Long-term opioid therapy (LTOT) for chronic cancer and non-cancer pain is commonly ineffective in... more Long-term opioid therapy (LTOT) for chronic cancer and non-cancer pain is commonly ineffective in providing its stated goal of improving function through good control of pain. Opioid tapering (slow dose reduction and/or discontinuation), the logical solution, also appears to be ineffective among many patients on LTOT as it often leads to even worse pain control and function, leaving the patients and providers managing LTOT in a clinical conundrum with little treatment choices. Complex persistent opioid dependence (CPOD) was recently offered as a heuristic to explain this clinical conundrum exemplified by the ineffectiveness of both LTOT and opioid tapering. This manuscript provides a detailed description of the neurobehavioral underpinnings of CPOD, explaining how long-term opioid use can lead to more pain even while experiencing relief with each opioid dose. CPOD is characterized by the allostatic opponent mechanisms of neuroadaptations related to the progression of opioid dependence and tolerance involving nociceptive/anti-nociceptive brain systems causing opioid-induced hyperalgesia and reward/anti-reward systems causing hyperkatefia or suffering that induces pain experience through the cognitive/emotional component of pain mechanisms. “Opioid Induced Chronic Pain syndrome” (OICP) is offered as an alternate clinical diagnostic term instead of CPOD that has several limitations as a diagnosis term including poor patient acceptance due to stigma towards addiction and clinical confounding with opioid use disorder, a related but separate clinical entity. OICP with LTOT is conceptualized as a recoverable iatrogenic problem that can be managed by pain providers. Broad guidance on management of OICP is also provided.
Although substance use disorder (SUD) is frequently complicated by pain, the prevalence and corre... more Although substance use disorder (SUD) is frequently complicated by pain, the prevalence and correlates of persistent pain and dysfunction following SUD remission have not been studied. Using a cross-sectional sample of United States (US) adults with SUD identified in the National Epidemiologic Survey on Alcohol and Related Conditions Wave III, we evaluated the prevalence of moderate/severe pain interference (PI) in subgroups with current and remitted SUD and the independent association of SUD remission and PI with self-reported psychosocial and physical function (Mental Health Composite Score [MCS] and Physical Function Score [PFS] from the Short Form 12). A fifth (20.6%; 7.6 million) of estimated 36.7 million US adults with past year SUD and a slightly higher proportion (25.6%; 9.6 million) of 37.4 million with SUD remission reported PI. MCS and PFS showed independent negative associations with PI among adults with both past year SUD and SUD remission. MCS had a positive independent association with SUD remission, but a stronger negative association with PI. While PFS had no statistically significant association with SUD remission, it had a strong negative association with PI. Analysis of interaction between SUD remission and PI revealed that SUD remission had no effect on the association of PI and MCS but had significant moderating influence on the association between PI and PFS. Moderate to severe pain interference continues to be a significant problem among a sizable population achieving SUD remission potentially impeding recovery, and deserves focused clinical attention both active SUD and its remission.
While the United States experienced a surge in morbidity and mortality associated with opioid pre... more While the United States experienced a surge in morbidity and mortality associated with opioid prescriptions after the year 2000, the country has since 2011 been mired in a growing crisis of overdose and addiction in which illicit opioids play a central role. The drastic increase in persons with prescription opioid use, misuse, and opioid use disorder prompted myriad public health and clinical interventions to curtail opioid-related harms. These approaches can be classified into three main categories: (1) curtailing opioid prescribing, (2) monitoring opioid prescribing, and (3) myriad public policies and initiatives to mitigate and treat opioid use, misuse, and opioid use disorder. Since many persons with opioid use disorder started with potentially prescribed opioids, efforts to curtail and control opioid prescriptions emerged as a primary policy response to address opioid-related morbidity and mortality in the United States. Central to these efforts were the landmark “CDC Guideline...
Collaborative on Countering the US Opioid Epidemic [8] has been focusing on comprehensive and col... more Collaborative on Countering the US Opioid Epidemic [8] has been focusing on comprehensive and collaborative efforts to fundamentally address the opioid epidemic crisis. All of these major initiatives emphasize pain education as a key component in the fight against the dual crises of chronic pain and the opioid epidemic. I am honored to represent the AAPM on the HHS Pain Management Task Force and the NAM Action Collaborative and contribute to these important initiatives of our nation on your behalf.
Unstable angina is frequently encountered by general practitioners and cardiovascular specialists... more Unstable angina is frequently encountered by general practitioners and cardiovascular specialists. In the United States, of the 2.5 million patients admitted to hospital every year with suspected acute coronary syndromes, 1.5 million have unstable angina. The rest have myocardial infarction with or without ST elevation. 1 Earlier published literature classified acute ischaemic episodes as unstable angina and either non-Q wave or Q wave infarction. As Q wave and non-Q wave infarctions can only be definitely distinguished by electrocardiography several days after the clinical event, the classification does not help with emergency patients. Moreover, the prognostic value of Q wave versus non-Q wave infarction classification is limited. 2 A new nosological scheme has derived from the need to rapidly assess patients at presentation so that powerful new treatments can be appropriately selected. All acute presentations suggesting acute coronary syndromes can be further divided into infarction with ST elevation (possibly including patients with new bundle branch blocks) and infarction without ST elevation and unstable angina combined. The distinction between the last two conditions can be reliably made by measuring serum markers. This classification makes sense because early thrombolytic treatment saves the lives of patients with infarction with ST elevation but has no beneficial, and probably some deleterious, effect in those with infarction without ST elevation or unstable angina. Moreover, the therapeutic approaches in the last two conditions are similar. 3 Hence we consider unstable angina and infarction without ST elevation as a single entity, especially regarding treatment. Figure 1 shows a plan for assessment and classification of suspected acute coronary syndrome. Methods We extracted data from the personal collection of journal articles of the authors and from Medline whenever necessary. We also obtained information from review articles on different subtopics. Pathophysiology of unstable angina Braunwald described unstable angina as a syndrome with five mutually non-exclusive causes; thrombosis, mechanical obstruction, dynamic obstruction (spasm of microvasculature and macrovasculature), inflammation or infection, and increased oxygen demand. 4 Unstable angina occurs from the interplay of these factors, with thrombosis and mechanical obstruction usually dominating. Transient or subtotal obstruction due to a platelet rich "white clot" over a fissured atherosclerotic plaque is considered causal in most episodes of unstable angina. This differs from the fibrin rich "red clot" associated with total coronary occlusion in infarction with ST elevation. In contrast to the Braunwald model, European investigators have advocated a central role for inflammation in unstable angina. 5 6 Increased concentrations of acute inflammatory markers, such as C reactive protein, are more often found in unstable angina than in chronic stable angina. Also, an increased concentration of C reactive protein at admission among patients with unstable angina has been correlated with worse outcomes both in hospital and after one year. 7-9 Several authors have shown varying associations of different subpopulations of T lymphocytes, granulocytes, macrophages, and cytokines with unstable angina. 5 6 Although the role of inflamma-Chest pressure, pain, or both, or angina equivalent Acute coronary syndrome Evaluation of initial electrocardiogram Early reperfusion strategy Evaluation of serum markers Evaluation after 48 hours Management strategy for unstable angina or infarction without ST elevation Non-cardiac cause ST elevation absent ST elevation present Unstable angina Infarction without ST elevation Infarction with ST elevation Unstable angina Non-Q wave infarction Q wave infarction Fig 1 Assessment and classification of suspected acute coronary syndrome
Although increased attention has been paid to sex and racial differences in the management of myo... more Although increased attention has been paid to sex and racial differences in the management of myocardial infarction, it is unknown whether these differences have narrowed over time. methods With the use of data from the National Registry of Myocardial Infarction, we examined sex and racial differences in the treatment of patients who were deemed to be "ideal candidates" for particular treatments and in deaths among 598,911 patients hospitalized with myocardial infarction between 1994 and 2002. results In the unadjusted analysis, sex and racial differences were observed for rates of reperfusion therapy (for white men, white women,
To measure high-sensitivity C-reactive protein (hsCRP) levels and to assess the presence of metab... more To measure high-sensitivity C-reactive protein (hsCRP) levels and to assess the presence of metabolic syndrome (MS) after puerperium in women diagnosed with various hypertensive disorders during pregnancy (HDP), a consecutive, cross-sectional case study at the 15th week after gestation. The sample consisted of 264 women who were admitted to a women's hospital. The diagnoses consisted of transient gestational hypertension (TGH¼43.2%), preeclampsia (PC¼29.5%), chronic hypertension (CH¼20.1%) and PC superimposed on CH (7.2%). A diagnosis of previous hypertension was present in 45.8% of the CH group. The prevalence of MS was 16.7% (CH¼42.1%, TGH¼13.9%, PC¼4.1%, Po0.001). The average hsCRP levels for the CH, TGH and PC groups were 3.79±2.76, 3.55±3.15 and 2.89±3.02, respectively (P¼0.040). The levels of hsCRP were higher in women with MS (4.71±3.15 vs. 3.01±2.88 mg l À1 in those without MS, Po0.001), and they increased when a higher number of MS criteria was fulfilled (Po0.001). The results demonstrated a positive correlation between hsCRP levels and body mass index (BMI) (r¼0.46), waist circumference (r¼0.50) or the number of fulfilled MS criteria (r¼0.56). The results suggest differences in vascular risk that depend on the type of HDP and on the prevalence of MS. The prevalence of MS was notably higher in the CH group, intermediate among the TGH group and much lower in the PC group. Differences in hsCRP levels also depended on the type of HDP (higher levels in CH and TGH patients in comparison with PC patients). Women with MS had higher hsCRP levels compared with women without MS, and the levels correlated with the number of MS criteria fulfilled. This result suggests that subclinical inflammatory status is correlated with the number of MS components present. Furthermore, hsCRP levels increased with increasing BMIs and waist circumferences.
Background The decreased number and senescence of circulating endothelial progenitor cells (EPCs)... more Background The decreased number and senescence of circulating endothelial progenitor cells (EPCs) are considered markers of vascular senescence associated with aging, atherosclerosis, and coronary artery disease (CAD) in elderly. In this study, we explore the role of vascular senescence in premature CAD (PCAD) in a developing country by comparing the numerical status and senescence of circulating EPCs in PCAD patients to controls. Methods EPCs were measured by flow cytometry in 57 patients with angiographically documented CAD, and 57 controls without evidence of CAD, recruited from random patients ≤ 50 years of age at All India Institute of Medical Sciences. EPC senescence as determined by telomere length (EPC-TL) and telomerase activity (EPC-TA) was studied by real time polymerase chain reaction (q PCR) and PCR– ELISA respectively. Result The number of EPCs (0.18% Vs. 0.039% of total WBCs, p < 0.0001), and EPC-TL (3.83 Vs. 5.10 kb/genome, p = 0.009) were markedly lower in PCAD p...
Immediate reperfusion therapy to restore coronary blood flow is recommended for all eligible pati... more Immediate reperfusion therapy to restore coronary blood flow is recommended for all eligible patients with acute myocardial infarction. However, reperfusion therapy is reportedly underutilized among African Americans, even when they are eligible. Reasons for the lack of use have not been fully explored. We examined the demographic, clinical, and treatment data of 10,469 African Americans with acute myocardial infarction who were eligible for reperfusion therapy, enrolled in the National Registry of Myocardial Infarction-2 from June 1994 through March 1998. The mean age was 62.58 (+/-14.4) years, and 44.7% were female. Although eligible, 47% of the African Americans in this study did not receive reperfusion therapy. In a multivariate analysis, the absence of chest pain at presentation (odds ratio [OR] 0.31, 95% CI 0.26-0.37) and initial admission diagnoses other than definite myocardial infarction (OR for receipt of reperfusion &lt;0.12) were the strongest predictors of lack of early reperfusion therapy. Progressive delays in hospital arrival and hospital evaluation predicted a lower likelihood of early reperfusion. Prior stroke (OR 0.63, 95% CI 0.50-0.78), myocardial infarction (OR 0.75, 95% CI 0.65-0.86), and congestive heart failure (OR 0.49, 95% CI 0.40-0.60) were all associated with lack of reperfusion therapy. Almost half of eligible African American patients with myocardial infarction did not receive reperfusion therapy. Potential reasons may include atypical presentation, patient and institutional delay, and underappreciation of myocardial infarction by care providers. Strategies to address these factors may improve the rate of use of reperfusion therapy.
Background Previous studies have suggested that thrombolysis is used less often in blacks than in... more Background Previous studies have suggested that thrombolysis is used less often in blacks than in whites. However, whether the greater prevalence of contraindications or less specific electrocardiographic manifestations of myocardial infarction (MI) account for this difference is unclear. Methods and Results We studied 498 consecutive patients (32% blacks) with first MI. Initial electrocardiograms were analyzed, blinded to race and outcome, for ST-segment deviation and bundle branch block to determine eligibility for thrombolysis. The relation of electrocardiographic eligibility for thrombolysis and actual use of thrombolysis in both races was explored. Among blacks, 45% received thrombolysis compared with 66% of whites (P < .001). A similar proportion of blacks and whites were eligible for thrombolysis (59% and 66% respectively, P = .116), but 62% of electrocardiography-eligible blacks were treated with thrombolysis compared with 75% of whites (P = .016). After accounting for eligibility for electrocardiography and other clinical variables likely to affect the decision to administer thrombolysis by means of conditional logistic regression, blacks were still less likely to receive thrombolysis (relative risk 0.73; 95% confidence interval 0.55 to 0.97). Conclusions We conclude that the differences in thrombolysis administration to blacks and whites are not accounted for by differences in electrocardiographic presentation or other measured variables. Unmeasured differences in clinical presentation of MI may explain racial differences in thrombolysis and merits further study.
BACKGROUND Substance use disorder (SUD) is a major risk factor for homelessness, but the specific... more BACKGROUND Substance use disorder (SUD) is a major risk factor for homelessness, but the specific association of opioid use disorder (OUD) and homelessness in the context of their shared risk factors has not been the focus of prior studies. We used national data from the United States Veterans Health Administration (VHA) to examine the association of OUD and homelessness in the context of shared risk factors. METHODS In this cross-sectional analysis of veterans who received VHA care during Fiscal Year 2012 (N = 5,450,078), we compared the prevalence of OUD and other sociodemographic, and clinical factors among homeless and non-homeless veterans. We estimated the odds ratio for homelessness associated with OUD alone, and after adjusting for other factors through multivariate logistic regression. RESULTS Homeless veterans had substantially higher prevalence of OUD than other VHA patients (7.7 % Vs 0.6 %) and OUD was associated with 13 times higher unadjusted odds of homelessness (Odds Ratio [OR] 13.36, 95 % CI 13.09-13.62), which decreased with adjustment for sociodemographic factors (black race, mean income and age), other SUD, medical, and psychiatric diagnoses (final OR 1.57, 95 % CI 1.53-1.61). Other SUDs (alcohol, cannabis, cocaine, and hallucinogens) showed similar or slightly higher odds of homelessness as OUD in the final model. CONCLUSIONS OUD was strongly associated with homelessness among US veterans although this association was largely but not entirely attenuated by shared sociodemographic and co-morbid risk factors including several other SUDs. Treatment of homeless veterans with OUD should address socio-economic vulnerabilities and other co-morbidities in addition to treatments for OUD.
Mayo Clinic Proceedings: Innovations, Quality & Outcomes, 2021
Objective: To establish the frequency of concordant, discordant, and clinically dominant comorbid... more Objective: To establish the frequency of concordant, discordant, and clinically dominant comorbidities among Medicare beneficiaries with knee osteoarthritis (KOA) and to identify common concordant condition subgroups. Participants and Methods: We used a 5% representative sample of Medicare claims data to identify beneficiaries who received a diagnosis of KOA between January 1, 2012, and September 30, 2015, and matched control group without an osteoarthritis (OA) diagnosis. Frequency of 34 comorbid conditions was categorized as concordant, discordant, or clinically dominant among those with KOA and a matched sample without OA. Comorbid condition phenotypes were characterized by concordant conditions and derived using latent class analysis among those with KOA. Results: The study sample included 203,361 beneficiaries with KOA and 203,361 non-OA controls. The largest difference in frequency between the two cohorts was for co-occurring musculoskeletal conditions (23.7% absolute difference), chronic pain syndromes (6.5%), and rheumatic diseases (4.5%), all with a higher frequency among those with knee OA. Phenotypes were identified as low comorbidity (53% of cohort with classification), hypothyroid/osteoporosis (27%), vascular disease (10%), and high medical and psychological comorbidity (10%). Conclusions: Approximately 47% of Medicare beneficiaries with KOA in this sample had a phenotype characterized by one or more concordant conditions, suggesting that existing clinical pathways that rely on single or dominant providers might be insufficient for a large proportion of older adults with KOA. These findings could guide development of integrated KOA-comorbidity care pathways that are responsive to emerging priorities for personalized, value-based health care.
OBJECTIVE To evaluate measurement and associations between pain severity and opioid craving in in... more OBJECTIVE To evaluate measurement and associations between pain severity and opioid craving in individuals with chronic pain on long-term opioid therapy and/or with opioid use disorder. STUDY DESIGN . Systematic review of randomized controlled trials and observational studies. METHODS . The PubMed, EMBASE, and PsycINFO databases were searched in October 2018. Eligible studies evaluated pain severity and opioid craving in individuals with chronic pain on long-term opioid therapy and/or with opioid use disorder. Two reviewers independently screened eligible studies, assessed risk of bias, and extracted data. RESULTS Of 625 studies, 16 fulfilled the inclusion/exclusion criteria of this review and were grouped by diagnostic focus (i.e., chronic pain on long-term opioid therapy, opioid use disorder, or both). Methods of assessment varied considerably across studies, especially with respect to opioid craving in chronic pain populations. Mean levels of pain were at what is considered moder...
Industrial settings, with their intramural resources and healthcare infrastructure, are ideal for... more Industrial settings, with their intramural resources and healthcare infrastructure, are ideal for initiating preventive activities to increase the awareness and control of cardiovascular diseases (CVD). However, there are no reliable estimates of CVD and risk factor burden, nor of its awareness and treatment status in urban Indian industrial settings. We aimed to evaluate the prevalence of CVD and its risk factors, and to assess the status of awareness and control of CVD risk factors among a large industrial population of northern India. We conducted a cross-sectional survey among all employees aged 20-59 years of a large industry near Delhi (n=2935), to evaluate their cardiovascular risk profile--by employing a structured questionnaire and clinical and biochemical estimations. The presence of coronary heart disease was ascertained by evidence of its treatment, Rose angina questionnaire and Minnesota coded electrocardiograms. The results for 2122 men, in whom complete information was available, are reported here. The mean age was 42 years and 90% of the men were below 50 years of age. The prevalence of major CVD risk factors (95% CI) was: hypertension 30% (28%-32%), diabetes 15% (14%-17%), high serum total cholesterol/HDL ratio (&amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;gt; or = 4.5) 62% (60%-64%) and current smoking 36% (34%-38%). Forty-seven per cent of the respondents had at least two of these risk factors. Another 44% (95% CI: 42%-46%) had pre-hypertension (INC VII criteria) and 37% (95% CI: 35%-39%) had evidence of either impaired fasting glucose or impaired glucose tolerance. Thirty-five per cent (95% CI: 33%-37%) of the individuals were overweight (BMI &amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;gt; or = 25 kg/m2) while 43% (95% CI: 40%-45%) had central obesity (waist circumference &amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;gt;90 cm). The metabolic syndrome was present in 28%-35% of the individuals depending on the diagnostic criteria used. The prevalence of several risk factors and the metabolic syndrome was high with increasing age, BMI and waist circumference. A third of those who had hypertension (31.5%) and diabetes (31%) were aware of their status. Among those aware, adequate control of blood pressure and blood glucose was present in only 38% of those with hypertension and 31% of those with diabetes, respectively. Coronary heart disease was present in 7.3% of the individuals while 0.3% had a history of stroke. This study demonstrates the high prevalence of CVD and its risk factors against a background of poor awareness and control among a comparatively young male population in a north Indian industrial setting.
have no conflict of interest or other disclosures to make. Jane C. Ballantyne was a paid consulta... more have no conflict of interest or other disclosures to make. Jane C. Ballantyne was a paid consultant in opioid litigation.
Long-term opioid therapy (LTOT) for chronic cancer and non-cancer pain is commonly ineffective in... more Long-term opioid therapy (LTOT) for chronic cancer and non-cancer pain is commonly ineffective in providing its stated goal of improving function through good control of pain. Opioid tapering (slow dose reduction and/or discontinuation), the logical solution, also appears to be ineffective among many patients on LTOT as it often leads to even worse pain control and function, leaving the patients and providers managing LTOT in a clinical conundrum with little treatment choices. Complex persistent opioid dependence (CPOD) was recently offered as a heuristic to explain this clinical conundrum exemplified by the ineffectiveness of both LTOT and opioid tapering. This manuscript provides a detailed description of the neurobehavioral underpinnings of CPOD, explaining how long-term opioid use can lead to more pain even while experiencing relief with each opioid dose. CPOD is characterized by the allostatic opponent mechanisms of neuroadaptations related to the progression of opioid dependence and tolerance involving nociceptive/anti-nociceptive brain systems causing opioid-induced hyperalgesia and reward/anti-reward systems causing hyperkatefia or suffering that induces pain experience through the cognitive/emotional component of pain mechanisms. “Opioid Induced Chronic Pain syndrome” (OICP) is offered as an alternate clinical diagnostic term instead of CPOD that has several limitations as a diagnosis term including poor patient acceptance due to stigma towards addiction and clinical confounding with opioid use disorder, a related but separate clinical entity. OICP with LTOT is conceptualized as a recoverable iatrogenic problem that can be managed by pain providers. Broad guidance on management of OICP is also provided.
Although substance use disorder (SUD) is frequently complicated by pain, the prevalence and corre... more Although substance use disorder (SUD) is frequently complicated by pain, the prevalence and correlates of persistent pain and dysfunction following SUD remission have not been studied. Using a cross-sectional sample of United States (US) adults with SUD identified in the National Epidemiologic Survey on Alcohol and Related Conditions Wave III, we evaluated the prevalence of moderate/severe pain interference (PI) in subgroups with current and remitted SUD and the independent association of SUD remission and PI with self-reported psychosocial and physical function (Mental Health Composite Score [MCS] and Physical Function Score [PFS] from the Short Form 12). A fifth (20.6%; 7.6 million) of estimated 36.7 million US adults with past year SUD and a slightly higher proportion (25.6%; 9.6 million) of 37.4 million with SUD remission reported PI. MCS and PFS showed independent negative associations with PI among adults with both past year SUD and SUD remission. MCS had a positive independent association with SUD remission, but a stronger negative association with PI. While PFS had no statistically significant association with SUD remission, it had a strong negative association with PI. Analysis of interaction between SUD remission and PI revealed that SUD remission had no effect on the association of PI and MCS but had significant moderating influence on the association between PI and PFS. Moderate to severe pain interference continues to be a significant problem among a sizable population achieving SUD remission potentially impeding recovery, and deserves focused clinical attention both active SUD and its remission.
While the United States experienced a surge in morbidity and mortality associated with opioid pre... more While the United States experienced a surge in morbidity and mortality associated with opioid prescriptions after the year 2000, the country has since 2011 been mired in a growing crisis of overdose and addiction in which illicit opioids play a central role. The drastic increase in persons with prescription opioid use, misuse, and opioid use disorder prompted myriad public health and clinical interventions to curtail opioid-related harms. These approaches can be classified into three main categories: (1) curtailing opioid prescribing, (2) monitoring opioid prescribing, and (3) myriad public policies and initiatives to mitigate and treat opioid use, misuse, and opioid use disorder. Since many persons with opioid use disorder started with potentially prescribed opioids, efforts to curtail and control opioid prescriptions emerged as a primary policy response to address opioid-related morbidity and mortality in the United States. Central to these efforts were the landmark “CDC Guideline...
Collaborative on Countering the US Opioid Epidemic [8] has been focusing on comprehensive and col... more Collaborative on Countering the US Opioid Epidemic [8] has been focusing on comprehensive and collaborative efforts to fundamentally address the opioid epidemic crisis. All of these major initiatives emphasize pain education as a key component in the fight against the dual crises of chronic pain and the opioid epidemic. I am honored to represent the AAPM on the HHS Pain Management Task Force and the NAM Action Collaborative and contribute to these important initiatives of our nation on your behalf.
Unstable angina is frequently encountered by general practitioners and cardiovascular specialists... more Unstable angina is frequently encountered by general practitioners and cardiovascular specialists. In the United States, of the 2.5 million patients admitted to hospital every year with suspected acute coronary syndromes, 1.5 million have unstable angina. The rest have myocardial infarction with or without ST elevation. 1 Earlier published literature classified acute ischaemic episodes as unstable angina and either non-Q wave or Q wave infarction. As Q wave and non-Q wave infarctions can only be definitely distinguished by electrocardiography several days after the clinical event, the classification does not help with emergency patients. Moreover, the prognostic value of Q wave versus non-Q wave infarction classification is limited. 2 A new nosological scheme has derived from the need to rapidly assess patients at presentation so that powerful new treatments can be appropriately selected. All acute presentations suggesting acute coronary syndromes can be further divided into infarction with ST elevation (possibly including patients with new bundle branch blocks) and infarction without ST elevation and unstable angina combined. The distinction between the last two conditions can be reliably made by measuring serum markers. This classification makes sense because early thrombolytic treatment saves the lives of patients with infarction with ST elevation but has no beneficial, and probably some deleterious, effect in those with infarction without ST elevation or unstable angina. Moreover, the therapeutic approaches in the last two conditions are similar. 3 Hence we consider unstable angina and infarction without ST elevation as a single entity, especially regarding treatment. Figure 1 shows a plan for assessment and classification of suspected acute coronary syndrome. Methods We extracted data from the personal collection of journal articles of the authors and from Medline whenever necessary. We also obtained information from review articles on different subtopics. Pathophysiology of unstable angina Braunwald described unstable angina as a syndrome with five mutually non-exclusive causes; thrombosis, mechanical obstruction, dynamic obstruction (spasm of microvasculature and macrovasculature), inflammation or infection, and increased oxygen demand. 4 Unstable angina occurs from the interplay of these factors, with thrombosis and mechanical obstruction usually dominating. Transient or subtotal obstruction due to a platelet rich "white clot" over a fissured atherosclerotic plaque is considered causal in most episodes of unstable angina. This differs from the fibrin rich "red clot" associated with total coronary occlusion in infarction with ST elevation. In contrast to the Braunwald model, European investigators have advocated a central role for inflammation in unstable angina. 5 6 Increased concentrations of acute inflammatory markers, such as C reactive protein, are more often found in unstable angina than in chronic stable angina. Also, an increased concentration of C reactive protein at admission among patients with unstable angina has been correlated with worse outcomes both in hospital and after one year. 7-9 Several authors have shown varying associations of different subpopulations of T lymphocytes, granulocytes, macrophages, and cytokines with unstable angina. 5 6 Although the role of inflamma-Chest pressure, pain, or both, or angina equivalent Acute coronary syndrome Evaluation of initial electrocardiogram Early reperfusion strategy Evaluation of serum markers Evaluation after 48 hours Management strategy for unstable angina or infarction without ST elevation Non-cardiac cause ST elevation absent ST elevation present Unstable angina Infarction without ST elevation Infarction with ST elevation Unstable angina Non-Q wave infarction Q wave infarction Fig 1 Assessment and classification of suspected acute coronary syndrome
Although increased attention has been paid to sex and racial differences in the management of myo... more Although increased attention has been paid to sex and racial differences in the management of myocardial infarction, it is unknown whether these differences have narrowed over time. methods With the use of data from the National Registry of Myocardial Infarction, we examined sex and racial differences in the treatment of patients who were deemed to be "ideal candidates" for particular treatments and in deaths among 598,911 patients hospitalized with myocardial infarction between 1994 and 2002. results In the unadjusted analysis, sex and racial differences were observed for rates of reperfusion therapy (for white men, white women,
To measure high-sensitivity C-reactive protein (hsCRP) levels and to assess the presence of metab... more To measure high-sensitivity C-reactive protein (hsCRP) levels and to assess the presence of metabolic syndrome (MS) after puerperium in women diagnosed with various hypertensive disorders during pregnancy (HDP), a consecutive, cross-sectional case study at the 15th week after gestation. The sample consisted of 264 women who were admitted to a women's hospital. The diagnoses consisted of transient gestational hypertension (TGH¼43.2%), preeclampsia (PC¼29.5%), chronic hypertension (CH¼20.1%) and PC superimposed on CH (7.2%). A diagnosis of previous hypertension was present in 45.8% of the CH group. The prevalence of MS was 16.7% (CH¼42.1%, TGH¼13.9%, PC¼4.1%, Po0.001). The average hsCRP levels for the CH, TGH and PC groups were 3.79±2.76, 3.55±3.15 and 2.89±3.02, respectively (P¼0.040). The levels of hsCRP were higher in women with MS (4.71±3.15 vs. 3.01±2.88 mg l À1 in those without MS, Po0.001), and they increased when a higher number of MS criteria was fulfilled (Po0.001). The results demonstrated a positive correlation between hsCRP levels and body mass index (BMI) (r¼0.46), waist circumference (r¼0.50) or the number of fulfilled MS criteria (r¼0.56). The results suggest differences in vascular risk that depend on the type of HDP and on the prevalence of MS. The prevalence of MS was notably higher in the CH group, intermediate among the TGH group and much lower in the PC group. Differences in hsCRP levels also depended on the type of HDP (higher levels in CH and TGH patients in comparison with PC patients). Women with MS had higher hsCRP levels compared with women without MS, and the levels correlated with the number of MS criteria fulfilled. This result suggests that subclinical inflammatory status is correlated with the number of MS components present. Furthermore, hsCRP levels increased with increasing BMIs and waist circumferences.
Background The decreased number and senescence of circulating endothelial progenitor cells (EPCs)... more Background The decreased number and senescence of circulating endothelial progenitor cells (EPCs) are considered markers of vascular senescence associated with aging, atherosclerosis, and coronary artery disease (CAD) in elderly. In this study, we explore the role of vascular senescence in premature CAD (PCAD) in a developing country by comparing the numerical status and senescence of circulating EPCs in PCAD patients to controls. Methods EPCs were measured by flow cytometry in 57 patients with angiographically documented CAD, and 57 controls without evidence of CAD, recruited from random patients ≤ 50 years of age at All India Institute of Medical Sciences. EPC senescence as determined by telomere length (EPC-TL) and telomerase activity (EPC-TA) was studied by real time polymerase chain reaction (q PCR) and PCR– ELISA respectively. Result The number of EPCs (0.18% Vs. 0.039% of total WBCs, p < 0.0001), and EPC-TL (3.83 Vs. 5.10 kb/genome, p = 0.009) were markedly lower in PCAD p...
Immediate reperfusion therapy to restore coronary blood flow is recommended for all eligible pati... more Immediate reperfusion therapy to restore coronary blood flow is recommended for all eligible patients with acute myocardial infarction. However, reperfusion therapy is reportedly underutilized among African Americans, even when they are eligible. Reasons for the lack of use have not been fully explored. We examined the demographic, clinical, and treatment data of 10,469 African Americans with acute myocardial infarction who were eligible for reperfusion therapy, enrolled in the National Registry of Myocardial Infarction-2 from June 1994 through March 1998. The mean age was 62.58 (+/-14.4) years, and 44.7% were female. Although eligible, 47% of the African Americans in this study did not receive reperfusion therapy. In a multivariate analysis, the absence of chest pain at presentation (odds ratio [OR] 0.31, 95% CI 0.26-0.37) and initial admission diagnoses other than definite myocardial infarction (OR for receipt of reperfusion &lt;0.12) were the strongest predictors of lack of early reperfusion therapy. Progressive delays in hospital arrival and hospital evaluation predicted a lower likelihood of early reperfusion. Prior stroke (OR 0.63, 95% CI 0.50-0.78), myocardial infarction (OR 0.75, 95% CI 0.65-0.86), and congestive heart failure (OR 0.49, 95% CI 0.40-0.60) were all associated with lack of reperfusion therapy. Almost half of eligible African American patients with myocardial infarction did not receive reperfusion therapy. Potential reasons may include atypical presentation, patient and institutional delay, and underappreciation of myocardial infarction by care providers. Strategies to address these factors may improve the rate of use of reperfusion therapy.
Background Previous studies have suggested that thrombolysis is used less often in blacks than in... more Background Previous studies have suggested that thrombolysis is used less often in blacks than in whites. However, whether the greater prevalence of contraindications or less specific electrocardiographic manifestations of myocardial infarction (MI) account for this difference is unclear. Methods and Results We studied 498 consecutive patients (32% blacks) with first MI. Initial electrocardiograms were analyzed, blinded to race and outcome, for ST-segment deviation and bundle branch block to determine eligibility for thrombolysis. The relation of electrocardiographic eligibility for thrombolysis and actual use of thrombolysis in both races was explored. Among blacks, 45% received thrombolysis compared with 66% of whites (P < .001). A similar proportion of blacks and whites were eligible for thrombolysis (59% and 66% respectively, P = .116), but 62% of electrocardiography-eligible blacks were treated with thrombolysis compared with 75% of whites (P = .016). After accounting for eligibility for electrocardiography and other clinical variables likely to affect the decision to administer thrombolysis by means of conditional logistic regression, blacks were still less likely to receive thrombolysis (relative risk 0.73; 95% confidence interval 0.55 to 0.97). Conclusions We conclude that the differences in thrombolysis administration to blacks and whites are not accounted for by differences in electrocardiographic presentation or other measured variables. Unmeasured differences in clinical presentation of MI may explain racial differences in thrombolysis and merits further study.
BACKGROUND Substance use disorder (SUD) is a major risk factor for homelessness, but the specific... more BACKGROUND Substance use disorder (SUD) is a major risk factor for homelessness, but the specific association of opioid use disorder (OUD) and homelessness in the context of their shared risk factors has not been the focus of prior studies. We used national data from the United States Veterans Health Administration (VHA) to examine the association of OUD and homelessness in the context of shared risk factors. METHODS In this cross-sectional analysis of veterans who received VHA care during Fiscal Year 2012 (N = 5,450,078), we compared the prevalence of OUD and other sociodemographic, and clinical factors among homeless and non-homeless veterans. We estimated the odds ratio for homelessness associated with OUD alone, and after adjusting for other factors through multivariate logistic regression. RESULTS Homeless veterans had substantially higher prevalence of OUD than other VHA patients (7.7 % Vs 0.6 %) and OUD was associated with 13 times higher unadjusted odds of homelessness (Odds Ratio [OR] 13.36, 95 % CI 13.09-13.62), which decreased with adjustment for sociodemographic factors (black race, mean income and age), other SUD, medical, and psychiatric diagnoses (final OR 1.57, 95 % CI 1.53-1.61). Other SUDs (alcohol, cannabis, cocaine, and hallucinogens) showed similar or slightly higher odds of homelessness as OUD in the final model. CONCLUSIONS OUD was strongly associated with homelessness among US veterans although this association was largely but not entirely attenuated by shared sociodemographic and co-morbid risk factors including several other SUDs. Treatment of homeless veterans with OUD should address socio-economic vulnerabilities and other co-morbidities in addition to treatments for OUD.
Mayo Clinic Proceedings: Innovations, Quality & Outcomes, 2021
Objective: To establish the frequency of concordant, discordant, and clinically dominant comorbid... more Objective: To establish the frequency of concordant, discordant, and clinically dominant comorbidities among Medicare beneficiaries with knee osteoarthritis (KOA) and to identify common concordant condition subgroups. Participants and Methods: We used a 5% representative sample of Medicare claims data to identify beneficiaries who received a diagnosis of KOA between January 1, 2012, and September 30, 2015, and matched control group without an osteoarthritis (OA) diagnosis. Frequency of 34 comorbid conditions was categorized as concordant, discordant, or clinically dominant among those with KOA and a matched sample without OA. Comorbid condition phenotypes were characterized by concordant conditions and derived using latent class analysis among those with KOA. Results: The study sample included 203,361 beneficiaries with KOA and 203,361 non-OA controls. The largest difference in frequency between the two cohorts was for co-occurring musculoskeletal conditions (23.7% absolute difference), chronic pain syndromes (6.5%), and rheumatic diseases (4.5%), all with a higher frequency among those with knee OA. Phenotypes were identified as low comorbidity (53% of cohort with classification), hypothyroid/osteoporosis (27%), vascular disease (10%), and high medical and psychological comorbidity (10%). Conclusions: Approximately 47% of Medicare beneficiaries with KOA in this sample had a phenotype characterized by one or more concordant conditions, suggesting that existing clinical pathways that rely on single or dominant providers might be insufficient for a large proportion of older adults with KOA. These findings could guide development of integrated KOA-comorbidity care pathways that are responsive to emerging priorities for personalized, value-based health care.
OBJECTIVE To evaluate measurement and associations between pain severity and opioid craving in in... more OBJECTIVE To evaluate measurement and associations between pain severity and opioid craving in individuals with chronic pain on long-term opioid therapy and/or with opioid use disorder. STUDY DESIGN . Systematic review of randomized controlled trials and observational studies. METHODS . The PubMed, EMBASE, and PsycINFO databases were searched in October 2018. Eligible studies evaluated pain severity and opioid craving in individuals with chronic pain on long-term opioid therapy and/or with opioid use disorder. Two reviewers independently screened eligible studies, assessed risk of bias, and extracted data. RESULTS Of 625 studies, 16 fulfilled the inclusion/exclusion criteria of this review and were grouped by diagnostic focus (i.e., chronic pain on long-term opioid therapy, opioid use disorder, or both). Methods of assessment varied considerably across studies, especially with respect to opioid craving in chronic pain populations. Mean levels of pain were at what is considered moder...
Industrial settings, with their intramural resources and healthcare infrastructure, are ideal for... more Industrial settings, with their intramural resources and healthcare infrastructure, are ideal for initiating preventive activities to increase the awareness and control of cardiovascular diseases (CVD). However, there are no reliable estimates of CVD and risk factor burden, nor of its awareness and treatment status in urban Indian industrial settings. We aimed to evaluate the prevalence of CVD and its risk factors, and to assess the status of awareness and control of CVD risk factors among a large industrial population of northern India. We conducted a cross-sectional survey among all employees aged 20-59 years of a large industry near Delhi (n=2935), to evaluate their cardiovascular risk profile--by employing a structured questionnaire and clinical and biochemical estimations. The presence of coronary heart disease was ascertained by evidence of its treatment, Rose angina questionnaire and Minnesota coded electrocardiograms. The results for 2122 men, in whom complete information was available, are reported here. The mean age was 42 years and 90% of the men were below 50 years of age. The prevalence of major CVD risk factors (95% CI) was: hypertension 30% (28%-32%), diabetes 15% (14%-17%), high serum total cholesterol/HDL ratio (&amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;gt; or = 4.5) 62% (60%-64%) and current smoking 36% (34%-38%). Forty-seven per cent of the respondents had at least two of these risk factors. Another 44% (95% CI: 42%-46%) had pre-hypertension (INC VII criteria) and 37% (95% CI: 35%-39%) had evidence of either impaired fasting glucose or impaired glucose tolerance. Thirty-five per cent (95% CI: 33%-37%) of the individuals were overweight (BMI &amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;gt; or = 25 kg/m2) while 43% (95% CI: 40%-45%) had central obesity (waist circumference &amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;gt;90 cm). The metabolic syndrome was present in 28%-35% of the individuals depending on the diagnostic criteria used. The prevalence of several risk factors and the metabolic syndrome was high with increasing age, BMI and waist circumference. A third of those who had hypertension (31.5%) and diabetes (31%) were aware of their status. Among those aware, adequate control of blood pressure and blood glucose was present in only 38% of those with hypertension and 31% of those with diabetes, respectively. Coronary heart disease was present in 7.3% of the individuals while 0.3% had a history of stroke. This study demonstrates the high prevalence of CVD and its risk factors against a background of poor awareness and control among a comparatively young male population in a north Indian industrial setting.
have no conflict of interest or other disclosures to make. Jane C. Ballantyne was a paid consulta... more have no conflict of interest or other disclosures to make. Jane C. Ballantyne was a paid consultant in opioid litigation.
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