MSD (Mexico)

OBJECTIVE AND IMPORTANCE: The present report explored the effect of electrical stimulation on the inferior thalamic peduncle in a patient with resistant major depression disorder (MDD). CLINICAL PRESENTATION: This report refers to a 49-year-old woman with a history of recurrent episodes of major depression for 20 years (12 episodes and 2 hospitalizations), fulfilling Diagnostic and Statistical Manual of Mental Disorders, 4th edition, revised, criteria for MDD; in addition, the patient met criteria for borderline personality disorder and bulimia. Her longest episode of depression with suicidal ideation began 5 years before surgery. The patient's symptom array responded poorly to different combinations of antidepressants, cognitive therapy, and electroconvulsive therapy, which induced improvement only for short periods of time. Immediately before surgery, her Global Assessment of Functioning score was 20 and her Hamilton Depression Scale score ranged from 33 to 42. The patient was proposed for surgery for MDD. INTERVENTION: The patient had bilateral eight-contact electrodes stereotactically implanted for stimulation of areas at and around the inferior thalamic peduncle. Electrode position was corroborated by unilateral electrical stimulation searching for recruiting responses and regional direct current shifts in the electroencephalogram. Recording electrodes were replaced by tetrapolar electrodes for deep brain stimulation and connected to an internalized stimulation system for continuous bipolar stimulation at 130 Hz, 0.45 milliseconds, 2.5 V. Bimonthly follow-up included psychiatric and neuropsychological evaluations performed over the course of 24 months. After 8 months of ON stimulation, the patient entered a double-blind protocol with stimulators turned OFF. Improvement of depression measured by the Hamilton Depression Scale score was evident after initial placement of electrodes without electrical stimulation. Depression relapsed partially at the end of the first week. Electrical stimulation further improved depression, normalizing depression scores and neuropsychological performance. Patient depression scores ranked between 2 and 8 during 8 months of ON stimulation without antidepressant medication. After stimulation was turned OFF, spontaneous fluctuations in patient symptoms reflected by Hamilton Depression Scale and Global Assessment of Functioning scores were documented; these fluctuations disappeared after stimulation was turned on by Month 20. CONCLUSION: Complicated patients with comorbid conditions are common referrals to psychosurgery services. In this report, we present promising results of electrical stimulation of the inferior thalamic peduncle to treat recurrent unipolar depression in a patient with MDD and borderline personality disorder who responded poorly to treatment.

Pincer ligands have become ubiquitous in organometallic chemistry and homogeneous catalysis. Recently, new varieties of pincer ligands with non-symmetrical backbones and/or ligating groups have been reported and their application in transition metal complexes has been exploited in a variety of catalytic transformations. This non-symmetric approach vastly increases the structural and electronic diversity of this class of ligand. This approach has proven beneficial in a variety of ways, such as the use of a single weakly coordinating moiety, which can dissociate and thereby create a vacant coordination site to increase the catalyst activity. Additionally, this provides further access to chiral ligands and complexes for asymmetric induction. This perspective highlights recent, important examples of non-symmetric pincer ligands, which feature aryl or pyridine backbones, and the synthesis and use of subsequent complexes in catalytic transformations, and discusses the future potential of this type of ligand system.

Upon transferring confluent monolayers of Madin-Darby canine kidney (MDCK) cells from a low-Ca2+ medium (1-5 microM) to one with 1.8 mM Ca2+ (Ca switch), tight junctions (TJs) assemble and seal, and transepithelial electrical resistance (TER) develops in 4-5 h, presumably through exocytotic fusion that incorporates junctional components to the surface membrane. In the present work we test this possibility and observe 1) that the Ca switch raises the cytosolic concentration of this ion; 2) that it also increases the membrane area by 22%; 3) that chloroquine, a drug which prevents exocytosis, blocks both the increase of surface membrane and the sealing of TJs; and 4) that if monolayers are not permanently switched to 1.8 mM Ca2+, but are subject to a 15-min pulse, cytosolic free Ca2+ concentration [( Ca2+]c) transiently increases but returns to low values (14 +/- 11 nM) and TER does not develop. Comparisons of the time course of TJ sealing with levels of [Ca2+]c, as well as the relationship between these parameters and extracellular Ca2+ levels, suggest that this ion may act from the extracellular side or in a narrow intracellular domain in the close vicinity of the plasma membrane.

A nationwide community-based survey for Helicobacter pylori infection had not been done. This study sought to determine the seroprevalence of infection in Mexico, and the socioeconomic and demographic variables that are risk factors for infection. The survey assessed 11,605 sera from a sample population representing persons ages 1-90 years from all socioeconomic and demographic levels and from all regions of Mexico. Antibodies against H. pylori were studied by ELISA using whole cell antigen. Among the findings were that 66% of the population was infected and that age was the strongest risk factor for infection. By age 1 year, 20% were infected and by age 10 years, 50% were infected. Crowding (odds ratio [OR], 1.4), low educational level (OR, 2.42), and low socioeconomic level (OR, 1.43) were risk factors for infection. Prevalence was similar in urban and in rural communities (OR, 0.95). This study is the largest community-based seroepidemiologic study of H. pylori to date.

Several unmet needs have been identified in allergic rhinitis: identification of the time of onset of the pollen season, optimal control of rhinitis and comorbidities, patient stratification, multidisciplinary team for integrated care pathways, innovation in clinical trials and, above all, patient empowerment. MASK-rhinitis (MACVIA-ARIA Sentinel NetworK for allergic rhinitis) is a simple system centred around the patient which was devised to fill many of these gaps using Information and Communications Technology (ICT) tools and a clinical decision support system (CDSS) based on the most widely used guideline in allergic rhinitis and its asthma comorbidity (ARIA 2015 revision). It is one of the implementation systems of Action Plan B3 of the European Innovation Partnership on Active and Healthy Ageing (EIP on AHA). Three tools are used for the electronic monitoring of allergic diseases: a cell phone-based daily visual analogue scale (VAS) assessment of disease control, CARAT (Control of Allergic Rhinitis and Asthma Test) and e-Allergy screening (premedical system of early diagnosis of allergy and asthma based on online tools). These tools are combined with a clinical decision support system (CDSS) and are available in many languages. An e-CRF and an e-learning tool complete MASK. MASK is flexible and other tools can be added. It appears to be an advanced, global and integrated ICT answer for many unmet needs in allergic diseases which will improve policies and standards.

BACKGROUND: The relationship between obesity and risk of complications described during the 2009 influenza pandemic is poorly defined for seasonal influenza and other viral causes of influenza-like illness (ILI). METHODS: An observational cohort of hospitalized and outpatient participants with ILI was conducted in six hospitals in Mexico. Nasopharyngeal swabs were tested for influenza and other common respiratory pathogens. RESULTS: A total of 4778 participants were enrolled in this study and had complete data. A total of 2053 (43.0%) had severe ILI. Seven hundred and seventy-eight (16.3%) were positive for influenza, 2636 (55.2%) were positive for other viral respiratory pathogens, and 1364 (28.5%) had no respiratory virus isolated. Adults with influenza were more likely to be hospitalized if they were underweight (OR: 5.20), obese (OR: 3.18), or morbidly obese (OR: 18.40) compared to normal-weight adults. Obese adults with H1N1 had a sixfold increase in odds of hospitalization over H3N2 and B (obese OR: 8.96 vs 1.35, morbidly obese OR: 35.13 vs 5.58, respectively) compared to normal-weight adults. In adults with coronavirus, metapneumovirus, parainfluenza, and rhinovirus, participants that were underweight (OR: 4.07) and morbidly obese (OR: 2.78) were more likely to be hospitalized as compared to normal-weight adults. All-cause influenza-like illness had a similar but less pronounced association between underweight or morbidly obesity and hospitalization. CONCLUSIONS: There is an increased risk of being hospitalized in adult participants that are underweight or morbidly obese, regardless of their viral pathogen status. Having influenza, however, significantly increases the odds of hospitalization in those who are underweight or morbidly obese.

BACKGROUND AND PURPOSE: Chloroquine (CLQ), an antimalarial drug, has a lysosomotropic effect associated with increased radiationsensibility, which is mediated by the leakage of hydrolytic enzymes, increased apoptosis, autophagy and increased oxidative stress in vitro. In this phase II study, we evaluated the efficacy and safety of radiosensibilization using CLQ concomitant with 30 Gray (Gy) of whole-brain irradiation (WBI) to treat patients with brain metastases (BM) from solid tumors. METHODS: Seventy-three eligible patients were randomized. Thirty-nine patients received WBI (30 Gy in 10 fractions over 2 weeks) concomitant with 150 mg of CLQ for 4 weeks (the CLQ arm). Thirty-four patients received the same schedule of WBI concomitant with a placebo for 4 weeks (the control arm). All the patients were evaluated for quality of life (QoL) using the EORTC Quality of Life (QoL) Questionnaire (EORTC QLQ-C30) (Mexican version) before beginning radiotherapy and one month later. RESULTS: The overall response rate (ORR) was 54% for the CLQ arm and 55% for the control arm (p=0.92). The progression-free survival of brain metastases (BMPFS) rates at one year were 83.9% (95% CI 69.4-98.4) for the CLQ arm and 55.1% (95% CI 33.6-77.6) for the control arm. Treatment with CLQ was independently associated with increased BMPFS (RR 0.31,95% CI [0.1-0.9], p=0.046).The only factor that was independently associated with increased overall survival (OS) was the presence of< 4 brain metastases (RR 1.9, 95% CI [1.12-3.3], p=0.017). WBI was associated with improvements in cognitive and emotional function but also with worsened nausea in both patients groups. No differences in QoL or toxicity were found between the study arms. CONCLUSION: Treatment with CLQ plus WBI improved the control of BM (compared with the control arm) with no increase in toxicity; however, CLQ did not improve the RR or OS. A phase III clinical trial is warranted to confirm these findings.

Sustainable Development Goals and the Paris Agreement stand as milestone diplomatic achievements. However, immense discrepancies between political commitments and governmental action remain. Combined national climate commitments fall far short of the Paris Agreement's 1.5/2°C targets. Similar political ambition gaps persist across various areas of sustainable development. Many therefore argue that actions by nonstate actors, such as businesses and investors, cities and regions, and nongovernmental organizations (NGOs), are crucial. These voices have resonated across the United Nations (UN) system, leading to growing recognition, promotion, and mobilization of such actions in ever greater numbers. This article investigates optimistic arguments about nonstate engagement, namely: (a) “the more the better”; (b) “everybody wins”; (c) “everyone does their part”; and (d) “more brings more.” However, these optimistic arguments may not be matched in practice due to governance risks. The current emphasis on quantifiable impacts may lead to the under‐appreciation of variegated social, economic, and environmental impacts. Claims that everybody stands to benefit may easily be contradicted by outcomes that are not in line with priorities and needs in developing countries. Despite the seeming depoliticization of the role of nonstate actors in implementation, actions may still lead to politically contentious outcomes. Finally, nonstate climate and sustainability actions may not be self‐reinforcing but may heavily depend on supporting mechanisms. The article concludes with governance risk‐reduction strategies that can be combined to maximize nonstate potential in sustainable and climate‐resilient transformations. This article is categorized under: Policy and Governance &gt; Multilevel and Transnational Climate Change Governance

BACKGROUND AND AIMS: ENHANCE was a phase 3 study that evaluated efficacy and safety of seladelpar, a selective peroxisome proliferator-activated receptor-δ (PPAR) agonist, versus placebo in patients with primary biliary cholangitis with inadequate response or intolerance to ursodeoxycholic acid (UDCA). APPROACH AND RESULTS: Patients were randomized 1:1:1 to oral seladelpar 5 mg (n=89), 10 mg (n=89), placebo (n=87) daily (with UDCA, as appropriate). Primary end point was a composite biochemical response [alkaline phosphatase (ALP) < 1.67×upper limit of normal (ULN), ≥15% ALP decrease from baseline, and total bilirubin ≤ ULN] at month 12. Key secondary end points were ALP normalization at month 12 and change in pruritus numerical rating scale (NRS) at month 6 in patients with baseline score ≥4. Aminotransferases were assessed. ENHANCE was terminated early following an erroneous safety signal in a concurrent, NASH trial. While blinded, primary and secondary efficacy end points were amended to month 3. Significantly more patients receiving seladelpar met the primary end point (seladelpar 5 mg: 57.1%, 10 mg: 78.2%) versus placebo (12.5%) ( p < 0.0001). ALP normalization occurred in 5.4% ( p =0.08) and 27.3% ( p < 0.0001) of patients receiving 5 and 10 mg seladelpar, respectively, versus 0% receiving placebo. Seladelpar 10 mg significantly reduced mean pruritus NRS versus placebo [10 mg: -3.14 ( p =0.02); placebo: -1.55]. Alanine aminotransferase decreased significantly with seladelpar versus placebo [5 mg: 23.4% ( p =0.0008); 10 mg: 16.7% ( p =0.03); placebo: 4%]. There were no serious treatment-related adverse events. CONCLUSIONS: Patients with primary biliary cholangitis (PBC) with inadequate response or intolerance to UDCA who were treated with seladelpar 10 mg had significant improvements in liver biochemistry and pruritus. Seladelpar appeared safe and well tolerated.

Although Ghana's abortion law is fairly liberal, unsafe abortion and its consequences remain among the largest contributors to maternal mortality in the country. This study analyzes data from the 2007 Ghana Maternal Health Survey to identify the sociodemographic profiles of women who seek to induce abortion and those who are able to obtain safe abortion services. We hypothesize that women who have access to safe abortion will not be distributed randomly across different social groups in Ghana; rather, access will be influenced by social and economic factors. The results confirm this hypothesis and reveal that the women who are most vulnerable to unsafe abortions are younger, poorer, and lack partner support. The study concludes with policy recommendations for improving access to safe abortion for all subgroups of women, especially the most vulnerable.

OBJECTIVE: The objective of the study was to determine the state of anxiety, depression, and stress present in the society during the development of the 2019 coronavirus pandemic. METHODS: Mixed methods study; a three-section questionnaire was developed which included sociodemographic, perceptions, emotions, and behaviors related to the 2019 coronavirus pandemic, and two emotional assessment psychometric tests. The proportions and confidence intervals of the variables were calculated and compared using the Chi-square test. RESULTS: More than 40% of the subjects presented some degree of anxiety and 41.3% depression; the proportion of stress was < 30%. Of the subjects who experienced anxiety, 18.6% also had moderate-to-very severe depression or stress. CONCLUSION: There are emotional indicators derived from the 2019 coronavirus pandemic in almost half of the study population. The identification and timely treatment of these states could lessen the psychological impact due to 2019 coronavirus.

Ionic liquids are novel, green and efficient compounds for the removal of contaminants from refinery feedstocks.

Chronopharmacologic studies of indomethacin have indicated that time of dosing influences tolerance and effectiveness. A double-blind, crossover chronotherapeutic trial was undertaken in 66 subjects with osteoarthritis of the hip or knee who were treated with an indomethacin sustained-release (ISR) oral preparation once a day. Varying the ISR dosing time resulted in a quadrupling of tolerance and a doubling of analgesic effectiveness. Three dosing times (8 a.m., noon, and 8 p.m.), each tested during 1-wk spans and randomized for sequencing, were compared in each subject. Subjects self-rated pain intensity every other hour before (1 to 2 days) and during each week of treatment. Morning dosing was associated with a 32% incidence of undesirable effects, whereas the comparable rate was 7% for evening dosing. Ninety-five percent of the subjects reported increased drug effectiveness with a change in ISR ingestion time. The time of dosing that resulted in optimal effectiveness differed among subjects. This was explainable by large interindividual differences in the circadian variation of self-rated pain intensity. Evening dosing was most effective in subjects with predominantly nocturnal or morning pain; conversely, morning or noon dosing was most effective in subjects with greater afternoon or evening pain. The differences that resulted from varying the timing of the identical ISR dose in the same subject greatly exceeded those reported for other nonsteroidal anti-inflammatory drugs.

Humanity has triggered the sixth mass extinction episode since the beginning of the Phanerozoic. The complexity of this extinction crisis is centred on the intersection of two complex adaptive systems: human culture and ecosystem functioning, although the significance of this intersection is not properly appreciated. Human beings are part of biodiversity and elements in a global ecosystem. Civilization, and perhaps even the fate of our species, is utterly dependent on that ecosystem's proper functioning, which society is increasingly degrading. The crisis seems rooted in three factors. First, relatively few people globally are aware of its existence. Second, most people who are, and even many scientists, assume incorrectly that the problem is primarily one of the disappearance of species, when it is the existential threat of myriad population extinctions. Third, while concerned scientists know there are many individual and collective steps that must be taken to slow population extinction rates, some are not willing to advocate the one fundamental, necessary, 'simple' cure, that is, reducing the scale of the human enterprise. We argue that compassionate shrinkage of the human population by further encouraging lower birth rates while reducing both inequity and aggregate wasteful consumption-that is, an end to growthmania-will be required. This article is part of the theme issue 'Ecological complexity and the biosphere: the next 30 years'.

BACKGROUND: HIV disproportionally affects key populations including men who have sex with men (MSM). HIV prevalence among MSM varies from 17% in Brazil and Mexico to 13% in Peru, whereas it is below 0.5% for the general population in each country. Pre-exposure prophylaxis (PrEP) with emtricitabine/tenofovir is being implemented in the context of combination HIV prevention. Reports on willingness to use PrEP among MSM have started to emerge over the last few years. Previously reported factors associated with willingness to use PrEP include awareness, higher sexual risk behavior, and previous sexually transmitted infection. OBJECTIVE: This study aimed to evaluate the factors associated with willingness to use daily oral PrEP among MSM in 3 Latin American, middle-income countries (Brazil, Mexico, and Peru). METHODS: This Web-based, cross-sectional survey was advertised in 2 gay social network apps (Grindr and Hornet) used by MSM to find sexual partners and on Facebook during 2 months in 2018. Inclusion criteria were being 18 years or older, cisgender men, and HIV-negative by self-report. Eligible individuals answered questions on demographics, behavior, and PrEP (awareness, willingness to use, barriers, and facilitators). Multivariable logistic regression modeling was performed to assess the factors associated with willingness to use daily oral PrEP in each country. RESULTS: From a total sample of 43,687 individuals, 44.54% of MSM (19,457/43,687) were eligible and completed the Web-based survey-Brazil: 58.42% (11,367/19,457), Mexico: 30.50% (5934/19,457), and Peru: 11.08% (2156/19,457); median age was 28 years (interquartile range: 24-34), and almost half lived in large urban cities. Most participants were recruited on Grindr (69%, 13,349/19,457). Almost 20% (3862/19,352) had never tested for HIV, and condomless receptive anal sex was reported by 40% (7755/19,326) in the previous 6 months. Whereas 67.51% (13,110/19,376) would be eligible for PrEP, only 9.80% (1858/18,959) of participants had high HIV risk perception. PrEP awareness was reported by 64.92% (12,592/19,396); this was lower in Peru (46.60%, 1002/2156). Overall, willingness to use PrEP was reported by 64.23% (12,498/19,457); it was highest in Mexico (70%, 4158/5934) and lowest in Peru (58%, 1241/2156). In multivariate regression models adjusted for age, schooling, and income in each country, willingness to use PrEP was positively associated with PrEP awareness and PrEP facilitators (eg, free PrEP and HIV testing) and negatively associated with behavioral (eg, concerned by daily pill regimen) and belief barriers (eg, sexual partners may expect condomless sex). CONCLUSIONS: In this first cross-country, Web-based survey in Latin America, willingness to use PrEP was found to be high and directly related to PrEP awareness. Interventions to increase awareness and PrEP knowledge about safety and efficacy are crucial to increase PrEP demand. This study provides important information to support the implementation of PrEP in Brazil, Mexico, and Peru.

Micromodels employing a two‐dimensional representation of pore space were used to observe directly (via microscope) water imbibition into a matrix and matrix‐fracture interactions between wetting and nonwetting fluids. Within a single field of view, some pores are responsible for the uptake of water, whereas immediately adjacent pores expel nonwetting phase into the fracture. When water flow through fractures is relatively slow and fluid transfer from the fracture is relatively rapid, imbibition is microscopically cocurrent and micromodel observations teach that uptake of the wetting phase by the matrix correlates directly with the volume of water injected. This mode of transfer is coined a filling fracture. On the other hand, when fractures fill with water quickly relative to the rate of matrix‐fracture transfer, the mass of water imbibed scales with the square root of time. Here imbibition is found to be countercurrent at the pore level. In the countercurrent mode, significant channeling of the nonwetting phase through the continuous wetting phase is observed that reduces the efficiency of water infiltration. Overall, it is found that the rate of water uptake from a fracture into an unsaturated matrix and the pore‐level pattern of water infiltration depend critically on the rate of water infiltration through fractures.

The efficacy of bicozamycin, a poorly absorbable antibiotic, in the treatment of acute diarrhea was assessed in a prospective, double-blind study of 140 adults from the United States visiting Guadalajara, Mexico. Patients randomly received bicozamycin (500 mg orally four times daily) or placebo for 3 days. The mean duration of illness was shorter in the bicozamycin than the placebo treatment groups for patients with diarrhea due to Shigella (37 versus 96 hours; p = 0.01), toxigenic Escherichia coli (31 versus 60 hours; p = 0.003), and unknown pathogens (18 versus 41 hours; p = 0.02). Cramps were significantly relieved by bicozamycin in all patients. Treatment failed in significantly fewer patients treated with bicozamycin than those treated with placebo when diarrhea was associated with Shigella, Salmonella or toxigenic E. coli. Bicozamycin was well tolerated and appears to be effective therapy for acute travelers' diarrhea of diverse causes. These data show the value of an antibiotic in the therapy of toxigenic E. coli infection and indicate a need to reevaluate the clinical dictum that nonabsorbable antibiotics are ineffective against invasive enteropathogens.

OBJECTIVES: The most common complication of herpes zoster (HZ) is postherpetic neuralgia (PHN), a persistent pain that can substantially affect quality of life (QoL). This analysis aimed to evaluate predictors of PHN in HZ patients. METHODS: A pooled analysis of prospective cohort studies of HZ patients aged ≥ 50 years from North America (Canada), Latin America (Brazil, Mexico, and Argentina), and Asia (Taiwan, South Korea, and Thailand) was performed. Patients within 14 days of rash onset were included. The incidence of PHN was defined as a worst pain score of ≥ 3, persisting/appearing at >90 days after rash onset. Socio-demographics, HZ disease characteristics, treatment, pain-related interference with activities of daily living, and health-related QoL were assessed. RESULTS: Of 702 patients with HZ, 148 (21.1%) developed PHN. Similar risks of PHN were observed across geographic regions. On multivariate analysis, older age, greater severity of pain at rash onset, employment status, walking problems at enrollment, and pain interference affecting social relationships were significantly associated with the development of PHN. CONCLUSIONS: In addition to older age and severe acute pain, this study suggests that impaired physical and social functioning from acute zoster pain may play a role in the development of PHN in this prospective cohort study of HZ patients from North and Latin America and Asia.

In mid-June 2021, B.1.671.2 (Delta) became the predominant variant of SARS-CoV-2, the virus that causes COVID-19, circulating in the United States. As of July 2021, the Delta variant was responsible for nearly all new SARS-CoV-2 infections in the United States.* The Delta variant is more transmissible than previously circulating SARS-CoV-2 variants (1); however, whether it causes more severe disease in adults has been uncertain. Data from the CDC COVID-19-Associated Hospitalization Surveillance Network (COVID-NET), a population-based surveillance system for COVID-19-associated hospitalizations, were used to examine trends in severe outcomes in adults aged ≥18 years hospitalized with laboratory-confirmed COVID-19 during periods before (January-June 2021) and during (July-August 2021) Delta variant predominance. COVID-19-associated hospitalization rates among all adults declined during January-June 2021 (pre-Delta period), before increasing during July-August 2021 (Delta period). Among sampled nonpregnant hospitalized COVID-19 patients with completed medical record abstraction and a discharge disposition during the pre-Delta period, the proportion of patients who were admitted to an intensive care unit (ICU), received invasive mechanical ventilation (IMV), or died while hospitalized did not significantly change from the pre-Delta period to the Delta period. The proportion of hospitalized COVID-19 patients who were aged 18-49 years significantly increased, from 24.7% (95% confidence interval [CI] = 23.2%-26.3%) of all hospitalizations in the pre-Delta period, to 35.8% (95% CI = 32.1%-39.5%, p<0.01) during the Delta period. When examined by vaccination status, 71.8% of COVID-19-associated hospitalizations in the Delta period were in unvaccinated adults. Adults aged 18-49 years accounted for 43.6% (95% CI = 39.1%-48.2%) of all hospitalizations among unvaccinated adults during the Delta period. No difference was observed in ICU admission, receipt of IMV, or in-hospital death among nonpregnant hospitalized adults between the pre-Delta and Delta periods. However, the proportion of unvaccinated adults aged 18-49 years hospitalized with COVID-19 has increased as the Delta variant has become more predominant. Lower vaccination coverage in this age group likely contributed to the increase in hospitalized patients during the Delta period. COVID-19 vaccination is critical for all eligible adults, including those aged <50 years who have relatively low vaccination rates compared with older adults.

BACKGROUND: Recent clinical trial results have suggested that programmed cell death ligand 1 (PD-L1) expression measured by immunohistochemistry may predict response to anti-programmed cell death 1 (PD-1) therapy. Results on the association between PD-L1 expression and survival among patients with advanced non-small cell lung cancer (NSCLC) treated with chemotherapy are inconsistent. MATERIAL AND METHODS: We evaluated the relationship between PD-L1 expression and overall survival (OS) among 204 patients with advanced NSCLC treated at Aarhus University Hospital, Aarhus, Denmark, from 2007 to 2012. PD-L1 expression was measured using a prototype immunohistochemistry assay with the anti-PD-L1 22C3 antibody (Merck). PD-L1 strong positivity and weak positivity were defined to be traceable to the clinical trial version of the assay. RESULTS: Twenty-five percent of patients had PD-L1 strong-positive tumors, and 50% had PD-L1 weak-positive tumors. No statistically significant association was found between PD-L1 expression and survival; adjusted hazard ratio of 1.34 (95% confidence interval, 0.88-2.03; median OS, 9.0 months) for the PD-L1 strong-positive group and 1.07 (0.74-1.55; median OS, 9.8 months) for the PD-L1 weak-positive group compared with the PD-L1-negative group (median OS, 7.5 months). No association was seen between PD-L1 expression and OS when PD-L1 expression levels were stratified by median or tertiles. CONCLUSIONS: In concordance with previous studies, we found PD-L1 measured by immunohistochemistry to be frequently expressed in patients with advanced NSCLC. However, PD-L1 expression is not a strong prognostic marker in patients with advanced NSCLC treated with chemotherapy.