Overtreatment Research Articles

Comorbidity rates of autism spectrum disorder and functional neurological disorders: A systematic review, meta-analysis of proportions and qualitative synthesis.

Autism spectrum disorder (ASD) and functional neurological disorders (FND) are relatively common conditions, and there has been recent interest in the overlap between them. Both conditions share core features of alexithymia, impaired interoception and deficits in attentional focus. To date, relatively little is known about the comorbidity rates between ASD and FND. This is the first meta-analysis and qualitative synthesis on the subject. We found that around 10% of children presenting with functional seizures have a comorbid ASD diagnosis. People with ASD are more likely than the neurotypical population to have functional somatic disorders, and there is also evidence that ASD rates are higher for other FNDs such as functional motor disorders. Since FND comes with risks of unnecessary medical procedures and investigations, it is important to recognize the potential for people with ASD to have an FND comorbidity.

Gastroesophageal Reflux Disease.

Gastroesophageal reflux disease (GERD) is a condition that occurs when reflux of gastric contents into the esophagus causes symptoms and/or complications. The prevalence of GERD in Western societies has been estimated at 30%, making it one of the most commonly encountered disorders in primary care. The spectrum of GERD includes typical symptoms of esophageal reflux (heartburn and/or regurgitation); esophageal injury (erosive esophagitis; stricture; Barrett esophagus; and, rarely, adenocarcinoma); and extraesophageal symptoms, such as hoarseness and chronic cough. Proper diagnosis and treatment of GERD includes symptom control, exclusion of other disorders, avoiding overuse of medications and invasive testing, and minimizing complications.

Preventive Cardiovascular Measures in Children with Elevated Blood Pressure.

Cardiovascular diseases are the leading cause of morbidity and mortality in developed countries and are becoming increasingly significant in developing nations. Many cardiovascular risk factors originate early in life, even prenatally. Elevated blood pressure and hypertension are gaining attention in paediatrics due to their rising prevalence and impact on early cardiovascular risk in adulthood. Along with non-modifiable risk factors for hypertension, several modifiable factors can be addressed through primordial and primary prevention, emphasising lifestyle modifications. When these measures fail and elevated blood pressure develops, early detection is crucial (secondary prevention). Regular blood pressure measurement, a simple and non-invasive procedure, should be a standard practice in paediatric clinical settings. Diagnosing elevated blood pressure and hypertension should adhere to recommended guidelines. Lifestyle modifications are the first-line therapy for primary hypertension in children; if a secondary cause is identified, targeted treatment can be implemented, but a healthy lifestyle remains essential. The early detection and treatment of high-risk blood pressure enable timely interventions to prevent complications (tertiary prevention). Collectively, these preventive measures aim to reduce the incidence of cardiovascular disease in adulthood. Furthermore, quaternary prevention seeks to avoid unnecessary or harmful medical interventions including unwarranted examinations and pharmacotherapy. This underscores the importance of accurate diagnosis and treatment of elevated blood pressure and hypertension and emphasises the need for primordial and primary prevention to minimise unnecessary clinical interventions.

Patient, caregiver and professional views on preventable emergency admissions of older patients, a multi-method study in three Dutch hospitals

BackgroundOlder adults are too often hospitalized from the emergency department (ED) without needing hospital care. Knowledge about rates and causes of these preventable emergency admissions (PEAs) is limited. This study aimed to assess the proportion of PEAs, the level of agreement on perceived preventability between physicians and patients, and to explore their underlying causes as perceived by patients, their relatives, and the admitting physician.MethodsA multi-center multi-method study at the ED of one academic and two regional hospitals in the Netherlands was performed. All patients aged > 70 years and hospitalized from the ED were consecutively sampled during a six-week period. Quantitative data regarding patient and clinical characteristics and perceived preventability of the admission were prospectively collected from the electronical medical record and analyzed using descriptive statistics. Agreement on preventability between patient, caregivers and physicians was assessed by using the Cohen’s kappa. Underlying causes of a PEA were subsequently collected by semi-structured interviews with patients and caregivers. Physician’s perceived causes of a PEA were collected by telephone interviews and by open-ended questions sent by email. Thematic content analysis was used to analyze the interview transcripts and email narratives.ResultsOut of 773 admissions, 56 (7.2%) were deemed preventable by patients or their caregivers. Admitting physicians regarded 75 (9.7%) admissions as preventable. The level of agreement between these two groups was low with a Cohen’s kappa score of 0.10 (p = 0.003). Perceived causes for PEAs related to six themes: (1) insufficient support at home, (2) suboptimal care in the community setting, (3) errors in hospital care, (4) time of presentation to ED and availability of resources, (5) delayed help seeking behavior, and (6) errors made by patients.ConclusionsOur findings contribute to the existing evidence that a substantial part (almost one out of ten) of the older adults visiting the ED is perceived as unnecessary hospital care by patients, caregivers and health care providers. Findings also provide valuable insight into the causes for PEAs from a patient perspective. Further research is needed to understand why the perspectives of those responsible for hospital admission and those being admitted vary considerably.

Retrospective analysis of serologic test requests in the diagnosis of viral hepatitis: Inappropriate test requests and cost.

The rational laboratory use and implementation of test ordering procedures aim to reduce unnecessary test requests. This study aimed to determine the financial burden caused by inappropriate serological test requests for viral hepatitis and to investigate physicians' reasons for making unnecessary test requests. We performed a retrospective evaluation of inappropriate requests for hepatitis serology testing and the financial burden they caused at a tertiary care hospital over a 1-year period. The study found 2183 (3.84%) inappropriate test requests, costing $3309.00. Of these, 357 were same-day repeat requests and 1826 were requests not following diagnostic algorithms. In the logistic regression analysis of the factors affecting unnecessary test requests, a statistically significant difference was found between whether the unit was internal or surgical, whether the request came from inpatient services or outpatient clinics, and the professional titles (P < .05). Both types of inappropriate requests were more common among male physicians (P < .05). The highest rates of inappropriate test requesting were in physical therapy and rehabilitation, pediatrics, and adult emergency units. To identify the reasons behind unnecessary test requests, 135 physicians from 23 different departments participated in the survey. The main reasons for requesting tests were identified as protecting against malpractice and fears of misdiagnosis or overlooking a diagnosis. It has been observed that physicians often order tests routinely, without being fully familiar with standard test ordering procedures based on diagnostic algorithms, and lacking knowledge about rational laboratory use. The cost of tests is mostly unknown to clinicians. The study concludes that there are laboratory tests that incur much higher costs. When this assessment is applied to the entire laboratory, it becomes clear how significant a financial burden, unnecessary workload, and loss of time this situation can cause. Identifying the presence of unnecessary test requests is the first step in preventing them. Appropriate measures include highlighting these issues, providing necessary information, and offering in-service training.

A pharmacist's guide to mitigating sleep dysfunction and promoting good sleep in the intensive care unit.

In an effort to expedite the publication of articles, AJHP is posting manuscripts online as soon as possible after acceptance. Accepted manuscripts have been peer-reviewed and copyedited, but are posted online before technical formatting and author proofing. These manuscripts are not the final version of record and will be replaced with the final article (formatted per AJHP style and proofed by the authors) at a later time. To review causes, risk factors, and consequences of sleep disruption in critically ill patients; evaluate the role of nonpharmacological and pharmacological therapies for management of sleep in the intensive care unit (ICU); and discuss the role of pharmacists in implementation of sleep bundles. Critically ill patients often have disrupted sleep and circadian rhythm alterations that cause anxiety, stress, and traumatic memories. This can be caused by factors such as critical illness, environmental factors, mechanical ventilation, and medications. Methods to evaluate sleep, including polysomnography and questionnaires, have limitations that should be considered. Multicomponent sleep bundles with a focus on nonpharmacological therapy aiming to reduce nocturnal noise, light, and unnecessary patient care may improve sleep disorders in critically ill patients. While pharmacological agents are often used to facilitate sleep in critically ill patients, evidence supporting their use is often of low quality, which limits use to patients who have sleep disruption refractory to nonpharmacological therapy. Dedicated interprofessional teams are needed for implementation of sleep bundles in the ICU. Extensive pharmacotherapeutic training and participation in daily patient care rounds make pharmacists vital members of the team who can help with all components of the bundle. This narrative review discusses evidence for elements of the multicomponent sleep bundle and provides guidance on how pharmacists can help with implementation of nonpharmacological therapies and management of neuroactive medications to facilitate sleep. Sleep bundles are necessary for patients in the ICU, and dedicated interprofessional teams that include pharmacists are vital for their successful creation and implementation.

Nursing Variables Predicting Readmissions in Patients With a High Risk: A Scoping Review.

Unplanned readmission endangers patient safety and increases unnecessary healthcare expenditure. Identifying nursing variables that predict patient readmissions can aid nurses in providing timely nursing interventions that help patients avoid readmission after discharge. We aimed to provide an overview of the nursing variables predicting readmission of patients with a high risk. The authors searched five databases-PubMed, CINAHL, EMBASE, Cochrane Library, and Scopus-for publications from inception to April 2023. Search terms included "readmission" and "nursing records." Eight studies were included for review. Nursing variables were classified into three categories-specifically, nursing assessment, nursing diagnosis, and nursing intervention. The nursing assessment category comprised 75% of the nursing variables; the proportions of the nursing diagnosis (25%) and nursing intervention categories (12.5%) were relatively low. Although most variables of the nursing assessment category focused on the patients' physical aspect, emotional and social aspects were also considered. This study demonstrated how nursing care contributes to patients' adverse outcomes. The findings can assist nurses in identifying the essential nursing assessment, diagnosis, and interventions, which should be provided from the time of patients' admission. This can mitigate preventable readmissions of patients with a high risk and facilitate their safe transition from an acute care setting to the community.

Systematic review of family and pediatric constipation: An overlooked piece of the puzzle.

The objective of this review is to summarize pertinent literature looking at family dynamics and/or adherence to treatment in pediatric functional constipation. A structured systematic literature search was conducted on MEDLINE, Embase, and Web of Science core collection libraries from the years 2000 to 2023 using specific search terms: constipation, treatment adherence, family dynamics, parenting style, and pediatrics. Seventy-one publications were identified and included for review. After screening based on alignment to the review, 20 publications remained. These publications were placed into three categories depending on their intent and findings: (1) recommendations to further increase adherence, (2) studies analyzing factors of adherence, and (3) studies stating a need for a better understanding of family factors. A future area of research is identifying the associations between family factors on adherence to constipation treatment regimens. Results from such studies would increase the amount of positive treatment outcomes and decrease unnecessary healthcare costs.

Thyroid nodules as an incidental finding : Value of sonography and scintigraphy in primary diagnostics

Due to the widespread use of high-resolution sonography, numerous thyroid nodules are diagnosed, often as incidental findings. The challenge lies in evaluating various criteria such as size, shape, and echogenicity to assess the nodules' malignancy risk. Risk stratification systems have been developed to enable systematic assessment as well as to avoid unnecessary medical interventions and malignant findings being overlooked. This article provides an overview of the current diagnostic standards in primary assessment of thyroid nodules.

Erenumab escalation in migraine - double dose without additional benefit - a retrospective experience.

Erenumab is a monoclonal antibody specifically targeting the CGRP-receptor. Several studies showed efficacy and safety in patients with migraine. Less is known regarding dosage increase, especially in a difficult to treat patients. The aim of the study is to evaluate the increased dosage under real world conditions with particular focus on 70mg non-responders. In a retrospective analysis, patients treated in tertiary headache centers (Halle or Jena, Germany) receiving 70mg erenumab for at least 3 months with a dosage increase to 140mg were analyzed. Data were evaluated regarding headache days, intake of acute medication, previous prophylaxis, and medication overuse. Baseline and all treatment intervals were determined as three-month periods. Datasets of 52 migraine patients (90.4% women) aged between 22 and 78 years (mean 50.4 years, SD 12.1 years) were analyzed. At baseline (mean headache-days 15.67 ± 6.37) 51.9% met criteria for chronic migraine and 56% were currently overusing acute medication. While therapy with 70mg showed significant improvement in headache days and 50% response, further improvement was not achieved for therapy escalation to 140mg. The same applies to the secondary endpoints and covers the entire study population as well as the subgroups of chronic and episodic migraine. The 50% response of the 70mg non-responders for escalation was only 5.14%. In this difficult-to-treat patient cohort we reconfirmed the effectiveness of erenumab, but could not detect any additional benefit for a dosage escalation from 70mg to 140mg erenumab.

Unnecessary care in orthopaedic surgery.

Unnecessary care, where the potential for harm exceeds the potential for benefit, is widespread in medical care. Orthopaedic surgery is no exception. This has significant implications for patient safety and health care expenditure. This narrative review explores unnecessary care in orthopaedic surgery. There is wide geographic variation in orthopaedic surgical practice that cannot be explained by differences in local patient populations. Furthermore, many orthopaedic interventions lack adequate low-bias evidence to support their use. Quantifying the size of the problem is difficult, but the economic burden and morbidity associated with unnecessary care is likely to be significant. An evidence gap, evidence-practice gap, cognitive biases, and health system factors all contribute to unnecessary care in orthopaedic surgery. Unnecessary care is harming patients and incurring high costs. Solutions include increasing awareness of the problem, aligning financial incentives to high value care and away from low value care, and demanding low bias evidence where none exists.

Penicillin Allergy in China: Consequences of Inappropriate Skin Testing Practices and Policies.

Penicillins are the most frequently prescribed class of medications worldwide and first-line antibiotic of choice for most bacterial infections. They are also commonly labelled as the culprit of drug 'allergy'; leading to obligatory use of second-line antibiotics, suboptimal antibiotic therapy and increased antimicrobial resistance. However, the majority of reported penicillin 'allergy' labels are found to be incorrect after allergy testing, emphasising the importance of proper drug allergy testing and evaluation. Penicillin skin testing (PST) remains an important component of drug allergy diagnosis; however, its practice and policies significantly differ across the world. Inappropriate and non-evidence-based PST practices can lead to consequences associated with allergy mislabelling. Even within different regions of China, with a population exceeding 1.4 billion, there are marked differences in the implementation, execution and interpretation of PST. This review aims to examine the differences in PST between Mainland China, Hong Kong and the rest of the world. We critically analyse the current practice of 'pre-emptive' PST in Mainland China, which has a significant false-positive rate leading to high levels of penicillin allergy mislabelling. Non-evidence-based practices further compound the high false-positive rates of indiscriminatory PST. We postulate that inappropriate PST policies and practices may exacerbate the mislabelling of penicillin allergy, leading to unnecessary overuse of inappropriate second-line antibiotics, increasing antimicrobial resistance and healthcare costs. We advocate for the importance of more collaborative research to improve the contemporary workflow of penicillin allergy diagnosis, reduce mislabelling and promote the dissemination of evidence-based methods for allergy diagnosis.

Efficacy of Atogepant in Chronic Migraine With and Without Acute Medication Overuse in the Randomized, Double-Blind, Phase 3 PROGRESS Trial.

Atogepant is an oral, calcitonin gene-related peptide receptor antagonist approved for the preventive treatment of migraine. We evaluated the efficacy of atogepant for the preventive treatment of chronic migraine (CM) in participants with and without acute medication overuse. This subgroup analysis of the phase 3, 12-week, randomized, double-blind, placebo-controlled PROGRESS trial evaluated adults with a ≥1-year history of CM, ≥15 monthly headache days (MHDs), and ≥8 monthly migraine days (MMDs) during the 4-week baseline period. Participants were randomized (1:1:1) to placebo, atogepant 30 mg twice daily (BID), or atogepant 60 mg once daily (QD) for 12 weeks and were analyzed by acute medication overuse status (triptans/ergots for ≥10 days per month, simple analgesics for ≥15 days per month, or combinations of triptans/ergots/simple analgesics for ≥10 days per month). Outcomes included change from baseline in mean MMDs, MHDs, and monthly acute medication use days; ≥50% reduction in mean MMDs across 12 weeks; and patient-reported outcome (PRO) measures. Of 755 participants in the modified intent-to-treat population, 500 (66.2%) met baseline acute medication overuse criteria (placebo, n = 169 [68.7%]; atogepant 30 mg BID, n = 161 [63.6%]; atogepant 60 mg QD, n = 170 [66.4%]). The least squares mean difference (LSMD) (95% CI) from placebo in MMDs was -2.7 (-4.0 to -1.4) with atogepant 30 mg BID and -1.9 (-3.2 to -0.6) with atogepant 60 mg QD. Mean MHDs (LSMD [95% CI] -2.8 [-4.0 to -1.5] and -2.1 [-3.3 to -0.8]) and mean acute medication use days (LSMD [95% CI] -2.8 [-4.1 to -1.6] and -2.6 [-3.9 to -1.3]) were reduced and a higher proportion of participants achieved ≥50% reduction in MMDs (odds ratio [95% CI] 2.5 [1.5-4.0] and 2.3 [1.4-3.7]) with atogepant 30 mg BID and atogepant 60 mg QD. There was a 52.1%-61.9% reduction in the proportion of atogepant-treated participants meeting acute medication overuse criteria over 12 weeks. Atogepant improved PRO measures. Similar results were observed in the subgroup without acute medication overuse. Atogepant was effective in participants with CM, with and without acute medication overuse, as evidenced by reductions in mean MMDs, MHDs, and acute medication use days; reductions in the proportion of participants meeting acute medication overuse criteria; and improvements in PROs. ClinicalTrials.gov NCT03855137. Submitted: February 25, 2019; first patient enrolled: March 11, 2019. clinicaltrials.gov/ct2/show/NCT03855137. This study provides Class II evidence that atogepant reduces mean MMDs, MHDs, and monthly acute medication use days in adult patients with or without medication overuse.

Using ensemble learning and hierarchical strategy to predict the outcomes of ESWL for upper ureteral stone treatment

Urinary tract stones are a common and frequently recurring medical issue. Accurately predicting the success rate after surgery can help avoid ineffective medical procedures and reduce unnecessary healthcare costs. This study collected data from patients with upper ureter stones who underwent extracorporeal shock wave lithotripsy, including cases of successful as well as unsuccessful stone removal after the first and second lithotripsy procedures, and constructed prediction systems for the outcomes of the first and second lithotripsy procedures. Features were extracted from three categories of information: patient characteristics, stone characteristics, and extracorporeal shock wave lithotripsy machine data, and additional features were created using Feature Creation. Finally, the impact of features on the models was analyzed using six methods to calculate feature importance. Our prediction model for the first lithotripsy, selected from among 43 methods and seven ensemble learning techniques, achieves an AUC of 0.91. For the second lithotripsy, the AUC reaches 0.76. The results indicate that the detailed and binary information provided by patients regarding their history of stone experiences contributes differently to the predictive accuracy of the first and second lithotripsy procedures. The prediction tool is available at https://predictor.isu.edu.tw/ks.

Gatekeeping and referral of patients holding private health insurance: a survey among general practitioners in Norway

Objective Private health insurance is becoming more common in Norway. The aim of this study was to investigate GPs’ opinions on private health insurance, and their experiences from consultations where health insurance can affect decisions about referring. Design A web based cross-sectional survey. Setting Norwegian general practice. Subjects All GPs in Norway were in 2019 invited to participate in an online survey. Main outcome measures The GPs’ opinions and experiences regarding health insurance were reported as proportions. Multiple logistic regression was used to test associations between how frequently GPs refer patients without further considerations and variables concerning their characteristics, opinions, and experiences. Results Of 1,309 GPs (response rate 27%), 93% stated that private health insurance raises the risk of overtreatment and 90% considered such insurance to contribute to inequality in health. Frequently being pressured to refer in the absence of a medical indication was reported by 42%. Moreover, 28% often or always chose to refer patients without further consideration, and this was associated with perceptions of pressure with an adjusted odds ratio (AOR) of 3.80, 95% confidence interval (CI) 2.73–5.29, and unpleasant reactions from patients following refusals (AOR 1.63, 95% CI 1.14–2.33). Conclusion Although most participating GPs associated private health insurance with overtreatment and inequality in health, more than one in four choose to refer without further consideration. GPs’ experience of pressure to refer and negative reactions from patients when they consider referrals not to be medically indicated, raises the risk of medical overuse for patients holding private health insurance.

Behavioral therapy in migraine: Expanding the therapeutic arsenal.

The US Headache Consortium developed evidence-based guidelines for the treatment of migraine and found grade A evidence in support of behavior therapy (BT). Understanding the mechanisms of BT may improve the management of migraine and reduce its burden. We performed a narrative review to define the current evidence of BT and determine its usefulness in migraine management. The information was obtained from 116 publications, with 56 of them retrieved through direct searches in PubMed (2011-2020) and the remainder selected by the authors to complete the content. BT might reduce migraine impact by decreasing the sympathetic nervous system's response to stress and increasing pain tolerance. Acting in headache-related surroundings can be improved, together with headache duration and self-efficacy. Applications such as mobile health and electronic health applications can help to carry out healthier lifestyle patterns. Regarding medication overuse, BT seems to be a good choice, with similar results to pharmacological prophylaxis. Advantages of using BT are the lack of adverse effects and the unrestricted use in children, where BT is postulated to be even more effective than the standardized pharmacopeia. BT is an interesting tool that can be used as an add-on therapy in migraine. Through BT, the autonomy and empowerment of migraine patients is enhanced. BT may not cure migraine, but it could help to reduce pain severity perception, disability, and migraine impact, adding an emotive and cognitive approach to the perceptive role of pharmacopeia. Thus, a better approach in migraine, implementing specific therapeutic management, can improve migraine control.

Insight into Current Practices of Community Pharmacists in Topical Corticosteroid Prescribing and Counseling: Cross-Sectional Survey Study from Saudi Arabia.

Topical corticosteroids are commonly used to treat several skin conditions, most notably atopic dermatitis. Many studies have found that patients lack knowledge about the safety, potency, and appropriate use of topical corticosteroids. This can be due to ineffective education by pharmacists and other healthcare providers. This study aims to evaluate the appropriateness of dispensing and counseling practices of community pharmacists towards topical corticosteroids in Saudi Arabia. A cross-sectional survey study was conducted in Saudi Arabia among 418 community pharmacists from different regions of Saudi Arabia. Data were collected using a validated questionnaire that covered community pharmacists' sociodemographic information, their perceptions of patient knowledge about topical corticosteroid use, and their dispensing and their counseling practices, in addition to their perceived barriers to counseling. The majority of the participating community pharmacists were Saudi (57.4%), female (66.7%), holding a bachelor's degree (63.4%), and full-time workers (91.1%). Most of the time, community pharmacists counseled patients on the frequency of application per day and the duration of treatment (75.8% and 74.8%, respectively). The median counseling practice score was 17, with an IQR of 14-21. The main barrier to counseling was lack of time (33.7%). Only 15% of community pharmacists accurately identified all scenarios that necessitate medical referrals. Dry skin, itchiness, and irritation were the most common side effects reported by community pharmacists for patients to complain about (69.4%). Most pharmacists agreed that misuse is the most likely cause of topical corticosteroid adverse drug events (53.7%), followed by medication overuse, such as patient self-treatment (48%). Community pharmacists counseling practices to their patients about the use of topical corticosteroids require improvement. Continuing education and hands-on training are needed for community pharmacists regarding counseling about topical corticosteroids use.

The impact of codeine rescheduling on non-opioid analgesic use by people who regularly use codeine: a prospective cohort study

BackgroundCodeine was rescheduled in Australia to prescription only in February 2018. Initial studies reported an increase in population level paracetamol and ibuprofen sales following codeine upscheduling. However, to date no study has been able to investigate changes in non-opioid analgesic use at the individual patient level to determine if sales data reflect actual consumption patterns.AimTo address this gap, we aimed to determine the impact of codeine rescheduling on non-opioid analgesic use in people who regularly used over-the-counter codeine, primarily for pain, prior to the rescheduling change.MethodWe conducted a prospective cohort study with 260 participants who reported regular over-the-counter codeine consumption at cohort entry. Surveys were completed at baseline (November 2017, 3 months before rescheduling) and at 1 month (February 2018), 4 months (June 2018), and 12 months (February 2019), following rescheduling. The primary outcomes were mean daily doses of non-opioid analgesics, captured through a 7 day medication diary.ResultsThe mean daily paracetamol dose decreased from 1754.4 mg (95% CI 1300.5–2208.3) at baseline to 1023.8 mg (95% CI 808.5–1239.1) at the final time-point (+ 12 months) (p = .009). The mean daily ibuprofen dose decreased from 305.1mg (95% CI 217.9–392.4) at baseline to 161.2 mg (95% CI 98.5–224.0) 12 months after rescheduling (p = .03). No significant change in doses of other medications remained was found.ConclusionIn people who regularly consumed over-the-counter codeine, doses of non-opioid analgesics either reduced or remained stable following codeine rescheduling, suggesting concerns of medication substitution or overuse following the change were not realised.

Anti‑CGRP monoclonal antibodies in resistant migraine: preliminary real-world effectiveness and clinical predictors of response at twoyears.

Monoclonal antibodies targeting calcitonin gene-related peptide (anti-CGRP mAbs) have shown clinical effectiveness and safety in randomized clinical studies. However, long-term studies in clinical practice remain limited. To assess the long-term effectiveness, clinical predictors and safety of three anti-CGRP mAbs (erenumab, galcanezumab, fremanezumab) in resistant migraine patients. A single-center retrospective study was conducted from December 2019 to June 2023 involving 120 resistant migraine patients who received at least a month of anti-CGRP mAbs treatment. Patients completed a headache diary that included monthly acute medication intake (MAM), monthly migraine days (MMD), adverse events as well as completed Patient-Reported Outcome questionnaires (MIDAS [Migraine Disability Assessment] and Headache Impact Test 6 [HIT-6]). The number of patients achieving a ≥ 50% reduction in monthly migraine days was determined and classified as ≥ 50% responders, and baseline parameters and logistic regression between responders and non-responders were analyzed to identify potential predictors of response. Adverse events were registered in every follow-up. Treatment with anti-CGRP mAbs led to reductions in MIDAS, HIT-6, MMD and MAM from baseline to 6-24months. At 6-12months, responders (61% and 57%, respectively) exhibited lower baseline MMD and MAM. Medication overuse was associated with non-responders from 6 to 24months and it was identified as a negative predictor of treatment effectiveness (OR 0.23, 95% CI 0.07-0.74; p = 0.014). Anti-CGRP mAbs prove effectiveness and safety over a 24-month period in a RM population. Patients with no medication overuse and lower basal MMDs and MAM may respond better to anti-CGRP mAbs.

The Endogenous Pain Modulatory System as a Healing Mechanism: A Proposal on How to Measure and Modulate It.

Chronic pain is highly burdening and multifactorial in etiology. The endogenous-pain-healing system restores body tissue to a non-painful state after an injury leading to pain, and its disruption could represent a relevant mechanism, especially for nursing interventions. To review the literature and summarize the results that support this hypothesis. We hypothesized that the mechanism behind this system mainly depends on the endogenous pain modulatory system (EPMS), which is responsible for inhibiting pain after tissue healing is complete and facilitating it when tissue damage is still present. Different biomarkers can quantify EPMS functioning. We reviewed the literature and included relevant information regarding this hypothesis. First, conditioned pain modulation (CPM) measures pain inhibition and is a possible predictor for pain chronification. Second, motor cortex excitability measures the cortical control of the EPMS, which can be assessed through transcranial magnetic stimulation (using intracortical inhibition) or electroencephalography. Modifiable factors disrupt its functioning, such as sleep deprivation, medication overuse, and mental health status, but could be protective, such as exercise, certain medications, mind-body techniques, and non-invasive neuromodulation therapies. The acquisition of neurophysiological knowledge of how the chronicity of pain occurs and the EPMS involvement in this process may allow for better management of these patients. We raised the hypothesis that the impairment of the EPMS (altered cortical excitability and descendent pain modulation pathways) seems to be related to the disruption of the pain healing process and its chronicity. Further longitudinal studies evaluating the relationship between these biomarkers and chronic pain development are necessary.