Several therapeutic strategies focus with limited scientific evidence solely on targeting anatomical structures

To effectively address this issue for people with schizophrenia, we recommend that policymakers permit reimbursement of HCV screening in behavioral health care settings. In 2012, the CDC newly recommended one-time HCV screening for adults born during 1945–1965 given the high prevalence of persistent chronic HCV infection in this population.During 2011–2016, significant HCV infection was most prevalent among those aged 50–64 years.However, our results among people with schizophrenia within the Medicaid program did not find this age group to be prioritized as expected. In fact, we found that as age increased, HCV screening decreased. For example, HCV screening was highest among patients aged 20–39 years in 2002 and 2012. One explanation is that the birth cohort recommendations published in August 2012 were not put into effect rapidly for the remainder of 2012. Another possibility is provider bias; providers may assume that younger individuals are more likely to engage in higher risk behaviors than older patients and providers may thereby be more likely to target younger patients for screening. For instance,cannabis grow racks rising acute HCV cases in younger people linked to the opioid epidemic may have prompted increased screening. Additional investigations to help elucidate the role of patient age on HCV screening might include surveying providers on how factors related to age inform their decisions to conduct HCV screening. We also found variation in HCV screening by race/ethnicity among people with schizophrenia. Similar to prior research,we found that Asian or Pacific Islanders had nearly double the HCV screening as Whites.

Nonetheless, our national sample had comparable screening for both Hispanic and multiracial enrollees. The high degree of unknown race/ethnicity status in this Medicaid cohort reduces the validity of this as a pre dictor; nearly 1 in 10 patients with schizophrenia were of unknown race/ethnicity. This finding aligns with recent work showing that race/ethnicity is largely incomplete for Medicaid patients.Addressing structural discrimination at the intersection of race/ethnicity and mental illness within the population covered by Medicaid will require accurate and complete patient demographic information. Most notably, we found that among patients with schizophrenia the highest likelihood of HCV screening was among those with comorbid HIV and HBV followed by chlamydia , HSV , and opioid use , as hypothesized, though comorbid diabetes predicted 15% higher odds. Our finding of higher HCV screening among people who have schizophrenia and also comorbid HIV, HBV, substance use disorders, and sexually transmitted infections is likely explained in part by 1998 and 1999 CDC recommendations for screening high-risk people,which remained in place throughout the study period.Because of shared risk, HBV and HCV screening are often combined, especially among those with substance use disorders, as chronic HCV infection is complicated by alcohol and other sub stance use. Hence, there appears to be some risk-based assessment of the need for HCV screening recommended by CDC policy, which is consistent with prior literature.Compared with prior literature, HCV screening in the 2012 Medicaid population with schizophrenia was similar to 2011 reports from California Medicaid recipients with SMI ,and lower than US persons enrolled in private healthcare during 2006– 2008 .

These combined results raise serious concerns about the overall effectiveness and implementation of early and ongoing public health policies aimed to prevent and treat HCV in this high risk population, and for Medicaid patients overall. Our study lays the ground work for future investigations to better understand how HCV prevention and treatment efforts are evolving in the United States for patients with schizophrenia. The low overall rate of HCV screening found in the cur rent study also has important policy implications. During the pandemic, COVID-19 infection in HCV patients has been linked to greater COVID-19 disease severity and hospitalization,liver impairment,and in-hospital mortality.Now that we have highly efficacious HCV therapies that can reduce the considerable morbidity and mortality associated with this infection,HCV screening should be added to routine panel screening of COVID-19 risk. Underdiagnosis of HCV will likely result in increased HCV transmission, prevalence, morbidity, and mortality, perhaps more for those infected with COVID-19. Moreover, restrictive policies can inadvertently under mine broader HCV prevention efforts. In addition to the CDC’s 2020 endorsement of universal HCV screening,the World Health Organization proposed a global strategy to eliminate HCV by 2030 through increases inscreening and treatment.Currently, most US states are not on track to achieve this goal, which is likely due in part to state Medicaid restrictions.Various states have implemented hepatic fibrosis, sobriety, and prescriber restrictions on access to HCV treatment.These discriminatory restrictions may exacerbate poor outcomes for those with schizophrenia, particularly for those with comorbidities.

For example, 2012 HCV screening was lowest in Hawaii, Alaska, and Maryland in the current study, all of which have maintained sobriety protocols to access treatment for nearly a decade.Removing dis criminatory Medicaid access restrictions and improving linkage to care for patients with schizophrenia can help reach the goal of eliminating HCV in the United States. There are several methodological considerations. First, our large population-based retrospective cohort was nationally representative, hence study findings are generalizable to the 45 states studied. Second, results reflect HCV screening for Medicaid patients without dual enrollment in Medicare and should not be generalized to dual enrolled patients, uninsured patients, and privately insured patients. Notably, approximately 40% of US adults with schizophrenia have Medicaid without Medicare coverage.Third, patients who were dual eligible for Medicare were excluded after matching; however, selection bias was likely minimal given the similar distributions of matching factors between cases and controls. Fourth, while case–control frequency matching accounted for confounding by age, sex, and race/ethnicity, there were unmeasured variables, such as incarceration frequency and housing stability, that may have confounded trends in the association between a schizophrenia diagnosis and being screened for HCV. Fifth, the absence of immigration data during the study period is a limitation since HCV screening is likely higher among immigrants upon entering the United States. However, this would lead to the underestimation of HCV screening. Sixth, internal validity could be further compromised by censoring, specifically patient changes in Medicaid eligibility during the study period and failure to capture infections. Seventh, because Medicaid claims data rely on clinicians to submit CPT billing codes for HCV screening and does not capture screening that occurs while individuals are incarcerated or receive care that is not paid for by Medicaid, inaccurate or under reporting can also result in underestimating HCV screening. Claims data analyses also rely on accurate clinical diagnoses. Finally, because the most recent data were collected in 2012, the HCV screening rates may not reflect contemporary practice. Nonetheless, our study fills a notable gap in knowledge by demonstrating that HCV screening in the Medicaid population changed by only 1.1% from 2002 to 2012 after 1998 CDC recommendations,cannabis grow system which suggests screening may have changed little over the subsequent decade. Despite the high risk of HCV among people with schizophrenia, fewer than 5% of Medicaid patients with schizophrenia received HCV screening each year. Implementing widespread HCV screening in the behavioral healthcare system nationwide could improve HCV detection and successful treatment for people with schizophrenia. While there appear to be screening improvements in US states, expanding integrative HCV prevention, screening, and treatment policies with fewer restrictions are needed to effectively reach this high-risk population. Implementation of such efforts nationwide can improve HCV primary and secondary prevention efforts, reduce HCV-related mortality, and contribute to HCV elimination efforts now that we have safe and highly effective HCV treatments.Chronic pain persists past the normal healing period and thus lacks the acute warning function of physiological nociception.

The bio-psychosocial model recognizes chronic pain as a combi nation of physical dysfunction, beliefs, coping strategies, distress, illness, behavior, and social interactions . One in five adults in Europe may experience chronic pain , and the scarcity of new and effective analgesics has an ongoing individual impact. It is also noteworthy that the new International Classification of Diseases has now included chronic pain as a separate entity. Significant disease burden, absences, loss of work, early retirement, and high social and healthcare costs are important effects, as well. Given the biopsychological nature of chronic pain, management is challenging and requires a multidisciplinary approach including psychological, sociological, and pharmaco logical interventions or physiotherapy to improve quality of life . The four main unmet needs related to chronic pain are awareness, prevention, efficacious therapies, and multi-modal plus interdisciplinary care.Although basic science and pre-clinical pain research have elucidated many bio molecular mechanisms of pain and identified promising novel targets, little of this work has translated into better clinical management of chronic pain. This objective of this state-of-the-art review was to summarize current concepts of chronic pain syndromes and to describe potential novel treatment strategies. The pathophysiology of persistent pain includes peripheral and central, neuronal, neuroimmune, and vascular mechanisms. Inflammatory responses are critical in many chronic pain conditions and may contribute to neuropathic and inflammatory pain . Recently, there has been a significant drive to identify molecular mediators of pain-related functional plasticity leading to chronicity and to understand the interplay between the periphery and the central nervous system . The pathophysiology of pain is complex, and the CNS plays a crucial role in its development. Nociceptive afferent neurons are specialized sensory neurons mediating the response to noxious stimuli. Their somaslie in the dorsal root ganglion or trigeminal ganglion. They extend their axons to almost all regions of the body, including deep somatic tissues like muscles, joints, and bones . These neurons are quite heterogeneous in neurotransmitter and receptor expression . They can be classified based on content of neuropeptides, such as substance P or calcitonin gene-related peptide , or expression of the high-affinity nerve growth factor receptor tropomyosin receptor kinase A or voltage-gated channels . Nociceptors respond to noxious events that may lead to tissue damage, and nociceptive sensory neurons are essential for acute and chronic pain signaling in humans. Acute pain has an important protective role, warning the organism of imminent danger, and it can be recurrent because of persistent stimuli. After 12 weeks, assuming that a lesion has healed, acute pain can transition into chronic pain, with more prominent peripheral and central sensitization, and pathophysiological changes in the peripheral nervous system as well as in the CNS . The resultant pain usually persists beyond its biological usefulness and compromises quality of life . Chronic pain is not an extension of acute pain but rather a result of persistent nociceptor activation experienced over time . Peripheral sensitization can be defined as an increased sensitivity to afferent nerve stimuli following tissue insult or inflammation . Central sensitization, in contrast, is a condition of the CNS associated with chronic pain development and its maintenance. Sensitization manifests thus as a persistent state of reactivity with a lowered threshold for pain stimuli. This reduced threshold develops because of temporal summation, in which post-synaptic action potentials generated by the same stimulus in the same population of nociceptors add up , eliciting a stronger outcome . A further crucial step to sensitization is the “awakening” of “sleeping” nociceptors, which do not respond to thermal or mechanical stimuli in non-inflamed tissues. This “awakening” is termed spatial summation, in which action potentials are generated by the same stimulus in more than one nociceptor . Together, these mechanisms synergize to cause the psychophysical phenomenon of hyperalgesia, an increase in pain sensation related to thermal or mechanical stimuli. The result also can be changes in pain threshold as well as in the temporal and spatial manifestation of pain. The mechanisms responsible for central sensitization differ from those triggering peripheral sensitization. Central sensitization results from CNS changes that can alter the response to sensory inputs, even in the absence of noxious stimuli . Nociceptors are thus a vital bodily defense, providing protective sensitivity to transient threats. The pivotal role of nociceptors for the generation of pain is strikingly obvious in individuals with congenital insensitivity to pain . At first, these individuals manifest with structural small fiber neuropathy and premature death of nociceptors resulting from TrkA mutation, consequently reducing or ceasing NGF signaling through TrkA . A loss of function mutation in the SCN9A gene coding for Nav1.7 voltage-gated channels then also may impede action potential propagation in nociceptive terminals . Of note, in people with the Nav1.7 channelopathy, no overt structural neuropathy is noted and the ability to detect thermal stimuli remains intact.