The Impact of Integrated Palliative Care on Survival in Idiopathic Pulmonary Fibrosis: A Retrospective Multicenter Comparison.

Background: Early and integrated palliative care is recommended for patients with idiopathic pulmonary fibrosis. Unfortunately, palliative care delivery remains poor due to various barriers in practice. This study describes various palliative care delivery models in a real-world cohort of patients with idiopathic pulmonary fibrosis, examines the predictors of survival in this cohort of patients, and explores the impact of palliative care on survival. Design: Charts were reviewed retrospectively and analyzed. The primary outcome was survival during a 4-year follow-up period. Two multivariable models were created to examine the impact of therapeutic strategies including palliative intervention on survival. Results: 298 patients with idiopathic pulmonary fibrosis were enrolled from 3 interstitial lung disease clinics with different palliative care models in Edmonton, Canada; Bristol, UK; and Kingston, Canada. 200 (67%) patients received palliative care and 119 (40%) died during follow up. Primary palliative care models (Edmonton and Bristol) delivered palliative care to 96% and 100% respectively compared 21% in the referral model (Queens). Palliative care [adjusted hazard ratio (aHR) .28 (.12-.65)] along with the use of antifibrotics [aHR .56 (.37-.84)], and body mass index >30 [aHR .47 (.37-.85)] reduced the risk of death in our idiopathic pulmonary fibrosis cohort. Opioid use was associated with worse survival [aHR 2.11 (1.30-23.43)]. Conclusions: Both palliative care and antifibrotic use were associated with survival benefit in this cohort of patients with idiopathic pulmonary fibrosis after adjusting for covariates. The benefit was seen despite differences in disease severity and different palliative care delivery models.

Progress Toward Measles and Rubella Elimination - Indonesia, 2013-2022.

In 2019, Indonesia and the other countries in the World Health Organization South-East Asia Region adopted the goal of measles and rubella elimination by 2023. This report describes Indonesia's progress toward measles and rubella elimination during 2013-2022. During this period, coverage with a first dose of measles-containing vaccine (MCV) decreased from 87% to 84%, and coverage with a second MCV dose decreased from 76% to 67%. After rubella vaccine was introduced in 2017, coverage with the first dose of rubella-containing vaccine increased approximately fivefold, from 15% in 2017 to 84% in 2022. During 2013-2021, annual reported measles incidence decreased by 95%, from 33.2 to 1.4 cases per million population; reported rubella incidence decreased 89%, from 9.3 to 1.0 cases per million population. However, a large surge in measles and rubella cases occurred in 2022, with a reported measles incidence of 29 cases per million and a reported rubella incidence of 3 per million, primarily related to disruption in immunization services caused by the COVID-19 pandemic. In 2022, approximately 26 million children (an estimated 73% of the target population) received a combined measles- and rubella-containing vaccine during supplementary immunization activities completed in 32 provinces. Progress toward measles and rubella elimination in Indonesia has been made; however, continued and urgent efforts are needed to restore routine immunization services that were adversely affected by the COVID-19 pandemic and close immunity gaps to accelerate progress toward measles and rubella elimination.

Progress Toward Rubella Elimination - World Health Organization South-East Asia Region, 2013-2021.

During 2013, the 11 countries of the World Health Organization (WHO) South-East Asia Region* (SEAR) adopted the goals of measles elimination and rubella and congenital rubella syndrome (CRS) control† by 2020. During 2019, SEAR countries declared a broader goal for eliminating both measles and rubella§ by 2023 (1). Before 2013, only five SEAR countries had introduced rubella-containing vaccine (RCV). This report updates a previous report and describes progress toward rubella elimination in SEAR during 2013-2021 (2). During 2013-2021, six SEAR countries introduced RCV; all countries in the Region now use RCV in routine immunization. Routine immunization coverage with the first dose of a rubella-containing vaccine (RCV1) increased >600%, from 12% during 2013 to 86% during 2021, and an estimated 515 million persons were vaccinated via RCV supplementary immunization activities (SIAs)¶ during 2013-2021. During this time, annual reported rubella incidence declined by 80%, from 5.5 to 1.1 cases per million population. Maldives and Sri Lanka are verified as having achieved rubella elimination; Bhutan, North Korea, and Timor-Leste have halted endemic transmission of rubella virus for >36 months. SEAR has made substantial progress toward rubella elimination; however, intensified measures are needed to achieve elimination.

Behavioural Economics to Improve Antihypertensive Therapy Adherence (BETA): protocol for a pilot randomised controlled trial in Los Angeles.

INTRODUCTION: Non-adherence to antihypertensive therapy is one of the major barriers to reducing the risk of cardiovascular disease. Several interventions have targeted higher medication adherence, yet most do not result in sustained adherence. Routinisation has emerged as a potential method for mitigating this problem, but requires high motivation during the relatively long habit formation phase. This pilot randomised controlled trial aims to test the feasibility, acceptability, and preliminary efficacy of behavioural economics-based incentives and text messages to support the routinisation of the medication-taking behaviour for promoting long-term medication adherence. METHODS AND ANALYSIS: This study will recruit and randomly assign 60 adult patients seeking care for hypertension at the Cedars-Sinai Medical Center in Los Angeles to one of the three groups, Control (n=20), Messages (n=20) and Incentives (n=20) in a 1:1:1 ratio. All participants will receive information about the importance of routinisation and will select an existing behavioural routine ('anchor') to which they will tie their pill-taking to, and the corresponding time. Additionally, participants in the Messages group will receive daily text messages reminding them of the importance of routines, while those in the Incentives group will receive daily text messages and conditional prize drawings. The interventions will be delivered over three months. Participants will be followed for six months post-intervention to measure behavioural persistence. Surveys will be administered at baseline, month-3 and month-9 visits. Primary outcomes include: (1) electronically measured mean medication adherence during the intervention period and (2) post-intervention period; and (3) mean timely medication adherence based around the time of the participants' anchor during the intervention period, and (4) post-intervention period. ETHICS AND DISSEMINATION: The study was approved by the Cedars-Sinai Institutional Review Board (Study ID: Pro00057764). Findings will be published in scientific peer-reviewed journals. TRIAL REGISTRATION NUMBER: NCT04029883.

Progress Toward Measles and Rubella Elimination - India, 2005-2021.

In 2019, India, along with other countries in the World Health Organization (WHO) South-East Asia Region,* adopted the goal of measles and rubella elimination by 2023,† a revision of the previous goal of measles elimination and control of rubella and congenital rubella syndrome (CRS) by 2020§ (1-3). During 2017-2021, India adopted a national strategic plan for measles and rubella elimination (4), introduced rubella-containing vaccine (RCV) into the routine immunization program, launched a nationwide measles-rubella supplementary immunization activity (SIA) catch-up campaign, transitioned from outbreak-based surveillance to case-based acute fever and rash surveillance, and more than doubled the number of laboratories in the measles-rubella network, from 13 to 27. Strategies included 1) achieving and maintaining high population immunity with at least 95% vaccination coverage by providing 2 doses of measles- and rubella-containing vaccines; 2) ensuring a sensitive and timely case-based measles, rubella and CRS surveillance system; 3) maintaining an accredited measles and rubella laboratory network; 4) ensuring adequate outbreak preparedness and rapid response to measles and rubella outbreaks; and 5) strengthening support and linkages to achieve these strategies, including planning and progress monitoring, advocacy, social mobilization and communication, identification and utilization of synergistic linkages of integrated program efforts, research, and development. This report describes India's progress toward the elimination of measles and rubella during 2005-2021, with a focus on the years 2017-2021.¶ During 2005-2021, coverage with the first dose of a measles-containing vaccine (MCV) administered through routine immunization increased 31%, from 68% to 89%. During 2011-2021, coverage with a second MCV dose (MCV2) increased by 204%, from 27% to 82%. During 2017-2021, coverage with a first dose of RCV (RCV1) increased almost 14-fold, from 6% to 89%. More than 324 million children received a measles- and rubella-containing vaccine (MRCV) during measles-rubella SIAs completed in 34 (94%) of 36 states and union territories (states) during 2017-2019. During 2017-2021, annual measles incidence decreased 62%, from 10.4 to 4.0 cases per 1 million population, and rubella incidence decreased 48%, from 2.3 to 1.2 cases per 1 million population. India has made substantial progress toward measles and rubella elimination; however, urgent and intensified efforts are required to achieve measles and rubella elimination by 2023.

Progress Toward Rubella and Congenital Rubella Syndrome Control - South-East Asia Region, 2000-2016.

In 2013, the 66th session of the Regional Committee of the World Health Organization (WHO) South-East Asia Region (SEAR)* adopted the goal of elimination of measles and control† of rubella and congenital rubella syndrome (CRS) by 2020 (1). Rubella is the leading vaccine-preventable cause of birth defects. Although rubella typically causes a mild fever and rash in children and adults, rubella virus infection during pregnancy, especially during the first trimester, can result in miscarriage, fetal death, or a constellation of congenital malformations known as CRS, commonly including visual, auditory, and/or cardiac defects, and developmental delay (2). Rubella and CRS control capitalizes on the momentum created by pursuing measles elimination because the efforts are programmatically linked. Rubella-containing vaccine (RCV) is administered as a combined measles and rubella vaccine, and rubella cases are detected through case-based surveillance for measles or fever and rash illness (3). This report summarizes progress toward rubella and CRS control in SEAR during 2000-2016. Estimated coverage with a first RCV dose (RCV1) increased from 3% of the birth cohort in 2000 to 15% in 2016 because of RCV introduction in six countries. RCV1 coverage is expected to increase rapidly with the phased introduction of RCV in India and Indonesia beginning in 2017; these countries are home to 83% of the SEAR birth cohort. During 2000-2016, approximately 83 million persons were vaccinated through 13 supplemental immunization activities (SIAs) conducted in eight countries. During 2010-2016, reported rubella incidence decreased by 37%, from 8.6 to 5.4 cases per 1 million population, and four countries (Bangladesh, Maldives, Sri Lanka, and Thailand) reported a decrease in incidence of ≥95% since 2010. To achieve rubella and CRS control in SEAR, sustained investment to increase routine RCV coverage, periodic high-quality SIAs to close immunity gaps, and strengthened rubella and CRS surveillance are needed.

Immunogenicity of type 2 monovalent oral and inactivated poliovirus vaccines for type 2 poliovirus outbreak response: an open-label, randomised controlled trial.

BACKGROUND: Monovalent type 2 oral poliovirus vaccine (mOPV2) and inactivated poliovirus vaccine (IPV) are used to respond to type 2 poliovirus outbreaks. We aimed to assess the effect of two mOPV2 doses on the type 2 immune response by varying the time interval between mOPV2 doses and IPV co-administration with mOPV2. METHODS: We did a randomised, controlled, parallel, open-label, non-inferiority, inequality trial at two study clinics in Dhaka, Bangladesh. Healthy infants aged 6 weeks (42-48 days) at enrolment were randomly assigned (1:1:1:1) to receive two mOPV2 doses (each dose consisting of two drops [0·1 mL in total] of about 105 50% cell culture infectious dose of type 2 Sabin strain) at intervals of 1 week, 2 weeks, 4 weeks (standard or control group), or 4 weeks with IPV (0·5 mL of type 1 [Mahoney, 40 D-antigen units], type 2 [MEF-1, 8 D-antigen units], and type 3 [Saukett, 32 D-antigen units]) administered intramuscularly with the first mOPV2 dose. We used block randomisation, randomly selecting blocks of sizes four, eight, 12, or 16 stratified by study sites. We concealed randomisation assignment from staff managing participants in opaque, sequentially numbered, sealed envelopes. Parents and clinic staff were unmasked to assignment after the randomisation envelope was opened. Laboratory staff analysing sera were masked to assignment, but investigators analysing data and assessing outcomes were not. The primary outcome was type 2 immune response measured 4 weeks after mOPV2 administration. The primary modified intention-to-treat analysis included participants with testable serum samples before and after vaccination. A non-inferiority margin of 10% and p=0·05 (one-tailed) was used. This trial is registered at ClinicalTrials.gov, number NCT02643368, and is closed to accrual. FINDINGS: Between Dec 7, 2015, and Jan 5, 2016, we randomly assigned 760 infants to receive two mOPV2 doses at intervals of 1 week (n=191), 2 weeks (n=191), 4 weeks (n=188), or 4 weeks plus IPV (n=190). Immune responses after two mOPV2 doses were observed in 161 (93%) of 173 infants with testable serum samples in the 1 week group, 169 (96%) of 177 in the 2 week group, and 176 (97%) of 181 in the 4 week group. 1 week and 2 week intervals between two mOPV2 doses were non-inferior to 4 week intervals because the lower bound of the absolute differences in the percentage of immune responses were greater than -10% (-4·2% [90% CI -7·9 to -0·4] in the 1 week group and -1·8% [-5·0 to 1·5] in the 2 week group vs the 4 week group). The immune response elicited by two mOPV2 doses 4 weeks apart was not different when IPV was added to the first dose (176 [97%] of 182 infants with IPV vs 176 [97%] of 181 without IPV; p=1·0). During the trial, two serious adverse events (pneumonia; one [1%] of 186 patients in the 1 week group and one [1%] of 182 in the 4 week group) and no deaths were reported; the adverse events were not attributed to the vaccines. INTERPRETATION: Administration of mOPV2 at short intervals does not interfere with its immunogenicity. The addition of IPV to the first mOPV2 dose did not improve poliovirus type 2 immune response. FUNDING: US Centers for Disease Control and Prevention.

Specialist palliative care, psychology, interstitial lung disease (ILD) multidisciplinary team meeting: a novel model to address palliative care needs.

INTRODUCTION: Patients with progressive idiopathic fibrotic interstitial lung disease (ILD), such as those with idiopathic pulmonary fibrosis (IPF), can have an aggressive disease course, with a median survival of only 3-5 years from diagnosis. The palliative care needs of these patients are often unmet. There are calls for new models of care, whereby the patient's usual respiratory clinician remains central to the integration of palliative care principles and practices into their patient's management, but the optimal model of service delivery has yet to be determined. METHODS: We developed a novel, collaborative, multidisciplinary team (MDT) meeting between our palliative care, psychology and ILD teams with the principal aim of integrating specialist care to ensure the needs of persons with ILD, and their caregivers were identified and met by referral to the appropriate service. The objective of this study was to assess the effectiveness of this novel MDT meeting on the assessment of a patient's palliative care needs. RESULTS: Significant increases in advance care planning discussions were observed, in conjunction with increased referrals to community courses and teams, following introduction of this novel MDT. CONCLUSIONS: Our results suggest that our collaborative MDT is an effective platform to address patients' unmet palliative care needs. Further work is required to explore the effect of our model on achieving the preferred place of death and reductions in unplanned hospital admissions.

Differential effects of Calca-derived peptides in male mice with diet-induced obesity.

Key metabolic hormones, such as insulin, leptin, and adiponectin, have been studied extensively in obesity, however the pathophysiologic relevance of the calcitonin family of peptides remains unclear. This family includes calcitonin (CT), its precursor procalcitonin (PCT), and alpha calcitonin-gene related peptide (αCGRP), which are all encoded by the gene Calca. Here, we studied the role of Calca-derived peptides in diet-induced obesity (DIO) by challenging Calcr-/- (encoding the calcitonin receptor, CTR), Calca-/-, and αCGRP-/- mice and their respective littermates with high-fat diet (HFD) feeding for 16 weeks. HFD-induced pathologies were assessed by glucose tolerance, plasma cytokine and lipid markers, expression studies and histology. We found that DIO in mice lacking the CTR resulted in impaired glucose tolerance, features of enhanced nonalcoholic steatohepatitis (NASH) and adipose tissue inflammation compared to wildtype littermates. Furthermore, CTR-deficient mice were characterized by dyslipidemia and elevated HDL levels. In contrast, mice lacking Calca were protected from DIO, NASH and adipose tissue inflammation, and displayed improved glucose tolerance. Mice exclusively lacking αCGRP displayed a significantly less improved DIO phenotype compared to Calca-deficient mice. In summary, we demonstrate that the CT/CTR axis is involved in regulating plasma cholesterol levels while Calca, presumably through PCT, seems to have a detrimental effect in the context of metabolic disease. Our study provides the first comparative analyses of the roles of Calca-derived peptides and the CTR in metabolic disease.

The Multimodal Assessment of Adult Attachment Security: Developing the Biometric Attachment Test.

BACKGROUND: Attachment theory has been proven essential for mental health, including psychopathology, development, and interpersonal relationships. Validated psychometric instruments to measure attachment abound but suffer from shortcomings common to traditional psychometrics. Recent developments in multimodal fusion and machine learning pave the way for new automated and objective psychometric instruments for adult attachment that combine psychophysiological, linguistic, and behavioral analyses in the assessment of the construct. OBJECTIVE: The aim of this study was to present a new exposure-based, automatic, and objective adult-attachment assessment, the Biometric Attachment Test (BAT), which exposes participants to a short standardized set of visual and music stimuli, whereas their immediate reactions and verbal responses, captured by several computer sense modalities, are automatically analyzed for scoring and classification. We also aimed to empirically validate two of its assumptions: its capacity to measure attachment security and the viability of using themes as placeholders for rotating stimuli. METHODS: A total of 59 French participants from the general population were assessed using the Adult Attachment Questionnaire (AAQ), the Adult Attachment Projective Picture System (AAP), and the Attachment Multiple Model Interview (AMMI) as ground truth for attachment security. They were then exposed to three different BAT stimuli sets, whereas their faces, voices, heart rate (HR), and electrodermal activity (EDA) were recorded. Psychophysiological features, such as skin-conductance response (SCR) and Bayevsky stress index; behavioral features, such as gaze and facial expressions; as well as linguistic and paralinguistic features, were automatically extracted. An exploratory analysis was conducted using correlation matrices to uncover the features that are most associated with attachment security. A confirmatory analysis was conducted by creating a single composite effects index and by testing it for correlations with attachment security. The stability of the theory-consistent features across three different stimuli sets was explored using repeated measures analysis of variances (ANOVAs). RESULTS: In total, 46 theory-consistent correlations were found during the exploration (out of 65 total significant correlations). For example, attachment security as measured by the AAP was correlated with positive facial expressions (r=.36, P=.01). AMMI's security with the father was inversely correlated with the low frequency (LF) of HRV (r=-.87, P=.03). Attachment security to partners as measured by the AAQ was inversely correlated with anger facial expression (r=-.43, P=.001). The confirmatory analysis showed that the composite effects index was significantly correlated to security in the AAP (r=.26, P=.05) and the AAQ (r=.30, P=.04) but not in the AMMI. Repeated measures ANOVAs conducted individually on each of the theory-consistent features revealed that only 7 of the 46 (15%) features had significantly different values among responses to three different stimuli sets. CONCLUSIONS: We were able to validate two of the instrument's core assumptions: its capacity to measure attachment security and the viability of using themes as placeholders for rotating stimuli. Future validation of other of its dimensions, as well as the ongoing development of its scoring and classification algorithms is discussed.

Progress Toward Polio Eradication - Worldwide, 2015-2016.

In 1988, the World Health Assembly resolved to eradicate poliomyelitis. Wild poliovirus (WPV) transmission persists in only two countries (Afghanistan and Pakistan) after the removal of Nigeria from the list of countries with endemic polio in September 2015.* Indigenous WPV type 2 has not been detected since 1999 and was declared eradicated by the Global Commission for the Certification of Poliomyelitis Eradication in September 2015.(†) Since November 2012, when the last case of WPV type 3 was detected in Nigeria, WPV type 1 has been the sole circulating type of WPV (1). This report summarizes global progress toward polio eradication during 2015-2016 and updates previous reports (2). In 2015, 74 WPV cases were reported in two countries (Afghanistan and Pakistan), a decrease of 79% from the 359 WPV cases reported in 2014 in nine countries; 12 WPV cases have been reported in 2016 (to date), compared with 23 during the same period in 2015 (3). Paralytic polio caused by circulating vaccine-derived poliovirus (cVDPV) remains a risk in areas with low oral poliovirus vaccine (OPV) coverage. Seven countries, including Pakistan, reported 32 cVDPV cases in 2015 (4). In four of these countries, ≥6 months have passed since the most recent case or isolate. One country (Laos) with VDPV transmission in 2015 has reported three additional cVDPV cases in 2016 to date. Encouraging progress toward polio eradication has been made over the last year; however, interruption of WPV transmission will require focus on reaching and vaccinating every missed child through high quality supplementary immunization activities (SIAs) and cross-border coordination between Afghanistan and Pakistan (5,6).

Notes from the Field: Circulating Vaccine-Derived Poliovirus Outbreaks - Five Countries, 2014-2015.

In 2015, wild poliovirus (WPV) transmission was identified in only Afghanistan and Pakistan (1). The widespread use of live, attenuated oral poliovirus vaccine (OPV) has been key in polio eradication efforts. However, OPV use, particularly in areas with low vaccination coverage, is associated with the low risk for emergence of vaccine-derived polioviruses (VDPV), which can cause paralysis (2). VDPVs vary genetically from vaccine viruses and can cause outbreaks in areas with low vaccination coverage. Circulating VDPVs (cVDPVs) are VDPVs in confirmed outbreaks. Single VDPVs for which the origin cannot be determined are classified as ambiguous (aVDPVs), which can also cause paralysis. Among the three types of WPV, type 2 has been declared to be eradicated. More than 90% of cVDPV cases have been caused by type 2 cVDPVs (cVDPV2). Therefore, in April 2016, all OPV-using countries of the world are discontinuing use of type 2 Sabin vaccine by simultaneously switching from trivalent OPV (types 1, 2, and 3) to bivalent OPV (types 1 and 3) for routine and supplementary immunization. The World Health Organization recently broadened the definition of cVDPVs to include any VDPV with genetic evidence of prolonged transmission (i.e., >1.5 years) and indicated that any single VDPV2 event (a case of paralysis caused by a VDPV or isolation of a VDPV from an environmental specimen) should elicit a detailed outbreak investigation and local immunization response. A confirmed cVDPV2 detection should elicit a full poliovirus outbreak response that includes multiple supplemental immunization activities (SIAs); an aVDPV designation should be made only after investigation and response (3). Since 2005, there have been 1-8 cVDPV outbreaks and 3-12 aVDPV events per year. There are currently five active cVDPV outbreaks in Guinea, Laos, Madagascar, Myanmar, and Ukraine, and four other active VDPV events.