Stiff Person Syndrome: A Rare Presentation of a Rare Disorder

Stiff Person Syndrome (SPS) is a rare autoimmune disease that is caused by the lack of inhibition to excitatory neurotransmitters in the central nervous system (CNS) which then leads to inappropriate and excessive motor unit firing causing stiffness, a characteristic feature of the disease. SPS has an incidence of one case in a million and occurs in the middle-aged population with a female predominance. SPS mostly occurs in the background of autoimmune disorders like type 1 diabetes, thyroid disorders, pernicious anemia, and less often, vitiligo. The pathophysiology is not completely understood; however, there is a strong correlation between high titers of anti-glutamic acid decarboxylase antibody (anti-GAD Ab) and the disease. We present an 82 years old man who complained of stiffness and weakness, mostly on the right side, with multiple negative workups. He was then eventually diagnosed with SPS based on the characteristic history and physical examination findings and being positive for anti-GAD Ab. He was treated with a combination of baclofen, gabapentin, intravenous immunoglobulins (IVIG), and physical therapy. We review the case presentation which was unusual in terms of age and sex, and treatment options in the context of a severe presentation of this disabling disease

Efficacy and Safety of Bempedoic Acid as a Treatment Option for Hyperlipidemia: A Systematic Review

Introduction: Bempedoic acid (BA) is an inhibitor of ATP-citrate lyase (ACL) and is used in the treatment of hyperlipidemia by inhibiting cholesterol synthesis. Randomized clinical trials (RCTs) have shown the efficacy of BA in lowering LDL-C levels and it is currently approved as a treatment option for patients with hyperlipidemia to achieve target LDL-C levels. We conducted a systematic review to further elucidate the efficacy and safety profile of BA in patients with hyperlipidemia. Methods: We searched the electronic database Medline, Embase, and Cochrane Library for RCTs between 2013 and 2023. We used keywords (“Bempedoic Acid”) AND (“Hypercholesterolemia”) AND (“Lipid Lowering”) AND (Randomized Controlled Trials”) AND (“Humans”). Pairs of reviewers also manually searched for RCTs to identify studies comparing the efficacy and safety profile of BA either alone or in combination with other lipid-lowering therapies. Results: We identified 11 RCTs in our systematic review, and it showed that the addition of BA either alone or in addition to other lipid-lowering therapies (statins and ezetimibe) resulted in the lowering of LDL-C levels. In addition, BA also led to a reduction in total cholesterol (TC), non-high-density lipoprotein cholesterol (non-HDL-C), apolipoprotein B (ApoB), and high sensitivity C reactive protein (hs-CRP) levels. For the safety profile of BA, results from the studies show that there is no difference in the incidence of adverse events between the two treatment arms. However, a few studies found that the use of BA was associated with a higher incidence of gout as compared to standard lipid-lowering therapies. Conclusion: The use of BA in patients with hyperlipidemia leads to a decrease in the level of LDL-C both alone and in addition to other lipid-lowering therapies like statins and ezetimibe. The addition of BA also led to a reduction in TC, non-HDL-C, ApoB, and hs-CRP levels which resulted in reduction in cardiovascular events. The safety data shows that BA is largely safe to use and the adverse events were similar in both groups, however, the rate of gout was higher in patients receiving BA. Larger clinical trials with longer follow-up duration are needed to adequately assess its effect on cardiovascular mortality and the safety profile of BA

Is Routine Measurement of Post-operative Hemoglobin and Electrolytes Necessary in Every Patient After Transurethral Resection of the Prostate?

Objective: To evaluate the importance of post-operative hemoglobin and electrolyte monitoring after transurethral resection of the prostate (TURP) and establish the parameters to be considered for monitoring.Materials and Methods:Data of patients who underwent TURP between 2007 and 2017 were reviewed. Data regarding prostate size, irrigation fluid volume, resection time, pre- and post-operative electrolytes, hemoglobin levels taken within 48 hours before and after surgery, and blood transfusion information were collected. In order to establish parameters for post-operative laboratory monitoring, we categorized prostate size, resection time, and irrigation fluid into groups i.e. (80 g), (60 min) and (40 L) respectively.Results:A total of 1.000 patients were included. The median age was 66 years with the minimum of 46 years and maximum of 98 years. The median prostate size was 54.26 g. Among all pre- and post-operative laboratory parameters, only hemoglobin and sodium showed a significant change, which were analyzed further. Drop in hemoglobin was significantly associated with increasing prostate size and volume of irrigation fluid. Patients with a prostate size of >80 g had 27.3 times higher chance of significant (>2 g) drop in hemoglobin while 5.1 times higher when irrigation volume exceeded 40 liters. Low levels of sodium were strongly associated with prostate size, irrigation fluid volume, and resection time. However, all these factors become insignificant (p≥0.05) for their effect on low sodium, when these variables were adjusted with each other. Blood transfusion was performed in 27 patients. All these patients belonged to a group of patients with prostate size of more than 80 g with high resection time and irrigation fluid volume. Three patients had TUR syndrome. Post-operative hemoglobin and electrolytes monitoring contributed to a change in the management of only 14% of patients.Conclusion:Routine post-operative hemoglobin and electrolyte measurement is not required in every patient undergoing TURP. Use of risk stratification approach will help us to decide which patient needs post-operative lab testing

Global, regional, and national burden of disorders affecting the nervous system, 1990–2021: a systematic analysis for the Global Burden of Disease Study 2021

BACKGROUND: Disorders affecting the nervous system are diverse and include neurodevelopmental disorders, late-life neurodegeneration, and newly emergent conditions, such as cognitive impairment following COVID-19. Previous publications from the Global Burden of Disease, Injuries, and Risk Factor Study estimated the burden of 15 neurological conditions in 2015 and 2016, but these analyses did not include neurodevelopmental disorders, as defined by the International Classification of Diseases (ICD)-11, or a subset of cases of congenital, neonatal, and infectious conditions that cause neurological damage. Here, we estimate nervous system health loss caused by 37 unique conditions and their associated risk factors globally, regionally, and nationally from 1990 to 2021. METHODS: We estimated mortality, prevalence, years lived with disability (YLDs), years of life lost (YLLs), and disability-adjusted life-years (DALYs), with corresponding 95% uncertainty intervals (UIs), by age and sex in 204 countries and territories, from 1990 to 2021. We included morbidity and deaths due to neurological conditions, for which health loss is directly due to damage to the CNS or peripheral nervous system. We also isolated neurological health loss from conditions for which nervous system morbidity is a consequence, but not the primary feature, including a subset of congenital conditions (ie, chromosomal anomalies and congenital birth defects), neonatal conditions (ie, jaundice, preterm birth, and sepsis), infectious diseases (ie, COVID-19, cystic echinococcosis, malaria, syphilis, and Zika virus disease), and diabetic neuropathy. By conducting a sequela-level analysis of the health outcomes for these conditions, only cases where nervous system damage occurred were included, and YLDs were recalculated to isolate the non-fatal burden directly attributable to nervous system health loss. A comorbidity correction was used to calculate total prevalence of all conditions that affect the nervous system combined. FINDINGS: Globally, the 37 conditions affecting the nervous system were collectively ranked as the leading group cause of DALYs in 2021 (443 million, 95% UI 378–521), affecting 3·40 billion (3·20–3·62) individuals (43·1%, 40·5–45·9 of the global population); global DALY counts attributed to these conditions increased by 18·2% (8·7–26·7) between 1990 and 2021. Age-standardised rates of deaths per 100 000 people attributed to these conditions decreased from 1990 to 2021 by 33·6% (27·6–38·8), and age-standardised rates of DALYs attributed to these conditions decreased by 27·0% (21·5–32·4). Age-standardised prevalence was almost stable, with a change of 1·5% (0·7–2·4). The ten conditions with the highest age-standardised DALYs in 2021 were stroke, neonatal encephalopathy, migraine, Alzheimer's disease and other dementias, diabetic neuropathy, meningitis, epilepsy, neurological complications due to preterm birth, autism spectrum disorder, and nervous system cancer. INTERPRETATION: As the leading cause of overall disease burden in the world, with increasing global DALY counts, effective prevention, treatment, and rehabilitation strategies for disorders affecting the nervous system are needed

Effects of hospital facilities on patient outcomes after cancer surgery: an international, prospective, observational study

Background Early death after cancer surgery is higher in low-income and middle-income countries (LMICs) compared with in high-income countries, yet the impact of facility characteristics on early postoperative outcomes is unknown. The aim of this study was to examine the association between hospital infrastructure, resource availability, and processes on early outcomes after cancer surgery worldwide.Methods A multimethods analysis was performed as part of the GlobalSurg 3 study-a multicentre, international, prospective cohort study of patients who had surgery for breast, colorectal, or gastric cancer. The primary outcomes were 30-day mortality and 30-day major complication rates. Potentially beneficial hospital facilities were identified by variable selection to select those associated with 30-day mortality. Adjusted outcomes were determined using generalised estimating equations to account for patient characteristics and country-income group, with population stratification by hospital.Findings Between April 1, 2018, and April 23, 2019, facility-level data were collected for 9685 patients across 238 hospitals in 66 countries (91 hospitals in 20 high-income countries; 57 hospitals in 19 upper-middle-income countries; and 90 hospitals in 27 low-income to lower-middle-income countries). The availability of five hospital facilities was inversely associated with mortality: ultrasound, CT scanner, critical care unit, opioid analgesia, and oncologist. After adjustment for case-mix and country income group, hospitals with three or fewer of these facilities (62 hospitals, 1294 patients) had higher mortality compared with those with four or five (adjusted odds ratio [OR] 3.85 [95% CI 2.58-5.75]; p<0.0001), with excess mortality predominantly explained by a limited capacity to rescue following the development of major complications (63.0% vs 82.7%; OR 0.35 [0.23-0.53]; p<0.0001). Across LMICs, improvements in hospital facilities would prevent one to three deaths for every 100 patients undergoing surgery for cancer.Interpretation Hospitals with higher levels of infrastructure and resources have better outcomes after cancer surgery, independent of country income. Without urgent strengthening of hospital infrastructure and resources, the reductions in cancer-associated mortality associated with improved access will not be realised

Global, regional, and national prevalence and mortality burden of sickle cell disease, 2000–2021 : a systematic analysis from the Global Burden of Disease Study 2021

This online publication has been corrected. The corrected version first appeared at thelancet.com on July 31, 2023BACKGROUND : Previous global analyses, with known underdiagnosis and single cause per death attribution systems, provide only a small insight into the suspected high population health effect of sickle cell disease. Completed as part of the Global Burden of Diseases, Injuries, and Risk Factors Study (GBD) 2021, this study delivers a comprehensive global assessment of prevalence of sickle cell disease and mortality burden by age and sex for 204 countries and territories from 2000 to 2021. METHODS : We estimated cause-specific sickle cell disease mortality using standardised GBD approaches, in which each death is assigned to a single underlying cause, to estimate mortality rates from the International Classification of Diseases (ICD)-coded vital registration, surveillance, and verbal autopsy data. In parallel, our goal was to estimate a more accurate account of sickle cell disease health burden using four types of epidemiological data on sickle cell disease: birth incidence, age-specific prevalence, with-condition mortality (total deaths), and excess mortality (excess deaths). Systematic reviews, supplemented with ICD-coded hospital discharge and insurance claims data, informed this modelling approach. We employed DisMod-MR 2.1 to triangulate between these measures—borrowing strength from predictive covariates and across age, time, and geography—and generated internally consistent estimates of incidence, prevalence, and mortality for three distinct genotypes of sickle cell disease: homozygous sickle cell disease and severe sickle cell β-thalassaemia, sickle-haemoglobin C disease, and mild sickle cell β-thalassaemia. Summing the three models yielded final estimates of incidence at birth, prevalence by age and sex, and total sickle cell disease mortality, the latter of which was compared directly against cause-specific mortality estimates to evaluate differences in mortality burden assessment and implications for the Sustainable Development Goals (SDGs). FINDINGS : Between 2000 and 2021, national incidence rates of sickle cell disease were relatively stable, but total births of babies with sickle cell disease increased globally by 13·7% (95% uncertainty interval 11·1–16·5), to 515 000 (425 000–614 000), primarily due to population growth in the Caribbean and western and central sub-Saharan Africa. The number of people living with sickle cell disease globally increased by 41·4% (38·3–44·9), from 5·46 million (4·62–6·45) in 2000 to 7·74 million (6·51–9·2) in 2021. We estimated 34 400 (25 000–45 200) cause-specific all-age deaths globally in 2021, but total sickle cell disease mortality burden was nearly 11-times higher at 376 000 (303 000–467 000). In children younger than 5 years, there were 81 100 (58 800–108 000) deaths, ranking total sickle cell disease mortality as 12th (compared to 40th for cause-specific sickle cell disease mortality) across all causes estimated by the GBD in 2021. INTERPRETATION : Our findings show a strikingly high contribution of sickle cell disease to all-cause mortality that is not apparent when each death is assigned to only a single cause. Sickle cell disease mortality burden is highest in children, especially in countries with the greatest under-5 mortality rates. Without comprehensive strategies to address morbidity and mortality associated with sickle cell disease, attainment of SDG 3.1, 3.2, and 3.4 is uncertain. Widespread data gaps and correspondingly high uncertainty in the estimates highlight the urgent need for routine and sustained surveillance efforts, further research to assess the contribution of conditions associated with sickle cell disease, and widespread deployment of evidence-based prevention and treatment for those with sickle cell disease.Bill & Melinda Gates Foundation.www.thelancet.com/haematologyam2024School of Health Systems and Public Health (SHSPH)SDG-03:Good heatlh and well-bein

Global, regional, and national burden of disorders affecting the nervous system, 1990–2021: a systematic analysis for the Global Burden of Disease Study 2021

BackgroundDisorders affecting the nervous system are diverse and include neurodevelopmental disorders, late-life neurodegeneration, and newly emergent conditions, such as cognitive impairment following COVID-19. Previous publications from the Global Burden of Disease, Injuries, and Risk Factor Study estimated the burden of 15 neurological conditions in 2015 and 2016, but these analyses did not include neurodevelopmental disorders, as defined by the International Classification of Diseases (ICD)-11, or a subset of cases of congenital, neonatal, and infectious conditions that cause neurological damage. Here, we estimate nervous system health loss caused by 37 unique conditions and their associated risk factors globally, regionally, and nationally from 1990 to 2021.MethodsWe estimated mortality, prevalence, years lived with disability (YLDs), years of life lost (YLLs), and disability-adjusted life-years (DALYs), with corresponding 95% uncertainty intervals (UIs), by age and sex in 204 countries and territories, from 1990 to 2021. We included morbidity and deaths due to neurological conditions, for which health loss is directly due to damage to the CNS or peripheral nervous system. We also isolated neurological health loss from conditions for which nervous system morbidity is a consequence, but not the primary feature, including a subset of congenital conditions (ie, chromosomal anomalies and congenital birth defects), neonatal conditions (ie, jaundice, preterm birth, and sepsis), infectious diseases (ie, COVID-19, cystic echinococcosis, malaria, syphilis, and Zika virus disease), and diabetic neuropathy. By conducting a sequela-level analysis of the health outcomes for these conditions, only cases where nervous system damage occurred were included, and YLDs were recalculated to isolate the non-fatal burden directly attributable to nervous system health loss. A comorbidity correction was used to calculate total prevalence of all conditions that affect the nervous system combined.FindingsGlobally, the 37 conditions affecting the nervous system were collectively ranked as the leading group cause of DALYs in 2021 (443 million, 95% UI 378–521), affecting 3·40 billion (3·20–3·62) individuals (43·1%, 40·5–45·9 of the global population); global DALY counts attributed to these conditions increased by 18·2% (8·7–26·7) between 1990 and 2021. Age-standardised rates of deaths per 100 000 people attributed to these conditions decreased from 1990 to 2021 by 33·6% (27·6–38·8), and age-standardised rates of DALYs attributed to these conditions decreased by 27·0% (21·5–32·4). Age-standardised prevalence was almost stable, with a change of 1·5% (0·7–2·4). The ten conditions with the highest age-standardised DALYs in 2021 were stroke, neonatal encephalopathy, migraine, Alzheimer's disease and other dementias, diabetic neuropathy, meningitis, epilepsy, neurological complications due to preterm birth, autism spectrum disorder, and nervous system cancer.InterpretationAs the leading cause of overall disease burden in the world, with increasing global DALY counts, effective prevention, treatment, and rehabilitation strategies for disorders affecting the nervous system are needed