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Aim: To determine the prevalence of refractive error in 5- to 17-year-old schoolchildren in Puerto Rico., Methods: A quantitative descriptive study of 2867 children aged 5 to 17y from all seven educational regions of Puerto Rico was conducted from 2016-2019. Refractive error was determined via static and subjective refraction. Children with distance acuity ≤20/40 or near visual acuity ≤20/32 had a cycloplegic refraction. Data analysis included descriptive statistics, correlation coefficient, Kruskal-Wallis, Chi-square, and t test calculations., Results: Twenty percent of the children had a spherical equivalent refractive error ≤ -0.50 D, 3.2% had a spherical equivalent ≥ +2.00 D, and 10.4% had astigmatism ≥1 D. There was a statistically (but non-clinically) significant myopic change in spherical equivalent refractive error with age ( P <0.001). The prevalence of myopia increased with age ( P <0.001) but not hyperopia ( P =0.59) or astigmatism ( P =0.51). Males had a significantly higher hyperopic spherical equivalent than females ( P <0.001). Females had a higher prevalence of myopia ( P <0.001) than males, but there was no difference in the hyperopia ( P =0.74) or astigmatism prevalence ( P =0.87)., Conclusion: The prevalence of a spherical equivalent equal to or less than -0.50 D (myopia, 20.7%) is one of the highest among similar-aged children worldwide. Further studies should explore the rate of myopia progression in children in Puerto Rico. Individual children must be monitored to examine the need for treatment of myopia progression., (International Journal of Ophthalmology Press.)

Objective: Despite significant progresses in imaging and pathological evaluation, early differentiation between benign and malignant biliary strictures remains challenging. Endoscopic retrograde cholangiopancreatography (ERCP) is used to investigate biliary strictures, enabling the collection of bile. We tested the diagnostic potential of next-generation sequencing (NGS) mutational analysis of bile cell-free DNA (cfDNA)., Design: A prospective cohort of patients with suspicious biliary strictures (n=68) was studied. The performance of initial pathological diagnosis was compared with that of the mutational analysis of bile cfDNA collected at the time of first ERCP using an NGS panel open to clinical laboratory implementation, the Oncomine Pan-Cancer Cell-Free assay., Results: An initial pathological diagnosis classified these strictures as of benign (n=26), indeterminate (n=9) or malignant (n=33) origin. Sensitivity and specificity of this diagnosis were 60% and 100%, respectively, as on follow-up 14 of the 26 and eight of the nine initially benign or indeterminate strictures resulted malignant. Sensitivity and specificity for malignancy of our NGS assay, herein named Bilemut, were 96.4% and 69.2%, respectively. Importantly, one of the four Bilemut false positives developed pancreatic cancer after extended follow-up. Remarkably, the sensitivity for malignancy of Bilemut was 100% in patients with an initial diagnosis of benign or indeterminate strictures. Analysis of 30 paired bile and tissue samples also demonstrated the superior performance of Bilemut., Conclusion: Implementation of Bilemut at the initial diagnostic stage for biliary strictures can significantly improve detection of malignancy, reduce delays in the clinical management of patients and assist in selecting patients for targeted therapies., Competing Interests: Competing interests: None declared., (© Author(s) (or their employer(s)) 2022. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.)

Background: Biliary tract cancers (BTC) are rare but highly aggressive tumours with poor prognosis, usually detected at advanced stages. Herein, we aimed at identifying BTC-specific DNA methylation alterations., Methods: Study design included statistical power and sample size estimation. A genome-wide methylation study of an explorative cohort (50 BTC and ten matched non-tumoral tissue samples) has been performed. BTC-specific altered CpG islands were validated in over 180 samples (174 BTCs and 13 non-tumoral controls). The final biomarkers, selected by a machine-learning approach, were validated in independent tissue (18 BTCs, 14 matched non-tumoral samples) and bile (24 BTCs, five non-tumoral samples) replication series, using droplet digital PCR., Results: We identified and successfully validated BTC-specific DNA methylation alterations in over 200 BTC samples. The two-biomarker panel, selected by an in-house algorithm, showed an AUC > 0.97. The best-performing biomarker (chr2:176993479-176995557), associated with HOXD8, a pivotal gene in cancer-related pathways, achieved 100% sensitivity and specificity in a new series of tissue and bile samples., Conclusions: We identified a novel fully efficient BTC biomarker, associated with HOXD8 gene, detectable both in tissue and bile by a standardised assay ready-to-use in clinical trials also including samples from non-invasive matrices., (© 2022. The Author(s).)

Background: Latinx family caregivers of individuals with dementia face many barriers to caregiver support access. Interventions to alleviate these barriers are urgently needed., Objective: This study aimed to describe the development of CuidaTEXT, a tailored SMS text messaging intervention to support Latinx family caregivers of individuals with dementia., Methods: CuidaTEXT is informed by the stress process framework and social cognitive theory. We developed and refined CuidaTEXT using a mixed methods approach that included thematic analysis and descriptive statistics. We followed 6 user-centered design stages, namely, the selection of design principles, software vendor collaboration, evidence-based foundation, caregiver and research and clinical advisory board guidance, sketching and prototyping, and usability testing of the prototype of CuidaTEXT among 5 Latinx caregivers., Results: CuidaTEXT is a bilingual 6-month-long SMS text messaging-based intervention tailored to caregiver needs that includes 1-3 daily automatic messages (n=244) about logistics, dementia education, self-care, social support, end of life, care of the person with dementia, behavioral symptoms, and problem-solving strategies; 783 keyword-driven text messages for further help with the aforementioned topics; live chat interaction with a coach for further help; and a 19-page reference booklet summarizing the purpose and functions of the intervention. The 5 Latinx caregivers who used the prototype of CuidaTEXT scored an average of 97 out of 100 on the System Usability Scale., Conclusions: CuidaTEXT's prototype demonstrated high usability among Latinx caregivers. CuidaTEXT's feasibility is ready to be tested., (©Jaime Perales-Puchalt, Mariola Acosta-Rullán, Mariana Ramírez-Mantilla, Paul Espinoza-Kissell, Eric Vidoni, Michelle Niedens, Edward Ellerbeck, Ladson Hinton, Linda Loera, A Susana Ramírez, Esther Lara, Amber Watts, Kristine Williams, Jason Resendez, Jeffrey Burns. Originally published in JMIR Aging (https://aging.jmir.org), 28.04.2022.)

One of the critical issues to warrant the success of a proteome-wide analysis is sample preparation. Efficient protein extraction in the absence of interferent material is mandatory to achieve an ample proteome coverage by mass spectrometry. The study of biological fluids is always challenging due to their specific biochemical composition. However, there is increasing interest in their characterization as it will provide proteins that may advice disease setting, state, and progression. In particular, bile is proximal to liver and pancreas, and its study is especially attractive since it might provide valuable information for the clinical management of severe diseases afflicting these organs, which are at an urgent need of new biomarkers. Though previous efforts have been made to optimize protocols to analyze bile proteome, only partial descriptions were achieved due to its complex composition, where proteins represent less than 5% of the organic components. Here we describe a new method that significantly increases the bile proteome coverage while reducing by a factor of six the amount of sample required for the proteomic analysis., (© 2022. The Author(s), under exclusive license to Springer Science+Business Media, LLC, part of Springer Nature.)

Objective: Cultural backgrounds and values have a decisive impact on the phenomenon of the wish to die (WTD), and examination of this in Mediterranean countries is in its early stages. The objectives of this study were to establish the prevalence of WTD and to characterise this phenomenon in our cultural context., Methods: A cross-sectional study with consecutive advanced inpatients was conducted. Data about WTD ( Assessing Frequency & Extent of Desire to Die (AFFED) interview) and anxiety and depression ( Edmonton Symptom Assessment System-revised (ESAS-r)) were collected through two face-to-face clinical encounters. Data were analysed with descriptive statistics, χ 2 and analysis of variance., Results: 201 patients participated and 165 (82%) completed both interviews. Prevalence of WTD was 18% (36/201) in the first interview and 16% (26/165) in the second interview (p=0.25). After the first interview, no changes in depression (p=0.60) or anxiety (p=0.90) were detected. The AFFED shows different experiences within WTD: 11% of patients reported a sporadic experience, while 7% described a persistent experience. Thinking about hastening death (HD) appeared in 8 (22%) out of 36 patients with WTD: 5 (14%) out of 36 patients considered this hypothetically but would never take action, while 3 (8%) out of 36 patients had a more structured idea about HD. In this study, no relation was detected between HD and frequency of the appearance of WTD (p=0.12)., Conclusions: One in five patients had WTD. Our findings suggest the existence of different experiences within the same phenomenon, defined according to frequency of appearance and intention to hasten death. A linguistically grounded model is proposed, differentiating the experiences of the 'wish' or 'desire' to die, with or without HD ideation., Competing Interests: Competing interests: None declared., (© Author(s) (or their employer(s)) 2021. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.)

The analysis of biological fluids to identify proteins that may indicate a disease setting, state and progression, is an increasingly explored field. Despite the expectatives created, there are several hurdles that must be solved to reach an extensive proteome coverage using mass spectrometry, mainly due to the complex composition of the matrices. In this regard, bile is specially challenging and yet, very attractive, as a proximal fluid that might provide valuable information for the management of liver and pancreas associated diseases. Proteins account for less than 5% of bile organic components and, although optimized protocols for protein extraction have been developed, only partial descriptions of bile proteome have been achieved. In this manuscript a new procedure is described that significantly improves protein recovery from rat bile, which reduces by a factor of six the sample amount required for a typical proteomics analysis. Moreover, the number of proteins reliably identified in a single nanoLC-MS/MS run from 1 μg protein was increased by three-fold. This procedure provides a valuable resource to dig deeper into the molecular composition of bile and open new avenues to identify new hallmarks of disease such as cholangiocarcinoma, hepatocellular carcinoma and pancreatic cancer for their better clinical management., (Copyright © 2020 Elsevier B.V. All rights reserved.)

Cholangiocarcinoma (CCA) and pancreatic adenocarcinoma (PDAC) may lead to the development of extrahepatic obstructive cholestasis. However, biliary stenoses can also be caused by benign conditions, and the identification of their etiology still remains a clinical challenge. We performed metabolomic and proteomic analyses of bile from patients with benign ( n = 36) and malignant conditions, CCA ( n = 36) or PDAC ( n = 57), undergoing endoscopic retrograde cholangiopancreatography with the aim of characterizing bile composition in biliopancreatic disease and identifying biomarkers for the differential diagnosis of biliary strictures. Comprehensive analyses of lipids, bile acids and small molecules were carried out using mass spectrometry (MS) and nuclear magnetic resonance spectroscopy ( 1 H-NMR) in all patients. MS analysis of bile proteome was performed in five patients per group. We implemented artificial intelligence tools for the selection of biomarkers and algorithms with predictive capacity. Our machine-learning pipeline included the generation of synthetic data with properties of real data, the selection of potential biomarkers (metabolites or proteins) and their analysis with neural networks (NN). Selected biomarkers were then validated with real data. We identified panels of lipids ( n = 10) and proteins ( n = 5) that when analyzed with NN algorithms discriminated between patients with and without cancer with an unprecedented accuracy.

Background: Postherpetic neuralgia (PHN) is the most common complication of herpes zoster (HZ). Previous trials have reported that gabapentin can relieve chronic neuropathic pain, but its effect on prevention of PHN is unclear., Objective: To assess the efficacy of a 5-week course of gabapentin on acute herpetic pain and on the prevention of PHN at 12 weeks in patients with acute HZ., Methods: This was a randomized, double blind, placebo-controlled trial conducted in 17 primary care health centers in Mallorca, Spain. All patients were older than 50 years, presented with HZ within 72 h of rash onset, and had moderate-severe pain (≥4 on a 10-point visual analogue scale [VAS]). Ninety-eight patients were randomized to receive gabapentin or placebo. All patients received valaciclovir for 7 days and analgesia if needed. The treatment period was 5 weeks, followed by 7 weeks of follow-up. Gabapentin was initiated at 300 mg/day and gradually titrated to a maximum of 1800 mg/day. The main outcome measure was pain at 12 weeks., Results: Seventy-five patients completed the study, 33 in the gabapentin group and 42 in the control group. A total of 18.2% of patients in the gabapentin group and 9.5% in the control group reported pain at 12 weeks (p = 0.144). Four patients in the gabapentin group (12.1%), but no patients in the placebo group, reported pain of 4 or more on a 10-point VAS. Patients taking gabapentin reported worse health-related quality of life and poorer sleep quality. Three patients discontinued the trial due to adverse effects from gabapentin., Conclusion: Addition of gabapentin to the usual treatment of HZ within 72 h of rash onset provided no significant relief from acute herpetic pain or prevention of PHN., Trial Registration: ISRCTN Registry identifier: ISRCTN79871784., Competing Interests: The authors have declared that no competing interests exist.

Objective: The Patient Dignity Inventory (PDI) evaluates sources of distress related to the feeling of loss of dignity and was designed for patients at the end of life. The aim of the present work was to generate a better understanding of the experiences of healthcare staff when using the PDI., Method: An exploratory qualitative study is presented about the experience of 4 professionals who applied the PDI to 124 advanced-cancer patients. Our study consisted of an analysis of their experiences, taken from information generated in a focus group. A thematic analysis was performed on the information generated at that meeting by two researchers working independently., Results: The initial experiences with the PDI on the part of the professionals led them to systematically administer the questionnaire as part of an interview instead of having patients fill it out themselves in written form. What started out as an evaluation very often led to a profound conversation on the meaning of life, dignity, and other sensitive, key issues related to the process of the illness., Significance of Results: The PDI has intrinsic therapeutic value and is useful in clinical practice, and it is also a way of examining issues related to dignity and the meaning of life within the context of advanced-stage illness. There is a need for studies that examine patient experiences through a PDI-based interview.

Introduction: Peroral endoscopic myotomy (POEM) has been performed since 2008 on more than 5,000 patients. It has proven to be highly effective in the treatment of achalasia and has shown promising outcomes for other esophageal motility spastic disorders., Methods: A literature review of the efficacy of POEM compared to the previous invasive treatments for different esophageal motility disorders was performed. The application in the pediatric and elderly populations and its role as a rescue therapy after other procedures are also outlined., Results: Short-term outcomes are similar to laparoscopic Heller myotomy (LHM) and pneumatic endoscopic dilation (PD) (clinical success > 90%) for achalasia subtypes I and II. Mid-term outcomes are comparable to LHM and overcome the results obtained after PD (> 90% vs ~50%). With regard to type III achalasia, POEM efficacy is 98% compared to 80.8% for LHM and the PD success remains at 40%. With regard to spastic esophageal disorders (SED), POEM has an effectiveness of 88% and 70% for distal esophageal spasm (DES) and jackhammer esophagus (JE) respectively. A response of 95% in patients with sigmoid esophagus has been reported. POEM has been performed in pediatric and elderly populations and has obtained a higher efficacy than PD in pediatric series (100% vs 33%) without greater adverse events. Previous treatments do not seem to hinder POEM results with excellent response rates, including 97% in post LHM and 100% in a re-POEM series. Final considerations: POEM has shown excellent short and mid-term results for all subtypes of achalasia but long-term results are not yet available. The promising results in SED may make POEM the first-line treatment for SED. A high-safety profile and efficacy have been shown in elderly and pediatric populations. Previous treatments do not seem to diminish the success rate of POEM. Core tip: POEM has emerged as an efficient treatment option for all subtypes of achalasia and other scenarios (including previous treatments and elderly and pediatric populations). Short and mid-term results are comparable to LHM and are better than PD data. The clinical response rate of DES and JE may make POEM the first-line treatment for SED.

Background: Dignity therapy is psychotherapy to relieve psychological and existential distress in patients at the end of life. Little is known about its effect., Aim: To analyse the outcomes of dignity therapy in patients with advanced life-threatening diseases., Design: Systematic review was conducted. Three authors extracted data of the articles and evaluated quality using Critical Appraisal Skills Programme. Data were synthesized, considering study objectives., Data Sources: PubMed, CINAHL, Cochrane Library and PsycINFO. The years searched were 2002 (year of dignity therapy development) to January 2016. 'Dignity therapy' was used as search term. Studies with patients with advanced life-threatening diseases were included., Results: Of 121 studies, 28 were included. Quality of studies is high. Results were grouped into effectiveness, satisfaction, suitability and feasibility, and adaptability to different diseases and cultures. Two of five randomized control trials applied dignity therapy to patients with high levels of baseline psychological distress. One showed statistically significant decrease on patients' anxiety and depression scores over time. The other showed statistical decrease on anxiety scores pre-post dignity therapy, not on depression. Nonrandomized studies suggested statistically significant improvements in existential and psychosocial measurements. Patients, relatives and professionals perceived it improved end-of-life experience., Conclusion: Evidence suggests that dignity therapy is beneficial. One randomized controlled trial with patients with high levels of psychological distress shows DT efficacy in anxiety and depression scores. Other design studies report beneficial outcomes in terms of end-of-life experience. Further research should understand how dignity therapy functions to establish a means for measuring its impact and assessing whether high level of distress patients can benefit most from this therapy.

Background: Postherpetic neuralgia (PHN) is a chronic neuropathic pain that results from alterations of the peripheral nervous system in areas affected by the herpes zoster virus. The symptoms include pain, paresthesia, dysesthesia, hyperalgesia, and allodynia. Despite the availability of pharmacological treatments to control these symptoms, no treatments are available to control the underlying pathophysiology responsible for this disabling condition., Methods/design: Patients with herpes zoster who are at least 50 years old and have a pain score of 4 or higher on a visual analogue scale (VAS) will be recruited. The aim is to recruit 134 patients from the practices of general physicians. Participants will be randomized to receive gabapentin to a maximum of 1800 mg/day for 5 weeks or placebo. Both arms will receive 1000-mg caplets of valacyclovir three times daily for 7 days (initiated within 72 h of the onset of symptoms) and analgesics as needed. The primary outcome measure is the percentage of patients with a VAS pain score of 0 at 12 weeks from rash onset. The secondary outcomes measures are changes in quality of life (measured by the SF-12 questionnaire), sleep disturbance (measured by the Medical Outcomes Study Sleep Scale), and percentage of patients with neuropathic pain (measured by the Douleur Neuropathique in 4 Questions)., Discussion: Gabapentin is an anticonvulsant type of analgesic that could prevent the onset of PHN by its antihypersensitivity action in dorsal horn neurons., Trial Registration: ISRCTN Registry identifier: ISRCTN79871784 . Registered on 2 May 2013.

Context: Limited data exist about blood lead levels (BLLs) and potential exposures among children living in Puerto Rico. The Puerto Rico Department of Health has no formal blood lead surveillance program., Objectives: We assessed the prevalence of elevated BLLs (≥5 micrograms of lead per deciliter of blood), evaluated household environmental lead levels, and risk factors for BLL among children younger than 6 years of age living in Puerto Rico in 2010., Methods: We used a population-based, cross-sectional sampling strategy to enroll an island-representative sample of Puerto Rican children younger than 6 years. We estimated the island-wide weighted prevalence of elevated BLLs and conducted bivariable and multivariable linear regression analyses to ascertain risk factors for elevated BLLs., Results: The analytic data set included 355 households and 439 children younger than 6 years throughout Puerto Rico. The weighted geometric mean BLL of children younger than 6 years was 1.57 μg/dL (95% confidence interval [CI], 1.27-1.88). The weighted prevalence of children younger than 6 years with BLLs of 5 μg/dL or more was 3.18% (95% CI, 0.93-5.43) and for BLLs of 10 μg/dL or more was 0.50% (95% CI, 0-1.31). Higher mean BLLs were significantly associated with data collection during the summer months, a lead-related activity or hobby of anyone in the residence, and maternal education of less than 12 years. Few environmental lead hazards were identified., Conclusions: The prevalence of elevated BLLs among Puerto Rican children younger than 6 years is comparable with the most recent (2007-2010) US national estimate (BLLs ≥5 μg/dL = 2.6% [95% CI = 1.6-4.0]). Our findings suggest that targeted screening of specific higher-risk groups of children younger than 6 years can replace island-wide or insurance-specific policies of mandatory blood lead testing in Puerto Rico.

Context: The Patient Dignity Inventory (PDI) is an instrument to measure sources of distress related to dignity at the end of life., Objectives: To obtain a Spanish version of the PDI and measure psychometric aspects in patients with advanced cancer., Methods: A back-translation method was used to obtain the Spanish version. Inpatients and outpatients with advanced cancer were included. Patients completed the Spanish versions of the PDI (PDI-s), Edmonton Symptom Assessment System (ESAS), Hospital Anxiety and Depression Scale (HADS), and Functional Assessment of Chronic Illness Therapy-Spiritual Well-Being (FACIT-Sp-12) instruments. The psychometric properties evaluated were internal consistency; concurrent validity between PDI-s/ESAS, PDI-s/HADS, and PDI-s/FACIT-Sp-12; discriminant validity, test-retest reliability, and factor analysis. The usefulness of the instrument also was tested., Results: A Spanish version of the PDI was obtained. One hundred twenty-four patients completed the study. Cronbach's alpha coefficient for the PDI-s was 0.89. The PDI-s significantly correlated with the ESAS (rs = 0.669; P < 0.001), HADS (rs = 0.788; P < 0.001), and FACIT-Sp-12 (rs = -0.442; P = 0.008). The instrument distinguished outpatients from inpatients and between patients with differing Karnofsky Performance Status scores (rs = -0.328; P < 0.001). The test-retest method indicated excellent reproducibility (intraclass correlation coefficient = 0.931). Factor analysis showed three factors accounting for 79.4% of the variance. Factors were labeled psychological and existential distress, physical symptoms and dependency, and social support. Patients had no difficulties in understanding or completing the questionnaire (mean time to complete: 7.2 minutes)., Conclusion: The Spanish version of the PDI showed adequate psychometric properties when tested with advanced cancer patients. This research provides a three-factor alternative in Spanish to the PDI., (Copyright © 2015 American Academy of Hospice and Palliative Medicine. Published by Elsevier Inc. All rights reserved.)