepsis. In the current study, we extend our initial work to examine the effects of dextrose infusions, varying by route of administration, on inflammation and glycemic control in a more clinically relevant and translational model of Klebsiella pneumoniae (KP) bacteremia. Ten-week old C57BL6/J male mice (n = 31) underwent the implantation of indwelling vascular catheters, followed by inoculation with oropharyngeal KP. The mice were randomized 24 h after inoculation to (1) intravenous (IV) dextrose, (2) enteral dextrose, or (3) enteral saline (control) to study the effects on systemic inflammation, hemodynamics, and glycemic control. At 72 h, 77% of the control mice died, whereas IV dextrose induced 100% mortality, associated with increased inflammation, hyperglycemia, and hypotension. Enteral dextrose reduced mortality to 27%, promoted euglycemia, and reduced inflammation compared to IV dextrose. We conclude, in a bacteremic model of sepsis, that enteral (but not IV) dextrose administration is protective, suggesting that the route of nutrient support influences inflammation in sepsis.

Quality of life of patients with metastatic pancreatic adenocarcinoma initiating first-line chemotherapy in routine practice.

BACKGROUND: Despite advances in surgery, radiotherapy, and chemotherapy, pancreatic adenocarcinoma often progresses rapidly and causes death. The physical decline of these patients is expected to impact their quality of life (QoL). Therefore, in addition to objective measures of effectiveness, the evaluation of health-related QoL should be considered a matter of major concern when assessing therapy outcomes. METHODS: Observational, prospective, multicenter study including patients with metastatic pancreatic adenocarcinoma who started first-line chemotherapy in 12 Spanish centers. Treatment and clinical characteristics were recorded at baseline. Patients' health-related quality of life, ECOG, and Karnofsky index were measured at baseline, at Days 15 and 30, and every four weeks up to 6 months of chemotherapy. Health-related quality of life was measured using the EORTC-QLQ-C30 and EQ-5D questionnaires. Other endpoints included overall survival and progression-free survival. RESULTS: The study sample included 116 patients (median age of 65 years). Mean (SD) scores for the QLQ-C30 global health status scale showed a significant increasing trend throughout the treatment (p = 0.005). Patients with either a Karnofsky index of 70-80 or ECOG 2 showed greater improvement in the QLQ-C30 global health status score than the corresponding groups with better performance status (p ≤ 0.010). Pain, appetite, sleep disturbance, nausea, and constipation significantly improved throughout the treatment (p < 0.005). Patients with QLQ-C30 global health status scores ≥50 at baseline had significantly greater overall survival and progression-free survival (p = 0.005 and p = 0.021, respectively). No significant associations were observed regarding the EQ-5D score. CONCLUSIONS: Most metastatic pancreatic adenocarcinoma patients receiving first-line chemotherapy showed an increase in health-related quality of life scores throughout the treatment. Patients with lower performance status and health-related quality of life at baseline tended to greater improvement. The EORTC QLQ-C30 scale allowed us to measure the health-related quality of life of metastatic pancreatic adenocarcinoma patients receiving first-line chemotherapy.

Satisfaction of patients and primary care professionals with a teleophthalmology-based screening programme for diabetic retinopathy in a rural area in Castilla y León, Spain.

INTRODUCTION: Diabetic retinopathy (DR) is the leading cause of blindness in working-age adults in most developed countries. Early diagnosis and early treatment for retinopathy can reduce the incidence of severe loss of vision in a high percentage of sight-threatening DR. However, sight-threatening DR is asymptomatic in a high percentage of patients and no more than 50% of the diabetic patients are reviewed periodically in ophthalmology, mainly in rural areas. Telemedicine facilitates the exchange of information among professionals, reducing unnecessary journeys for patients who live in rural or remote areas. The survey of satisfaction is a highly useful quantitative instrument to obtain information directly from the users of a screening program. One aim of this study has been to determine the prevalence of DR in a sample of diabetic patients from a rural area of Spain and to classify DR patients according to the type and severity of this complication of the disease. The other main target was to evaluate the degree of satisfaction in both diabetic patients and professionals with a teleophthalmology-based screening program of DR. METHODS: A sample of 114 diabetic patients included in a new teleophthalmology program for the screening of DR in Castilla y León, Spain, were asked to take part in an in-person survey designed to evaluate the degree of satisfaction. This sample was obtained through a consecutive non-probability sampling technique, out of a total of 752 diabetic patients who underwent a retinography screening program in a distant rural healthcare center. The survey assessed aspects related to the information about the program the patients received, the organization of the center, the way the test was conducted and the reception of the results. All the included participants consented to participate in this study. Additionally, an anonymous survey was conducted via email. The sample was made up of 10 professionals responsible for taking the retinal images from the patients included in the study. This survey assessed their degree of satisfaction with their training, the way the test was carried out, the support from their managers and how this activity influenced their relationship with their patients. RESULTS: A high percentage of patients with DR in the study sample had a form of sight-threatening retinopathy (29.4%), which in this program is a criterion of referral to be assessed by an ophthalmologist. Of the surveyed patients, 93.8% scored eight points or higher for their degree of general satisfaction with the activity. All of them claimed they would prefer to continue their exploration at the healthcare center instead of going to the hospital. As regards the professionals, 70% scored eight points or more in terms of their degree of general satisfaction with the activity, whereas 20% scored between five and seven. One professional did not respond to the question. Finally, 90% stated that they would continue performing the activity, while the remaining 10% answered no. CONCLUSION: According to the high percentage of patients diagnosed with vision-threatening DR in this study, an early diagnosis of this complication of diabetes seems to be important. Teleophthalmology enhances patient accessibility to the healthcare system, making early diagnosis of DR easier, with a high degree of satisfaction among patients and healthcare professionals.