The frequency of infections caused by Burkholderia pseudomallei is increasing worldwide. Here, we report a case of B pseudomallei infection presenting with a lung abscess and osteomyelitis in an adult man.A 38-year-old man presented with high-grade fever, productive cough, and chronic joint pain of the limbs. Examinations revealed multiple nodules, soft tissue mass shadows, pulmonary cavitation in bilateral lungs, and fluid and soft tissue swelling in bilateral hips.The microbiologic diagnosis based on a positive culture revealed the etiologic agent to be B pseudomallei.The patient was treated with intravenous ceftazidime and levofloxacin, and out-of-hospital treatment continued with oral cotrimoxazole.The patient responded well to the treatment.subsections Because of its increasing incidence, B pseudomallei infection should be highly suspected among employees who work in laboratories and healthcare facilities. Misdiagnosis can lead to treatment failure and high mortality rates, especially among individuals working in laboratories in non-endemic areas; therefore, early and accurate diagnosis of B pseudomallei infection is essential. Adequate antimicrobial treatment and long-term follow-up are imperative to reduce morbidity and mortality. It is endemic in South-east Asia and Northern Australia and parts of South and Central America, an increasing number of emerging infectious diseases caused by B pseudomallei have been reported in many countries. The clinical presentation of the infection varies greatly, ranging from mild localized infection to acute fulminant sepsis with widespread bacterial dissemination. The lungs, subcutaneous tissue, musculoskeletal region, liver, and spleen are the organs predominantly affected. Although acute pulmonary infection is the most frequent form of the infection, acute septicemic infection with a high mortality rate is the most severe form of the infection. Osteomyelitis is described as the infection and destruction of bones and is mainly caused by aerobic or anaerobic mycobacterium and fungus; however, osteomyelitis of bilateral hips caused by B pseudomallei is rare. Here, we report a case of B pseudomallei infection presenting as a lung abscess and complicated osteomyelitis of bilateral hips in an adult man.Melioidosis is an anthropozoonosis caused by 22.1A 38-year-old man was referred to our hospital for joint pain of the limbs for >4 months, fever for 10 days, and cough for 2 weeks. Before the current admission, he was treated with methylprednisolone tablets, tongfengding capsules, and lansoprazole tablets; however, his symptoms did not improve over time. He had no history of travel to any melioidosis epidemic areas or was not exposed to any animals. He was employed as an agricultural worker and had a history of heavy alcohol consumption and excessive smoking.2.2On physical examination, the patient was toxic with high-grade fever (39.5°C), blood pressure of 121/65 mmHg, pulse rate of 106 per minute and respiratory rate of 21 per minute. In addition, he reported having >4 months of the bilateral shoulder, elbow, wrist, knuckle, hip, knee, ankle and left sternoclavicular pain that aggravated while performing daily activities. This limited his mobility and caused an inability to walk.9/L, including 92.3% neutrophils and 4.6% lymphocytes, platelet count of 841 × 109/L, and hemoglobin level of 68 g/L. The levels of fasting C-reactive protein (CRP) and procalcitonin (PCT) were 165.60 mg/L and 1.03 ng/ml, respectively. Erythrocyte sedimentation rate (ESR) was 143 mm/h, and rheumatoid factor (RF) was 30.30 IU/mL, which were markedly elevated compared with normal levels . Serum total bilirubin was 128.1 (1.00–28.0) μmol/L, total protein was 40.7 (65.0–85.0) g/L, albumin was 22.0 (40.0–55.0) g/L, alanine aminotransferase was 154 (9–50) U/L, aspartate transaminase was 214 (15–40) U/L, alkaline phosphatase was 269 (40–150) U/L, γ-glutamyl transferase was 1782 (10–60) U/L. The serum urea, creatinine, and uric acid levels were within the normal levels. Mycoplasma pneumoniae antibodies (both IgM and IgG) were detected using the Diagnostic Kit for Measurement of Antibodies to M pneumoniae (Passive Particle Agglutination) , and the mixed antibody titer was 1:160, indicating that the patient was likely infected with M pneumoniae . The chemiluminescence microparticle immunoassay was used to detect human immunodeficiency virus (HIV) antigen (p24)/antibody (HIV-1/HIV-2) combo and the Treponema pallidum antibody. The immune colloidal gold method was used to detect IgG antibodies against Mycobacterium tuberculosis. All of the test results were negative.Blood test results revealed a total leucocyte count of 13.7 × 102.3Chest contrast-enhanced computerized tomography (CECT) revealed multiple nodules, soft tissue mass shadows, and pulmonary cavitation in the lower zone of bilateral lungs; thus, a pulmonary abscess was considered. CECT of the hip joint showed the destruction of bone of bilateral acetabulum, femoral head, and proximal femur, and interruption of bone in the right femoral neck. Nuclear magnetic resonance imaging (MRI) revealed fluid and soft tissue swelling in bilateral hips. Therefore, infectious osteomyelitis was considered.TM FX  was positive. Sputum, joint fluid, and blood were subsequently submitted for routine cultures. Small colonies were cultured on the blood plate for 1 day. After 2 days, the colony with hemi-hemolytic had grown into a medium size, was gray-yellow, and was shaped like a wheel or chrysanthemum. Pinkish rugose colonies were observed on MacConkey's agar. The organism with turbid growth, and then formed a ruffled bacteria membrane in liquid culture. All the growth colonies had a strong foul musty odor. The 2 ends of the bacteria were concentrated with gram-negative bacteria and had multiple flagella in the single extreme. The results of conventional biochemical testing revealed that the organism could decompose glucose, lactose, maltose, mannitol, levo-ribose, and sucrose by producing acid but not gas. It was not able to decompose left wood. Additionally, the tests showed that the organism was positive for phosphatase, oxidase, nitrate reductase, and had a negative reaction when tested for urea, tellurite, acetamide, citrate, malonate, esculin, lysine, tryptophan, and DNase. A microorganism identification test was conducted using the Microflex LT/SH system  and the results suggested that the organism was B pseudomallei as was suspected. Antibiotic susceptibility testing using the BD Phoenix 100 system showed that the organism was sensitive to trimethoprim/sulfamethoxazole, ticarcillin/clavulanic acid, piperacillin/tazobactam, piperacillin, levofloxacin, meropenem, ciprofloxacin, co-trimoxazole, ceftazidime, and imipenem and resistant to amikacin, aztreonam, tobramycin, and gentamicin.The staining results of direct smears prepared from sputum and joint fluid from the hips for mycobacteria and fungi were negative. The blood culture using the BD BACTEC2.4On the basis of the culture results and the antibiotic susceptibility testing, the patient received 2 g of intravenous ceftazidime every 8 hours and 0.3 g of intravenous levofloxacin every 12 hours, in conjunction with proper nutrition therapy.2.5B pseudomallei was still isolated from the joint effusions. After 2 days of hospitalization, discharge plans were made as per the patient's request; the patient did not develop any complications during treatment in the hospital. Out-of-hospital treatment continued with 2 960 mg tablets of oral co-trimoxazole every 12 hourly for another 6 months and he was seen for follow-up visits once a month. At the 6-month follow-up visit, his joint effusions had disappeared without relapse. The diagnosis and treatment information for this case are summarized in Figure His fever and cough resolved after 7 days. The sputum culture was negative after 4 weeks and the blood culture was negative after 7 weeks. Chest CECT showed remarkable absorption of the pulmonary abscess after 2 months; however, there was still a small number of effusions in bilateral hips observed using MRI, and 2.6This study was prospectively performed and approved by the Institutional Ethics Committees of the First Affiliated Hospital of Guangxi University of Chinese Medicine and conducted according to the ethical guidelines of the Declaration of Helsinki. The patient gave written informed consent for publication.3B pseudomallei is an environmental gram-negative bacillus that was first described by Whitmore and Krishnaswami in 1912; it was predominately endemic in Southeast Asia in the 1990s. It commonly presents in soil and surface water of infected areas and can infect humans through entry through open cuts or wounds. The patient presented here was a farmer whose occupation was working on the farmland. This might have been the source of his melioidosis, however, ingestion, inhalation, and laboratory-acquired infection can also cause melioidosis. With the enhanced mobility of the global population, an increasing number of people with B pseudomallei infection have been reported from other parts of the world. In China, patients with B pseudomallei infection were mainly from the southern coastal region of China, for example, Hannan, Fujian, and Guangdong,6; however, cases of infectious osteomyelitis of bilateral hips caused by B pseudomallei, as described in this report, are uncommon and rarely reported.B pseudomallei infection include thalassemia, soil/water exposure, diabetes mellitus, excessive alcohol consumption, chronic lung disease, renal disease, systemic lupus erythematosus, and being of the male sex. The patient in our report consumed large amounts of alcohol and smoked cigarettes heavily. He was previously diagnosed with alcoholic liver disease, community-acquired pneumonia, and gouty arthritis, which significantly increased his risk of B pseudomallei infection. The incubation period for B pseudomallei infection is known to last for a few days up to several years. In this patient, the time from onset of symptoms to diagnosis was approximately 4.5 months. The clinical presentation of the disease varies greatly; it is often asymptomatic or presents with only mild fever and cough during the early period. The current patient was a farmer with a history of heavy smoking and drinking; thus, he probably did not realize that he was infected by a pathogen. He did not live in a B pseudomallei endemic area; there were no previous cases in which locals were infected with this disease in his area. Therefore, the patient likely did not seek timely treatment because of the lack of information and public awareness about the disease. B pseudomallei was recently recognized as an emerging infection in India; a study showed that the majority of patients were males from rural areas, however, the majority of cases remain to be diagnosed and reported. In countries where melioidosis is likely to occur, education on sanitation is needed in order to enhance knowledge on the epidemiology of disease in the countryside, to ensure that people fully understand the dangers and harms associated with the disease. If one suspects infection with B pseudomallei, it is recommended that medical treatment be sought in a timely manner and that doctor's instructions are adhered to. With increasing reports of this disease, we believe that B pseudomallei should be considered, particularly among farmers who are at higher risk of B pseudomallei infection. If sick farmers on standard flu medications do not see an improvement in health over time, microbiologic identification should be conducted to test for B pseudomallei infection. If diagnosed with B pseudomallei infection, adequate antimicrobial treatment and long-term follow-up are imperative to reduce morbidity and mortality.Risk factors for acquiring B pseudomallei is acute septicemic infection, which is accompanied by a high mortality rate. The current patient was diagnosed with bacteremia based on the results of the blood culture.Patients with increased serum levels of CRP and PCT should be highly suspected of bacterial infection. However, CRP levels are not a consistent marker of the severity of infection. PCT is a better diagnostic marker of general bacterial infections and it is very useful in distinguishing bacterial infections from non-bacterial infections. The serum PCT level of the patient was markedly elevated (1.03 ng/mL) compared with the normal level (0.00–0.05 ng/mL), indicating that he was more likely to be infected with bacteria. In such cases, blood cultures should be performed as quickly as possible as the most severe form of B pseudomallei infections have been reported globally, as diagnosing B pseudomallei has become common. The “gold standard” method for the diagnosis of B pseudomallei is still the isolation of B pseudomallei from clinical specimens; culture-based methods have a low diagnostic sensitivity in patients with melioidosis. A high index of suspicion is needed both among employees in laborites and healthcare facilities as phenotypic differences in B pseudomallei are not easily recognized and they might be misinterpreted as Burkholderia cepacia, especially in laboratories in non-endemic areas. It takes approximately 1 week to confirm species using conventional biochemical tests; traditional biochemical tests and rapid automatic identification systems often experience errors in identification. Molecular tests for the rapid confirmation and differentiation of B pseudomallei have been widely used;,12 although the sequencing of the 16S ribosomal RNA (rRNA) gene is widely used for the identification of this organism, it cannot confidently separate B pseudomallei and closely related species such as Burkholderia thailandensis. Commercial identification systems also have the same problems. The groEL gene sequences offer a higher discriminatory power between the 2 species than the 16S rRNA. Molecular detection is a reliable method to identify the bacteria but requires special equipment, which is not available in some microbiology laboratories, particularly in non-endemic areas, and diagnostic problems encountered in culture-negative cases remain largely unresolved. The sensitivities and specificities of serological tests for diagnosis remain to be evaluated. Immediate and accurate identification of B pseudomallei is essential as treatment of these infections require intensive and prolonged treatment.Although the clinical presentation of the disease varies greatly with acute, chronic, or subacute forms, an increasing number of ,17 Acute pulmonary infection is the most frequent form of the infection; thus, it is essential that sputum cultures are conducted when the presenting symptoms do not improve after “conventional therapy” , and that blood cultures are performed if necessary. Many clinical trials have reported the efficacy of various antimicrobial regimens for B pseudomallei.,18–20 When B pseudomallei infection is diagnosed, intravenous antimicrobial therapy is initiated and should be continued for 10 to 14 days; thereafter 3 to 6 months of oral maintenance therapy should be provided to patients until abscesses are completely absorbed. Patients should be seen for a follow-up visit at least 6 months after the complete resolution of any abscess.The results of antibiotic susceptibility testing in our case revealed that the organism was sensitive to the majority of antibiotics, which is similar to the findings from previous studies.B pseudomallei infections have been described in a number of previous studies; B pseudomallei infections were reversible or effectively controlled in some cases, however, some patients died because they were not able to access diagnosis and treatment. The immunity of our patient did not significantly decrease; the organism was sensitive to most antibiotics, particularly ceftazidime and imipenem, which is one of the primary reasons and antibacterial treatment was effective. Ceftazidime has been considered to be effective in the treatment of B pseudomallei infection. Simpson et al reported that ceftazidime and imipenem had the similar efficacy for the treatment of acute severe B pseudomallei, but more frequent treatment failure was observed in patients treated with ceftazidime. This was the first case of B pseudomallei diagnosed and treated in our hospital. Ceftazidime, given in combination with levofloxacin and out-of-hospital treatment that was continued with oral co-trimoxazole, seemed to be efficacious in the treatment of our patient. A previous case of B pseudomallei infection in a patient with diabetes was reported in Hunan province, but the bacteria were resistant to imipenem and was considered a carbapenem producing strain causing ineffective treatment with many antibiotic drugs. Furthermore, a bacterial culture was not performed when the patient first visited hospital with left arm suppurative infection, therefore, failure to appropriately diagnose and treat the patient with antibiotic therapy, likely lead to the death of this patient. Out-of-hospital treatment remains an important modality to reduce morbidity and mortality; Huffam et al suggested that out-of-hospital management of melioidosis with 24 hourly infusions of ceftazidime through a peripherally inserted central catheter line was safe and effective. Based on the findings from our case, a significant antibacterial effect was observed when adequate antimicrobial treatment, including ceftazidime and levofloxacin, was administered as quickly as possible, and out-of-hospital treatment was continued with oral co-trimoxazole therapy. In similar cases, we recommend that such therapy, including out-of-hospital treatment, be continued until the bacteria isolated from all materials is negative. The relapse rates of B pseudomallei are high; thus, it is highly important to complete therapy and engage in long-term follow-up to avoid recurrence. We did not identify any relapse during the regular clinical and biologic monitoring visits our patient attending in the year proceeding treatment.Treatment of B pseudomallei infection, we do not know exactly how he became infected. Second, the adverse effects or unanticipated events associated with treatment were not recorded. Third, follow-up was interrupted 1 year after discharge because of the inability to contact the patient; therefore, the long-term outcome and prognosis are unknown. Fourth, this case shows that ceftazidime plus levofloxacin were feasible and effective in the treatment of B pseudomallei infection; whether this treatment strategy has the same efficacy for other patients with B pseudomallei infection needs to be confirmed in future studies. Although this is the first case of B pseudomallei infection reported in our hospital, the patient received timely and accurate diagnosis and treatment, which makes us more confident regarding the future diagnosis and treatment of this disease. Additionally, we were able to collate relevant information and summarize our experience in the diagnosis and treatment of this rare case. We believe that our experiences in the management of this case will be useful for the diagnosis and treatment of B pseudomallei infection in future, in both our hospital and those in other settings.This case report was subject to several limitations. First, although this patient had some risk factors for Conceptualization: Jun-rong Wu.Data curation: Lei Huang.Formal analysis: Xiao-Ping Zhou.Resources: Lei Huang, Zhi Yang.Software: Zhi Yang.Writing – original draft: Xiao-Ping Zhou.Writing – review & editing: Jun-rong Wu.


This cross-sectional study is aimed at assessing the quality of life in a cohort of breast cancer patients at the Oncology Department, King Abdulaziz University Hospital (KAUH), King Abdulaziz University (KAU), Jeddah, Saudi Arabia (SA), and to differentiate QoL among different groups. Mean time since diagnosis was 3.97±1.90 years. European Organization for Research and Treatment of Cancer Quality of Life Questionnaires—Core30 and BR23 (EORTC QLQ-C30 & BR23) were used to assess QoL in breast cancer survivors. ANOVA and independent t-test (parametric tests) were used for the categorical variables and Kruskal-Wallis and Mann-Whitney tests used for non-parametric tests. Linear regression analysis was done to measure predictors’ significance and to calculate the coefficient of determination. Two hundred and eighty-four patients completed the survey. Global health status and functional scales, in most of the domains, were high, while symptom scales were moderate-to-low for most items, showing better QoL. Insomnia and fatigue were the most disturbing symptoms. Patients exhibited higher scores for body image and future perspective, while the least score is for sexual functioning. Global health, physical functioning, and role functioning were better in the age group ≤50 years (p<0.05). Premenopausal and perimenopausal patients showed a better level of functioning as compared to postmenopausal patients (p = 0.001). Premenopausal patients scored higher for sexual enjoyment, as compared to peri- and post-menopausal patients (p = 0.04). Systemic therapy side effects were more evident in the breast conservative surgery group. Predictors explained 8% of the variation in Physical functioning (R-squared = 0.08). A predictor that had a remarkable influence on physical functioning, as compared to the other predictors in the model, was menopausal status (P = 0.02). So, it was concluded that the breast cancer patients visiting our institute had a better quality of life regarding overall global health status as well as functional and symptom scales. Some issues, for instance, fatigue, insomnia, hair loss, and others, warrant good supportive therapy. Breast cancer is the most commonly diagnosed malignancy and the leading cause of death among women worldwide. It is revealed that breast cancer alone is responsible for 30% of newly diagnosed cancer cases in women and there is a probability that one in eight women will develop breast cancer in her lifetime, while 14% of cancer-related deaths are attributed to it . It is eMalignancies, especially in advanced stages, are associated with a compromised quality of life (QoL), which can be attributed to physical, psychological and social factors . While cDifferent tools have been used to assess the quality of life of patients. European Organization for Research and Treatment of Cancer (EORTC) Quality of Life Questionnaires—Core-30 and Breast-23 (QLQ-C30 and QLQ-BR23)—are valid and reliable tools to assess QoL in breast cancer survivors –20. EvenThe literature search indicates that there are several factors, which individually or collectively influence the cancer patients’ quality of life (QoL). These contributing factors could be depression, sexual problems and fertility-issues , the excKeeping in mind the importance of QoL in breast cancer patients and the scarcity of data from Saudi Arabia, especially from the Western region, this study was conducted to assess the quality of life in breast cancer patients by using EORTC QLQ-C30 and BR23 questionnaires in the western region of Saudi Arabia. The present study investigated the quality of life in a cohort of breast cancer patients at the Oncology Department, KAUH, Jeddah, SA, and differentiated QoL among different groups and also explored association of different variables with the domains of QoL. Our study results might help in managing such patients.The Research Ethics Committee of King Abdulaziz University gave the approval for this study, with the research ref. no. 333–15. Written consent was obtained from all the participants on a consent form; the purpose of the study was briefly explained to the participants; and the strict confidentiality of the participants’ information was maintained.The present survey-based study was carried out in the Oncology Department at KAUH, KAU, Jeddah, SA, and data collection was completed in four months. Being a tertiary care center, a variety of patients with different stages of cancer, age-differences, and modes of presentation, receive treatment here. Management of patients with breast cancer is based on a preset protocol, and each step in the management is evidence-based.Female breast cancer patients, who were managed at KAUH, with their diagnosis established at least 6 months ago, were eligible to participate in the study. We used the European Organization for Research and Treatment of Cancer Quality of Life QuestionnaireCore-30 and Breast-23 (EORTC QLQ-C30 & -BR23), a tool mostly in use to evaluate QoL in cancer patients, after taking permission from the concerned authorities. Written consent was obtained from all the participants on a consent form, the purpose of the study was briefly explained to the participants and the strict confidentiality of the participants’ information was maintained.Cohorts of patients being treated at KAUH were asked to fill the questionnaire in Arabic or English language. EORTC QLQ-C30 and -BR23 are validated and reliable tools to assess QoL in patients with breast cancer, and the questionnaires are found to be acceptable in Arab Population as well ,20,24. TAdditional data were also collected regarding age, place of residence, number of family members, history of cancer in the family, marital status, number of kids, employment status, socioeconomic conditions, history of any addictions, and others.1-α/2 = standard normal variate (at 5% type 1 error (P<0.05) it is 1.96, p = proportion of breast cancer described by a previous study (27.4%) [The calculated sample size for this study was 280 using the following formula,Five hundred patients were approached to complete the survey. The researchers of the study, and the data collectors, who were undergraduate medical students, approached the patients. All the patients of breast cancer, visiting the Oncology Department, were contacted in the outpatient department (OPD). Three hundred and ten patients agreed to participate in the research, while 190 patients declined the request. The patients who agreed to participate were given the option to fill the questionnaires in the waiting area. There was a separate comfortable room, used for counselling patients, so the patients sat there at ease and completed the survey. A female staff member, either the female research participant or the data collector, who was briefed about the research questions, accompanied the patients to help clarify any confusing item.Several types of therapies were given to patients including surgery, chemotherapy, hormone therapy, and radiotherapy. As mentioned, the main purpose of the study was to evaluate the QoL of patients irrespective of the management offered to them. However, certain parameters were taken into consideration to compare the QoL and patients were divided into groups for such variables to compare the results. Variables included: age ≤ or > 50 years; cancer staging—patients with stage 0, 1 and 2 were included in group A, while patients with stages 3 and 4 were included in group B; type of surgery—conservative breast surgery or mastectomy; menopausal status—pre-, peri- and post-menopausal women. The patients were separated according to menopausal status, because it is likely that premenopausal females, being young and dynamic, may have more hopes and passion for fighting the disease and therefore, their QoL is less compromised because of their motivation to cure the problem.The data were coded and analysed on SPSS 21. We calculated the relevant descriptive statistics for both the questionnaire items. Patients were divided into two groups according to their scores; the patients who scored ≤33 for the functional scales and the global QoL were considered problematic, while the patients who scored ≥66 were considered in good condition. For symptom scales, the score is reversed, i.e., the patients who scored ≤33 were considered in good condition and the patients who scored ≥66 were considered problematic ,26. The The linear regression analysis was done to measure predictors’ significance and to calculate the coefficient of determination. The dependent variables were global health, physical, emotional, cognitive and social functioning scores, while age, menopausal status, cancer staging, and types of surgery were the independent variable, and were labeled into “Yes” and “No” groups and considered as the model’s predictors. The value of R squared was calculated, and p≤0.05 was taken as significant where the comparison was conducted.Three hundred and ten patients completed the survey questionnaire. Twenty-six questionnaires were excluded from the study due to multiple errors. Two hundred and eighty-four patients were included in the study. Their mean and median ages were 51.74±11.59 and 52 years respectively and the mean time since diagnosis was 3.97±1.90 years. Distribution of patients according to their age, cancer-stage, type of surgery, and menopausal status are shown in Overall, for EORTC-C30, global health status was high; functional scale in most of the domains especially social functioning and cognitive functioning were high; while, symptom scales were moderate-to-low for most items. The higher scores in global health status showed better QoL. Similarly, higher scores in functional scales indicate better QoL. On the other hand, higher scores in symptom scales show worse QoL . Most ofQuality of life was compared according to different parameters in QLQ-C30 . Global Comparison of different variables in QLQ-BR-23 is shown in The predictors explained 8% of the variation in physical functioning (R-squared = 0.08). The predictor that had a remarkable influence on physical functioning as compared to the other predictors in the model was menopausal status (P = 0.02). The same model was built for every domain in QLQ-C30, but no other significant predictors were found in any model .Our study shows that, overall, scores of global health status and functional scales are high, while scores of symptom scales are moderate to low. These scores indicate better QoL in our patients. Insomnia and fatigue are the most distressing symptoms in our study. Pain and appetite loss are other symptoms that affect QoL to a moderate level, while diarrhea and financial difficulties are the least disturbing symptoms . This liA positive correlation of perceived social support was found with global health status in a Malaysian study . This faIn our study, the functional scale of QLQ-BR23 shows higher scores and better QoL for body image and future perspective. Sexual functioning shows the least score with worse QoL. Hair loss, systemic therapy side effects, arm symptoms, and breast symptoms were the most disturbing among our study group, and these results were compatible with other studies. A study found that hair loss was the leading side effect that affected the quality of life . Jassim We could not elicit a significant difference among different groups in most of the parameters of QLQ-BR-23. Premenopausal women exhibited better scores, in sexual enjoyment than their counterparts—peri- and post-menopausal women. Another significant finding is the higher score for systematic therapy side effects in the group with conservative breast surgery . No signSpecific interpretation can be drawn from our study. Overall, QoL is better among our patients and the findings are compatible with other studies. QoL in breast cancer survivors is compromised in different domains and these areas need attention. Patients of different age groups may elicit different problems associated with that age group. In a study, it was emphasized that quality of life is not static, and patients have altered QoL at different disease stages, for instance, after diagnosis, before and after treatment, and long-term effects of cancer and treatment modalities . It was Our study had limitations. This study was conducted to evaluate overall QoL in breast cancer survivors, so, a few specific issues were not evaluated in detail. Being a questionnaire study, a detailed discussion could not be possible with patients regarding specific matters. Many patients did not respond to the questions about educational status and income, so the comparison was not possible among patients according to their educational level and income.The breast cancer patients who visited our institute had a better quality of life regarding overall global health status as well as functional and symptom scales. Patients scored highest in social functioning and lowest in physical functioning. Insomnia and fatigue were the most disturbing symptoms. Similarly, patients scored better in functional scale (QLQ-BR-23), body image and future perspective. Hair loss and systemic therapy side effects were the most disturbing symptoms. Patients of younger-age-group showed better QoL. Some issues, for instance, fatigue, insomnia, hair loss, etc., warrant good supportive therapy to reduce the concerns of patients and to give them psychological support. Future studies can be performed keeping in view specific problems in detail.S1 File(SAV)Click here for additional data file.


To investigate the prevalence of burnout syndrome among physicians of all specialties, including residents and non-specialists, on a national level in Croatia.This cross-sectional study, conducted in October 2017, used anonymous online survey based on the Maslach Burnout Inventory Human Services Survey. The Croatian version of the inventory was assessed for acceptability, factorial validity, and reliability. Key dimensions of burnout – emotional exhaustion, depersonalization, and lack of personal accomplishment were assessed. Respondents scoring high for emotional exhaustion or depersonalization were defined as burned-out.The response rate was 18% (2557/14 427). Respondents’ median age was 41 years (range 25-80), and 68% (1737/2557) were women. Good sampling adequacy and scale reliability were confirmed. Factorial validity suggested the presence of three overall factors, and no items were eliminated. Sixty-three percent of physicians were burned-out. High score on emotional exhaustion, depersonalization, and reduced personal accomplishment were found in 58%, 29%, and 52% of respondents, respectively. As many as 16% of the respondents simultaneously experienced high levels of all three burnout dimensions. Multivariate logistic regression analysis revealed that residents and physicians in tertiary or primary care were at an increased risk of burnout, while physicians working in institutes were at a decreased risk.Active national measures are needed to reduce the high prevalence of burnout among Croatian physicians. Chronic workplace stressors can lead to burnout, a psychological syndrome characterized by three key dimensions – emotional exhaustion (EE), depersonalization (DP), and feelings of reduced personal accomplishment (PA). EE refers to feelings of being overextended and depleted of one's emotional and physical resources, DP represents an excessively detached response to various job aspects, while lack of PA refers to feelings of job-related incompetence and lack of achievement . The MasBurnout is etiologically, clinically, and nosologically similar to depression . Burned-Causes and predictors of burnout are various and linked not only to workload. According to several former studies, stressors in health care workers can be both environmental and individual. Some of the important ones are intrinsic factors of work, administration, stressors related to financial opportunities, contact with patients, relationships with coworkers, organizational structure and climate, interference of private and work life, and role ambiguity ,9.Although nationwide burnout syndrome studies among physicians have been conducted in Europe, these studies only included specific physician groups, such as solely family physicians or residents -12. FurtThe Croatian health care system experiences a deficit of human resources, with approximately 4% of all Croatian physicians having gone to work abroad in a three-year period (2013-2016), leaving the remaining personnel with an increasing workload . The aimThis cross-sectional study was conducted through an online survey, which was freely available for participation between October 17 and October 27 in 2017. The survey was completely anonymous. Data were collected through an online Google Forms platform. The study inclusion criteria were set to include physicians practicing in the Croatian health care system, from both public and private sector, and regardless of their age, specialty, geographical region, level of health care, title or working status. The only exclusion criterion was practicing outside of Croatia.An e-mail invitation to participate in the survey with dedicated instructions was sent to the members of the Croatian Medical Chamber, a regulatory body of physicians practicing in Croatia with mandatory membership. The email also included a cover letter for the physicians, asking for their voluntary participation, explaining the purpose of the research, and providing a hyperlink to the survey. One reminder email was sent five days after the initial invitation and the survey was closed five days subsequently. This study was approved by the Committee for Medical Ethics and Deontology of the Croatian Medical Chamber .korisnik” (Croatian for recipient) with the word “pacijent” (Croatian for patient). This is a common practice since this survey is intended to be used by people in a wide variety of occupations. The MBI – HSS includes 22 items on a 7-point Likert-type frequency scale . The 22-item assessment evaluates and scores three burnout dimensions: EE, DP, and lack of PA. Scores are then categorized based on the provided scoring key as low level , moderate level , or high level . PA scoring is inversed in order to measure the lack of PA. Except for the questions of the MBI – HSS, some demographic descriptors were also collected. Demography questionnaire included participant age, sex, marital status, number of children, professional title, specialty, academic title, country of practice, institution of employment, length of employment, and county of practice.The survey was based on the Croatian version of the MBI Human Services Survey (HSS) . The insEE and DP have been suggested to be the foundation of burnout . Partici2 test . All statistical tests were two-sided. The significance level was set at P < 0.05.Data were summarized by using standard descriptive statistics. Normality of distribution of continuous variables was tested by the Shapiro-Wilk test and Quantile-Quantile Plots. The continuous data are presented as mean ± standard deviations or medians with interquartile range (IQR) or range, where appropriate. Categorical variables are presented as absolute numbers and percentages. Difference between participants with and without burnout was evaluated using the independent-samples Mann-Whitney U test (for continuous variables) or χP < 0.05 and P > 0.1, respectively. In order to control for age and sex, the two variables were forced into the final model after the backward elimination process. Adjusted odds ratios (OR) and 95% confidence intervals (CI) were calculated for the variables in the equation.Multivariate binary logistic regression analysis was performed to identify burnout risk factors. We selected the potential risk factors for the multivariate analysis based on the variables available in the single factor analysis of respondents with and without burnout. The variables selected for the multivariate analysis were age, sex, marital status, number of children, title, specialty, length of employment, working environment, and academic title. To establish the logistic regression model, we used a backward algorithm. The criteria for entry and removal from the model at each step were set at We validated the inventory for the population of Croatian physicians. An exploratory factor analysis was used to uncover any latent variables that cause the manifest variables to covary in the Croatian version of the MBI – HSS questionnaire. During factor extraction, the questionnaire items are grouped depending on the variance they share, which is captured by factors that are interpreted as latent dimensions. To assess for sampling adequacy, we ran the Kaiser-Meyer-Olkin test. The suitability of the item correlation matrix for factoring was tested with the Bartlett’s test of sphericity. In exploratory factor analysis we used the maximum likelihood estimation with direct oblimin rotation. We included the extracted factors with the eigenvalue >1, which accounted for more >10% of the variance, and which passed the visual inspection on the scree plot. Cronbach’s alpha with 95% CI was used to assess internal consistency, a measure of scale reliability. Statistical analyses were performed using the open-source R software, version 3.5.1 .There were 2557 respondents eligible for the study. Median age of respondents was 41 years  and 68% (n = 1737) were women. The median length of service was 15 years . About two thirds of respondents had completed a training program , were married , and had children . Likewise, 66% (n = 1697) worked in either secondary or tertiary care institutions. The most common specialty was family medicine . For the EE dimension it was 0.70 (0.68-0.72), for DP – 0.83 (0.82-0.84), and for the lack of PA – 0.92 (0.91-0.92). All values were ≥0.7, indicating good scale reliability.The means for EE and lack of PA scores were in the high level range, while the mean for DP score was in the moderate level range . A totalThere was no significant difference between the groups in age, sex, marital status, and number of children, while there were significant differences in title, specialties, working environment, and academic title. The frequency of burnout was higher among respondents in training (residents), those with non-surgical specialties, and those working in tertiary hospitals. The frequency of burnout was lower among respondents working in institutes and those with a master’s degree .2 were 0.022 and 0.030 respectively. Physicians in training (residents) and those in tertiary or primary care working environment were at an increased risk of burnout, as well as those without an academic title or holding a doctorate (Some of the variables that were shown to be significantly different in univariate analysis did not show the same tendency in the multivariate analysis. The variable selection for the multivariate analysis was based on the comparison of respondents with and without burnout. The multivariate logistic regression model showed the risk factors for burnout. The model was significant and the Cox & Snell’s and Nagelkerke’s Roctorate . On the The MBI – HSS questionnaire revealed that the two crucial dimensions for the definition of burnout, EE or DP, were high in 63% of the respondents. This confirms that burnout is common in the population of Croatian physicians. Although the analysis did not identify any one particular specialty group to be at risk of burnout, physicians in training and those in tertiary or primary institutions, as well as those without an academic title and those holding a doctorate, were found to be at risk.Since the questionnaire used was not previously validated for the population of Croatian physicians, we assessed its validity and reliability. The validation methods used deemed the Croatian version of the MBI – HSS questionnaire suitable for the population of Croatian physicians. We acknowledge that the reliability of the EE dimension is not very high, since the confidence interval spans below the boundary margin. However, the alpha coefficient for all three dimensions was 0.84, suggesting relatively high overall internal consistency. Exploratory factor analysis grouped the items of the MBI – HSS questionnaire into three latent dimensions. The three extracted factors correspond to the three key dimensions of burnout assessment. None of the items of the inventory split across all three extracted factors with high loadings and therefore no item was discarded.Several studies focused only on EE and DP among physicians ,18 and cBurnout among Croatian physicians was previously investigated in two subpopulations of physicians: in a tertiary hospital environment at the University Hospital Center Rijeka  and amonEven though among demographic characteristics we did not find independent risk factors for burnout, the risk was increased in residents. These results are in line with a study that confirmed residents to be especially prone to burnout . ContrarWhen exploring the effect of working environment on burnout we found that physicians working in tertiary hospitals were mostly affected and at the greatest risk, followed by those working in primary care. The study on prospective predictors of professional burnout in hospital nurses of University Hospital Center Rijeka showed that EE and DP were most significantly influenced by role conflict and work overload . Based oWhile Tomljenović et al did not find any difference between surgical, non-surgical, and diagnostic groups of respondents , in our An important strength of our study is the cross-sectional design, with a good response rate for an online survey , as wellOther studies have shown that burnout syndrome can lead to physicians wishing to leave their current work position or the entire field of medicine . The Cro


This study shows that a better cross-cultural social adaptation was positively connected to a higher level of overseas life satisfaction in general, and more specifically to higher levels of satisfaction with food, housing, transportation, entertainment, and security. This knowledge can be utilized in promoting cross-cultural social adaptation and overseas life satisfaction among CMATMs in Africa.This study evaluated the relationship between cross-cultural social adaptation and overseas life satisfaction among Chinese medical aid team members (CMATMs) in Africa. A revised Chinese version of the Sociocultural Adaptation Scale (CSCAS) was used to measure participants’ cross-cultural social adaptation. The self-designed survey of the CMATMs’ overseas life satisfaction includes the following five aspects: food, housing, transportation, entertainment, and security. Electronic questionnaires were distributed non-randomly. Linear regression models were established to explore the association between cross-cultural social adaptation and all dimensions of overseas life satisfaction. After adjusting all the confounders, compared with moderate adaptation, poor adaptation was negatively correlated with all dimensions of overseas life satisfaction (B for food = −0.71, B for housing = −0.76, B for transportation = −0.70, B for entertainment = −0.53, B for security = −0.81, B for overall satisfaction = −0.71, all  With the acceleration of globalization, a greater degree of political, economic, and cultural exchanges have increasingly been occurring among different countries and regions . An incrHowever, despite China’s active efforts toward expanding the scope of China–Africa health cooperation, CMATMs have not shown strong willingness to participate in foreign medical aid to African countries ,8. CMATMLife satisfaction reflects individuals’ overall cognition and self-assessment of their living conditions from a subjective psychological aspect, by comparing individuals’ living conditions with the satisfaction criteria that they hold for their lives, or at least for a certain period of their lives ,12. HoweThe present study adopted a cross-sectional design. All CMATMs who were carrying out medical assistance missions in African countries during the period from 15 August 2016 to 20 November 2016 were our potential study subjects. Our potential study subjects were all the CMATMs who were in service in African countries. The study was commissioned by the former National Health and Family Planning Commission of the People’s Republic of China (NHFPC). Prior to conducting this cross-sectional survey study, a QQ (a mobile instant messaging app with the largest user base in China.) group that included most of the CMATMs in African countries was created by the NHFPC. By using the QQ group, all of the relevant information (including the contents and procedures) of the investigation were effectively publicized in advance, and related questions raised by the CMATMs in African countries were also answered in time during the investigation. The questionnaire was designed by experts in the relevant fields, and a pilot study was previously conducted among the team leaders of the CMATMs in Africa. All electronic questionnaires were distributed non-randomly by the information platform of the Global Health Institute of Wuhan University. Three hundred and thirty-five questionnaires were returned. Out of all the questionnaires returned from the potential participants, a total of 18 questionnaires were completed with poor quality . Therefore, these questionnaires were excluded from the final analysis. Consequently, three hundred and seventeen valid questionnaires were selected, and the effective recovery rate of the present study was 94.63%. The investigation was conducted anonymously and all the CMATMs in African countries were asked to answer the questionnaires independently. The research teams believe that potential bias should have been avoided to a certain extent.The questionnaire used in this study included three sections: participants’ essential information, participants’ cross-cultural social adaptation, and participants’ overseas life satisfaction in African countries.The first section determined the demographic characteristics of the participants, including the participants’ gender , age groups , marital status (not married/married), educational level , prior overseas experience (yes/no), type of service regions , gross annual income , and length of service . These indicators were considered as confounding factors in this study.This section adopted the Chinese version of the Sociocultural Adaptation Scale (CSCAS), as developed by Qi and Li . The CSCThe third section was the self-assessment questionnaire of the CMATMs’ overseas life satisfaction in African countries. This self-designed measurement tool included a total of 18 questions in five aspects, including food, housing, transportation, entertainment, and security. The questionnaire also adopted a 5-point Likert scale, and the various aspects and the overall average scores were calculated. A higher score indicated a higher level of overseas life satisfaction in African countries. In this study, the Cronbach’s alpha coefficient of the questionnaire was 0.91.p-value of less than 5% for all tests indicating statistically significant differences. The content of the analysis was composed of three main parts. First, the overall characteristics of the study population as well as the characteristics of the study population by level of cross-cultural adaptation were initially summarized by descriptive analysis. Chi-square tests were used to examine the differences in demographic characteristics among the CMATMs with different levels of cross-cultural adaptation  version 22.0 for Windows  was used to perform all the data analyses, with a two-sided aptation . The aveaptation . FinallyThe participants were guaranteed no risk involved in participating in the survey, and the survey was conducted anonymously online. Participants were assured that the data would be treated confidentially. Our study was conducted in accordance with the Declaration of Helsinki, and the study protocol was reviewed and approved by the institutional review board of School of Health Science of Wuhan University (Project Identification Code: 2016-S-0011-4/03).2 = 13.724, p = 0.008), prior overseas experience , and the length of service  among the CMATMs with different levels of cross-cultural adaptation  women and 208 (65.62%) men were involved in the cross-sectional study, including 108 (34.07%) respondents with poor cross-cultural adaptation, 148 (46.69%) with moderate adaptation, and 61 (19.24%) with good adaptation. Most of the participants were in their forties (46.37%) and married (85.80%). Of the respondents, 63.09% received undergraduate education and 72.87% had no prior overseas experience. Slightly more than a quarter (27.44%) of participants worked in class II hard regions and nearly one-third (32.18%) earned between 130,000 and 190,000 CNY a year. About 40% participants had provided service for 6–12 months. Significant differences were revealed on the distribution of age (χaptation .p < 0.001). Furthermore, the life satisfaction scores increased with increases in the degree of cross-cultural adaptation across all dimensions , housing , transportation , entertainment , security , and the overall satisfaction , whereas good adaptation was positively associated with the life satisfaction of food , housing , transportation , entertainment , security , and the overall life satisfaction .As demonstrated in From the perspective of global governance, providing medical assistance to African countries is a typical manifestation of China’s provision of public goods for the global health governance system . FurtherChina is playing an increasingly essential role in the development of health assistance in other countries. Undoubtedly, the importance of medical teams—one of the primary ways in which China helps provide medical aid to Africa—cannot be trivialized . PreviouIn this study, we examined the correlation between intercultural adjustment and the life satisfaction of workers in foreign aid medical teams. The results revealed positive relationships between cross-cultural social adaptation and each dimension of life satisfaction, and the association still remained the same after adjustment for all confounders. A longitudinal analysis conducted in Portuguese college students indicated that higher academic adaptation may lead to better global life satisfaction . MoreoveIn the life satisfaction assessment, transportation scored the highest, whereas entertainment scored the lowest regardless of the degree of adaptation. There are several explanations for this phenomenon. As indicated by Davies et al., a large number of concessional loans provided by The Export-Import Bank of China were invested in infrastructure development . AdditioThis study also found that security was positively correlated with cross-cultural adaptation. Insecurity may be caused by the danger of infectious diseases and terrorist attacks. For one thing, the destinations of foreign aid are usually developing countries with high prevalence of infectious diseases, such as malaria, Dengue, and Ebola. As mentioned in a previous article, morbidity was relatively high among travelers who visited developing countries, and the type of disease was correlated with travel destinations . In termAssociations of intercultural adjustment with satisfaction of food and housing were revealed in our study as well. The results were similar to the findings of Schure et al., who showed that food and housing insecurity may be detrimental to physical and psychological health . As a maA number of limitations of this study should be elucidated. For instance, some confounders, especially those that are more related to subjective well-being and other variables more related to psycho-social aspects, were not included as covariates in the data analyses. Secondly, this study may have provided a general overview of the association between cross-cultural social adaptation and overseas life satisfaction among CMATMs in Africa, yet there are still a lot of knowledge gaps that need to be filled . For future studies, it is necessary to explore this issue from different research perspectives in combination with a multidisciplinary approach in order to allow for a more in-depth study.In conclusion, our study showed that overseas life satisfaction in general, and also more specifically in terms of food, housing, transportation, entertainment, and security, was positively related to cross-cultural social adaptation among Chinese medical aid team members (CMATMs) in Africa. The present study indicated the possibility that improving the overseas living conditions, especially the food, housing, transportation, entertainment, and security conditions, could be an effective way to promote cross-cultural social adaptation for CMATMs in Africa.


Objective: Additional and comorbid diagnoses are common among suicide victims with major depressive disorder (MDD) and have been shown to increase the suicide risk. The aim of the present study was first, to investigate whether patients with severe depression/melancholia who had died by suicide showed more additional psychiatric disorders than a matched control group. Second, general rates of comorbid and additional diagnoses in the total group of patients were estimated and compared with literature on MDD. Method: A blind record evaluation was performed on 100 suicide victims with severe depression/melancholia (MDD with melancholic and/or psychotic features: MDD-M/P) and matched controls admitted to the Department of Psychiatry, Lund, Sweden between 1956 and 1969 and monitored to 2010. Diagnoses in addition to severe depression were noted. Results: Less than half of both the suicides and controls had just one psychiatric disorder (47% in the suicide and 46% in the control group). The average number of diagnoses was 1.80 and 1.82, respectively. Additional diagnoses were not related to an increased suicide risk. Anxiety was the most common diagnosis. Occurrence of suspected schizophrenia/schizotypal or additional obsessive-compulsive symptoms were more common than expected, but alcohol use disorders did not appear very frequent. Conclusions: The known increased risk of suicide in MDD with comorbid/additional diagnoses does not seem to apply to persons with MDD-M/P (major depressive disorder-depression/Melancholia). Some diagnoses, such as schizophrenia/schizotypal disorders, were more frequent than expected, which is discussed, and a genetic overlap with MDD-M/P is proposed. Patients with an affective disorder have an increased risk of suicide compared to the general population , and 4–6Several studies have also shown that people who have committed suicide often had more than one psychiatric disorder. Psychiatric comorbidity usually implies a secondary psychiatric diagnosis or alcohol/drug abuse. Comorbidity is common in all mental illness, including depression . The mosComorbid psychiatric diagnoses have more frequently been found in suicide victims than in non-suicides . HenriksVery few studies have examined depression with melancholic features and suicide. Parker et al. found that subjects with depression with melancholic features had a greater prevalence of suicidal ideation ,17. HoweMelancholia is described, not as a specific diagnosis, but as a specifier of MDD according to DSM-5 , who develop depression due to overconsumption of alcohol. This difference may have an impact on suicidal behaviour and suicide risk. Secondary depressives were therefore excluded.) These subjects were compared with 100 matched controls. Case records and multiaxial schedules were evaluated.The first aim of the study was to compare additional and comorbid disorders for suicides and controls to examine whether these disorders were related to an increased suicide risk in MDD-M/P as has been found for other mental disorders, such as MDD.Were comorbid/additional psychiatric disorders more frequently found in suicides with MDD-M/P than in controls?Did any specific type of additional disorder discriminate between suicides and controls?A second aim was to find out whether there was a different spectrum of comorbid/additional diagnoses in MDD-M/P as compared MDD (as found in literature):• How frequent are different psychiatric disorders in addition to MDD-M/P in the total group?In the 1950s and 1960s, all inpatients at the Department of Psychiatry, University Hospital, Lund were rated on a multiaxial diagnostic schedule by a senior doctor with at least three years of training at discharge . The schA total of 1206 patients were given this diagnosis (506 men and 700 women). Their mortality was followed-up in three sessions: to 1 January 1984 ,25, 1 JaThe case records of the suicides and matched controls were prepared for blind evaluation by omitting the last sheet with possible information on the suicide, as has previously been described , and a sCase-record studies on all 200 patients included validation of diagnoses on the multiaxial rating scale against DSM-IV criteria  for MDD-Good correspondence was found, as 91% of the patients in both the suicide and control group could be shown to meet the criteria for MDD-M/P. The mean number of depressive episodes was 3.2 (range 1–32), and average time of follow-up was 14.5 (SD+/−10.7) years. There were 44 men and 56 women in each group. The mean age at first depressive episode was 41 (SD+/−15.07). No significant differences in social class between suicides and controls had been found in a previous study .In the present sample, 20 cases of bipolar disorder were found in both suicides and controls . In all Diagnoses additional to MDD-M/P were assessed according to ratings in the case records. They sometimes occurred during the depressive episode and were then comorbid, but they could also occur during another admission. There was sometimes a switch between different types of episodes during the long-term follow-up. These diagnoses were ‘suspected schizophrenia/schizotypal disorder’, ‘organic disorder’ (including dementia), and ‘schizoaffective disorder’. Comorbid symptoms of ‘anxiety’ and ‘obsessive-compulsive symptomatology’ were also rated. Finally, some patients developed AUD. These were secondary to depression, as primary cases were excluded. The additional diagnoses were evaluated in the same way in both the suicide and control groups, but often the description of symptoms was not sufficiently detailed to allow validation against DSM-IV . ‘AnxietA logistic regression was performed to compare rates of different diagnoses in suicides and controls. Mann-Whitney’s U-test was used to compare number of episodes. The study was approved by Lund University Medical Ethics Committee in 1985 and 2003.The number of disorders, including the index diagnosis MDD-M/P, is presented in A similar number of patients in the suicide and control groups had two disorders (32% versus 33%). Similar numbers were also found in the groups for three, four or more disorders without any significant differences. The suicide group had an average of 1.80 psychiatric diagnoses, including the index depression, compared to the control group, which had 1.82. Female suicides had 1.9 episodes versus 2.0 for controls, and the corresponding figures for males were 1.6 versus 1.6. Comorbid/additional disorders did not appear to be a risk factor for suicide in MDD-M/P.The individual disorders apart from MDD-M/P are presented in Schizophrenia/schizotypal disorders, including one case of paranoid schizophrenia, occurred in 9.5% of the total sample. In five cases the episode preceded the depressive episode, and in ten cases episodes succeeded the depression. Three cases were mixed and in one case the schizotypal episode occurred between the depressive episodes.Comorbid anxiety was common and found in 39.5% of the patients.A schizoaffective disorder was found in 3.5% of the patients. Organic syndromes, including dementia, occurred in 10% of the patients. OCS was found in 10%, and alcohol use disorders in 4%. Finally, one suicide had a personality disorder according to the multiaxial schedule. The present results indicate that comorbid or additional diagnoses did not increase the risk of suicide in patients with MDD-M/P. Less than half of the patients among suicides and controls had only one psychiatric diagnosis, and the average number of diagnoses was 1.8 in both groups. The pattern of comorbidity/additional disorders in MDD-M/P appears to be different from MDD, with high rates of schizotypal disorders/schizophrenia, and OCS and AUD were not common.Most studies show an increased suicide risk with comorbid disorders ,14. DataThe apparent lack of impact of comorbid/additional disorders on suicide risk in MDD-M/P, as opposed to MDD, could be interpreted as melancholia being a separate entity, as has been proposed by some authors . MelanchAnother finding in the present study was that the overall comorbidity was somewhat different from what is usually found in non-melancholic depression. There were high rates of schizophrenia/schizotypal disorders, and obsessive/compulsive symptomatology, but low rates of AUD, regardless of the suicidal outcome.In the present study anxiety 39.5%) was the most common comorbid diagnosis, which agrees with other studies. Thaipisuttikul et al. suggested in 2014 that almost 21% of patients with MDD had at least one type of anxiety disorder . A large.5% was tThe frequency of schizophrenia (9.5%) was much higher than the estimated median lifetime morbid risk of schizophrenia in a systematic review, which was 7.2/1000 persons , and theDepressed mood is common both during the prodrome of schizophrenia and after the onset of psychosis. A population-based study of first episode of schizophrenia showed that the most frequent initial symptom of schizophrenia was depressed mood. It was also found that 71% of the subjects with schizophrenia presented with clinically relevant depressive symptoms, and 23% fulfilled the ICD-10 criteria for a depressive episode in their first psychotic episode . SchizopGenetic studies have shown that schizophrenia, bipolar disorder and MDD share genetic risk factors ,33. SeveIt has been suggested that there is a subgroup of MDD that is causally related to schizophrenia . The preOCS was quite common in the present sample, 12% versus 8% in suicides and controls, unlike another study where these disorders were rare among persons with MDD , and a fDepression may represent the first sign of dementia , and it Comorbid diagnoses often include AUD, i.e., alcohol and drug abuse. Patients with primary alcohol abuse were excluded. Secondary alcohol abuse was included (4%). According to Parker et al. the comorbid alcohol abuse was small in melancholics and non-melancholics, 2.2% in both, which corresponds with the findings in the present study . AUD mayOne strength was the good correspondence between MDD-M/P and severe depression/melancholia according to DSM-IV in a previous evaluation of the present sample. The long-term follow-up and fairly large sample size are other strengths. However, the additional disorders could not be evaluated against DSM-IV, which is a limitation. All symptoms may not be noted in the case records, which may also lead to an underestimate of symptomatology. AUD is probably underestimated, as there was no systematic inquiry, but this probably does not affect the comparison between suicides and controls, as the evaluation is the same in both groups.Another limitation is the in-patient sample, which is not fully representative of a community sample.When estimating the rates of comorbid/additional disorders for the total sample, there is a question about the representativity of control group for the total sample of non-suicides. Although the patients were matched for age and index admission year, some sociodemographic factors may be risk factors for suicide. However, there were similar female/male rates in the total sample (700/506 = 1.38) and in the present controls (56/44 = 1.27). Social group did not discriminate between suicides and controls in a previous study on the same sample . In thatComorbid/additional diagnoses were common in the present sample of patients with MDD-M/P. However, there were no increased rates among suicides compared to controls, so there was no indication of increased suicide risk with additional diagnoses. This contrasts to what has been found for MDD. Severe depression/melancholia may have a high suicide risk per se, and additional diagnoses do not appear to increase the risk.Schizophrenic/schizotypal disorders were unexpectedly frequent, and a common genetic disposition with MDD-M/P, possibly higher than for MDD, is proposed. This finding may be an interesting topic for future research on a larger sample of patients with more systematic diagnostics and genetic testing. Other common disorders were anxiety and OCS. These findings support the view of MDD-M/P being qualitatively different from MDD.


Background: Lower urinary tract symptoms (LUTS) suggestive of benign prostatic hyperplasia (BPH) is a common condition affecting men. Studies have shown that the prevalence of LUTS/BPH increases with age, which will cause considerable economic burden to the healthcare system and society. The aim of the present study was to evaluate the long term cost effectiveness of dutasteride and tamsulosin therapy compared to tamsulosin alone in men with BPH in Hong Kong.Methods: A Markov decision model was constructed to estimate the economic impact from a healthcare payers’ perspective, which only included direct costs. Analyses were conducted for a 4-year time frame.Results: When compared to tamsulosin alone, combination therapy was more expensive but also more effective in preventing complications and reduced the need for surgery. Over life-time projection suggest that combination therapy will be cost-effective if the willingness-to pay threshold of USD 20,000.Conclusion: Findings of this study found that combination therapy of tamsulosin and dutasteride was more cost-effective compared to tamsulosin alone across a wide range of scenario. Lower urinary tract symptom (LUTS) suggestive of benign prostatic hyperplasia (BPH) is a common condition among middle-aged to elderly men. It is characterized by a cluster of chronic urinary symptoms in the bladder, prostate, and a major cause of benign prostatic hyperplasia. Population based studies suggested that nearly one in every four men aged 50 and above is affected by LUTS . SimilarTM (dutasteride) and tamsulosin (CombAT) trial . Currently, international guidelines  recommenT) trial , 2011. IIn terms of economic burden, BPH/LUTS is associated with high personal and societal costs, which are evident in direct medical costs and indirect losses in daily functioning, and through its negative impact on quality of life (QoL) for both patients and partners . Treatme®), compared with oral, daily tamsulosin 0.4 mg in Hong Kong (HK).In view of this, the objective of our study was to evaluate the long-term cost-effectiveness of oral, daily, single-dose combination therapy dutasteride/tamsulosin , or die due to natural causes. After experiencing an AUR episode, the patient could transition back to BPH state. After TURP, a patient would receive medical intervention or have a repeated TURP procedure if the initial surgical procedure is not successful. Patients who have undergone TURP could die due to complications of the procedure, or they could die due to other causes. A patient in TURP, repeated TURP or medical intervention state could recover back to healthy state.The model was structured according to the HK-specific treatment practice, and is shown in The analysis was performed from the healthcare payers’ perspective, which only included direct costs. A cycle length of 1 year was adopted to capture the full effect of both intervention in terms of resource use and quality of life. In the base-case scenario, the model was simulated over 4 years, i.e., duration of the trial. To assess the sensitivity of the model results to the time horizon, the model was also run for 35 years, i.e., patients’ life span. A discount rate of 3% was applied to both cost and outcome.There are a few assumptions made in our model as described in the following:(1)In reality, BPH state can be classified according to severity, i.e., mild, moderate, and severe states. However, due to the lack of granular data on symptom severity as measured by the International Prostate Symptom Score (IPSS) of BPH patients, we modeled patients into one BPH state;(2)It is assumed that high proportion of acute urinary retention (AUR) patients (80%) will receive transurethral resection of the prostate (TURP) procedure. This uncertainty will be addressed using 1-way and multivariate probabilistic sensitivity analyses;(3)Patients who recover from the first TURP procedure are assumed to incur only one follow-up cost. Medical intervention means the use of pharmacological agents for follow-up management;(4)Post-TURP death due to TURP-related complications is defined as death which occurs within 30 days after TURP procedure;(5)The second TURP procedure will require different amount of resources compared to the first TURP; Based on local literature, post-TURP death due to second TUPR is assumed to be the same as that from first TURP;(6)It is assumed that patients will receive at most 2 TURP procedures.Table 1, model parameters including transition probabilities, efficacy, costs, and utilities were derived from HK-specific sources, literatures and assumptions based on clinical inputs.As summarized in The majority of the transition probabilities were derived from a cohort of 200 BPH patients from Prince of Wales Hospital. Those patients comprised of roughly 10% of overall BPH patients in HK thus were considered representative of all BPH patients’ profile in HK. The remaining probabilities were obtained from published literature where available. In addition to mortality due to TURP procedure, the model also allowed for patients to die from all-cause mortality which was obtained from HK life table. The efficacy of the different interventions were derived from a 4-years, multicentre, randomized, double-blind, parallel-group CombaT clinical trial which included 4,844 men ≥50 years of age with a clinical diagnosis of BPH, International Prostate Symptom Score ≥12 . The acqOutcome measure is expressed as incremental cost per quality-adjusted life year (QALY) gained. As of now, there is no cost-effectiveness threshold in Hong Kong, 3 times Hong Kong GDP per capita 2017  recommended by WHO-CHOICE  The CHOITo identify key model parameters, OWSA was conducted over the range of pre-defined values of each parameter’s point estimate . Results were plotted in a tornado diagram according to the extent of the parameter’s impact on the incremental cost-effectiveness ratio (ICER).Table 2 presents the categories of model parameters, probability distributions as well as the upper and lower values used in the multivariate probabilistic sensitivity analysis.To assess the simultaneous influence of model parameters on the ICER, a multivariate probabilistic sensitivity analysis was performed using second-order Monte Carlo simulation . A total of 10,000 Monte-Carlo iterations were simulated, each generating a model-estimated value for the cost and QALY. The cost-effectiveness plane was produced depicting the scatterplot of the 10,000 simulated sets of cost and QALY estimates. In addition, a cost-effectiveness acceptability curve (CEAC) was generated to display the probability of cost-effectiveness of both interventions at each willingness-to-pay threshold. The model was implemented in TreeAge pro 2017 . A microsimulation of 10,000 patients was executed to enable the tracking of the number of clinical events.Table 3, the Markov microsimulation based on 10,000 iterations showed that, over 4 years, compared to tamsulosin, combination therapy could prevent 0.03 AURs (∼27% reduction) per patient, 0.07 TURPs (∼32% reduction) per patient, and 0.002 deaths (∼3.5% reduction) over 4 years. Compared to tamsulosin, combination therapy can lead to cost reduction of US$31, US$1,029, and US$2 per patient due to reduced episodes of AUR, TURP and need of medical intervention, respectively and additionally a delay in patient’s progression to AUR and TURP. However, those benefits came with an incremental drug cost of US$1,543 per patient over 4-year period. The increased number of BPH (3.43) for combination therapy compared to that (3.3) of monotherapy was mainly due to the delayed progression of BPH patients to AUR and TURP health states. In addition, the analysis showed that a patient on combination therapy would experience more QALYs (3 vs. 2.93 QALYs) than those on monotherapy. As a result, replacing monotherapy by combination therapy was expected to lead to US$11,651 per QALY gained.As shown in As the modeling time horizon was extended to life-time, compared to monotherapy, more health benefits were projected for patients receiving combination therapy, i.e., a reduction of 0.35 AURs per patient, 0.37 TURPs per patient and 0.0109 deaths, which translated into 0.42 QALY gained per patient. In addition, using combination therapy at an incremental drug cost of US$6,617 compared to tamsulosin could potentially save US$451 per patient in managing AUR and US$5,470 per patient in TURP procedure. Similarly, as the combination therapy reduced risks of a patient progressing to AUR and TURP health states, therefore, an incremental cost of US$749 in managing BPH was incurred.Figure 2).The OWSA showed that the top five most influential parameters on ICER were annual cost of tamsulosin/dutasteride, efficacy of tamsulosin/dutasteride against TURP, and probability of BPH patients who experienced AUR, cost of providing TURP procedure and utility of BPH. The remaining parameters had only a moderate influence on ICER estimates causing ICER to vary by no more than US$2,000. On the whole, all the ICERs were found to be between US$6,000 and US$17,000 per QALY when parameters were varied over their uncertainty range  threshold is above US$40,000. Besides, the combination therapy had a probability of 97% of being cost-effective over monotherapy at one time HK GDP per capita of US$45,887. Over life-time projection, combination therapy would have a probability of cost-effectiveness of more than 95% if WTP threshold is above US$20,000. It will achieve a probability of 99% being cost-effective at one time HK GDP per capita.As shown in Hong Kong’s healthcare system comprises of the public and private sector, with the former being the cornerstone of the healthcare system, acting as a safety net for the population. The public system currently serves 90% of all inpatient needs and ∼30% of outpatient services . It has It is worth noting that based on hospital data 80% of all patients with AUR would eventually go through the most common surgical procedure for BPH treatment, i.e., TURP. This is reflective of the reality as a small number of patients would not be fit for surgery due to various medical reasons, and besides TURP there are other surgical options for the management of TURP, e.g., laser prostatectomy. However, in the setting of the local health care system, TURP is still the majority. Such assumption for the construction of the Markov model would give a good estimation of the results.Despite the differences in epidemiology and costs, our findings were consistent with the other published cost-effectiveness analyses which also showed that combination therapy led to the potential incremental cost and benefit of QALYs gained, leading to cost-effectiveness of the new intervention. For example, a study in Canady by The present study has several limitations. Firstly, in our Markov model, due to data availability, we did not separate the state of symptomatic BPH into patients with mild, moderate and severe symptoms according to IPSS score. Instead, these 3 groups of patients were analyzed as a single group. Such categorization might have made the prediction of AUR probability less precise. As shown in OWSA, the utility of BPH has substantial impact on ICER. Future study on classification of BPH severity was thus warranted. Secondly, we didn’t model the occurrence of adverse events because, as reported in the ComBAT trial, the incidences of adverse events were very similar between combination therapy and monotherapy. In a 2015 study, complete absence of ejaculation was experienced by 23% of patients on combination therapy, and 15% on tamsulosin alone . In the In conclusion, our study shows that combination therapy as compared with monotherapy is cost-effective due to substantial reduction in the number of AUR and TURP and the associated direct cost in BPH patients in Hong Kong.Data sharing is not applicable to this article as no datasets were generated or analyzed during the current study.DW played a principal role in the study concept and design, performed the statistical analysis, interpreted the results, and wrote the draft. CY designed the study, provided statistical support, reviewed, and edited the manuscript. C-FN, KL, SL, and NC contributed to data acquisition or interpretation of data. Y-SC provided inputs in reviewing the methodology part and assisted with model calibration using TreeAge software. KL obtained the funding. All authors approved the final manuscript.The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest.


The purpose of the present study is to investigate the effect of congruence between music and paintings on the aesthetic preference of paintings. Congruence was specified as the similarity in perceived regularity and the complexity of jazz compositions and abstract paintings (the ratings of regularity and complexity in both sets of stimuli were obtained in the pilot study). In the main experiment, 32 participants rated the aesthetic pleasantness of paintings with congruent, incongruent, and no music background. In addition, they rated the music-paintings matching (how well the music goes with the painting). The results show no effect of congruence on aesthetic pleasantness ratings. The effect on the perceived matching was significant; matching is higher in the congruent compared to the incongruent condition. These findings suggest that congruency has a strong effect on the perceptual aspect of the music-paintings compatibility (visuo-auditory similarity) and no effect on the aesthetic aspect (liking). Cross-modal correspondence refers to the experience of the similarity of information from different sensory modalities ,2,3,4. IIn the present study we focused on the correspondence between two more complex auditory and visual stimuli music and paintings. Previous studies suggested that certain melodies are regularly associated with particular colors: while “sad” music (minor key) dominantly induces associations of blue, “happy” music (major key) is usually associated with yellow ,11. OtheStimuli that were used in the previous studies were usually classified in broad categories, such as figural and abstract art or classical music and jazz . These cThe main purpose of the present study was to evaluate the relevance of regularity and complexity as factors of cross-modal correspondence in a paintings-music matching task. In order to reduce the confounding effect of explicit meanings, we used only abstract paintings and instrumental jazz compositions. Other possible confounding factors, such as familiarity and aesthetic pleasantness were also controlled.The second aim of this study was to replicate the previous findings that (a) paintings followed by congruent music were preferred compared to an incongruent situation ,13,15; aTwo experiments were conducted. In the preliminary study, stimuli for the main experiment were selected. In the main experiment participants rated (a) paintings-music correspondence (matching ratings) and (b) the liking of paintings (aesthetic ratings) in different conditions—congruent, incongruent and silent.The aim of this study was to create the stimulus sets for the main experiment.Thirty-five undergraduate students from the Department of Psychology participated in the experiment .In a pre-selection session three art experts selected 71 abstract paintings and 36 jazz excerpts, so to cover the widest possible range of different styles and sub-genres. Images of paintings were downloaded from Google, while musical compositions were downloaded from the YouTube channel (The Audacity program was used for cropping the 30 s excerpts).Paintings were displayed online via the Qualtrics platform. They were presented in a random order, lasting 5 s. The same sample of participants was exposed to the randomized jazz excerpts via stereo sound system. Participants rated paintings and jazz excerpts on the four 7-step bipolar scales: Irregular-Regular, Simple-Complex, Unpleasant-Pleasant, and Unfamiliar-Familiar.Thirty-two abstract paintings and eight jazz excerpts were selected. Four sets of both paintings (8 stimuli per set) and jazz excerpts (2 stimuli per set) were specified, so that all sets had similar average ratings on pleasantness and familiarity, but different combinations of regularity/complexity ratings: low regularity–low complexity, low regularity–high complexity, high regularity–low complexity, and high regularity–high complexity see .p < 0.001, and complexity F = 86.54, p < 0.001. A post hoc test (Bonferroni) indicated significant differences between R+ and R− sets on regularity and C+ and C− sets for complexity . The effects for pleasantness and familiarity were missed, showing that the sets were equalized by those two variables.The analyses of variance have shown the significant effects of paintings sets for regularity, F = 72.59, p < 0.001, and complexity F = 381.11, p < 0.001. A post hoc test (Bonferroni) indicated the significant differences between R+ and R− sets on regularity and C+ and C− sets for complexity . The effects for pleasantness and familiarity were missed, showing that the sets were equalized by those two variables.The analyses of variance have shown the significant effects of sets of music excerpts for regularity, F = 23.38, All stimuli are listed in In the main experiment the painting-music correspondence (matching) was investigated. Also, the aim of this experiment was to evaluate the hypothesis that a higher congruence between the paintings and the music should induce a higher aesthetic liking of the paintings.32 volunteers employed by the “VIP Mobile” company, predominantly from HR, Marketing, and IT sectors .32 abstract paintings and 8 one-minute excerpts of jazz compositions that were classified in four sets specified in the pilot study (see Stimulus section).In the first part of the experiment, participants were asked to rate paintings (1) simultaneously presented with congruent music ; and (2) simultaneously presented with incongruent music . The instruction did not mention music. Namely, participants were asked to rate the paintings, not to evaluate the overall experience of the picture and music. All combinations of stimuli were shown in Congruence (C/I conditions);Congruence/silence ;Incongruence/silence .The experiment included three one-factorial designs:Ratings of paintings liking.Ratings of paintings-music matching.Dependent variables:p < 0.01  = −3.25, 0.01 see .p > 0.05.No difference between congruent and incongruent conditions was obtained, t(30) = −0.57, p > 0.05.No difference in preference between music condition and silent condition was obtained, t(31) = 0.7, The finding that paintings and music are perceived as more corresponding in congruent conditions suggests that (in)congruent situations were specified appropriately in the pilot study. In other words, our results indicate that congruence based on perceptual dimensions such as regularity and complexity could be taken as the basis of evaluation of a paintings-music matching.On the other hand, our results suggest that music per se has not appeared to be a significant factor in navigating the preference of paintings. One of the possible explanations could be the instruction which the participants were given. By asking them to evaluate only the preference of the painting, they could easily divide the aesthetic experience of two art modalities and focus only on the experience of the paintings while ignoring the experience of the music. Instead of that, further experiments should adopt a more gestaltistic approach and focus on the aesthetic experience of the whole multimodal percept. Apart from the effect of instructions, these results might also be caused by the genre homogeneity of stimuli (abstract paintings and jazz). Namely, it is possible that an increase in the genre variability would induce a stronger expression of the effect of music, similar to that identified in a previous study . In orde