Improved Early Recognition of Coronavirus Disease-2019 (COVID-19): Single-Center Data from a Shanghai Screening Hospital

Background: In December 2019, an outbreak of a novel coronavirus disease (COVID-19; previously known as 2019-nCoV) was reported in Wuhan, Hubei province, China, which has subsequently affected more than 200 countries worldwide including Europe, North America, Oceania, Africa and other places. The number of infected people is rapidly increasing, while the diagnostic method of COVID-19 is only by nucleic acid testing. Objective: To explain the epidemiological characteristics, clinical features, imaging manifestations and to judge diagnostic value of COVID-19 by analyzing the clinical data of COVID-19 suspected and confirmed patients in a non-outbreak, Shanghai, China. To clarify the early epidemiology and clinical characteristics about COVID-19. Methods: Cross-sectional, single-center case reports of the 86 patients screened at Zhoupu Hospital in Pudong New District, Shanghai, China, from January 23 to February 16, 2020. Epidemiology, demography, clinical, laboratory and chest CTs were collected and analyzed. The screened patients were divided into COVID-19 and non-COVID-19 based on nucleic acid test results. Results: Of the 86 screened patients, 11 were confirmed (12.8%) by nucleic acid testing (mean age 40.73 ± 11.32, 5 males). No significant differences were found in clinical symptoms including fever, cough, dyspnea, sore throat, and fatigue (P > 0.05). No statistical difference was observed in plasma C-reactive protein (CRP) between the two groups (COVID-19 and non-COVID-19 ) of patients (P = 0.402), while the white blood cell count and lymphocyte count of the confirmed patients were slightly lower than those of the suspected patients (P < 0.05). Some non-COVID-19 chest CTs also showed subpleural lesions, such as ground-glass opacities (GGO) combined with bronchiectasis; or halo nodules distributed under the pleura with focal GGO; consolidation of subpleural distribution or combined with air bronchi sign and vascular bundle sign, etc. Conclusion: The early clinical manifestations and imaging findings of COVID-19 are not characteristic in non-outbreak areas. Etiological testing should be performed as early as possible for clinically suspected patients.

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Clinical and laboratory findings of patients with the possible diagnosis of influenza hospitalized in affiliated hospitals of Babol University of Medical Sciences, 2015-2016

Current Issues in Pharmacy and Medical Sciences ◽

10.1515/cipms-2018-0022 ◽

2018 ◽

Vol 31 (3) ◽

pp. 113-116 ◽

Cited By ~ 1

Author(s):

Mostafa Javanian ◽

Arefeh Babazadeh ◽

Soheil Ebrahimpour ◽

Mehran Shokri ◽

Masomeh Bayani

Keyword(s):

Clinical Laboratory ◽

Clinical Symptoms ◽

Clinical Signs ◽

Clinical Manifestations ◽

Gastrointestinal Symptoms ◽

Medical Sciences ◽

Laboratory Findings ◽

Cross Sectional ◽

Number Of Patients ◽

Epidemiological Characteristics

Abstract The clinical and para clinical manifestations of influenza in various patients have range from an autoimmune disease to a life-threatening respiratory infection. In addition, the severity of the disease is influenced by factors such as demographic factors, underlying diseases, and immune response. Therefore, in this study, we evaluated the clinical, laboratory and epidemiological characteristics of patients with this type of influenza in Babol (north of Iran). This study was conducted as a descriptive cross-sectional study from October 2015 to March 2016. Subsequently, in this study, records of 123 patients with clinical signs of the influenza-like disease who have undergone the clinical sign in hospitals affiliated to Babol University of Medical Sciences were reviewed. Of 123 patients admitted to a possible diagnosis of influenza, 58 patients (47.2%) were PCR positive for H1N1, while seventy nine (64.2%) participants were women and 21 (17.1%) had diabetes or underlying lung disease. Most of the involved age groups were of individuals above the age of 50. These were followed by the 21-35 years-old. Fever (78%), cough (65.9%), shivering (58.5%) and myalgia (56.1%) were the most common clinical symptoms. Increased levels of transaminases (43.1%), leukocytosis (35.8%) and thrombocytopenia (34.2%) were as well reported in patients as the most frequently reported para clinical findings. In the present study, the most usual clinical symptoms were fever, cough, chill, and myalgia, while gastrointestinal symptoms were also noticeably observed in patients. In an experimental study, a significant number of patients showed leukocytosis and thrombocytopenia and increased transaminases.

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Gastrointestinal symptoms and fecal nucleic acid testing of children with 2019 coronavirus disease: a systematic review and meta-analysis

Scientific Reports ◽

10.1038/s41598-020-74913-0 ◽

2020 ◽

Vol 10 (1) ◽

Author(s):

Ji-gan Wang ◽

Hai-rong Cui ◽

Hua-bo Tang ◽

Xiu-li Deng

Keyword(s):

Nucleic Acid ◽

Respiratory Tract ◽

Case Reports ◽

Meta Analysis ◽

Clinical Manifestations ◽

Gastrointestinal Symptoms ◽

Nucleic Acid Detection ◽

Nucleic Acid Testing ◽

Pooled Prevalence ◽

Positive Rate

Abstract In order to understand the clinical manifestations and incidence of gastrointestinal symptoms of coronavirus disease (COVID-19) in children and discuss the importance of fecal nucleic acid testing.We retrospectively analyzed studies on gastrointestinal symptoms and fecal nucleic acid detection in pediatric COVID-19 patients from January 1, 2020 to August 10, 2020, including prospective clinical studies and case reports. The results of fecal nucleic acid detection were analyzed systematically. Stata12.0 software was used for meta-analysis.The results showed that the most common gastrointestinal symptoms in children with COVID-19 were vomiting and diarrhea, with a total incidence of 17.7% (95% Cl 13.9–21.5%). However, the prevalence of gastrointestinal symptoms in other countries (21.1%, 95% CI 16.5–25.7%) was higher compared to China (12.9%, 95% CI 8–17.7%). In Wuhan, the pooled prevalence was much higher (41.3%, 95% CI 3.2–79.4%) compared to areas outside Wuhan in China (7.1%, 95% CI 4.0–10.3%). The positive rate of fecal nucleic acid testing in COVID-19 children was relatively high at 85.8% (91/106). Additionally, 71.2% (52/73) were still positive for fecal nucleic acid after respiratory tract specimens turned negative. One and two weeks after the respiratory tract specimens turned nucleic acid-negative, 45.2% (33/73) and 34.2% (25/73) patients, respectively, remained fecal nucleic acid-positive. The longest interval between the respiratory tract specimens turning negative and fecal specimens turning negative exceeded 70 days. Conclusions and relevance: gastrointestinal symptoms in pediatric COVID-19 are relatively common. Attention should be paid to the detection of fecal nucleic acids in children. Fecal nucleic acid-negative status should be considered as one of the desegregation standards.

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Gastrointestinal symptoms and fecal nucleic acid testing of children with 2019 coronavirus disease: a systematic review and meta-analysis

10.21203/rs.3.rs-34733/v3 ◽

2020 ◽

Author(s):

Ji-Gan Wang ◽

Hairong Cui ◽

Huabo Tang ◽

Xiu-li Deng

Keyword(s):

Nucleic Acid ◽

Respiratory Tract ◽

Case Reports ◽

Meta Analysis ◽

Clinical Manifestations ◽

Gastrointestinal Symptoms ◽

Nucleic Acid Detection ◽

Nucleic Acid Testing ◽

Pooled Prevalence ◽

Positive Rate

Abstract In order to understand the clinical manifestations and incidence of gastrointestinal symptoms of coronavirus disease (COVID-19) in children and discuss the importance of fecal nucleic acid testing.We retrospectively analyzed studies on gastrointestinal symptoms and fecal nucleic acid detection in pediatric COVID-19 patients from January 1, 2020 to August 10, 2020, including prospective clinical studies and case reports. The results of fecal nucleic acid detection were analyzed systematically. Stata12.0 software was used for meta-analysis.The results showed that the most common gastrointestinal symptoms in children with COVID-19 were vomiting and diarrhea, with a total incidence of 17.7% (95% Cl: 13.9%-21.5%). However, the prevalence of gastrointestinal symptoms in other countries (21.1%, 95% CI: 16.5%-25.7%) was higher compared to China (12.9%, 95% CI: 8%-17.7%). In Wuhan, the pooled prevalence was much higher (41.3%, 95 % CI: 3.2%-79.4%) compared to areas outside Wuhan in China (7.1%, 95 % CI: 4.0%-10.3%).The positive rate of fecal nucleic acid testing in COVID-19 children was relatively high at 85.8% (91/106). Additionally, 71.2% (52/73) were still positive for fecal nucleic acid after respiratory tract specimens turned negative. One and two weeks after the respiratory tract specimens turned nucleic acid-negative, 45.2% (33/73) and 34.2% (25/73) patients, respectively, remained fecal nucleic acid-positive. The longest interval between the respiratory tract specimens turning negative and fecal specimens turning negative exceeded 70 days.Conclusions and Relevance:Gastrointestinal symptoms in pediatric COVID-19 are relatively common. Attention should be paid to the detection of fecal nucleic acids in children. Fecal nucleic acid-negative status should be considered as one of the desegregation standards.

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Gastrointestinal symptoms and fecal nucleic acid testing of children with coronavirus disease 2019: a systematic review and meta-analysis

10.21203/rs.3.rs-34733/v1 ◽

2020 ◽

Author(s):

Ji-Gan Wang ◽

Hairong Cui ◽

Huabo Tang

Keyword(s):

Nucleic Acid ◽

Respiratory Tract ◽

Case Reports ◽

Meta Analysis ◽

Clinical Manifestations ◽

Gastrointestinal Symptoms ◽

Nucleic Acid Detection ◽

Nucleic Acid Testing ◽

Negative Results ◽

Pooled Prevalence

Abstract Objective: To understand the clinical manifestations and incidence of gastrointestinal symptoms of Coronavirus disease (COVID-19) in children and discuss the importance of fecal nucleic acid testing.Methods: Retrospective analysis of studies of gastrointestinal symptoms and fecal nucleic acid detection in pediatric COVID-19 since the outbreak of COVID-19, as well as prospective clinical studies and case reports to understand the clinical characteristics of gastrointestinal symptoms and feces in children. Nucleic acid detection results were also analyzed.Results: 1. The clinical manifestations of gastrointestinal symptoms in children with COVID-19 are mostly vomiting and diarrhea, with a total incidence rate of 21.1% (95%Cl=0.14-0.28).2.When analyzing by country (studies from China versus studies from other countries), the pooled prevalence of gastrointestinal symptoms in studies from countries other than China was much lower at 18.2% (95% CI0.05 to 0.31). This is in comparison to studies from China where the prevalence was higher: 23.3% (95% CI 0.153 to 0.310) .3.In Wuhan patients, the pooled prevalence was much higher at 41.2% (95 % CI 0.147 to 0.678) as compared to areas outside Wuhan，China：15.1%(95 % CI 0.075 to 0.227).4.Fecal nucleic acid detection is as accurate as respiratory specimen nucleic acid detection. The positive rate of fecal nucleic acid testing in COVID-19 patients was 92.5% (25/27). In patients where nucleic acid tests of respiratory tract specimens produced negative results, a positive fecal nucleic acid test result was present in 83.3% (20/24); one week after the respiratory tract specimen was nucleic acid-negative, 54.1% (13/24) were fecal nucleic acid-positive; two weeks after the respiratory tract nucleic acid negative test, 37.5% (9/24) were fecal nucleic acid-positive. The longest interval between a negative respiratory system result and positive fecal specimen result exceeded 19 days.Conclusions and Relevance: Gastrointestinal symptoms in pediatric COVID-19 are relatively common. Attention should be paid to the detection of fecal nucleic acids in children. Fecal nucleic acid-negative status should be considered as one of the desegregation standards.

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Epidemiological Characteristics of COVID-19 in Seremban, Negeri Sembilan, Malaysia

Open Access Macedonian Journal of Medical Sciences ◽

10.3889/oamjms.2020.5461 ◽

2020 ◽

Vol 8 (T1) ◽

pp. 471-475

Author(s):

Mohd ‘Ammar Ihsan Ahmad Zamzuri ◽

Farah Edura Ibrahim ◽

Muhammad Alimin Mat Reffien ◽

Mohd Fathulzhafran Mohamed Hanan ◽

Muhamad Hazizi Muhamad Dasani ◽

...

Keyword(s):

Local Community ◽

Clinical Symptoms ◽

Early Recognition ◽

Close Contact ◽

Intervention Strategy ◽

Cross Sectional Study ◽

Asymptomatic Infection ◽

Skewed Distribution ◽

Cross Sectional ◽

Epidemiological Characteristics

BACKGROUND: Coronavirus disease (COVID)-19 has become a global pandemic with an increasing burden on healthcare. Early recognition of the trend and pattern of the chain of transmission is necessary to slow down the spread. AIM: Therefore, the study aimed to describe the epidemiology of COVID-19 at a local setting. METHODS: A retrospective cross-sectional study was done to all COVID-19 cases registered in Seremban Health District. Statistical analysis, using Chi-square test, was employed to compare the sociodemographic characteristic of COVID-19 patients between the red zone area and the non-red zone area in Seremban. RESULTS: As of April, a total of 214 number of COVID-19 cases reported in Seremban district alone. The trend of cases registered has changed as more asymptomatic infection outnumbered patients with clinical symptoms from the aggressive active case detection (ACD) activity. Majority of the cases affecting Malay ethnicity were due to a large religious gathering event held 1 month earlier than subsequently spread the infection within the community. CONCLUSION: The first wave of COVID-19 cases in Seremban was sudden and unexpected, with a skewed distribution affecting a particular race group regardless red zone area and non-red zone area. Therefore, identifying the pattern of infection in the local community is important for a focused intervention strategy. ACD strategy, isolation of patients, quarantine the exposed, tracking down the close contact, and continuous health promotion and education will ultimately break the chain of transmission.

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Clinical and CT features of mild-to-moderate COVID-19 cases after two sequential negative nucleic acid testing results: a retrospective analysis

10.21203/rs.3.rs-29848/v1 ◽

2020 ◽

Author(s):

Yan Rong ◽

Jing Wang ◽

Jinfei Tian ◽

Xinhua Liang ◽

Yang Zhou ◽

...

Keyword(s):

Nucleic Acid ◽

Clinical Laboratory ◽

Clinical Symptoms ◽

Ground Glass Opacity ◽

Ct Imaging ◽

Ground Glass ◽

Imaging Features ◽

Nucleic Acid Testing ◽

Imaging Data ◽

Negative Results

Abstract Background Numerous studies have been focused on the clinical and imaging features among COVID-19 patients positive for SARS-CoV-2, but the data after negative is limited. We aims to describe these features after negative respiratory nucleic acid testing results.Methods From January 31 to February 28, 2020, 51 mild-to-moderate COVID-19 cases (median: 34.0 years and 47.1% male) were retrospectively enrolled. Demographic, clinical, laboratory, and CT imaging data were collected before and after two sequential negative results for respiratory SARS-CoV-2 .Results After negative for respiratory SARS-CoV-2, the clinical symptoms continued to recover and the abnormal imaging were observed for all of the moderate cases. 77.4% of the moderate patients had multi-lobar involvement and lesions were more frequent in the lower lobes. The most common CT imaging manifestations were ground glass opacity (51.6%) and fibrous stripes (54.8%%). Among 12 out of 31 moderate patients with repeated chest CT scan after negative for SARS-CoV-2, 7 patients (58.3%) with ground-glass absorption reduced over 60% within one week, but there were still 4 cases (13.8%) with absorption less than 5%.Conclusions The clinical symptoms and abnormal imaging persisted but continued to recover after negative for respiratory SARS-CoV-2.

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Evaluation of Subacute Thyroiditis: Frequency, Clinical Manifestation and Laboratory Findings

10.21203/rs.3.rs-460073/v1 ◽

2021 ◽

Author(s):

Marziyeh Bagheri ◽

farhad Abbasi ◽

Kamran Mirzaei ◽

Manizhe mohamadi ◽

mohammadreza kalantarhormozi

Keyword(s):

Sore Throat ◽

Clinical Laboratory ◽

Clinical Symptoms ◽

Clinical Manifestations ◽

Cross Sectional Study ◽

Subacute Thyroiditis ◽

Laboratory Findings ◽

Cross Sectional ◽

Inappropriate Treatment ◽

One Year

Abstract Introduction: Subacute thyroiditis (SAT) is a type of viral thyroiditis, which is often a self-limiting illness, but it causes diagnostic mistakes due to a number of clinical symptoms and leads to inappropriate treatment. In this study, clinical, laboratory and demographic findings of patients have been investigatedMethods: This descriptive cross-sectional study was performed on 40 patients (27 female-13 male) with subacute thyroiditis during one year. Data included age, sex, clinical symptoms (fever, sore throat, otalgia, fatigue, sweating ...) and laboratory findings. (ESR, CRP, TSH, T4 and WBC). Their files were extracted and analyzed with SPSS.Results: In this study, 67% of the patients were women with the mean age of 38.48 ± 8.7. Female to male ratio was 2.7 to 1. The most common clinical symptoms were fever (57.5%) and sore throat (55%). Laboratory findings: ESR, TSH,T4 and WBC with average of 67.32, 0.283, 15.368 and 12.456, respectively. CRP positive in 80% of patients who underwent this test. 80 percent of the patients responded to the treatment. The recurrence rate was estimated 42% and 11% for those who received NSAIDs and Prednisolone, respectivelyConclusion: In this study, SAT was most prevalent in women in their fourth decade of life. Clinical symptoms were consistent with most studies in terms of prevalence and incidence. There was no significant association between the age and sex of the patients and their clinical manifestations and laboratory results from laboratory considerations, low concentrations of TSH, high levels of ESR and positive CRP were found to be helpful in diagnosis. Prednisolone proved to be more effective in treating SAT.

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Gastrointestinal symptoms and fecal nucleic acid testing of children with 2019 coronavirus disease: a systematic review and meta-analysis

10.21203/rs.3.rs-34733/v2 ◽

2020 ◽

Cited By ~ 1

Author(s):

Ji-Gan Wang ◽

Hairong Cui ◽

Huabo Tang ◽

Xiu-li Deng

Keyword(s):

Nucleic Acid ◽

Respiratory Tract ◽

Case Reports ◽

Meta Analysis ◽

Clinical Manifestations ◽

Gastrointestinal Symptoms ◽

Nucleic Acid Detection ◽

Nucleic Acid Testing ◽

Pooled Prevalence ◽

Positive Rate

Abstract In order to understand the clinical manifestations and incidence of gastrointestinal symptoms of coronavirus disease (COVID-19) in children and discuss the importance of fecal nucleic acid testing.We retrospectively analyzed studies on gastrointestinal symptoms and fecal nucleic acid detection in pediatric COVID-19 patients from January 1, 2020 to August 10, 2020, including prospective clinical studies and case reports. The results of fecal nucleic acid detection were analyzed systematically. Stata12.0 software was used for meta-analysis.The results showed that the most common gastrointestinal symptoms in children with COVID-19 were vomiting and diarrhea, with a total incidence of 17.7% (95% Cl: 13.9%-21.5%). However, the prevalence of gastrointestinal symptoms in other countries (21.1%, 95% CI: 16.5%-25.7%) was higher compared to China (12.9%, 95% CI: 8%-17.7%). In Wuhan, the pooled prevalence was much higher (41.3%, 95 % CI: 3.2%-79.4%) compared to areas outside Wuhan in China (7.1%, 95 % CI: 4.0%-10.3%).The positive rate of fecal nucleic acid testing in COVID-19 children was relatively high at 85.8% (91/106). Additionally, 71.2% (52/73) were still positive for fecal nucleic acid after respiratory tract specimens turned negative. One and two weeks after the respiratory tract specimens turned nucleic acid-negative, 45.2% (33/73) and 34.2% (25/73) patients, respectively, remained fecal nucleic acid-positive. The longest interval between the respiratory tract specimens turning negative and fecal specimens turning negative exceeded 70 days.Conclusions and Relevance:Gastrointestinal symptoms in pediatric COVID-19 are relatively common. Attention should be paid to the detection of fecal nucleic acids in children. Fecal nucleic acid-negative status should be considered as one of the desegregation standards.

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THE CLINICAL, LABORATORY MANIFESTATIONS AND HISTOPATHOLOGY IN NEPHROTIC PATIENTS WITH LUPUS NEPHRITIS

Journal of Medicine and Pharmacy ◽

10.34071/jmp.2018.2.9 ◽

2018 ◽

pp. 52-58

Author(s):

Le Thuan Nguyen ◽

Bui Bao Hoang

Keyword(s):

Systemic Lupus Erythematosus ◽

Lupus Nephritis ◽

Lupus Erythematosus ◽

Clinical Laboratory ◽

Activity Index ◽

Clinical Manifestations ◽

Systemic Lupus ◽

Cross Sectional ◽

Organ Systems ◽

Tubulointerstitial Lesions

Introduction: Systemic lupus erythematosus (SLE) is an autoimmune disease involving multiple organ systems. The kidney appears to be the most commonly affected organ, especially nephrotic is a serious kidney injury. The clinical, laboratory manifestations and histopathology are very useful for diagnosis, provide the means of predicting prognosis and guiding therapy in nephrotic patients with lupus nephritis. Methods: Descriptive cross-sectional study of nephrotic patients with lupus treated in the Department of Nephrology Trung Vuong Hospital and Cho Ray Hospital between May/2014 and May/2017. Renal histopathological lesions were classified according to International Society of Nephrology/Renal Pathology Society - ISN/RPS ’s 2003. The clinical, laboratory manifestations and histopathological features were described. Results: Of 32 LN with nephritic range proteinuria cases studied, 93.7% were women. The 3 most common clinical manifestations were edema (93.8%), hypertension (96.8%) and pallor (68.9%), musculoskeletal manifestions (46.9%), malar rash (40.6%). There was significant rise in laboratory and immunological manifestions with hematuria (78.1%), Hb < 12g/dL (93.5%), increased Cholesterol (100%), and Triglycerid (87.5%), Creatinine > 1.4 mg/dL (87.5%), increased BUN 71.9%, ANA (+) 93.8%, Anti Ds DNA(+) 96.9%, low C3: 96.9%, low C4: 84.4%. The most various and severe features were noted in class IV with active tubulointerstitial lesions and high activity index. Conclusion: Lupus nephritis with nephrotic range proteinuria has the more severity of histopathological feature and the more severity of the more systemic organ involvements and laboratory disorders were noted. Key words: Systemic lupus, erythematosus (SLE) lupus nepphritis, clinical

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Cardio-Pulmonary Sequelae in Recovered COVID-19 Patients: Considerations for Primary Care

Journal of Primary Care & Community Health ◽

10.1177/21501327211023726 ◽

2021 ◽

Vol 12 ◽

pp. 215013272110237

Author(s):

Zouina Sarfraz ◽

Azza Sarfraz ◽

Alanna Barrios ◽

Radhika Garimella ◽

Asimina Dominari ◽

...

Keyword(s):

Primary Care ◽

Primary Infection ◽

Clinical Laboratory ◽

Point Of Care ◽

Case Reports ◽

Case Series ◽

Infectious Complications ◽

Care Physician ◽

Cross Sectional ◽

Infection Period

Background: Current literature lacks characterization of the post-recovery sequelae among COVID-19 patients. This review characterizes the course of clinical, laboratory, radiological findings during the primary infection period, and the complications post-recovery. Primary care findings are presented for long-COVID care. Methods: Adhering to PRISMA guidelines, 4 databases were searched (PubMed, Embase, CINAHL Plus, Scopus) through December 5, 2020, using the keywords “COVID-19 and/or recovered and/or cardiovascular and/or long-term and/or sequelae and/or sub-acute and/or complication.” We included published peer-reviewed case reports, case series, and cross-sectional studies providing the clinical course of COVID-19 infection, and cardiopulmonary complications of patients who recovered from COVID-19, while making healthcare considerations for primary care workers. Results: We identified 29 studies across 9 countries including 37.9% Chinese and 24.1% U.S. studies, comprising 655 patients (Mean Age = 45) with various ethnical backgrounds including Asian and European. Based on the WHO COVID-19 severity classification scale, initial disease severity was mild for 377 patients and severe for 52 patients. Treatments during primary infection included corticosteroids, oxygen support, and antivirals. The mean value (in days) for complication onset after acute recovery was 28 days. Complete blood counts and RT-PCR tests were the most common laboratory results described. In 22 of the studies, patients showed signs of clinical improvement and were prescribed medications such as anticoagulants or corticosteroids. Conclusion: Post-recovery infectious complications are common in long-COVID-19 patients ranging from mild infections to life-threatening conditions. International thoracic and cardiovascular societies need to develop guidelines for patients recovering from COVID-19 pneumonia, while focused patient care by the primary care physician is crucial to curb preventable adverse events. Recommendations for real-time and lab-quality diagnostic tests are warranted to establish point-of-care testing, detect early complications, and provide timely treatment.

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