Survival and predictors of mortality among colorectal cancer patients on follow-up in Hawassa University Comprehensive Specialized Hospital, Sidama region, Southern Ethiopia, 2022. A 5-year retrospective cohort study.

BACKGROUND: The incidence and mortality of colorectal cancer were still rising rapidly in many low-income and middle-income countries, which was linked to ongoing societal and economic status. Colorectal cancer is the leading cancer in Ethiopia with relatively lower survival. However, colorectal cancer patients' survival time and predictors have not been well studied in Southern Ethiopia. OBJECTIVE: This study aimed to assess five-year survival and predictors of mortality among colorectal cancer patients at Hawassa Comprehensive Specialized Hospital, Ethiopia. METHOD: Facility-based retrospective cohort study was conducted among 323 patients who visited Hawassa Comprehensive Specialized Hospital from May 1st, 2017 to April 30th, 2022. The Kaplan-Meier survival curve with the Log-rank test was used to estimate the survival time. Bivariable and multivariable Cox proportional hazards regression models were used to determine the net effect of each independent variable on time to death after diagnosis. RESULT: Over the 5-year observation period, the overall mortality rate was 38.5%, with an incidence density of 31 fatalities per 100 person-years observation. Survival at 1, 2, 3, 4, and 5 years was 78%, 53, 32.4%, 23.3%, and 18.7% respectively. The multivariable analysis showed that metastatic disease (AHR = 4.2, CI: 1.5-11.5), baseline carcinoembryonic antigen level ≥5ng/ml (AHR: 2.4, CI: 1.2-5.8), living in rural areas (AHR = 2.2, CI:1.03-4.8) and mucinous carcinoma (AHR = 0.33, CI: 0.13-0.87) were independent predictors of colorectal cancer mortality. CONCLUSION: Overall survival of colorectal cancer patients in the study was low compared to similar studies in developing and developed worlds. A significantly low survival rate was observed for patients with advanced stage, elevated carcinoembryonic antigen levels, and rural residents indicating the key role of early detection and timely initiation of treatment to improve survival and quality of life of patients with colorectal cancer.

Factors affecting need and utilization of palliative care services among Ethiopian women in an oncology department: A hospital-based cross-sectional study.

Background: Palliative care, which aims to alleviate physical and emotional distress from cancer, is underutilized in many African healthcare systems. Therefore, there is a lack of data on the need and utilization of palliative care services among women with breast cancer in Ethiopia. Objectives: The goal of this study was to identify the level of need and utilization of palliative care services and identify associated factors among women in an oncology department of Hawassa comprehensive and specialized hospitals. Design: Hospital-based cross-sectional study. Methods: A total of 121 women age ⩾18 years old with breast cancer participated from 1 August to 30 October 2021. A hospital-based consecutive sampling technique was used. Data regarding the need and utilization of palliative care services were collected via questionnaire and interview, entered using EpiData 4.6.0.6, and analyzed by SPSS version 25. Variables with p < 0.25 were considered for multivariate analysis, and those with p < 0.05 indicate an association with palliative care utilization. Result: Seventy-two (59.5%) had worse utilization of palliative care services, with higher odds in rural areas (adjusted odds ratio = 11.82). Conclusion: The study findings indicated that more than half of the study participants had worse utilization of palliative care services, with rural living being a contributing factor.

Building pathology capacity in sub-Saharan Africa to improve breast cancer diagnosis and treatment: training laboratory technicians in high-quality manual immunohistochemistry.

BACKGROUND: To address the need for a skilled workforce in breast cancer (BC) pathology in sub-Saharan Africa (SSA), we implemented an education program to train laboratory technicians in manual immunohistochemistry (IHC). METHODS: A quality improvement education project was developed. Interactive webinars were held every six months with didactics and presentations from African experts with experience in IHC. We conducted knowledge assessments and surveys on current practice, equipment, and human resources. A digital mentorship platform (DMP) was created for discussions, sharing SOPs, and networking. For one year (2022-2023), we followed developments in pathology capacity, practice changes, and educational needs. A paired t-test was used to calculate the significance of changes in knowledge immediately after the webinar and comfort level with topics 35 days after the webinar. RESULTS: Two hundred and sixty six participants from 10 SSA countries attended the first webinar, a series of six lectures on IHC theory, methods, and practice. Ninety-five participants from nine SSA countries provided a baseline assessment of pathology capacity and feedback. Mean knowledge increased by 17.4% immediately after the webinar (from 41.8% pre-webinar to 59.2% post, p = < 0.0001). Self-reported comfort level in topics 35 days after the webinar increased by 11.3%, but this was not statistically significant (mean 3.36 pre- to 3.74 post, p = 0.1). Over six months, recordings were accessed 412 times. After six months, the second webinar had 93 participants from eight SSA countries. Membership in the DMP increased from 64 to 172; recordings were viewed 412 times in six months; and 113 participants from nine SSA countries completed surveys. Among 74 respondents who perform IHC, 43.5% reported moderate or significant positive practice changes such as improved antigen retrieval techniques and optimization of preanalytical variables. Over half (52.7%, n = 39) reported the quality of slides had moderately or significantly improved. After one year, a third webinar had 98 participants from eight SSA countries. Thirty-eight completed surveys, DMP membership increased to 199, and 1 reported launching IHC in a lab in Nigeria. CONCLUSIONS: Our program 1) reached hundreds of participants and provided a baseline assessment of pathology capacity across nine SSA countries; 2) created a novel mechanism to build pathology capacity and assess progress with this cohort; and 3) improved practices and the preparation of slides for over half performing manual IHC. After one year, interest was sustained. Tracking impact on diagnosis and treatment of BC in the region is needed long-term.

Immunohistochemistry-derived subtypes of breast cancer distribution in four regions of Ethiopia.

Purpose: Different biological characteristics, therapeutic responses, and disease-specific outcomes are associated with different molecular subtypes of breast cancer (BC). Although there have been different studies on BC in the Ethiopian capital city of Addis Ababa, there have been few studies in other parts of the nation, and none have evaluated biological characteristics in other locations in the context of the extensive ethnic and genetic diversity found in Ethiopia. This study was carried out to evaluate the distribution of immunohistochemistry (IHC) subtypes of BCs throughout four Ethiopian regions. Methods: A total of 227 formalin-fixed paraffin-embedded (FFPE) tissue blocks were collected from tertiary hospitals in four Ethiopian regions between 2015 and 2021. The IHC staining was performed for subtyping, ER, PR, HER2, and Ki-67 proliferation markers. Results: The mean age at diagnosis was 43.9 years. The percentage of ER and PR-negative tumors were 48.3% and 53.2%, respectively. The IHC subtypes showed the following distribution: 33.1% triple-negative breast cancer (TNBC), 27.6% luminal B, 25.2% luminal A, and 14.1% HER2 enriched. In multiple logistic regression analysis, grade III and HER2 positivity were associated with larger tumor size, and also originating from Jimma compared to Mekele. Conclusion: Patients with ER-negative, PR-negative, and TNBC were found in 48.3%, 53.2%, and 33.1% of cases, respectively, showing that half the patients could potentially benefit from endocrine treatment. A considerably high prevalence of TNBC was reported in our study, demanding additional research that includes genetic predisposition factors. Additionally, aggressive tumors were found in a high percentage of younger age groups, which must be considered when planning personalized treatment strategies.

Exploring Challenges Related to Breast Cancer to Identify Opportunities for Advocacy in Hawassa City, Southern Ethiopia: A Community-Based, Qualitative Study.

PURPOSE: The aim of this study was to explore breast cancer (BC) challenges to identify opportunities for advocacy in southern Ethiopia in 2022. METHODS: Twenty-five participants from four local districts (kebeles) in Hawassa City were selected as key contributors to future work. Semistructured in-depth interviews were held for two clinicians, two local health bureau managers, two media managers, and three religious leaders. Two focus group discussions were conducted: one included six BC survivors and a caregiver; the other included two health extension workers, three members of the Women's Development Group, two community volunteers, one kebele leader, and one traditional healer. RESULTS: To our knowledge, our study was the first time that most participants had assembled. Many referred to patients as victims and BC as a killer disease or curse. Community and religious leaders were concerned about challenges and willing to collaborate. Survivors, providers, and religious leaders were identified as key sources of information, positive messages, and leadership. CONCLUSION: Recommendations for advocacy work in Hawassa include lobbying for BC as a health priority; including BC within the health extension package; initiating programs for earlier detection; educating the community to remove stigmas of the disease and treatments; working with media to disseminate messages that are inclusive of people in remote areas and speaking different languages; improving availability, affordability, and access to care; and assisting patients with psychosocial support. A strategic collaboration between religious leaders and health care providers was identified to increase community awareness and support advocacy for patients.

Utilization of palliative care and its associated factors among adult cancer patients in Hawassa University comprehensive specialized hospital oncology center, Hawassa, Ethiopia, 2021: a cross-sectional study.

OBJECTIVE: To assess the utilization of palliative care (PC) and its associated factors among adult cancer patients in Hawassa University Comprehensive Specialized Hospital (HUCSH) oncology center, Hawassa, Ethiopia, 2021. METHODS: An institution-based cross-sectional study was conducted among adult cancer patients. Randomly selected adult cancer patients (≥ 18 years of age) attending their treatment at HUCSH oncology center PC unit were included. Data was collected from June to August, 2021. The aim was to interview 185 patients. A structured questionnaire was used to collect the data. Data entry was done using Epi-Data version 4.6 and bivariate and multivariate logistic regression models were used in SPSS for analysis. RESULTS: Out of 180 study respondents, 66% were aged 50 years or older. Sixty-three percent were characterized to have a better utilization of PC services. Patients aged below 50 years (adjusted odds radio (AOR) = 2.7; 95% CI = 1.13-6.63), with a higher educational status (grade 9 to 12 or college/university graduation (AOR = 1.46; 95% CI = 0.41-5.21, and AOR = 3.23; 95% CI = 0.98-10.61, respectively), with a higher income >5,500 Birr (AOR = 2.7; 95% CI = 0.51-5.76), with and good accessibility of PC services (AOR = 2.99; 95% CI = 1.21-3.28) were significantly associated with better utilization of PC services. CONCLUSION: The current study revealed two thirds of patients had better utilization of PC services. Older patients with low educational status and income and those living in rural areas had worse access to PC services. It is recommended to improve information provision about PC especially for older patients and patients with low education and to improve accessibility for patients in suburban and rural areas.

Pathways and Referral of Patients with Cancer in Rural Ethiopia: A Multi-center Retrospective Cohort Study.

INTRODUCTION: Well-organized patient pathways are essential to achieve early diagnosis and timely treatment of patients with cancer in Sub-Saharan Africa. This retrospective cohort study describes pathways and referral patterns of cancer patients in rural Ethiopia. PATIENTS AND METHODS: The retrospective study took place from October to December 2020 at 2 primary- and 6 secondary-level hospitals in southwestern Ethiopia. Of 681 eligible patients diagnosed with cancer between July 2017 and June 2020, 365 patients were included. Structured interviews on the patients' pathways were conducted by telephone. The primary outcome was successful referral, which was defined as occurring when the intended procedure was initiated at the receiving institution. Logistic regression was used to assess factors associated with successful referrals. RESULTS: Patients visited on average 3 health care institutions from their first encounter with a provider until their final treatment initiation. After diagnosis, only 26% (95) of patients were referred for further cancer treatment, of which 73% were successful. Patients referred for diagnostic tests were 10 times more likely to complete referrals successfully than patients referred for treatment. Overall, 21% of all patients remained without any therapy. CONCLUSION: We found that referral pathways of patients with cancer in rural Ethiopia were largely cohesive. The majority of patients referred for diagnostic or treatment services followed the advice. Nevertheless, an unacceptable number of patients remained without any treatment. Capacity for cancer diagnosis and treatment at primary- and secondary-level health facilities in rural Ethiopia must be expanded to enable early detection and timely care.

Survival and predictors of breast cancer mortality in South Ethiopia: A retrospective cohort study.

BACKGROUND: Breast cancer is the most frequently diagnosed cancer and the leading cause of cancer death in over 100 countries. In March 2021, the World Health Organization called on the global community to decrease mortality by 2.5% per year. Despite the high burden of the disease, the survival status and the predictors for mortality are not yet fully determined in many countries in Sub-Saharan Africa, including Ethiopia. Here, we report the survival status and predictors of mortality among breast cancer patients in South Ethiopia as crucial baseline data to be used for the design and monitoring of interventions to improve early detection, diagnosis, and treatment capacity. METHODS: A hospital-based retrospective cohort study was conducted among 302 female breast cancer patients diagnosed from 2013 to 2018 by reviewing their medical records and telephone interviews. The median survival time was estimated using the Kaplan-Meier survival analysis method. A log-rank test was used to compare the observed differences in survival time among different groups. The Cox proportional hazards regression model was used to identify predictors of mortality. Results are presented using the crude and adjusted as hazard ratios along with their corresponding 95% confidence intervals. Sensitivity analysis was performed with the assumption that loss to follow-up patients might die 3 months after the last hospital visit. RESULTS: The study participants were followed for a total of 4,685.62 person-months. The median survival time was 50.81 months, which declined to 30.57 months in the worst-case analysis. About 83.4% of patients had advanced-stage disease at presentation. The overall survival probability of patients at two and three years was 73.2% and 63.0% respectively. Independent predictors of mortality were: patients residing in rural areas (adjusted hazard ratio = 2.71, 95% CI: 1.44, 5.09), travel time to a health facility ≥7 hours (adjusted hazard ratio = 3.42, 95% CI: 1.05, 11.10), those who presented within 7-23 months after the onset of symptoms (adjusted hazard ratio = 2.63, 95% CI: 1.22, 5.64), those who presented more than 23 months after the onset of symptoms (adjusted hazard ratio = 2.37, 95% CI: 1.00, 5.59), advanced stage at presentation (adjusted hazard ratio = 3.01, 95% CI: 1.05, 8.59), and patients who never received chemotherapy (adjusted hazard ratio = 6.69, 95% CI: 2.20, 20.30). CONCLUSION: Beyond three years after diagnosis, patients from southern Ethiopia had a survival rate of less than 60% despite treatment at a tertiary health facility. It is imperative to improve the early detection, diagnosis, and treatment capacities for breast cancer patients to prevent premature death in these women.

Intrinsic subtypes in Ethiopian breast cancer patient.

PURPOSE: The recent development of multi-gene assays for gene expression profiling has contributed significantly to the understanding of the clinically and biologically heterogeneous breast cancer (BC) disease. PAM50 is one of these assays used to stratify BC patients and individualize treatment. The present study was conducted to characterize PAM50-based intrinsic subtypes among Ethiopian BC patients. PATIENTS AND METHODS: Formalin-fixed paraffin-embedded tissues were collected from 334 BC patients who attended five different Ethiopian health facilities. All samples were assessed using the PAM50 algorithm for intrinsic subtyping. RESULTS: The tumor samples were classified into PAM50 intrinsic subtypes as follows: 104 samples (31.1%) were luminal A, 91 samples (27.2%) were luminal B, 62 samples (18.6%) were HER2-enriched and 77 samples (23.1%) were basal-like. The intrinsic subtypes were found to be associated with clinical and histopathological parameters such as steroid hormone receptor status, HER2 status, Ki-67 proliferation index and tumor differentiation, but not with age, tumor size or histological type. An immunohistochemistry-based classification of tumors (IHC groups) was found to correlate with intrinsic subtypes. CONCLUSION: The distribution of the intrinsic subtypes confirms previous immunohistochemistry-based studies from Ethiopia showing potentially endocrine-sensitive tumors in more than half of the patients. Health workers in primary or secondary level health care facilities can be trained to offer endocrine therapy to improve breast cancer care. Additionally, the findings indicate that PAM50-based classification offers a robust method for the molecular classification of tumors in the Ethiopian context.

Breast Nurse Intervention to Improve Adherence to Endocrine Therapy Among Breast Cancer Patients in South Ethiopia.

INTRODUCTION: Many women in rural Ethiopia do not receive adjuvant therapy following breast cancer surgery despite the majority being diagnosed with estrogen-receptor-positive breast cancer and tamoxifen being available in the country. We aimed to compare a breast nurse intervention to improve adherence to tamoxifen therapy for breast cancer patients. METHODS AND MATERIALS: The 8 hospitals were randomized to intervention and control sites. Between February 2018 and December 2019, patients with breast cancer were recruited after their initial surgery. The primary outcome of the study was adherence to tamoxifen therapy by evaluating 12-month medication-refill data with medication possession ratio (MPR) and using a simplified medication adherence scale (SMAQ) in a subjective assessment. RESULTS: A total of 162 patients were recruited (87 intervention and 75 control). Trained nurses delivered education and provided literacy material, gave additional empathetic counselling, phone call reminders, and monitoring of medication refill at the intervention hospitals. Adherence according to MPR at 12 months was high in both the intervention (90%) and control sites (79.3%) (P = .302). The SMAQ revealed that adherence at intervention sites was 70% compared with 44.8% in the control sites (P = .036) at 12 months. Persistence to therapy was found to be 91.2% in the intervention and 77.8% in the control sites during the one-year period (P = .010). CONCLUSION: Breast nurses can improve cost-effective endocrine therapy adherence at peripheral hospitals in low-resource settings. We recommend such task sharing to overcome the shortage of oncologists and distances to central cancer centers.

Breast cancer morbidity and mortality in rural Ethiopia: data from 788 verbal autopsies.

INTRODUCTION: In Ethiopia, breast cancer is the leading cause of cancer among women. Little is known about the duration of disease and symptoms of patients who died from breast cancer in rural Ethiopia. The objective of this study was to assess breast cancer mortality with a particular focus on the self-reported duration of illness including suffering of symptoms, and need for medical care. METHODS: The cause of death was determined among randomly selected Ethiopian women residing in western Ethiopia. A modified standard verbal autopsy (VA) questionnaire was completed by women whose sisters had died. The questionnaires were reviewed by two independent local physicians to assign a cause of death. We analyzed pattern of cause of deaths, duration of suffering, symptoms, and treatment received. RESULT: In our study, the age at death was very similar to other population-based data from Ethiopia. We found 32% of 788 deaths were caused by communicable diseases, 12.1% by neoplasms, and 9.4% by pregnancy/maternal mortality. Breast cancer was the second leading neoplasm, responsible for 21 (2.7%) of all deaths (95% CI 1.5-3.7%), and was among the top five causes of non-communicable deaths. The median age of breast cancer death was 37 years, younger than for other causes of death. The median duration of illness with breast cancer was around 1 year. This was substantially more compared to the duration of infectious diseases, but less than the duration of reproductive neoplasms, diabetes, and epilepsy. DISCUSSION/CONCLUSION: Breast cancer deaths are common causes of death in women of rural Ethiopia. When assessing the total duration of illness according to specific causes of death, breast and other cancers accounted for a large share of the burden. This has practical implications and highlights the need for palliative care for cancer patients. Substantial efforts are necessary to improve early detection and treatment for breast cancer to reduce premature death in women.

Short Stay Management of Locally Advanced Breast Cancer Using Immediate Local Thoracoabdominal Advancement Flap and Enhanced Recovery After Surgery Protocol.

BACKGROUND: Patients with locally advanced invasive breast cancer (LABC) are often considered inoperable, because of the anticipated chest wall defect and need for complex reconstruction. We present a series of patients who underwent mastectomy with extensive skin resection and immediate chest wall reconstruction using a local thoracoabdominal advancement flap (TAAF). All patients were managed after surgery with an ERAS (Enhanced Recovery After Surgery) protocol, to decrease length of stay in hospital. We also present 1 patient who subsequently had satisfactory bilateral delayed breast reconstruction with pedicled latissimus dorsi myocutaneous flaps with prepectoral silicone implants. METHODS: This is a single-surgeon, single-institution retrospective chart review of patients with LABC who underwent mastectomy with skin resection and local TAAF from May 2017 to October 2019, with minimum 3-month follow-up. RESULTS: Thirteen patients met inclusion criteria. Twelve of 13 patients presented with stage III or IV invasive breast cancer, with skin involvement. The mean chest wall defect measured 248.7 cm2 (140-336 cm2; SD, 63.2 cm2), and all were successfully reconstructed with immediate local TAAF. There were no intraoperative complications, but 1 patient developed a postop hematoma. The mean hospital stay was 1.3 nights, with 9 patients (69.2%) staying less than 23 hours and 4 patients (30.8%) staying 2 nights. Nine patients (69.2%) underwent adjuvant therapy, beginning on average 32 days (13-55 days; SD, 13.1 days) after surgery. The mean follow-up time was 13.8 months (4.5-31.6 months; SD, 9.2 months). One patient underwent successful delayed bilateral breast reconstruction with pedicled latissimus dorsi myocutaneous flaps and silicone implant placement. CONCLUSIONS: Our study demonstrates that reconstruction with local TAAF is an outpatient procedure that reliably provides durable, immediate chest wall coverage, after mastectomy in patients with LABC. This technique has a short operative time, low blood loss, and low complication rate, allowing timely adjuvant therapy. Using an ERAS postop protocol we were able to reduce mean hospital stay to 1.3 days. Compared with other described techniques of reconstruction, the additional scars and donor site morbidity are minimal, allowing for delayed breast reconstruction. We also present survival outcomes data on these surgically managed patients.

Breast Awareness, Self-Reported Abnormalities, and Breast Cancer in Rural Ethiopia: A Survey of 7,573 Women and Predictions of the National Burden.

BACKGROUND: Breast cancer (BC) is the most frequently diagnosed cancer and leading cause of cancer deaths among women in low-income countries. Ethiopia does not have a national BC screening program, and over 80% of patients are diagnosed with advanced stage disease. The aim of this study was to assess how many women self-report a breast abnormality and to determine their diagnoses in rural Ethiopia. METHODS: A community-based cross-sectional study was conducted among 7,573 adult women. Women were interviewed and educated about breast awareness, and those who reported breast abnormalities underwent clinical examination by experienced surgeons. Ultrasound-guided fine needle aspiration cytology (FNAC) was obtained, and cytological analysis was performed. The findings were projected to the female population of Ethiopia to estimate current and future burden of diseases. FINDINGS: Of the 7,573 women surveyed, 258 (3.4%) reported a breast abnormality, 246 (3.2%) received a physical examination, and 49 (0.6%) were found to be eligible for ultrasound-guided FNAC or nipple discharge evaluation. Of all the cases, five (10.2%) breast malignancies were diagnosed. We projected for Ethiopia that, approximately, 1 million women could self-report a breast abnormality, 200,000 women could have a palpable breast mass, and 28,000 women could have BC in the country. CONCLUSION: The health care system needs to build capacity to assess and diagnose breast diseases in rural areas of Ethiopia. These data can be used for resource allocation to meet immediate health care needs and to promote detecting and treating BC at earlier stages of disease. IMPLICATIONS FOR PRACTICE: Routine mammography screening in a resource-limited country with a young population is neither sensitive nor affordable. Clinical breast examination with consecutive ultrasound-guided fine needle aspiration cytology may ensure early diagnosis, downstage disease, and reduce breast cancer mortality. This study had the unique opportunity to educate over 7,573 rural women about breast abnormalities and offer clinical and cytological diagnosis for reported breast abnormalities. The findings were extrapolated to show the nationwide burden of breast abnormalities and unmet diagnostic needs. These data will serve as policy guide to improve adequate referral mechanisms and breast diagnostic and treatment facilities.

Late-Stage Diagnosis and Associated Factors Among Breast Cancer Patients in South and Southwest Ethiopia: A Multicenter Study.

BACKGROUND: Breast cancer is a leading cause of cancer death in women in low- and middle-income countries, largely because of late-stage diagnosis. Yet studies are very limited in the Ethiopian context. Therefore, we determined the occurrence of late-stage disease and associated factors in selected public hospitals in south and southwest Ethiopia. PATIENTS AND METHODS: A 5-year retrospective cross-sectional study was conducted on breast cancer patient medical records from January 2013 to December 2017 in 6 hospitals. Multivariable logistic regression was performed to identify factors associated with late-stage disease (stage III and IV). Adjusted odds ratios (AOR) with 95% confidence intervals were used. P < .05 was considered statistically significant. RESULTS: Overall, 426 breast cancer patients were identified, and 72.5% were diagnosed with late-stage disease. The mean ± standard deviation patient age was 42.8 ± 13.4 years. Factors associated with late diagnosis were patient delay in seeking care (AOR = 2.50; 95% confidence interval [CI], 1.51-4.16); health system delays (AOR = 1.62; 95% CI, 1.02-2.59); female sex (AOR = 3.46; 95% CI, 1.50-7.98); rural residence (AOR = 2.37; 95% CI, 1.45-3.86); chief complaint of breast lump (AOR = 3.01; 95% CI, 1.49-6.07); and history of comorbidities (AOR = 1.72; 95% CI, 1.02-2.91). CONCLUSION: The majority of patients were diagnosed with late-stage diagnosis of breast cancer. Patient delays in seeking care, health system delays, being female, rural residence, and patient comorbidities were associated factors. These findings provide evidence that efforts to increase public and health provider awareness to promote early breast cancer diagnosis, particularly in rural areas, are needed in south and southwest Ethiopia.

Cardiorespiratory considerations for return-to-play in elite athletes after COVID-19 infection: a practical guide for sport and exercise medicine physicians.

SARS-CoV-2 is the causative virus responsible for the COVID-19 pandemic. This pandemic has necessitated that all professional and elite sport is either suspended, postponed or cancelled altogether to minimise the risk of viral spread. As infection rates drop and quarantine restrictions are lifted, the question how athletes can safely resume competitive sport is being asked. Given the rapidly evolving knowledge base about the virus and changing governmental and public health recommendations, a precise answer to this question is fraught with complexity and nuance. Without robust data to inform policy, return-to-play (RTP) decisions are especially difficult for elite athletes on the suspicion that the COVID-19 virus could result in significant cardiorespiratory compromise in a minority of afflicted athletes. There are now consistent reports of athletes reporting persistent and residual symptoms many weeks to months after initial COVID-19 infection. These symptoms include cough, tachycardia and extreme fatigue. To support safe RTP, we provide sport and exercise medicine physicians with practical recommendations on how to exclude cardiorespiratory complications of COVID-19 in elite athletes who place high demand on their cardiorespiratory system. As new evidence emerges, guidance for a safe RTP should be updated.

A Phase 2, Double-Blind, Placebo-Controlled Trial to Investigate Potential Drug-Drug Interactions Between Cannabidiol and Clobazam.

We investigated the effects of cannabidiol (CBD; 21-day maintenance dose) on the pharmacokinetics (PK) of clobazam (CLB) and monitored the safety of CBD (or placebo) plus CLB in 20 patients with uncontrolled epilepsy on stable doses of CLB. Blood samples collected until 24 hours postdose were evaluated by liquid chromatography tandem mass spectrometry. PK parameters of CLB and major metabolite N-desmethylclobazam (N-CLB), valproic acid, stiripentol, levetiracetam, topiramate, plant-derived highly purified CBD (Epidiolex in the United States; 100 mg/mL oral solution) and its major metabolites were derived using noncompartmental analysis. There was no evidence of a drug-drug interaction (DDI) between CBD and CLB: geometric mean ratio (GMR) of day 33:day 1 CLB was 1.0 (90%CI, 0.8-1.2) for Cmax and 1.1 (90%CI, 0.9-1.2) for AUCtau . There was a significant DDI between CBD and N-CLB: the GMR of day 33:day 1 N-CLB was 2.2 (90%CI, 1.4-3.5) for Cmax and 2.6 (90%CI, 2.0-3.6) for AUCtau . Placebo had no effect on CLB or N-CLB; CBD had no effect on levetiracetam. Data were insufficient regarding DDIs with other antiepileptic drugs. The safety profile of CBD (20 mg/kg/day) with CLB was acceptable; all but 1 adverse events (AEs) were mild or moderate. One serious AE (seizure cluster) led to CBD discontinuation. One patient withdrew after intolerable AEs. Although there was no evidence of a CBD and CLB DDI, there was a significant DDI between CBD and N-CLB. The safety profile of GW Pharmaceuticals' CBD formulation with CLB was consistent with other GW-sponsored trials.

Perceived barriers to early diagnosis of breast Cancer in south and southwestern Ethiopia: a qualitative study.

BACKGROUND: Early diagnosis is a key determinant of breast cancer prognosis and survival. More than half of breast cancer cases are diagnosed at an advanced stage in Ethiopia, and the barriers to early diagnosis in this country are not well understood. We aimed to identify the perceived barriers to early diagnosis of breast cancer from the perspective of patients and health care providers in south and southwestern Ethiopia. METHODS: A qualitative study was conducted from March to April 2018 using in-depth interviews of breast cancer patients and breast cancer health care providers from six public hospitals located in urban and rural areas of south and southwestern Ethiopia. All participants provided verbal consent before participating. A thematic analysis was performed using Open Code 4.02. RESULTS: Twelve breast cancer patients and thirteen health care providers were included in the study. Patient and health-system related barriers to early diagnosis of breast cancer were identified. Patient-related barriers were lack of knowledge and awareness of breast cancer, belief in traditional medicine and religious practices for treatment, and lack of social and financial support to seek care at a medical facility. Health-system related barriers were misdiagnosis of breast cancer, long distance to referral facilities, high cost of diagnostic services, long waiting time for diagnostic tests, and lack of screening and diagnostic tests in local facilities. CONCLUSIONS: Early diagnosis of breast cancer is affected by multiple barriers in south and southwestern Ethiopia. Awareness campaigns and education about the disease, prevention, and early detection are needed to increase early diagnosis of breast cancer. Opportunities exist to improve early diagnosis and timely treatment in rural areas.

Abrupt withdrawal of cannabidiol (CBD): A randomized trial.

RATIONALE: The rationale of this study was to assess occurrence of withdrawal symptoms induced by abrupt cessation of cannabidiol (CBD) after prolonged administration in healthy volunteers. METHODS: Thirty volunteers were randomized to receive 750 mg of a plant-derived pharmaceutical formulation of highly purified CBD in oral solution (100 mg/mL; Epidiolex® in the United States and Epidyolex® in Europe) twice daily (b.i.d.) for 4 weeks (Part 1) followed by 2 weeks of 750 mg b.i.d. CBD (Part 2, Arm 1) or matched placebo (Part 2, Arm 2). All volunteers completed the Cannabis Withdrawal Scale (CWS) and the 20-item Penn Physician Withdrawal Checklist (PWC-20) on days -1, 21, 28, 31, 35, 42, and at follow-up. RESULTS: Median CWS and PWC-20 scores slightly decreased from Part 1 to Part 2. Median CWS scores ranged from 0.0 to 4.0 (out of a possible 190) in Arm 1 and 0.0 to 0.5 in Arm 2. Median PWC-20 scores were 0.0 (out of a possible 60) in both arms. Twenty-nine (97%) volunteers in Part 1 reported all-causality treatment-emergent adverse events (AEs); the most commonly reported was diarrhea (63%). In Part 2, Arm 1, 6 (67%) volunteers reported all-causality AEs; the most commonly reported was diarrhea (44%). In Part 2, Arm 2, 9 (75%) volunteers reported all-causality AEs; the most commonly reported was headache (58%). Nine volunteers withdrew because of AEs in Part 1; 1 withdrew in Part 2, Arm 2, because of an AE that began in Part 1. Four severe AEs were reported in Part 1; the remainder were mild or moderate. No serious AEs were reported. CONCLUSION: In healthy volunteers, no evidence of withdrawal syndrome was found with abrupt discontinuation of short-term treatment with CBD.