Cellular iron governs the host response to malaria.

Malaria and iron deficiency are major global health problems with extensive epidemiological overlap. Iron deficiency-induced anaemia can protect the host from malaria by limiting parasite growth. On the other hand, iron deficiency can significantly disrupt immune cell function. However, the impact of host cell iron scarcity beyond anaemia remains elusive in malaria. To address this, we employed a transgenic mouse model carrying a mutation in the transferrin receptor (TfrcY20H/Y20H), which limits the ability of cells to internalise iron from plasma. At homeostasis TfrcY20H/Y20H mice appear healthy and are not anaemic. However, TfrcY20H/Y20H mice infected with Plasmodium chabaudi chabaudi AS showed significantly higher peak parasitaemia and body weight loss. We found that TfrcY20H/Y20H mice displayed a similar trajectory of malaria-induced anaemia as wild-type mice, and elevated circulating iron did not increase peak parasitaemia. Instead, P. chabaudi infected TfrcY20H/Y20H mice had an impaired innate and adaptive immune response, marked by decreased cell proliferation and cytokine production. Moreover, we demonstrated that these immune cell impairments were cell-intrinsic, as ex vivo iron supplementation fully recovered CD4+ T cell and B cell function. Despite the inhibited immune response and increased parasitaemia, TfrcY20H/Y20H mice displayed mitigated liver damage, characterised by decreased parasite sequestration in the liver and an attenuated hepatic immune response. Together, these results show that host cell iron scarcity inhibits the immune response but prevents excessive hepatic tissue damage during malaria infection. These divergent effects shed light on the role of iron in the complex balance between protection and pathology in malaria.

Excess lifetime cancer risk due to ingestion of fish from a dam reservoir associated with a nuclear facility in Brazil.

Fish from a Funil dam reservoir associated with a Nuclear Fuel Factory were sampled aiming to assess the radiological risk due to ingestion. Funil dam reservoir is a strategic site, once it receives effluent from the industrial complex that performs isotopic enrichment of uranium and conversion of UF6. The mean activity concentrations obtained for 40K, 226Ra, 228Ra and 228Th were 57.81, 0.41, 0.92 and 0.49 Bq·kg-1, respectively. Lifetime cancer risk was estimated in ∼10-5 and no action needs to be taken.

Application of radiological assessment as water quality criterion for effluent release in a Brazilian uranium mine.

Uranium mining causes several radiological impacts on the surrounding environment, notably in the water bodies, mainly due to the release of long half-life radionuclides from the 238U and 232Th series. The Ore Treatment Unit, an old uranium mine undergoing decommissioning, has three points of liquid effluent release (#014, #025, and #076). For current study, 78 samples of water were collected at #014, 33 samples at #025, and 63 samples at #076. The radionuclides were analyzed by gross alpha count, gross beta count, and by arsenazo spectrophotometry. Analyses were carried out using the radiological water quality criterion established by World Health Organization and other organizations, together with the Brazilian legislation, to assess if the released effluents may be used unrestrictedly by the individuals of the public. At #014, the mean values of activity concentration (AC), in Bq·L-1, were as follows: Unat = 0.107, 226Ra = 0.035, 210Pb = 0.031, 232Th = 0.007, and 228Ra = 0.049. At #025 the mean values of AC, in Bq·L-1, were as follows: Unat = 0.086, 226Ra = 0.015, 210Pb = 0.028, 232Th = 0.006, and 228Ra = 0.032. Finally, at point #076, the mean AC values, in Bq·L-1, were as follows: Unat = 3.624, 226Ra = 0.074, 210Pb = 0.054, 232Th = 0.013, and 228Ra = 0.069. The current study showed that natural radionuclides were not in secular equilibrium. Despite uranium presented its values outside the limits of guidance levels, it can be state that the unrestricted use of effluents released in the three water bodies is authorized from the radiological point of view. In terms of dose rate, the releases at three points were within the radiological limits of potability. On the other hand, in an additional analysis, #76 presented chemical toxicity above the authorized value, pointing the need of restricted use of water from the point of view of chemical toxicity.

Pertuzumab in Combination with Trastuzumab and Docetaxel in the Neoadjuvant Treatment for HER2-Positive Breast Cancer.

Introduction: This study aims to assess safety and effectiveness of pertuzumab in combination with trastuzumab and docetaxel in the neoadjuvant treatment (NeoT) of HER2-positive breast cancer. Methods: Two consecutive retrospective cohorts (n = 94, 2012-2015 and 2015-2017) of adult women with HER2-positive breast cancer, receiving NeoT at the breast clinic in Portugal (IPO-Porto), were followed. All patients had surgery and received trastuzumab as adjuvant therapy. The 2012-2015 cohort received doxorubicin, cyclophosphamide, docetaxel plus trastuzumab, whereas the 2015-2017 cohort was treated with the same protocol plus pertuzumab. Results: The 2012-2015 cohort was older (median 53 years), with locally advanced tumors (48.1%), mostly hormone receptor positive (59.3%). The 2015-2017 cohort was younger (median 43 years) with 60% operable tumors. Pathologic complete response (pCR) improved in the second cohort, while maintaining a good safety profile and tolerability. Clinical staging (p = 0.001) and hormone receptor (p = 0.003) were significant predictors of pCR, but not treatment regimen (p = 0.304). Conclusion: Further research with larger samples and longer follow-up is needed to understand the clinical differences. Clinical effectiveness of treatment should also be measured through overall and progression-free survival.

Acceptance and Adherence to COVID-19 Vaccination-The Role of Cognitive and Emotional Representations.

Vaccine hesitation is a topic of utmost importance, with the COVID-19 pandemic serving as a clear reminder of its timeliness. Besides evaluating COVID-19 vaccine acceptance in a sample of Portuguese people, this study aims at understanding cognitive and emotional representations related to vaccination, and their influence on vaccination hesitation. A cross-sectional online survey was conducted between 27 December 2020 and 27 January 2021. It assessed cognitive and emotional COVID-19 representations; vaccination status; cognitive and emotional representations of vaccination and perceived necessity and concerns about vaccines. Of 31 × 58 participants, 91% accepted taking a COVID-19 vaccine. Among several other significant findings, women (71.3%) more often considered that the pandemic affected their lives (p < 0.001) and were more often concerned with being infected (p < 0.001). Likewise, there were significantly more female participants concerned about taking a COVID-19 vaccine and its possible effects, when compared to the number of male participants (p < 0.001). The number of participants with a higher education level that were more worried about becoming infected was greater (p = 0.001), when compared with those less educated. Regarding age groups, people aged 18 to 24 had fewer concerned participants (9.6%), while the number of individuals aged 55 to 64 had the most (p < 0.001). Somewhat surprisingly, perceiving oneself as extremely informed about COVID-19 was not associated with greater vaccine acceptance (OR = 1.534 [1.160−2.029]; (p = 0.003)). Moreover, people aged 25 to 64 years old and with lower education level were more likely not to accept vaccination (OR = 2.799 [1.085−7.221]; (p = 0.033)). Finally, being more concerned about taking a vaccine lowers its acceptance (OR = 4.001 [2.518−6.356]; (p < 0.001)). Cognitive and emotional representations have a great impact and are reliable predictors of vaccine acceptance. Thus, it is of extreme importance that public health messages be adapted to the different characteristics of the population.

Absorbed dose rate for marine biota due to the oil spilled using ICRP reference animal and Monte Carlo simulation.

The current study aimed to obtain dose conversion coefficients for marine animals due to an oil spill accident using two variables: crude oil activity concentration and organism depth. Thorium series presented a dose contribution twice that uranium series for similar conditions. Bi-214 and Tl-208 stood out for delivering a higher dose rate for uranium and thorium series, respectively. Results obtained can be used to assess the maximum exposure time for emergency oil control, removal, and mitigation in an oil spill accident.

Assessment of released natural radionuclides by waste rock pile and mining pit associated with a uranium mine at Caldas, Minas Gerais, Brazil.

The Ore Treatment Unit was a uranium mining company that is currently being decommissioned. The local rainfall index makes it necessary to release effluents into the environment. After releasing, the wastewater is available for unrestricted use. Current study aims to use national and international recommendations to assess the radiological potability of released effluents at one of the three points of company's interface with the environment. Twenty-four samples of water were collected and activity concentrations (AC) were obtained by gross alpha count, gross beta count, and for arsenazo spectrophotometry. Statistical analysis techniques were applied to the data with the purpose of understanding the results for the soluble, particulate, and total fractions. The mean AC for effluents were 3.580, 0.082, 0.103, 0.063, and 0.090 Bq L-1 for Unat, 226Ra, 210Pb, 232Th, and 228Ra, respectively, for the total fraction. The analysis of variance pointed to Unat as a critical radionuclide, since it presented more than 90% of the total AC released into the environment. Pearson's R2 pointed to soluble fraction as a major contributor to the total AC released. The guidance level proposed by WHO was used to assess the radiological potability of the effluents. The results obtained indicated the need for trigger other analyses. Committed effective dose was estimated due to the unrestricted use of effluents and the value obtained, 0.23 mSv year-1, was below the maximum allowed limit. Finally, the radiotoxicity of the released effluent was evaluated and the value obtained was ~ 50% of the maximum allowed limit. In conclusion, the present study showed that the level of radioactivity released into the environment by the Ore Treatment Unit does not present a radiological risk to the surrounding population.

LRP1B Expression as a Putative Predictor of Response to Pegylated Liposomal Doxorubicin Treatment in Ovarian Cancer.

BACKGROUND: Pegylated liposomal doxorubicin (PLD) is among the most active therapies for recurrent/progressive ovarian cancer (OC). Low-density lipoprotein receptor-related protein 1B (LRP1B) is one of the 10 most significantly deleted genes in human cancers. It mediates endocytosis of several factors from the cellular environment including liposomes. Although the LRP1B role in cancer has not been fully disclosed, its contribution to resistance to liposomal therapies has been hypothesized. This study aimed to evaluate the impact of LRP1B protein as a possible marker of response to PLD in patients with OC. METHODS: LRP1B expression and response to PLD were analyzed in OC cell lines by qRT-PCR and PrestoBlue viability assay, respectively. LRP1B protein expression was evaluated for the first time, in tumor samples from PLD-treated patients and controls (other chemotherapies) by immunohistochemistry. Association of LRP1B staining score (determined based on intensity and percentage of positively stained cells) with clinicopathological features, response to therapy and survival outcomes was evaluated. RESULTS: OC cells with increased expression of LRP1B were more sensitive to PLD. LRP1B staining score was associated with clinicopathological features, response to therapy, and survival outcomes. Higher LRP1B levels were associated with prolonged progression-free survival. This association was more evident in patients treated with PLD and in responders to PLD. CONCLUSION: Our results support a possible role of LRP1B as a predictor of response to PLD in patients with OC.

Portuguese Version of the Intentional Non-Adherence Scale: Validation in a Population of Chronic Pain Patients.

Objective: Despite the effectiveness of pain medicines, nonadherence to prescribed medication remains a major problem faced by healthcare systems. The aim of present study was to perform the translation, cultural adaptation, and validation of the Intentional Non-Adherence Scale (INAS) for the European Portuguese language in a sample of chronic pain patients. Methods: A Portuguese version of the INAS scale was constructed through a process of translation, back translation, and expert's panel evaluation. A total of 133 chronic pain patients were selected from two chronic pain clinics from tertiary hospitals in Porto, Portugal. The protocol interview included the assessment of pain beliefs (PBPI), beliefs about medicine (BMQ), medication adherence (MARS-P9), and two direct questions about adherence previously validated. Results: The internal consistency in all subscales was α = 0.902 for testing treatment; α = 0.930 for mistrust treatment; α = 0.917 for resisting treatment; and α = 0.889 for resisting illness. Exploratory and confirmatory factor analysis revealed a four-factor structure that explained 74% of the variance. The construct validity of the INAS was shown to be adequate, with the majority of the previously defined hypotheses regarding intercorrelations with other measures confirmed. Conclusion: The Portuguese version of INAS could be a valuable and available instrument for Portuguese researchers and clinicians to assess the intentional nonadherence determinants during the management of chronic pain.

Lifetime cancer risk increase due to consumption of some foods from a High Background Radiation Area.

Activity concentration (AC) in foods produced and commonly consumed in a High Background Radiation Area (HBRA) was analyzed. The AC were obtained by spectrophotometry and by the radiochemical separation method. The AC were up to 104 times higher than the AC for both UNSCEAR suggested values and non-HBRA. It was noted that the lifetime cancer risk was increased in 4 decimal places, taking the risk from the "statistically negligible range" (<10-6) to "middle range" (between 10-4 and 10-6).

Hepcidin-Mediated Hypoferremia Disrupts Immune Responses to Vaccination and Infection.

BACKGROUND: How specific nutrients influence adaptive immunity is of broad interest. Iron deficiency is the most common micronutrient deficiency worldwide and imparts a significant burden of global disease; however, its effects on immunity remain unclear. METHODS: We used a hepcidin mimetic and several genetic models to examine the effect of low iron availability on T cells in vitro and on immune responses to vaccines and viral infection in mice. We examined humoral immunity in human patients with raised hepcidin and low serum iron caused by mutant TMPRSS6. We tested the effect of iron supplementation on vaccination-induced humoral immunity in piglets, a natural model of iron deficiency. FINDINGS: We show that low serum iron (hypoferremia), caused by increased hepcidin, severely impairs effector and memory responses to immunizations. The intensified metabolism of activated lymphocytes requires the support of enhanced iron acquisition, which is facilitated by IRP1/2 and TFRC. Accordingly, providing extra iron improved the response to vaccination in hypoferremic mice and piglets, while conversely, hypoferremic humans with chronically increased hepcidin have reduced concentrations of antibodies specific for certain pathogens. Imposing hypoferremia blunted the T cell, B cell, and neutralizing antibody responses to influenza virus infection in mice, allowing the virus to persist and exacerbating lung inflammation and morbidity. CONCLUSIONS: Hypoferremia, a well-conserved physiological innate response to infection, can counteract the development of adaptive immunity. This nutrient trade-off is relevant for understanding and improving immune responses to infections and vaccines in the globally common contexts of iron deficiency and inflammatory disorders. FUNDING: Medical Research Council, UK.

Committed effective dose and lifetime cancer risk due to ingestion of natural radionuclides in grains grown in an area of high background radiation.

The current study aimed at estimating committed effective dose and cancer risk due to the intake of K-40, Ra-226, Ra-228 and Th-228 present in grains grown in an HBRA. The highest activity concentrations found were (606.2 ± 25.13), (8.07 ± 6.37), (10.01 ± 1.45), (43.97 ± 5.54) Bq.kg-1 for K-40, Ra-226, Ra-228 and Th-228, respectively. The committed effective dose estimated was 0.5 mSv.y-1, and the estimated cancer risk suggested that uninterrupted and unrestricted consumption of beans grown in this HBRA is not desirable.

Predictive Biomarkers and Patient Outcome in Platinum-Resistant (PLD-Treated) Ovarian Cancer.

Identification of predictive biomarkers for ovarian cancer (OC) treatment, particularly in the platinum-resistant/refractory setting, is highly relevant for clinical management. E-cadherin, vimentin, and osteopontin (OPN) are proteins associated with tumor microenvironment (TME) remodelling that play key roles in cancer. This study aimed to evaluate the association between the staining patterns of these proteins with survival outcomes in a series of OC patients, namely in patients with platinum-resistant/refractory disease. Low E-cadherin expression and high vimentin expression in all patient groups (as well as for E-cadherin in the platinum-resistant arm) were significantly associated with longer overall survival (OS). Low cytoplasmic OPN expression (and cytoplasmic and membrane OPN in the platinum-resistant arm) were significantly associated with longer OS. In patients that responded to treatment (pegylated liposomal doxorubicin (PLD) or other), low cytoplasmic OPN expression was also associated with longer progression-free survival (PFS). In the other hand, high nuclear OPN-c expression in patients that respond to treatment was associated with longer OS and longer PFS. Longer PFS was also associated with high expression of both nuclear and cytoplasm OPN-c, in platinum-resistant patients and in those that responded to PLD. Our study indicates that the expression of E-cadherin, vimentin, and OPN may have prognostic implications. Nuclear OPN-c and cytoplasm OPN expression are putative predictive markers in platinum-resistant (PLD treated) ovarian cancer patients.

Molecular Genetic Features of Primary Nonurachal Enteric-type Adenocarcinoma, Urachal Adenocarcinoma, Mucinous Adenocarcinoma, and Intestinal Metaplasia/Adenoma: Review of the Literature and Next-generation Sequencing Study.

The diagnosis of primary adenocarcinoma of the urinary bladder may be challenging in routine practice. These tumors may morphologically and immunohistochemically overlap with urachal adenocarcinoma and colorectal adenocarcinoma. Further, their genetic background is poorly understood. We systematically searched the PubMed database for results of complex genetic evaluation of primary bladder adenocarcinoma subtypes. Subsequently, we designed our own series of bladder lesions. We evaluated 36 cases: 16 primary enteric-type adenocarcinomas, 7 urachal enteric adenocarcinomas, 3 primary mucinous/colloid adenocarcinomas, and 10 intestinal-type metaplasia/villous adenoma. Detailed clinical data were collected, and all cases were examined using targeted next-generation sequencing. On the basis of the literature, the first mutated gene in these tumors was reported to be KRAS in 11.3% of cases, followed by TERT promoter mutations in 28.5%. In addition to KRAS and TERT, other genes were also found to be frequently mutated in primary bladder adenocarcinoma, including TP53, PIK3CA, CTNNB1, APC, FBXW7, IDH2, and RB1. In our series, the most frequent gene mutations in primary enteric-type adenocarcinomas were as follows: TP53 (56%); BRCA2, KMT2B (both 33%); NOTCH2, KDR, ARID1B, POLE, PTEN, KRAS (all 28%); in urachal enteric adenocarcinoma they were as follows: TP53 (86%); PTEN, NOTCH (both 43%); in primary mucinous/colloid adenocarcinomas they were as follows: KRAS, GRIN2A, AURKB (all 67%); and, in intestinal-type metaplasia/villous adenoma, they were as follows: APC, PRKDC (both 60%); ROS1, ATM, KMT2D (all 50%). No specific mutational pattern was identified using cluster analysis for any of the groups. Herein, we describe the pathologic features and immunohistochemical staining patterns traditionally used in the differential diagnoses of glandular lesions of the bladder in routine surgical pathology. We outline the mutational landscape of these lesions as an aggregate of published data with additional data from our cohort. Although diagnostically not discriminatory, we document that the most common genetic alterations shared between these glandular neoplasms include TP53, APC (in the Wnt pathway), and KRAS (in the MAPK pathway) mutations.

Non-Adherence to Pharmacotherapy: A Prospective Multicentre Study About Its Incidence and Its Causes Perceived by Chronic Pain Patients.

OBJECTIVE: Pharmacological interventions remain the cornerstone of chronic pain treatment; however, nearly 40% of the prescription medicines are not taken as prescribed. The present study aims at understanding and describing non-adherence from the perspective of chronic pain patients during a 1-year follow-up study. METHODS: A cohort of 950 consecutive patients referred to a first consultation in Multidisciplinary Chronic Pain Clinics was followed with a standardized protocol for 1 year. This included assessment of pain characteristics; prescribed medication; therapeutic adherence; effectiveness of treatment, non-adherence and its perceived reasons; clinical outcomes and quality of life. We used a mixed methods approach, including qualitative and quantitative analyses. RESULTS: Forty-nine percent of the 562 patients who responded to all assessments during follow-up were adherent after 1 year of chronic pain treatment. The core associations between each "non-adherence reason" and Anatomical Therapeutic Chemical Code (ATC) group were perceived side effects (p=0.019) and delayed start (p=0.022) for narcotic analgesics (opioids); perceived non-efficacy (p=0.017) and delayed start (p=0.004) for antiepileptics and anticonvulsants; perceived low necessity (p=0.041) and delayed start (p=0.036) for analgesics antipyretics; change in prescriptions because of a new clinical condition for antidepressants (p=0.024); high concerns (p=0.045) and change in prescriptions because of a new clinical condition (p<0.001) for non-steroidal anti-inflammatory drugs; delayed start (p=0.016) and financial constraints (p=0.018) for other medications. DISCUSSION: This study emphasizes the patient's perspective regarding non-adherence to pharmacological treatment of chronic pain, providing valuable and novel information to be used in future interventions to help patients make an informed choice about their adherence behavior.

Improving perioperative pain management: a preintervention and postintervention study in 7 developing countries.

INTRODUCTION: The burden of untreated postoperative pain is high. OBJECTIVE: This study assessed feasibility of using quality improvement (QI) tools to improve management of perioperative pain in hospitals in multiple developing countries. METHODS: The International Pain Registry and Developing Countries working groups, from the International Association for the Study of Pain (IASP), sponsored the project and PAIN OUT, a QI and research network, coordinated it, and provided the research tools. The IASP published a call about the project on its website. Principal investigators (PIs) were responsible for implementing a preintervention and postintervention study in 1 to 2 surgical wards in their hospitals, and they were free to choose the QI intervention. Trained surveyors used standardized and validated web-based tools for collecting findings about perioperative pain management and patient reported outcomes (PROs). Four processes and PROs, independent of surgery type, assessed effectiveness of the interventions. RESULTS: Forty-three providers responded to the call; 13 applications were selected; and PIs from 8 hospitals, in 14 wards, in 7 countries, completed the study. Interventions focused on teaching providers about pain management. Processes improved in 35% and PROs in 37.5% of wards. CONCLUSIONS: The project proved useful on multiple levels. It offered PIs a framework and tools to perform QI work and findings to present to colleagues and administration. Management practices and PROs improved on some wards. Interpretation of change proved complex, site-dependent, and related to multiple factors. PAIN OUT gained experience coordinating a multicentre, international QI project. The IASP promoted research, education, and QI work.

Portuguese version of the Medication Adherence Report Scale (MARS-9): Validation in a population of chronic pain patients.

AIM: The aim of present study was to perform the translation, cultural adaptation, and validation of the Medication Adherence Report Scale (MARS-P9) for the European Portuguese language in a sample of chronic pain patients. METHODS: A Portuguese version of the nine-item MARS (©Professor Rob Horne) scale (MARS-P9) was constructed through a process of translation, back translation, and experts' panel evaluation. A total of 141 chronic pain patients were subsequently evaluated at four time assessments during a 1-year pain medication treatment. The protocol interview included the assessment of pain intensity and interference (BPI), clinical outcomes and quality of life (S-TOPS), and MARS-P9. RESULTS: The internal consistency coefficient was acceptable for the total scale (α = 0.84). Exploratory factor analysis revealed a two-factor structure (intentional and unintentional nonadherence) that explained 61% of the variance. Convergent and discriminant validity were demonstrated by correlations between MARS scores and pain interference (r = 0.180, P ≤ 0.01) and S-TOPS (r = 0.242, P ≤ 0.05). CONCLUSION: MARS-P9 has been shown to be an adequate instrument for Portuguese researchers and clinicians to assess the pattern of adherence during the management of chronic pain.

Effectiveness of Opioids for Chronic Noncancer Pain: A Two-Year Multicenter, Prospective Cohort Study With Propensity Score Matching.

Opioid use in chronic non cancer pain (CNCP) is still controversial regarding their effectiveness and safety. We conducted a 2-year prospective cohort study in 4 multidisciplinary chronic pain clinics to assess long-term opioid effectiveness in CNCP patients. All adult CNCP patients consecutively admitted to their first consultation were recruited. Demographic and clinical data were collected, and propensity score matching was used to adjust for differences between opioid users and nonusers. The Brief Pain Inventory and the Short version of Treatment Outcomes in Pain Survey were used to measure pain outcomes and quality of life. A total of 529 subjects were matched and included in our analysis. Rate of prescription opioid use was 59.7% at baseline, which increased to 70.3% over 2 years, of which 42.7% of the prescriptions were for strong opioids. Opioid users reported no improvement regarding pain symptoms, physical function, emotional function, and social/familiar disability. Opioid users reported higher satisfaction with care and outcomes at 1 year of follow-up, but at 2 years, they only reported improvement in satisfaction with outcomes. Opioids have shown limited effectiveness in long-term CNCP management, as opioid users presented no improvements regarding functional outcomes and quality of life. These findings emphasize the need for proper selection and outcome assessment of CNCP patients prescribed opioids. PERSPECTIVE: This study adds important additional evidence concerning the controversial use of opioids in CNCP management. Opioid users presented no improvement regarding pain relief, functional outcomes and quality of life over 2 years of follow-up. Therefore, our results support and highlight the limited effectiveness of opioids in long-term CNCP management.

A Two-Year Prospective Multicenter Study of Opioid Therapy for Chronic Noncancer Pain: Prescription Trends and Predictors.

OBJECTIVES: Opioid use in chronic pain has increased worldwide in recent years. The aims of this study were to describe the trends and patterns of opioid therapy over two years of follow-up in a cohort of chronic noncancer pain (CNCP) patients and to assess predictors of long-term opioid use and clinical outcomes. METHODS: A prospective cohort study with two years of follow-up was undertaken in four multidisciplinary chronic pain clinics. Demographic data, pain characteristics, and opioid prescriptions were recorded at baseline, three, six, 12, and 24 months. RESULTS: Six hundred seventy-four CNCP patients were recruited. The prevalence of opioid prescriptions at baseline was 59.6% (N = 402), and 13% (N = 86) were strong opioid prescriptions. At 24 months, opioid prescription prevalence was as high as 74.3% (N = 501), and strong opioid prescription was 31% (N = 207). Most opioid users (71%, N = 479) maintained their prescription during the two years of follow-up. Our opioid discontinuation was very low (1%, N = 5). Opioid users reported higher severity and interference pain scores, both at baseline and after two years of follow-up. Opioid use was independently associated with continuous pain, pain location in the lower limbs, and higher pain interference scores. CONCLUSIONS: This study describes a pattern of increasing opioid prescription in chronic pain patients. Despite the limited improvement of clinical outcomes, most patients keep their long-term opioid prescriptions. Our results underscore the need for changes in clinical practice and further research into the effectiveness and safety of chronic opioid therapy for CNPC.

Impact of the economic crisis on pain research: a bibliometric analysis of pain research publications from Ireland, Greece, and Portugal between 1997 and 2017.

Background and aims The recent economic crisis started in the USA in 2008 but quickly had worldwide impact. Ireland, Greece, and Portugal were in economic distress in 2009 and received rescue monetary packages from the European Union (EU) and the International Monetary Fund (IMF) in the following years. Meanwhile, the economic recovery has begun for those countries, but at different paces. The aim of the present study was to evaluate if the economic crisis influenced pain research outcomes, by performing a bibliometric analysis based on the ISI Web of Science to evaluate the evolution of the scientific production and performance in the field of pain research between 1997 and 2017. Methods Articles search was conducted using the ISI Web of Science, search keywords "pain or nocicep*", between 1997 and 2017, and one author affiliated in an Irish, Greek or Portuguese institution. The total number of published articles per country, total citations, h-index, document types and authors' institution were tabulated to determine the quantity and quality of the publications in this field. Results The search retrieved 2,368 publications over the 20 years' period, increasing from 26 in 1997 to 230 in 2017. The number of Irish publications per year increased steadily along the studied period, while the number of Greek publications stabilized from 2008 onward and Portuguese publications started to increase only in 2007 but declined slightly after 2014. In total, Irish authors published 1,143 articles, Greek authors 624 and Portuguese authors 618. There were nine articles with more than 100 citations, and Irish publications had a higher h-index (52) than Greek's (45) or Portuguese's (36) publications. Ireland had the highest number of pain publications per capita, but in 2016 Portugal had the lowest cost per publication, as measured by the GDP per capita per publication (in 1997 Portugal had the highest cost). The three major research fields of the publications were neurosciences/neurology (19%), general internal medicine (16%) and anaesthesiology (13%), and the affiliation institutions were mostly universities or universities hospitals. Conclusions The number of Irish, Greek, and Portuguese pain publications increased between 1997 and 2017, but at different paces. It appears that the economic crisis had no impact on the rate of pain publications in Ireland, had a delayed impact in Portugal, and affected mostly Greek pain scientific research. This may be related to the fact that Greece was the country that received more rescue packages and where the economic crisis was deepest and lasted longer. Implications Economics and scientific production have a mutual influence: usually research investment decreases in recession times (reducing grants and scientific employment), but health scientific production can improve health and quality of life and also benefit the economy. So in crisis periods, governments should create means to protect and foster scientific work.