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Nevin Manimala Statistics

When does the placebo effect have an impact on network meta-analysis results?

BMJ Evid Based Med. 2023 Jun 29:bmjebm-2022-112197. doi: 10.1136/bmjebm-2022-112197. Online ahead of print.

ABSTRACT

The placebo effect is the ‘effect of the simulation of treatment that occurs due to a participant’s belief or expectation that a treatment is effective’. Although the effect might be of little importance for some conditions, it can have a great role in others, mostly when the evaluated symptoms are subjective. Several characteristics that include informed consent, number of arms in a study, the occurrence of adverse events and quality of blinding may influence response to placebo and possibly bias the results of randomised controlled trials. Such a bias is inherited in systematic reviews of evidence and their quantitative components, pairwise meta-analysis (when two treatments are compared) and network meta-analysis (when more than two treatments are compared). In this paper, we aim to provide red flags as to when a placebo effect is likely to bias pairwise and network meta-analysis treatment effects. The classic paradigm has been that placebo-controlled randomised trials are focused on estimating the treatment effect. However, the magnitude of placebo effect itself may also in some instances be of interest and has also lately received attention. We use component network meta-analysis to estimate placebo effects. We apply these methods to a published network meta-analysis, examining the relative effectiveness of four psychotherapies and four control treatments for depression in 123 studies.

PMID:37385716 | DOI:10.1136/bmjebm-2022-112197

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Perifocal Edema in Patients with Meningioma is Associated with Impaired Whole-Brain Connectivity as Detected by Resting-State fMRI

AJNR Am J Neuroradiol. 2023 Jun 29. doi: 10.3174/ajnr.A7915. Online ahead of print.

ABSTRACT

BACKGROUND AND PURPOSE: Meningiomas are intracranial tumors that usually carry a benign prognosis. Some meningiomas cause perifocal edema. Resting-state fMRI can be used to assess whole-brain functional connectivity, which can serve as a marker for disease severity. Here, we investigated whether the presence of perifocal edema in preoperative patients with meningiomas leads to impaired functional connectivity and if these changes are associated with cognitive function.

MATERIALS AND METHODS: Patients with suspected meningiomas were prospectively included, and resting-state fMRI scans were obtained. Impairment of functional connectivity was quantified on a whole-brain level using our recently published resting-state fMRI-based marker, called the dysconnectivity index. Using uni- and multivariate regression models, we investigated the association of the dysconnectivity index with edema and tumor volume as well as cognitive test scores.

RESULTS: Twenty-nine patients were included. In a multivariate regression analysis, there was a highly significant association of dysconnectivity index values and edema volume in the total sample and in a subsample of 14 patients with edema, when accounting for potential confounders like age and temporal SNR. There was no statistically significant association with tumor volume. Better neurocognitive performance was strongly associated with lower dysconnectivity index values.

CONCLUSIONS: Resting-state fMRI showed a significant association between impaired functional connectivity and perifocal edema, but not tumor volume, in patients with meningiomas. We demonstrated that better neurocognitive function was associated with less impairment of functional connectivity. This result shows that our resting-state fMRI marker indicates a detrimental influence of peritumoral brain edema on global functional connectivity in patients with meningiomas.

PMID:37385680 | DOI:10.3174/ajnr.A7915

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Anakinra versus etoposide-based therapy added to high-dose steroids for the treatment of secondary hemophagocytic lymphohistiocytosis

Eur J Haematol. 2023 Jun 29. doi: 10.1111/ejh.14030. Online ahead of print.

ABSTRACT

OBJECTIVE: Hemophagocytic lymphohistiocytosis (HLH) is a rare life-threatening, hyperinflammatory syndrome usually treated with high-dose steroids (HDS), often complemented with adjunct therapies, such as etoposide (HLH-94 protocol). Anakinra has been reported to effectively treat HLH; however, has not been comparatively examined with etoposide-based therapies. We sought to evaluate the effectiveness and durability of these treatment approaches.

METHODS: We performed a retrospective analysis of all adult patients diagnosed with secondary HLH between January 2011 and November 2022 who received anakinra and HDS, the HLH-94 protocol, HDS alone, or supportive care.

RESULTS: Thirty adult patients with secondary HLH were included. Cumulative incidence (CI) of response at 30 days was 83.3%, 60%, and 36.4% for patients treated with anakinra, the HLH-94 protocol, and HDS alone, respectively. CI of relapse at 1 year was 50%, 33.3%, and 0% with the HLH-94 protocol, HDS, and anakinra and HDS, respectively. Overall survival at 1 year was higher with anakinra and HDS compared to the HLH-94 protocol, yet was not statistically significant (77.8% vs. 33.3%; hazard ratio: 0.29; p = .25).

CONCLUSION: Treatment with anakinra and HDS in adults with secondary HLH was associated with higher response rates with longer survival compared with alternative therapies and should be further investigated in this setting.

PMID:37385631 | DOI:10.1111/ejh.14030

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Value for combination of T1WI star-VIBE with TWIST-VIBE dynamic contrast-enhanced MRI in distinguishing lung nodules

Zhong Nan Da Xue Xue Bao Yi Xue Ban. 2023 Apr 28;48(4):581-593. doi: 10.11817/j.issn.1672-7347.2023.220588.

ABSTRACT

OBJECTIVES: With the increasing detection rate of lung nodules, the qualitative problem of lung nodules has become one of the key clinical issues. This study aims to evaluate the value of combining dynamic contrast-enhanced (DCE) MRI based on time-resolved imaging with interleaved stochastic trajectories-volume interpolated breath hold examination (TWIST-VIBE) with T1 weighted free-breathing star-volumetric interpolated breath hold examination (T1WI star-VIBE) in identifying benign and malignant lung nodules.

METHODS: We retrospectively analyzed 79 adults with undetermined lung nodules before the operation. All nodules of patients included were classified into malignant nodules (n=58) and benign nodules (n=26) based on final diagnosis. The unenhanced T1WI-VIBE, the contrast-enhanced T1WI star-VIBE, and the DCE curve based on TWIST-VIBE were performed. The corresponding qualitative [wash-in time, wash-out time, time to peak (TTP), arrival time (AT), positive enhancement integral (PEI)] and quantitative parameters [volume transfer constant (Ktrans), interstitium-to-plasma rate constant (Kep), and fractional extracellular space volume (Ve)] were evaluated. Besides, the diagnostic efficacy (sensitivity and specificity) of enhanced CT and MRI were compared.

RESULTS: There were significant differences in unenhanced T1WI-VIBE hypo-intensity, and type of A, B, C DCE curve type between benign and malignant lung nodules (all P<0.001). Pulmonary malignant nodules had a shorter wash-out time than benign nodules (P=0.001), and the differences of the remaining parameters were not statistically significant (all P>0.05). After T1WI star-VIBE contrast-enhanced MRI, the image quality was further improved. Compared with enhanced CT scan, the sensitivity (82.76% vs 80.50%) and the specificity (69.23% vs 57.10%) based on MRI were higher than that of CT (both P<0.001).

CONCLUSIONS: T1WI star-VIBE and dynamic contrast-enhanced MRI based on TWIST-VIBE were helpful to improve the image resolution and provide more information for clinical differentiation between benign and malignant lung nodules.

PMID:37385621 | DOI:10.11817/j.issn.1672-7347.2023.220588

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Clinical and genetic diagnosis for 26 paitents with hereditary spherocytosis

Zhong Nan Da Xue Xue Bao Yi Xue Ban. 2023 Apr 28;48(4):565-574. doi: 10.11817/j.issn.1672-7347.2023.220390.

ABSTRACT

OBJECTIVES: Hereditary spherocytosis (HS) is the most common hereditary defect of the red cell membrane, mainly characterized by anemia, jaundice, and splenomegaly. Due to the atypical clinical manifestations and negative family history of some patients, as well as the low sensitivity and specificity of traditional laboratory examinations, it is easy for it to escape diagnosis or be misdiagnosed. At present, it has been confirmed that the mutation of ANK1, SPTB, SPTA1, SLC4A1 and EPB42 genes can cause the deletion of their corresponding coding proteins, and thus lead to the defect of erythrocyte membrane. This study aims to analyze the feasibility and clinical application value of HS gene diagnosis.

METHODS: Data of 26 patients from Hunan, China with HS admitted to the Department of Hematology, Second Xiangya Hospital of Central South University from January 2018 to September 2021 were retrospectively collected, and their clinical manifestations and results of laboratory examinations were analyzed. Next-generation sequencing (NGS) combined with Sanger sequencing were applied. The mutation of HS pathogenic gene and the variation of uridine diphosphate-glucuronosyl transferase 1 family polypeptide A1 (UGT1A1), a key enzyme in the regulation of bilirubin metabolism, were detected. The results of pathogenic gene variations were interpreted pathogenic gene variations in accordance with the Standards and guidelines for the interpretation of sequence variants published by the American College of Medical Genetics and Genomics (ACMG). The clinical characteristics of patients with different gene variants were analyzed, and the clinical diagnosis and genetic diagnosis were compared.

RESULTS: Among the 26 patients with HS, there were 23 cases of anemia, 25 cases of jaundice, 24 cases of splenomegaly, and 14 cases of cholelithiasis. There were 16 cases with family history and 10 cases without family history. The results of HS mutation test were positive in 25 cases and negative in 1 case. A total of 18 heterozygous mutations of HS pathogenic genes were detected in 19 families, among which 14 were pathogenic, 1 was likely pathogenic and 3 were of unknown significance. SPTB mutations (12) and ANK1 mutations (4) were the most common. The main variation types were nonsense mutation (9). There were no significant differences in peripheral blood cell parameters and hemolysis indicators between the SPTB mutant group and the ANK1 mutant group (all P>0.05). The rate of splenectomy in ANK1 mutation group was higher than that in SPTB mutation group, and the difference was statistically significant (χ2=6.970, P=0.014). There were no significant differences in peripheral blood cell parameters and hemolysis indicators among different mutation types (nonsense mutation, frameshift mutation, splice site mutation and missense mutation) (all P>0.05). Among the 18 clinically confirmedpatients, there were 17 cases whose diagnosis is consistent with the genetic diagnosis. Eight patients were clinically suspected, and all of them were confirmed by detection of HS gene mutation. Twenty-four patients with HS underwent UGT1A1 mutation detection, among which 5 patients carried UGT1A1 mutation resulting in a decrease in enzyme activity, and 19 patients had normal enzyme activity. The level of total bilirubin (TBIL) in the group with reduced enzyme activity was higher than that in the group with normal enzyme activity, and the difference was statistically significant (U=22, P=0.038).

CONCLUSIONS: Most patients with HS have anemia, jaundice and splenomegaly, often accompanied by cholelithiasis. SPTB and ANK1 mutations are the most common mutations in HS pathogenic genes among patients in Hunan, China, and there was no significant correlation between genotype and clinical phenotype. Genetic diagnosis is highly consistent with clinical diagnosis. The decrease of UGT1A1 enzyme activity can lead to the aggravation of jaundice in HS patients. Clinical combined gene diagnosis is beneficial for the rapid and precision diagnosis of HS. The detection of UGT1A1 enzyme activity related gene variation plays an important role in evaluation of HS jaundice.

PMID:37385619 | DOI:10.11817/j.issn.1672-7347.2023.220390

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Mediation effect of resilience on pregnancy stress and prenatal depression in pregnant women

Zhong Nan Da Xue Xue Bao Yi Xue Ban. 2023 Apr 28;48(4):557-564. doi: 10.11817/j.issn.1672-7347.2023.220338.

ABSTRACT

OBJECTIVES: Pregnancy stress is the psychological confusion or threat caused by various stress events and adverse factors during pregnancy. Pregnant women exposed to many stressors, they will be easy to produce bad mood and prenatal depression if they cannot adapt to their own changes. Prenatal depression is one of the major global public health problems, with a higher incidence in developing countries and a negative impact on the health of pregnant women and fetus. Resilience refers to pregnant women using their own positive psychological capital, can self-emotional adjustment and improve their ability to adapt to the response state. A better level of resilience can enable pregnant women to face various negative and adaptive problems positively. This study aims to investigate the relationship between pregnancy stress, resilience and prenatal depression through a mental health survey of pregnant women.

METHODS: A total of 750 pregnant women in a Grade A tertiary hospital in Urumqi were investigated by self-designed demographic questionnaire, Pregnancy Pressure Scale (PPS) and Patient Health Questionnaire-9 (PHQ-9), Connor-Davidson Resilience Scale (CD-RISC), and the levels of stress during pregnancy, prenatal depression and resilience were analyzed. Pearson correlation analysis was used to explore the correlation between the three. Bootstrap mediation effect test was used to test the mediation effect relationship among the three. If the mediation effect was confirmed, AMOS software was used to establish the mediation effect structural equation model to analyze the mediation effect among the three.

RESULTS: Among 750 respondents, 709 (94.53%) had mild or above pregnancy pressure, 459 (61.20%) had mild or above depressive symptoms and 241 (32.13%) had a good or above level of resilience. Pearson correlation analysis showed that prenatal depression was significantly positively correlated with pregnancy stress (P<0.01), prenatal depression and pregnancy stress were significantly negatively correlated with resilience (all P<0.01). Mediation effect test analysis showed that all the pathways were statistically significant (P<0.01). Mediation effect of resilience between pregnancy stress and prenatal depression was significantly found (95% CI 0.022-0.068, P<0.001). Pregnancy pressure negatively affected resilience (β=-0.38, P<0.01), and resilience negatively affected prenatal depression (β=-0.10, P<0.01). The mediation effect of resilience was 6.5%.

CONCLUSIONS: Pregnant women’s pregnancy pressure, resilience and prenatal depression are significantly correlated, and the mediation variable resilience plays a partial mediating role in the impact of pregnancy pressure on prenatal depression. Pregnant women can reduce the incidence of prenatal depression and promote their physical and mental health by exercising their resilience.

PMID:37385618 | DOI:10.11817/j.issn.1672-7347.2023.220338

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Clinical features of 102 patients with different types of Herlyn-Werner-Wunderlich syndrome

Zhong Nan Da Xue Xue Bao Yi Xue Ban. 2023 Apr 28;48(4):550-556. doi: 10.11817/j.issn.1672-7347.2023.220336.

ABSTRACT

OBJECTIVES: Herlyn-Werner-Wunderlich syndrome (HWWS) is a rare female genital tract malformation, and there are few large sample studies reported at home and abroad. The clinical manifestations of this syndrome are diverse, and insufficient understanding may delay the diagnosis and treatment of the patients. This study aims to analyze the clinical characteristics of different types of HWWS patients, and to improve the diagnosis and treatment of HWWS.

METHODS: The clinical data of patients with HWWS who were hospitalized in the Department of Obstetrics and Gynecology, Third Xiangya Hospital of Central South University from October 1, 2009 to April 5, 2022 were retrospectively analyzed. The age, medical history, physical examination, imaging examination and treatment of the patients were collected for statistical analysis. The patients were divided into an imperforate oblique vaginal septum type, a perforate oblique vaginal septum type, and an imperforate oblique vaginal septum and cervical fistula type. The clinical characteristics of different types of HWWS patients were compared.

RESULTS: A total of 102 HWWS patients were enrolled, with age of 10-46 years old, including 37 (36.27%) patients with type I, 50 (49.02%) type II, and 15 (14.71%) type III. All patients were diagnosed after menarche, with an average age of (20.5±7.4) years. There were significant differences in the age of diagnosis and course of disease among the 3 types of HWWS patients (both P<0.05). Patients with type I had the youngest age of diagnosis [(18.0±6.0) years] and the shortest course of disease (median course of 6 months), while patients with type III had the oldest age of diagnosis [(22.9±9.8) years] and the longest course of disease (median course of 48 months). The main clinical manifestation of type I was dysmenorrhea, and the main clinical manifestation of type II and type III was abnormal vaginal bleeding. Of the 102 patients, 67 (65.69%) patients had double uterus, 33 (32.35%) had septate uterus, and 2 (1.96%) had bicornuate uterus. The vast majority of patients had renal agenesis on the oblique septum, and only 1 patient had renal dysplasia on the oblique septum. The oblique septum located on the left side in 45 (44.12%) patients and on the right side in 57 (55.88%) patients. There were no significant differences in uterine morphology, urinary system malformation, pelvic mass, and oblique septum among the 3 types of HWWS patients (all P>0.05). Six (5.88%) patients had ovarian chocolate cyst, 4 (3.92%) patients had pelvic abscess, and 5 (4.90%) patients had hydrosalpinx. All patients underwent vaginal oblique septum resection. Among them, 42 patients underwent hysteroscopic incision of the oblique vaginal septum without destroying the intact hymen because they had no sexual life history, and the remaining 60 patients underwent traditional oblique vaginal septum resection. Among the 102 patients, 89 patients were followed up for 1 month to 12 years. The symptoms of vaginal oblique septum in 89 patients such as dysmenorrhea, abnormal vaginal bleeding and vaginal discharge were improved after operation. Among the 42 patients who underwent hysteroscopic incision of the oblique vaginal septum without destroying the intact hymen, 25 patients underwent hysteroscopies again 3 months after operation, and there was no obvious scar formation at the oblique septum incision site.

CONCLUSIONS: Different types of HWWS have different clinical manifestations, but all can be manifested as dysmenorrhea. The patient’s uterine morphology can be manifested as double uterus, septate uterus, or bicornuate uterus. The possibility of HWWS should be considered if uterine malformation is combined with renal agenesis. Vaginal oblique septum resection is an effective treatment.

PMID:37385617 | DOI:10.11817/j.issn.1672-7347.2023.220336

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Association of insulin signaling pathway-related gene polymorphisms and gene-gene interactions with MAFLD in obese children

Zhong Nan Da Xue Xue Bao Yi Xue Ban. 2023 Apr 28;48(4):516-525. doi: 10.11817/j.issn.1672-7347.2023.220295.

ABSTRACT

OBJECTIVES: Insulin signaling pathway plays an important role in metabolic associated fatty liver disease (MAFLD), however, the association between polymorphisms of genes related to insulin signaling pathway and MAFLD remains unclear. This study aims to investigate the association between insulin signaling pathway-related gene polymorphisms and gene-gene interactions with MAFLD susceptibility in obese children so as to provide scientific basis for further study of genetic mechanism.

METHODS: A total of 502 obese children with MAFLD who admitted to Hunan Provincial Children’s Hospital from September 2019 to October 2021, were recruited as a case group, and 421 obese children with non-MAFLD admitted during the same period were recruited as a control group. Socio-demographic information, preterm birth history, eating habits, and exercise status of the subjects were collected by inquiry survey, and anthropometric information was collected by physical measurement. At the same time, 2 mL of venous blood was collected to extract DNA, and the polymorphism of insulin signaling pathway-related genes (5 representative candidate genes, 12 variants) was detected. Multivariate Logistic regression analysis was used to investigate the association between insulin signaling pathway-related gene polymorphisms and MAFLD in obese children.

RESULTS: After adjusting for confounder factors, INS rs3842748 was significantly associated with the risk of MAFLD in obese children in allele, heterozygous, and dominant models [OR and 95% CI 1.749 (1.053 to 2.905), 1.909 (1.115 to 3.267), 1.862 (1.098 to 3.157), all P<0.05]; INS rs3842752 was significantly associated with the risk of MAFLD in obese children in heterozygous and dominant models [OR and 95% CI 1.736 (1.028 to 2.932), 1.700 (1.015 to 2.846), all P<0.05]. NR1H3 rs3758674 was significantly correlated with the risk of MAFLD in obese children in allele model [OR and 95% CI 0.716 (0.514 to 0.997), P<0.05]. SREBP-1c rs2297508 was significantly associated with the risk of MAFLD in obese children in allele and dominant models [OR and 95% CI 0.772 (0.602 to 0.991) and 0.743 (0.557 to 0.991), all P<0.05]. SREBP-1c rs8066560 was significantly associated with the risk of MAFLD in obese children in allele, heterozygous, and dominant models [OR and 95% CI 0.759 (0.589 to 0.980), 0.733 (0.541 to 0.992), 0.727 (0.543 to 0.974), all P<0.05]. NR1H3 rs3758674 mutant C and SREBP-1c rs2297508 mutant G had interaction in the development of MAFLD in obese children [OR and 95% CI 0.407 (0.173 to 0.954), P<0.05].

CONCLUSIONS: The INS, NR1H3, and SREBP-1c gene polymorphisms in the insulin signaling pathway are associated with the susceptibility of MAFLD in obese children, but the functions and mechanisms of these genes need to be further studied.

PMID:37385614 | DOI:10.11817/j.issn.1672-7347.2023.220295

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Agreement of cardiac output measurements by esophageal Doppler and transesophageal echocardiography with intermittent pulmonary artery thermodilution during pharmacologic manipulation of hemodynamics in anesthetized dogs

Am J Vet Res. 2023 Jul 3:1-11. doi: 10.2460/ajvr.23.05.0101. Online ahead of print.

ABSTRACT

OBJECTIVE: To compare cardiac output (CO) measurements by transesophageal echocardiography (TEECO) and esophageal Doppler monitor (EDMCO) with pulmonary artery thermodilution (PATDCO) in anesthetized dogs subjected to pharmacological interventions. The effect of treatments on EDM-derived indexes was also investigated.

ANIMALS: 6 healthy male dogs (10.8 ± 0.7 kg).

METHODS: Dogs were anesthetized with propofol and isoflurane, mechanically ventilated, and monitored with invasive mean arterial pressure (MAP), end-tidal isoflurane concentration (ETISO), PATDCO, TEECO, EDMCO, and EDM-derived indexes. Four treatments were administered to all dogs by randomization. Baseline data were collected before each treatment: (1) dobutamine infusion; (2) esmolol infusion; (3) phenylephrine infusion; and (4) ETISO > 3%. Data were collected after 10-minute stabilization and after 30 minutes of washout between treatments. Statistical tests were pairwise t test, Bland-Altman analysis, Lin’s concordance correlation (ρc), and polar plot analysis with P < .05 set as significance.

RESULTS: The mean ± SD relative bias (limits of agreement) for TEECO was 0.35 ± 25.2% (-49.1% to 49.8%) and for EDMCO was -27.2 ± 22.5% (-71.4% to 17%) versus PATDCO. The percent error for TEECO and EDMCO was 27.6% and 44.1%, respectively. The ρc value was 0.82 for TEECO and 0.66 for EDMCO. TEECO and EDMCO showed good trending ability. EDM-derived indexes displayed significant changes specific to the drug administered (P < .001).

CLINICAL RELEVANCE: For minimally invasive CO monitoring, TEE may provide more favorable performance than EDM in clinical settings; however, EDM-derived indexes yield valuable hemodynamic information that reliably follows trends in CO, thus supporting critical decision-making in canine patients.

PMID:37385599 | DOI:10.2460/ajvr.23.05.0101

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Analysis of Palliative Care Knowledge and Symptom Burden Among Female Veterans With Serious Illness: A Cross-Sectional Study

Am J Hosp Palliat Care. 2023 Jun 29:10499091231187341. doi: 10.1177/10499091231187341. Online ahead of print.

ABSTRACT

Background: The female Veteran population is rapidly growing, as is their use of Veterans Affairs (VA) medical centers (VAMCs). Additionally, 90% of female Veterans are under 65 years old, meaning healthcare providers at VAMCs must be ready to manage the complex serious illnesses that affect female Veterans as they age. These serious illnesses require proper medical management, which can include palliative care. However, little palliative care research includes female Veterans. Aims: The aims of this cross-sectional study were to examine palliative care knowledge and symptom burden among female Veterans’ and examine factors associated a symptom burden scale. Methods: Consenting participants completed online questionnaires, including the Palliative Care Knowledge Scale (PaCKS), Condensed Memorial Symptom Assessment Scale (CMSAS), and demographics. Descriptive statistics characterized the sample, bivariate association were carried out with a Chi-square and t test. A generalized linear model explored associations between CMSAS and its subscales with sociodemographic, number of serious illnesses, and facility type (VAMC vs civilian facility). Results: 152 female Veterans completed the survey. PaCKS scores were consistent across our sample. Physical symptoms were rated higher for those receiving care at VAMCs compared to civilian facilities (P = .02) in the bivariate analysis. The factors associated with CMSAS were age, employment status and number of serious illnesses (all P < .05). Conclusions: Palliative care can assist female Veterans with serious illness. More research is needed to further explore variables associated with symptom burden among female Veterans such as age, employment status, and number of serious illnesses.

PMID:37385594 | DOI:10.1177/10499091231187341