Neuroprotection provided by hypothermia initiated with high transnasal flow with ambient air in a model of pediatric cardiac arrest.

Clinical trials of hypothermia after pediatric cardiac arrest (CA) have not seen robust improvement in functional outcome, possibly because of the long delay in achieving target temperature. Previous work in infant piglets showed that high nasal airflow, which induces evaporative cooling in the nasal mucosa, reduced regional brain temperature uniformly in half the time needed to reduce body temperature. Here, we evaluated whether initiation of hypothermia with high transnasal airflow provides neuroprotection without adverse effects in the setting of asphyxic CA. Anesthetized piglets underwent sham-operated procedures (n=7) or asphyxic CA with normothermic recovery (38.5°C; n=9) or hypothermia initiated by surface cooling at 10 (n=8) or 120 (n=7) minutes or transnasal cooling initiated at 10 (n=7) or 120 (n=7) minutes after resuscitation. Hypothermia was sustained at 34°C with surface cooling until 20 hours followed by 6 hours of rewarming. At four days of recovery, significant neuronal loss occurred in putamen and sensorimotor cortex. Transnasal cooling initiated at 10 minutes significantly rescued the number of viable neurons in putamen, whereas levels in putamen in other hypothermic groups remained less than sham levels. In sensorimotor cortex, neuronal viability in the four hypothermic groups was not significantly different from the sham group. These results demonstrate that early initiation of high transnasal airflow in a pediatric CA model is effective in protecting vulnerable brain regions. Because of its simplicity, portability, and low cost, transnasal cooling potentially could be deployed in the field or emergency room for early initiation of brain cooling after pediatric CA.

EPOS2020/EUFOREA expert opinion on defining disease states and therapeutic goals in CRSwNP.

Severe chronic rhinosinusitis with nasal polyps (CRSwNP), a form of diffuse bilateral (usually type 2) CRS, is a debilitating disease with a significant impact on quality of life (QoL). With novel knowledge and treatment options becoming available, there is a growing need to update or revise key definitions to enable communication across different specialties dealing with CRS, and to agree on novel goals of care in CRSwNP. The European Forum for Research and Education in Allergy and Airway diseases (EUFOREA) and EPOS expert members discussed how to measure treatment responses and set new treatment goals for CRSwNP. In this paper a consensus on a list of definitions related to CRSwNP is provided: control, remission, cure, recurrence/exacerbation, treatable traits, remodeling, progression, and disease modification. By providing these definitions, the involved experts hope to improve communication between all stakeholders involved in CRSwNP treatment for use in routine care, basic and clinical research and international guidelines aimed to harmonize and optimize standard of care of patients with CRSwNP in the future.

Measuring control of disease in Chronic Rhinosinusitis; assessing the correlation between SinoNasal Outcome Test-22 and Visual Analogue Scale item scores.

BACKGROUND: In chronic rhinosinusitis (CRS), aim of treatment is control of disease. EPOS2020 suggests the use of visual analogue scale (VAS) measurements on several symptoms. We aim to determine if individual VAS items can be replaced by widely used SinoNasal Outcome Test-22 (SNOT-22) items when determining control of disease, to avoid using double measurements and to stimulate its use in clinical practice. METHODS: Analyses were made on correlations between individual SNOT-22 scores and symptom-specific questions from consecutive patients with CRS visiting our tertiary referral rhinologic clinic for the first time. RESULTS: 157 CRS patients were included. Correlations of individual items were strong (r greater than 0.8). Best parity in sensitivity, specificity, positive predicting value, negative predicting value, odds ratio and Receiver Operating Characteristic curves were found in individual item score of VAS greater than 5 and SNOT item-score. This cut off is valid for measuring control of disease, combining several nasal, facial pain and sleep symptoms (controlled, partially controlled and uncontrolled). CONCLUSION: There is strong correlation between individual items measured as SNOT or VAS. For the definition of CRS disease control, as proposed in EPOS2020, the use of symptoms specific SNOT 23 is predictive of VAS greater than 5.

Prevalence of olfactory dysfunction in D614G, alpha, delta and omicron waves: a psychophysical case-control study.

BACKGROUND: The purpose of this study was to compare the prevalence of olfactory dysfunction (OD) at different stages of the COVID-19 pandemic by evaluating subjects diagnosed with SARS-CoV-2 infection during the Omicron wave with psychophysical tests and comparing the results with those obtained from patients infected during the D614G, Alpha and Delta waves and with those of a control group. METHODOLOGY: The study included adult patients diagnosed with SARS-CoV-2 infection. Depending on the time of diagnosis, the subjects were divided into four study groups: D614G; Alpha, Delta and Omicron variant groups. A group of uninfected individuals was used as control. All subjects underwent psychophysical evaluation of the olfactory function with the Connecticut Chemosensory Clinical Research Center olfactory test (D614G and Alpha groups) or the extended version of the Sniffin'Sticks test (Delta, Omicron and control groups). RESULTS: 372 cases (134 D614G group, 118 Alpha group, 32 in Delta group and 88 Omicron group) were recruited and evaluated within 10 days of infection, alongside 80 controls. Patients self-reported olfactory loss in 72.4% of cases in the D614G group, in 75.4% of cases in the Alpha group, in 65.6% of cases in the Delta group and in 18.1% in the Omicron group. Psychophysical evaluation revealed a prevalence of OD: 80.6%, 83.0%, 65.6% and 36.3% in the D614G, Alpha, Delta and Omicron group respectively. The differences between the D614G, Alpha and Delta groups were not statistically significant. The Omicron group demonstrated a significantly lower prevalence of OD than the other variants but still significantly higher than the controls. CONCLUSIONS: During the Omicron wave OD was less prevalent than during the D614G, Alpha and Delta periods. One-third of patients have reduced olfactory function on psychophysical evaluation during the Omicron wave. Our results should be considered with caution as the VOC has not been determined with certainty.

EPOS/EUFOREA update on indication and evaluation of Biologics in Chronic Rhinosinusitis with Nasal Polyps 2023.

Severe chronic rhinosinusitis with nasal polyps (CRSwNP) is a debilitating disease with a significant impact on the quality of life (QoL). It is typically characterized by a type 2 inflammatory reaction and by comorbidities such as asthma, allergies and NSAID-Exacerbated Respiratory Disease (N-ERD). Here, the European Forum for Research and Education in Allergy and Airway diseases discusses practical guidelines for patients on biologic treatment. Criteria for the selection of patients who would benefit from biologics were updated. Guidelines are proposed concerning the monitoring of the drug effects that provide recognition of responders to the therapy and, subsequently, the decision about continuation, switching or discontinuation of a biologic. Furthermore, gaps in the current knowledge and unmet needs were discussed.

Evaluating treatment response to mepolizumab in patients with severe CRSwNP.

BACKGROUND: The SYNAPSE study (NCT03085797) demonstrated that mepolizumab decreased nasal polyp (NP) size and nasal obstruction in patients with chronic rhinosinusitis with NP (CRSwNP). METHODS: SYNAPSE, a randomized, double-blind study, included patients with recurrent, refractory, severe CRSwNP, eligible for repeated surgery despite receiving standard of care (SoC). Patients received 4-weekly mepolizumab 100 mg or placebo subcutaneously plus SoC for 52 weeks. This post hoc analysis further characterized treatment responses and association with patient characteristics. The proportion of patients meeting any and each of five response criteria indicating improvement in disease-specific quality of life, NP size, nasal obstruction, loss of smell, and overall symptoms at Weeks 24 and 52, were assessed in subgroups: 1) no surgery; 2) neither surgery nor systemic corticosteroids (SCS). RESULTS: Of 407 patients in the intention-to-treat population, 381 and 343 patients had no sinus surgery by Weeks 24 and 52, respectively. More mepolizumab- versus placebo-treated patients without surgery by Weeks 24 and 52 met each response criteria. Of the mepolizumab-treated patients without surgery by Week 24, 109 (55%) responded across >=3 criteria, increasing to 126 (67%) by Week 52. Similar response trends were seen for patients with neither surgery nor SCS by Weeks 24 and 52. At either timepoint, there were no major differences in baseline characteristics between mepolizumab-treated full- (5/5 categories) and non-responders (0/5 categories). CONCLUSIONS: Most patients who completed SYNAPSE required neither surgery nor SCS use and in addition achieved a progressive and sustained clinical response to mepolizumab underscoring the therapeutic benefits of mepolizumab in severe CRSwNP.

Consensus criteria for chronic rhinosinusitis disease control: an international Delphi Study.

BACKGROUND: Chronic rhinosinusitis (CRS) disease control is a global metric of disease status for CRS. While there is broad acceptance that it is an important treatment goal, there has been inconsistency in the criteria used to define CRS control. The objective of this study was to identify and develop consensus around essential criteria for assessment of CRS disease control. METHODS: Modified Delphi methodology consisting of three rounds to review a list of 24 possible CRS control criteria developed by a 12-person steering committee. The core authorship of the multidisciplinary EPOS 2020 guidelines was invited to participate. RESULTS: Thirty-two individuals accepted the invitation to participate and there was no dropout of participants throughout the entire study (3 rounds). Consensus essential criteria for assessment of CRS control were: overall symptom severity, need for CRS-related systemic corticosteroids in the prior 6 months, severity of nasal obstruction, and patient-reported CRS control. Near-consensus items were: nasal endoscopy findings, severity of smell loss, overall quality of life, impairment of normal activities and severity of nasal discharge. Participants’ comments provided insights into caveats of, and disagreements related to, near-consensus items. CONCLUSIONS: Overall symptom severity, use of CRS-related systemic corticosteroids, severity of nasal obstruction, and patient-reported CRS control are widely agreed upon essential criteria for assessment of CRS disease control. Consideration of near-consensus items to assess CRS control should be implemented with their intrinsic caveats in mind. These identified consensus CRS control criteria, together with evidence-based support, will provide a foundation upon which CRS control criteria with wide-spread acceptance can be developed.

The EUFOREA pocket guide for chronic rhinosinusitis.

Chronic rhinosinusitis (CRS) is known to affect around 5 % of the total population, with major impact on the quality of life of those severely affected (1). Despite a substantial burden on individuals, society and health economies, CRS often remains underdiagnosed, under-estimated and under-treated (2). International guidelines like the European Position Paper on Rhinosinusitis and Nasal Polyps (EPOS) (3) and the International Consensus statement on Allergy and Rhinology: Rhinosinusitis 2021 (ICAR) (4) offer physicians insight into the recommended treatment options for CRS, with an overview of effective strategies and guidance of diagnosis and care throughout the disease journey of CRS.

Position paper on olfactory dysfunction: 2023

BACKGROUND: Since publication of the original Position Paper on Olfactory Dysfunction in 2017 (PPOD-17), the personal and societal burden of olfactory disorders has come sharply into focus through the lens of the COVID-19 pandemic. Clinicians, scientists and the public are now more aware of the importance of olfaction, and the impact of its dysfunction on quality of life, nutrition, social relationships and mental health. Accordingly, new basic, translational and clinical research has resulted in significant progress since the PPOD-17. In this updated document, we present and discuss currently available evidence for the diagnosis and management of olfactory dysfunction. Major updates to the current version include, amongst others: new recommendations on olfactory related terminology; new imaging recommendations; new sections on qualitative OD and COVID-19 OD; updated management section. Recommendations were agreed by all co-authors using a modified Delphi process. CONCLUSIONS: We have provided an overview of current evidence and expert-agreed recommendations for the definition, investigation, and management of OD. As for our original Position Paper, we hope that this updated document will encourage clinicians and researchers to adopt a common language, and in so doing, increase the methodological quality, consistency, and generalisability of work in this field.

Ethical dilemmas associated with the introduction of biologic treatments in chronic rhinosinusitis with nasal polyps.

This review considers ethical dilemmas which may present when introducing the use of biologic treatments alongside existing treatments in the management of chronic rhinosinusitis with nasal polyps. Biologic therapies offer hope to patients with diseases recalcitrant to conventional therapies but are often significantly more expensive. Reducing the need for surgery may act as a disincentive for use within surgical specialities, while reimbursement for administration has the potential to encourage inappropriate use. Any treatment should be used considering the principles of beneficence (offering the most effective treatment to the patient) and non-maleficence (minimising the risk of harm); the challenges of comparing the different available treatment options are considered. Patient autonomy should be involved a process of shared decision making, but when a third-party payor is involved they may seek to place restrictions on access to treatments that limit the choice of both patient and physician. Such decisions are often based on the cost-effectiveness of novel treatments relative to standard of care; published models suggest that at current market prices, biologics are less cost-effective in all groups that standard care. Social justice (fair distribution of limited healthcare resources) therefore may mandate rationing of access. To this end, working as part of professional organisations or research groups, physicians often produce guidelines that help to identify those in greatest need of novel treatments. The challenges in creating and applying these guidelines are also considered.

Investigating the secondary care system burden of CRSwNP in sinus surgery patients with clinically relevant comorbidities using the HES database.

BACKGROUND: Chronic rhinosinusitis with nasal polyps (CRSwNP) is a chronic condition that can adversely affect quality of life for patients. There is no cure for CRSwNP, and patients may require intermittent systemic corticosteroids (SCS) and surgery in addition to intranasal treatment throughout their lifetime. This places a significant burden on the NHS which can be compounded by comorbid conditions such as asthma or NSAID-exacerbated respiratory disease (NERD). Patients with comorbidities are likely to experience higher rates of surgery and more secondary care visits. The aim of this study was to evaluate revision rates and the associated burden for patients with CRSwNP undergoing surgery and compare this to sub-cohorts of patients with comorbidities. MATERIALS AND METHODS: This study has utilised the Hospital Episodes Statistics (HES) database across a ten-year time period (April 2010 to March 2020) to investigate the NHS resource use attributable to CRSwNP for all patients with the condition who have undergone sinus surgery, and to examine the burden of clinically relevant sub-groups. RESULTS: Our results showed that 101,054 patients underwent at least one sinus surgery in relation to their nasal polyps, with Kaplan Meier survival analysis estimating that the 10-year probability of revision is between 71-90% for comorbid patients, and 51% for non-comorbid patients. Patients with a relevant comorbid condition in addition to their CRSwNP were up to 4.7 times more likely to undergo at least one revision surgery during the ten-year analytical time window when compared to patients without a comorbidity. Further to this, comorbid patients had a higher tariff associated with their CRSwNP care across the analytical time window and were therefore likely to be more costly to the healthcare system. CONCLUSIONS: In conclusion, this study demonstrates that there is a high burden attached to CRSwNP-related sinus surgery and that comorbidities are a key driver of NHS resource use.

Endoscopic grading systems for nasal polyps: are we comparing apples to oranges?

Endoscopic grading of nasal polyps (NP) is typically a coprimary endpoint in clinical trials evaluating treatments for chronic rhinosinusitis with nasal polyps (CRSwNP). However, a consensus on the most effective way to grade nasal polyps has not been reached. Different scales have been used, hampering the interpretation of data across trials. This review compares the characteristics of NP grading systems used in registration trials for approved NP treatments. These fundamental differences in grading systems make quantitative comparison of outcomes between trials inaccurate and potentially misleading. In lieu of a universal grading system, reporting the baseline distribution of polyp grades (unilateral and/or summed/total grades), as well as changes from baseline over time by baseline grade may help improve interpretability of outcomes and reduce inaccuracy when attempting cross-trial comparisons and making therapeutic decisions.

Mepolizumab improves quality of life and reduces activity impairments in patients with CRSwNP.

Mepolizumab improves quality of life and reduces activity impairments in patients with CRSwNP.

The COVANOS trial - insight into post-COVID olfactory dysfunction and the role of smell training.

BACKGROUND: Olfactory dysfunction is a cardinal symptom of COVID-19 infection, however, studies assessing long-term olfactory dysfunction are limited and no randomised-controlled trials (RCTs) of early olfactory training have been conducted. METHODOLOGY: We conducted a prospective, multi-centre study consisting of baseline psychophysical measurements of smell and taste function. Eligible participants were further recruited into a 12-week RCT of olfactory training versus control (safety information). Patient-reported outcomes were measured using an electronic survey and BSIT at baseline and 12 weeks. An additional 1-year follow-up was open to all participants. RESULTS: 218 individuals with a sudden loss of sense of smell of at least 4-weeks were recruited. Psychophysical smell loss was observed in only 32.1%; 63 participants were recruited into the RCT. The absolute difference in BSIT improvement after 12 weeks was 0.45 higher in the intervention arm. 76 participants completed 1-year follow-up; 10/19 (52.6%) of participants with an abnormal baseline BSIT test scored below the normal threshold at 1-year, and 24/29 (82.8%) had persistent parosmia. CONCLUSIONS: Early olfactory training may be helpful, although our findings are inconclusive. Notably, a number of individuals who completed the 1-year assessment had persistent smell loss and parosmia at 1-year. As such, both should be considered important entities of long-Covid and further studies to improve management are highly warranted.

Does time from previous surgery predict subsequent treatment failure in Chronic Rhinosinusitis with Nasal Polyps?

INTRODUCTION: When considering the introduction of biological treatments for Chronic Rhinosinusitis with nasal polyps (CRSwNP), treatment guidelines must consider not only which patients will best respond to biologicals, but also which patients derive least benefit from current treatment pathways. Using data collected as part of the National Audit of Surgery for Chronic Rhinosinusitis and Nasal Polyps, we sought to evaluate if patients with a history of prior surgery are more likely to need a further revision operation, and whether the interval between surgery may help predict the need for further surgical intervention. METHODS: In the original study, patients were prospectively and consecutively enrolled at the time of sinus surgery in multiple centres in England and Wales. Follow-up captured symptomatic outcomes and revision surgery rates at 3, 12, 36 and 60 months after surgery. Revision surgery rates 5 years after the index procedure, in patients with CRSwNP were analysed with regards to baseline demographics. RESULTS: Complete data were available for 980 subjects, with a 5 year revision rate of 15.1%. 45.9% had a history of previous surgery before the index procedure, and this group had significantly higher rates of additional surgery compared with those undergoing their first sinus surgery (20.2% versus 9.8%). Patients with an interval of 3 years or less between their previous surgery and the index procedure had the highest rates of further surgery. In a multiple regression, time interval between previous operations was a better prediction of subsequent revision surgery than asthma. Having N-ERD was the strongest predicator of need for further surgery while more extensive surgery was associated with lower revision rates. CONCLUSIONS: Patients presenting with a symptomatic recurrence within 3 years of surgery have a high risk of treatment failure, defined as the need for further surgery. Time to failure after previous surgery may be used to help select patients who may not benefit from current treatment pathways and may be good candidates for alternative strategies, including biologicals.

Six month follow-up of self-reported loss of smell during the COVID-19 pandemic.

INTRODUCTION: Loss of smell and taste is now recognised as amongst the most common symptoms of COVID-19 and the best predictor of COVID-19 positivity. Long term outcomes are unknown. This study aims to investigate recovery of loss of smell and the prevalence of parosmia. METHODOLOGY: 6-month follow-up of respondents to an online surgery who self-reported loss of smell at the onset of the CO- VID-19 pandemic in the UK. Information of additional symptoms, recovery of loss of smell and the development of parosmia was collected. RESULTS: 44% of respondents reported at least one other ongoing symptom at 6 months, of which fatigue (n=106) was the most prevalent. There was a significant improvement in self-rating of severity of olfactory loss where 177 patients stated they had a normal smell of smell while 12 patients reported complete loss of smell. The prevalence of parosmia is 43.1% with median interval of 2.5 months (range 0-6) from the onset of loss of smell. CONCLUSIONS: While many patients recover quickly, some experience long-term deficits with no self-reported improvement at 6 months. Furthermore, there is a high prevalence of parosmia even in those who report at least some recovery of olfactory func- tion. Longer term evaluation of recovery is required.

Rhinology in review: from COVID-19 to biologicals.

We look back at the end of what soon will be seen as an historic year, from COVID-19 to real-world introduction of biologicals influencing the life of our patients. This review describes the important findings in Rhinology over the past year. A large body of evidence now demonstrates loss of sense of smell to be one of the most common symptoms of COVID-19 infection; a meta-analysis of 3563 patients found the mean prevalence of self-reported loss to be 47%. A number of studies have now shown long-term reduced loss of smell and parosmia. Given the high numbers of people affected by COVID-19, even with the best reported recovery rates, a significant number worldwide will be left with severe olfactory dysfunction. The most prevalent causes for olfactory dysfunction, besides COVID-19 and upper respiratory tract infections in general, are trauma and CRSwNP. For these CRSwNP patients a bright future seems to be starting with the development of treatment with biologics. This year the Nobel prize in Medicine 2021 was awarded jointly to David Julius and Ardem Patapoutian for their discoveries of receptors for temperature and touch which has greatly enhanced our understanding of nasal hyperreactivity and understanding of intranasal trigeminal function. Finally, a new definition of chronic rhinitis has been proposed in the last year and we have seen many papers emphasizing the importance of endotyping patients in chronic rhinitis and rhinosinusitis in order to optimise treatment effect.

Efficacy of corticosteroid therapy in the treatment of long- lasting olfactory disorders in COVID-19 patients.

BACKGROUND: The growing number of COVID-19 patients with long-lasting olfactory disorders makes it necessary to identify ef- fective treatments that enhance the spontaneous recovery of olfactory function. METHODS: Multicentre randomised case-control study that involved 18 patients with COVID-19 related anosmia or severe hyposmia for more than 30 days. Nine patients were prescribed systemic prednisone and nasal irrigation with betamethasone, ambroxol and rinazine for 15 days. The other 9, untreated, patients were used as controls. The olfactory function was evaluated with CCCRC test at 20 and 40 days from the first evaluation. RESULTS: In the control group, a median olfactory score of 20 (IQR 30) was detected at baseline. At the 20-day control there was no significant improvement in olfactory function. The improvement in olfactory performance became significant at the 40-day follow-up compared to baseline scores [60 (IQR 60) versus 20 (IQR 30)]. In the treatment group, patients had a mean olfactory score of 10 (IQR 15) at initial control. At the 20-day control, a significant im-provement in the olfactory scores, compared to the baseline, was detected [70 (IQR 40) versus 10 (IQR 15)]. Olfactory function further improved at 40 days [median score 90 (IQR 50)]. Patients in the treatment group reported significantly higher improvements of the olfactory scores than the controls at both the 20-day [40 (IQR 45) versus 10 (IQR 15)] and 40-day [60 (IQR 40) versus 30 (IQR 25)] evaluations. CONCLUSIONS: Based on the results of this study, the mix of drugs including steroids could represent a useful specific therapy to reduce the prevalence of this long-term morbidity.

High prevalence of long-term olfactory, gustatory, and chemesthesis dysfunction in post-COVID-19 patients: a matched case-control study with one-year follow-up using a comprehensive psychophysical evaluation.

BACKGROUND: Using an age and gender matched-pair case-control study, we aimed to estimate the long-term prevalence of psychophysical olfactory, gustatory , and chemesthesis impairment at least one year after SARS-CoV-2 infection considering the background of chemosensory dysfunction in non-COVID-19 population. METHODOLOGY: This case-controlled study included 100 patients who were home-isolated for mildly symptomatic COVID-19 between March and April 2020. One control regularly tested for SARS-CoV-2 infection and always tested negative was matched to each case according to gender and age. Chemosensory function was investigated by a comprehensive psychophysical evaluation including ortho- and retronasal olfaction and an extensive assessment of gustatory function. Differences in chemosensory parameters were evaluated through either Fisher’s exact test or Kruskal-Wallis test. RESULTS: The psychophysical assessment of chemosensory function took place after a median of 401 days from the first SARS-CoV-2 positive swab. The evaluation of orthonasal smell identified 46% and 10% of cases and controls, respectively, having olfactory dysfunction, with 7% of COVID-19 cases being functionally anosmic. Testing of gustatory function revealed a 27% of cases versus 10% of controls showing a gustatory impairment. Nasal trigeminal sensitivity was significantly lower in cases compared to controls. Persistent chemosensory impairment was associated with emotional distress and depression. CONCLUSION: More than one year after the onset of COVID-19, cases exhibited an excess of olfactory, gustatory , and chemesthesis disturbances compared to matched-pair controls with these symptoms being associated to emotional distress and depression.

EPOS 4 Patients.

EPOS2020 is the 4th and most recent version of the European Position Paper on Rhinosinusitis and Nasal Polyps which was first published in 2005. It aims to provide the most up to date scientifically robust information on the topic published in the literature which has been critically analysed by an international group of clinicians drawn from all disciplines dealing with these problems together with patients. The guidelines offer evidence-based recommendations and care pathways for acute and chronic rhinosinusitis in both adults and children. Management of these diseases from the patients' perspective is an important part of EPOS2020. Not only is this included in the main document but, for the first time, we have produced a separate supplement dedicated to and in collaboration with patients, EPOS4Patients, which aims to provide information in an accessible format, to answer frequently asked questions about these diseases and their treatment options as well as including useful patient resources and websites. It has never been more important for patients to be actively involved in their care. Being well informed helps you to make the best decisions together with your doctor.