IMscin001 Part 2: a randomised phase III, open-label, multicentre study examining the pharmacokinetics, efficacy, immunogenicity, and safety of atezolizumab subcutaneous versus intravenous administration in previously treated locally advanced or metastatic non-small-cell lung cancer and pharmacokinetics comparison with other approved indications.

BACKGROUND: Atezolizumab intravenous (IV) is approved for the treatment of various solid tumours. To improve treatment convenience and health care efficiencies, a coformulation of atezolizumab and recombinant human hyaluronidase PH20 was developed for subcutaneous (SC) use. Part 2 of IMscin001 (NCT03735121) was a randomised phase III, open-label, multicentre, noninferiority study comparing the drug exposure of atezolizumab SC with atezolizumab IV. PATIENTS AND METHODS: Eligible patients with locally advanced/metastatic non-small-cell lung cancer were randomised 2 : 1 to receive atezolizumab SC (1875 mg; n = 247) or IV (1200 mg; n = 124) every 3 weeks. The co-primary endpoints were cycle 1 observed trough serum concentration (Ctrough) and model-predicted area under the curve from days 0 to 21 (AUC0-21 d). The secondary endpoints were steady-state exposure, efficacy, safety, and immunogenicity. Exposure following atezolizumab SC was then compared with historical atezolizumab IV values across approved indications. RESULTS: The study met both of its co-primary endpoints: cycle 1 observed Ctrough {SC: 89 µg/ml [coefficient of variation (CV): 43%] versus IV: 85 µg/ml (CV: 33%); geometric mean ratio (GMR), 1.05 [90% confidence interval (CI) 0.88-1.24]} and model-predicted AUC0-21 d [SC: 2907 µg d/ml (CV: 32%) versus IV: 3328 µg d/ml (CV: 20%); GMR, 0.87 (90% CI 0.83-0.92)]. Progression-free survival [hazard ratio 1.08 (95% CI 0.82-1.41)], objective response rate (SC: 12% versus IV: 10%), and incidence of anti-atezolizumab antibodies (SC: 19.5% versus IV: 13.9%) were similar between arms. No new safety concerns were identified. Ctrough and AUC0-21 d for atezolizumab SC were consistent with the other approved atezolizumab IV indications. CONCLUSIONS: Compared with IV, atezolizumab SC demonstrated noninferior drug exposure at cycle 1. Efficacy, safety, and immunogenicity were similar between arms and consistent with the known profile for atezolizumab IV. Similar drug exposure and clinical outcomes following SC and IV administration support the use of atezolizumab SC as an alternative to atezolizumab IV.

[Comparison of epidemic characteristics and clinical manifestation of chickenpox between adults and children in Shandong Province from 2019 to 2021].

Objective: To analyze the differences between adults and children in the epidemic characteristics and clinical manifestations of chickenpox and provide a reference for the prevention strategy adjustment of chickenpox. Methods: The incidence data of chickenpox surveillance in Shandong Province from January 2019 to December 2021 were collected. Descriptive epidemiological methods were used to analyze the distribution of cases, and the chi-square test was used to compare the differences in epidemiological characteristics and clinical manifestations of varicella cases between adults and children. Results: A total of 66 182 cases of chickenpox were reported from 2019 to 2021, including 24 085 cases of adults chickenpox, the male to female sex ratio was 1∶1 (12 032∶12 053), basically the same for men and women, and 42 097 cases of children chickenpox, with a gender ratio of 1.4∶1, the male to female ratio was 1.4∶1 (24 699∶17 398). Fever in chickenpox cases was mainly low and moderate, but the proportion of moderate fever with temperature between 38.1 and 39.0 ℃ in children cases (35.0%,14 744/42 097) was significantly higher than that in adults (32.0%,7 696/24 085). The number of herpes in chickenpox cases was mainly less than 50, but the proportion of severe cases with 100-200 herpes in children was higher than that in adults. The incidence rate of complications was 1.4% (333/24 085) in adults chickenpox, the incidence rate of complications was 1.7% (731/42 097) in children chickenpox. The incidence of encephalitis and pneumonia in children was higher than in adults, and the difference was statistically significant (P<0.05). The proportion of chickenpox cases was mainly outpatient, but the hospitalization rate of children cases was 14.4% (6 049/42 097), higher than that of adults, which was 10.7% (2 585/24 085). Conclusions: There were differences between adult chickenpox and child chickenpox in terms of epidemic and clinical manifestations; the symptoms of child chickenpox were more serious than adult chickenpox. However, the adult chickenpox population is generally susceptible and lacks immune strategy protection, which calls for more attention.

Who posted #MeToo, why, and what happened: A mixed methods examination.

Objectives: The #MeToo social media campaign raised awareness about sexual harassment. The purpose of the current study was to address three unexplored research questions. First, what factors influenced whether a person posted #MeToo? Second, how did posting (or not) influence participants' wellbeing? Finally, what motivated participants' posting (or not) #MeToo? Method: This mixed-methods study explores how #MeToo was experienced by full-time employees (N = 395) who could have posted #MeToo (i.e., experienced a sexual harassment event), whether or not they did so. Participants completed surveys in July of 2018 assessing social media use, sexual harassment history, relational variables such as relative power and social support, and job and life satisfaction. Participants also responded to open-ended survey questions about the context of and decisions about #MeToo posting. Results: Quantitative results indicated that sexual harassment history was the most powerful predictor of #MeToo posting, while power and interpersonal contact also contributed. Qualitative analyses (N = 74) using a grounded theory approach indicated themes associated with decisions to disclose, including feeling a responsibility to post, need for support, and affective benefits. Decisions not to disclose were event-related negative affect, posting-related negative affect, timing of the event, fit with the #MeToo movement, privacy concerns, and fear of consequences. Conclusion: This study contributes to the literature on sexual harassment disclosure by focusing on informal means of disclosure and drawing on comparisons to formal reporting and implications for workplaces. Online sexual harassment disclosure, in many ways, reflects the impediments to formal reporting procedures. Given the increased use of social media for purposes of disclosure, these findings suggests that organizations should recognize the legitimacy of sexual harassment reports made online and consider the possible failings of their formal reporting systems as reasons for online disclosure.

[Evaluation of p16/Ki-67 double-stained immunohistochemistry in diagnosis of human papilloma virus-positive oropharyngeal squamous cell carcinoma].

Objective: To explore the diagnostic value of p16/Ki-67 double-stained immunohistochemistry in the diagnosis of human papilloma virus (HPV)-positive oropharyngeal squamous cell carcinoma(opscc) and find out the optimal index to improve the accuracy of HPV detection. Methods: A total of 153 cases, from May 2014 to May 2020, diagnosed OPSCC in Shanghai Ninth People's Hospital, Shanghai Jiao Tong University School of Medicine, were selected. This cohort included 130 males and 23 females, aged (58.6±10.0) years old. HPV RNA in situ hybridization was chosen as the gold standard to detect their HPV status. p16 immunohistochemistry and p16/Ki-67 double-stained immunohistochemistry were performed on all cases, and the p16/Ki-67 double positive index including 20%, 40%, and 60% were used as the thresholds to compare their sensitivity, specificity, and positive prediction value (PPV), negative prediction value (NPV) and prognosis prediction ability. Results: Among the 153 patients with OPSCC, 114 were HPV-negative and 39 were HPV-positive, and the HPV infection rate of OPSCC patients was 25.5% (39/153). Only 58.1% (36/62) of single p16 positive cases were HPV-positive, and the prognosis of patients could not be distinguished using p16 immunohistochemistry only. Using p16/Ki-67 double staining, the accuracy of HPV positive diagnosis has been improved. The HPV diagnostic ability was the highest when the p16/Ki-67 double positive index was 40% (sensitivity=86.8%, specificity=94.8%, PPV=84.6%, NPV=95.6%, area under the curve=0.897), which could distinguish the prognosis of patients (P=0.012). Conclusions: The p16/Ki-67 double-stained immunohistochemistry can improve the accuracy of HPV positive diagnosis rate and diagnosis of HPV-positive oropharyngeal cancer is the most accurate when the double-positive index is 40% as the threshold to judge HPV status and could serve as better surrogate marker for HPV detection.

[Study of incidence and economic burden of herpes zoster based on community investigation among the aged in Laiwu district, Jinan city, Shandong Province of China].

Objective: To understand the incidence and economic burden of herpes zoster among the aged in Laiwu district, Jinan city. Methods: Retrospective cohort study was conducted in 5 communities in Laiwu District, Jinan City from July to September, 2019. A total of 8 300 residents born before July 1, 1959 and aged ≥60 years old were included in the investigation. At the same time, an economic burden survey was carried out among 220 cases who developed herpes zoster after July 1, 2017. A questionnaire was used to collect information on incidence and economic burden of HZ, and comparisons were carried out about the incidence and economic burden of herpes zoster among older people with different characteristics. Results: The age of 8 300 subjects was (71.46±6.71) years old. Male and female accounted for 44.10% and 55.90%, respectively. The cumulative incidence of disease after the age of 60 was 73.61‰ among population aged ≥60 years old. The cumulative incidence was 28.03‰, 71.26‰, 86.09‰, 93.48‰ and 88.10‰ among population aged 60-64, 65-69, 70-74, 75-79 and ≥80 years old,respectively. The average annual incidence of HZ was 9.49‰ and annual incidence was 7.59‰, 7.23‰, 8.43‰, 10.24‰ and 13.98‰ in 2014-2018, respectively. HZ cost was (2 626±667) RMB per patient with a median cost of 715 RMB (interquartile range 303-2 358) on 220 cases who developed disease after July 1, 2017. The cost of outpatient cases was (1 329±1 835) RMB per patient with a median cost of 560 RMB (interquartile range 300-1 320), and the cost of inpatient cases was (14 303±16 571) RMB per patient with a median cost of 8 190 RMB (interquartile range 4 368-15 160). Conclusion: The incidence of HZ is high among population aged≥60 years old, which could cause heavy economic burden for them.

Global genetic diversity of Spirometra tapeworms.

Spirometra larvae are etiological agents of human sparganosis. However, the systematics of spirometrid cestodes has long been controversial. In order to determine the current knowledge on the evolution and genetic structure of Spirometra, an exhaustive population diversity analysis of spirometrid cestodes using the mitochondrial gene: cytochrome c oxidase subunit 1 (cox1) was performed. All publicly available cox1 sequences available in the GenBank and 127 new sequencing genes from China were used as the dataset. The haplotype identify, network, genetic differentiation and phylogenetic analysis were conducted successively. A total of 488 sequences from 20 host species, representing four spirometrid tapeworms (S. decipiens, S. ranarum, S. erinaceieuropaei and Sparganum proliferum) and several unclassified American and African isolates from 113 geographical locations in 17 countries, identified 45 haplotypes. The genetic analysis revealed that there are four clades of spirometrid cestodes: Clade 1 (Brazil + USA) and Clade 2 (Argentina + Venezuela) included isolates from America, Clade 3 contained African isolates and one Korean sample, and the remainders from Asia and Australia belonged to Clade 4; unclassified Spirometra from America and Africa should be considered the separate species within the genus; and the taxonomy of two Korea isolates (S. erinaceieuropaei KJ599680 and S. decipiens KJ599679) was still ambiguous and needs to be further identified. In addition, the demographical analyses supported population expansion for the total spirometrid population. In summary, four lineages were found in the spirometrid tapeworm, and further investigation with deeper sampling is needed to elucidate the population structure.

Global genetic diversity of Spirometra tapeworms

@#Spirometra larvae are etiological agents of human sparganosis. However, the systematics of spirometrid cestodes has long been controversial. In order to determine the current knowledge on the evolution and genetic structure of Spirometra, an exhaustive population diversity analysis of spirometrid cestodes using the mitochondrial gene: cytochrome c oxidase subunit 1 (cox1) was performed. All publicly available cox1 sequences available in the GenBank and 127 new sequencing genes from China were used as the dataset. The haplotype identify, network, genetic differentiation and phylogenetic analysis were conducted successively. A total of 488 sequences from 20 host species, representing four spirometrid tapeworms (S. decipiens, S. ranarum, S. erinaceieuropaei and Sparganum proliferum) and several unclassified American and African isolates from 113 geographical locations in 17 countries, identified 45 haplotypes. The genetic analysis revealed that there are four clades of spirometrid cestodes: Clade 1 (Brazil + USA) and Clade 2 (Argentina + Venezuela) included isolates from America, Clade 3 contained African isolates and one Korean sample, and the remainders from Asia and Australia belonged to Clade 4; unclassified Spirometra from America and Africa should be considered the separate species within the genus; and the taxonomy of two Korea isolates (S. erinaceieuropaei KJ599680 and S. decipiens KJ599679) was still ambiguous and needs to be further identified. In addition, the demographical analyses supported population expansion for the total spirometrid population. In summary, four lineages were found in the spirometrid tapeworm, and further investigation with deeper sampling is needed to elucidate the population structure.

[Construction and application of immunization information system based on children cases collected by vaccination clinic clients in Shandong Province, China].

Construction and application of immunization information system is an important part of health information, which is very useful to improve the quality, efficiency and safety of vaccination. The background, system architecture, functions and applications, working conditions and characteristics of Shandong province Immunization Information System (IIS) are introduced in this article. It is expected to provide experiences for the development of immunization information system of other provinces.

[A clinical study of allogeneic hematopoietic stem cell transplantation in 23 patients with early T-cell precursor acute lymphoblastic leukemia].

Objective: Early T-cell precursor acute lymphoblastic leukemia (ETP-ALL) is a recently recognized high-risk T lymphoblastic leukemia subgroup. The optimal therapeutic approaches to adult patients with ETP-ALL are poorly characterized. In this study, we explore the efficacy and outcome of allogeneic hematopoietic stem cell transplantation (allo-HSCT) for ETP-ALL. Methods: The clinical data of 23 patients with ETP-ALL receiving allo-HSCT from 2010 to 2018 were retrospectively analyzed. Patients with ETP-ALL were diagnosed based on the characteristic immunophenotypes. Second-generation sequencing was done in all patients. As to the donors, 12 patients had haploidentical donors (Haplo-HSCT) , 7 HLA-matched sibling donors (Sib-HSCT) and 4 HLA-matched unrelated donors (URD-HSCT) . Before transplantation, 19 patients achieved complete remission (CR) and 4 patients without. Results: The main clinical features of ETP-ALL included high white blood cell counts in 5 patients, splenomegaly in 14, lymphadenopathy in 19, and thymus masses in 5. According to cytogenetic and molecular characteristics, 11 patients had gene mutations related to myeloid tumors, and 7 with high risk Karyotype. After first induction regimen, 14/23 patients achieved CR. 5 patients reached CR after more than 2 cycles of chemotherapy, while another 4 patients did not reach CR. After allo-HSCT, 22 patients were successfully implanted. The median time of granulocyte and platelet reconstitution was +12 and +19 days. One patient died of transplant-related infection at +14 days. The estimated 18-month overall survival (OS) and relapse-free survival (RFS) rates were (55.0±14.4) % and (48.1±14.7) % respectively. Transplant-related mortality was 4.3%. The median OS in patients achieving CR before transplantation was 20 months, however, that in patients without CR was only 13 months. OS and RFS between haplo-HSCT and sib-HSCT were comparable (P=0.460 and 0.420 respectively) . Conclusions: Allo-HSCT is an effective therapy in some patients with ETP-ALL. Salvage HSCT cannot overcome the poor outcome. Haplo-HSCT and sib-HSCT in ETP-ALL patients have the similar clinical outcome.

[Similar coronal curvature may not represent the same 3-dimensional deformity in adolescent idiopathic scoliosis: a matched-pair study using EOS imaging system].

Objective: To analyze the preoperative axial plane and the surgical outcomes of the Lenke type 1A patients with adolescent idiopathic scoliosis (AIS) whose coronal curve type was matched but thoracic kyphosis (TK) was different. Methods: This study retrospectively reviewed a series of Lenke type 1A female AIS patients who underwent corrective surgery in the Department of Spine Surgery of Nanjing Drum Tower Hospital from May to August 2017. After matched with the Cobb angle of the main thoracic curve, the apical vertebral, the vertebra number included in the curve, the lumber modifier in the Lenke classification and Risser sign, 12 pairs of AIS patients, whose coronal curve was matched but thoracic kyphosis was different, were included in this study. The patients were divided into normal TK group and thoracic hypokyphosis group. EOS whole-body images were taken preoperatively and reconstructed by three-dimensional reconstruction. The whole spine anteroposterior X-ray was taken at 3 weeks after surgery. The radiographic parameters were measured on the preoperative and postoperative two-dimensional X-ray images: coronal Cobb angle, TK, lumbar lordosis (LL), pelvic incidence (PI) and pelvic tilt (PT). The vertebra rotation was obtained on the EOS three-dimensional reconstructed image, and the average vertebral rotation of the major thoracic curve (MTR), the average vertebral rotation of the proximal thoracic curve (PTR) and the average vertebral rotation of the lumbar curve (LR) were calculated. The paired sample t test was used to compare the difference of preoperative and postoperative radiographic parameters between the groups. Results: A total of 24 patients (12 pairs) were included in this study with an average age of (13.7±2.9) years. The preoperative Cobb angle was similar in the two groups (53.8°±10.2° vs 51.0°±11.1°, t=0.27, P=0.81). The average preoperative TK of the normal TK groups was 28.2°±6.1°, while that of the thoracic hypokyphosis group was 11.2°±5.6°(t=7.68, P<0.01). The MTR in the normal TK group was significantly smaller than that in the thoracic hypokyphosis group (10.2° vs 12.7°, t=-3.74, P<0.01), and there was a significant correlation between TK and MTR (r=0.30, P=0.03). As for the lumbar curve rotation, the LR of the normal TK group was significantly smaller than that in the thoracic hypokyphosis group (t=-2.65, P=0.002), but the absolute value of the two groups was similar (t=-0.33, P=0.31). The lumbar Cobb angle correction rate was significantly greater in patients with thoracic and lumbar curve rotating in the same direction than that in the opposite direction (81.1% vs 61.9%, t=4.24, P=0.005). Conclusions: It indicated that when the coronal deformity is matched, the MTR of the patients with thoracic hypokyphosis is significantly larger than that in the patients with normal thoracic kyphosis. The direction of the thoracic and lumbar curve rotation is required to be well concerned in the preoperative surgical planning.

Intracavernosal alprostadil is effective for the treatment of erectile dysfunction in diabetic men.

The efficacy and safety of intracavernosal alprostadil was evaluated for the treatment of erectile dysfunction in men with type I or type II diabetes mellitus. This was an open-label, flexible dose-escalating study involving 336 men (77% of whom were Asian/Oriental) enrolled by 15 centres in Australia, Canada and seven countries in Asia. The effective alprostadil dose, ie the dose producing penile rigidity adequate for intercourse and lasting up to 60 min, was established by titration at the clinic prior to entry into the 6 month self-treatment home phase. All men were fully trained in the self-injection technique before entry into the home phase. Efficacy and safety were assessed using patient and partner diaries and by interview at clinic visits during the titration phase and after 1, 3 and 6 months of treatment. An effective home dose was established by titration for 94% of the 336 men (median dose 20 microg, range 2.5-60 microg). Of 278 (83%) men who entered the home phase, 277 men (247 with type II diabetes and 30 with type I diabetes) had evaluable data for alprostadil dosage and clinical response. During the home phase, a satisfactory erectile response was achieved after 99% of injections, and the median alprostadil dose remained unchanged. The initial home dose and clinical response were similar in type I and type II diabetic men. Treatment was generally well tolerated with a low incidence of penile pain (24%) In conclusion, intracavernosal alprostadil was effective and well tolerated in type I and type II diabetic men with erectile dysfunction of mixed aetiology.

Change of core conflicts of schizophrenic patients who received brief psychodynamic psychotherapy: a pilot study in Taiwan.

BACKGROUND: This study examined the change of core conflicts of schizophrenic patients who received brief psychodynamic psychotherapy (BPP). METHODS: The change of core conflicts and relationship patterns over dynamic psychotherapy sessions were assessed by the core conflictual relationship theme (CCRT) method. Patients were enrolled either from the psychiatric outpatient department or day hospital in a medical center. Transcripts of psychotherapy sessions were used for CCRT analysis. In each extracted transcript, 3 components, i.e., wishes, responses from others and responses of self, were identified and were used to formulate the CCRT. CCRT pervasiveness was calculated to compare the change of each component from early to late sessions. RESULTS: The main other person most frequently mentioned was the family member. The changes of positive and negative responses of self were found to be statistically significant. Wishes were not so pervasive as those of non-psychotic patients. A high drop-out rate characterized the schizophrenic patients. CONCLUSION: Self-understanding and self-control may well explain the significant change in responses of self, even in patients with essentially poor ego strength like schizophrenics.

The study on core conflictual relationship of short-term counseling.

This study utilizes the Core Conflictual Relationship Theme Method (CCRT; Luborsky and Crits-Christoph, 1997) on process study of short-term counseling. The purpose was to evaluate the formation and variation of interpersonal conflicts presented by nine clients, so as to enhance the understanding of the core conflicts of each client and how these clients were influenced by short-term counseling. CCRT was conducted by two raters to analyze the content of core conflictual relationship themes. The raters started with taking a twenty-minute vignette from four tapes of the counseling sessions which were the 1st, 2nd, 11th and the 12th. A transcript was taken for each session and the raters searched for relationship episodes (REs) in it. Further, other main persons were identified in REs. Three components, including wish(W), response from others(RO), and response of self(RS) were investigated and analyzed. The raters calculated the appearance frequency of each component and transferred them into formulation of relationship theme in written language. The findings are as follows. (1) The interrater reliabilities between the two raters over W, RO, RS are significant (Kappa = .21-.82, P < .01) (2) The most frequently described other main persons in 201 REs were 'clleague' (N = 87, 43. 3%), the second 'self' (N = 42, 32.8%) and the third 'family members' (N = 41, 20. 4%). The first three described wishes were 'to assert self and be independent' (N = 66, 32.8%), 'to be close and accepted' (N = 48, 23.9%), and 'to be loved and understood' (N = 35, 17.4%) (3) The change of pervasiveness scores of each component in terms of positive and negative responses evaluated by t-test were found to decrease significantly in NRO (r = -2.73, p < .05). The score was most significantly decreased in 'rejecting and opposing' item (t = -3.83, p < .01). Conclusions and suggestions regarding application of the Core Conflictual Relationship Theme analytical and categorization methods in the Chinese context are presented.