Access to essential cancer medicines for children: a comparative mixed-methods analysis of availability, price, and health-system determinants in east Africa.

BACKGROUND: Access to essential childhood cancer medicines is a core determinant of childhood cancer outcomes. Available evidence, although scarce, suggests that access to these medicines is highly variable across countries, particularly in low-income and middle-income countries, where the burden of childhood cancer is greatest. To support evidence-informed national and regional policies for improved childhood cancer outcomes, we aimed to analyse access to essential childhood cancer medicines in four east African countries-Kenya, Rwanda, Tanzania, and Uganda-by determining the availability and price of these medicines and the health system determinants of access. METHODS: In this comparative analysis, we used prospective mixed-method analyses to track and analyse the availability and price of essential childhood cancer medicines, investigate contextual determinants of access to childhood cancer medicines within and across included countries, and assess the potential effects of medicine stockouts on treatment. Eight tertiary care hospitals were included, seven were public sites (Kenyatta National Hospital [KNH; Nairobi, Kenya], Jaramogi Oginga Odinga Referral and Teaching Hospital [JOORTH; Kisumu, Kenya], Moi University Teaching and Referral Hospital [MTRH; Eldoret, Kenya], Bugando Medical Centre [BMC; Mwanza, Tanzania], Muhimbili National Hospital [MNH; Dar es Salaam, Tanzania], Butaro Cancer Centre of Excellence [BCCE; Butaro Sector, Rwanda], and Uganda Cancer Institute [UCI; Kampala, Uganda]) and one was a private site (Aga Khan University Hospital [AKU; Nairobi, Kenya]). We catalogued prices and stockouts for 37 essential drugs from each of the eight study siteson the basis of 52 weeks of prospective data that was collected across sites from May 1, 2020, to Jan 31, 2022. We analysed determinants of medicine access using thematic analysis of academic literature, policy documents, and semi-structured interviews from a purposive sample of health system stakeholders. FINDINGS: Recurrent stockouts of a wide range of cytotoxic and supportive care medicines were observed across sites, with highest mean unavailability in Kenya (JOORTH; 48·5%), Rwanda (BCCE; 39·0%), and Tanzania (BMC; 32·2%). Drugs that had frequent stockouts across at least four sites included methotrexate, bleomycin, etoposide, ifosfamide, oral morphine, and allopurinol. Average median price ratio of medicines at each site was within WHO's internationally accepted threshold for efficient procurement (median price ratio ≤1·5). The effect of stockouts on treatment was noted across most sites, with the greatest potential for treatment interruptions in patients with Hodgkin lymphoma, retinoblastoma, and acute lymphocytic leukaemia. Policy prioritisation of childhood cancers, health financing and coverage, medicine procurement and supply chain management, and health system infrastructure emerged as four prominent determinants of access when the stratified purposive sample of key informants (n=64) across all four countries (Kenya n=19, Rwanda n=15, Tanzania n=13, and Uganda n=17) was interviewed. INTERPRETATION: Access to childhood cancer medicines across east Africa is marked by gaps in availability that have implications for effective treatment delivery for a range of childhood cancers. Our findings provide detailed evidence of barriers to access to childhood cancer medicine at multiple points in the pharmaceutical value chain. These data could inform national and regional policy makers to optimise cancer medicine availability and affordability as part of efforts to improve childhood cancer outcomes specific regions and internationally. FUNDING: American Childhood Cancer Organization, Childhood Cancer International, and the Friends of Cancer Patients Ameera Fund.

A ketamine package for use in emergency cesarean delivery when no anesthetist is available: An analysis of 401 consecutive operations.

OBJECTIVE: To evaluate the safety and effectiveness of a ketamine-based anesthesia package to support emergency cesarean section when no anesthetist is available. METHODS: A prospective case-series was conducted between December 11, 2013 and September 30, 2021 across nine sub-county hospitals in Kenya. Non-anesthetist healthcare providers undertook an evidence-based five-day training course. A structured instrument was used to collect preoperative, intraoperative, and postoperative data, and patients were contacted 6 months following the surgery to collect outcomes. The primary outcome measures were maternal and newborn survival and the ability of the ketamine package (ESM-Ketamine) to safely support cesarean deliveries. RESULTS: A total of 401 emergency cesarean sections were performed using ketamine, administered by 54 non-anesthetist providers. All mothers survived to discharge. Brief oxygen desaturations were recorded among 33 (8.2%) mothers, and agitation and hallucinations occurred among 13 (3.2%). There were no maternal serious adverse events. At 6-month follow-up, 94.2% of mothers who could be reached reported no complaints. Additionally, 402 (92.4%) of the 435 operative births survived to discharge. CONCLUSION: The ESM-Ketamine package can be used by trained non-anesthetist providers to support emergency cesarean sections when no anesthetist is available. Ketamine has significant potential to increase access to emergency cesarean deliveries in resource-limited settings.

Intraoperative awareness and experience with a ketamine-based anaesthesia package to support emergency and essential surgery when no anaesthetist is available.

INTRODUCTION: Five of the 7.2 billion people on earth have limited access to emergency and essential surgical procedures. The lack of safe, affordable and timely anaesthesia services are primary barriers to universal surgical coverage. The objective of this study was to assess intraoperative awareness when the 'Every Second Matters for Emergency and Essential Surgery - Ketamine' (ESM-Ketamine) package was used to support emergency and essential surgeries and painful procedures in rural Kenya when no anaesthetist was available. METHODS: Forty-seven consecutive adult patients that underwent an operative procedure under ESM-Ketamine at Sagam Community Hospital in Luanda, Kenya were enrolled. Participants underwent two semi-structured interviews that explored the patient's experience with ESM-Ketamine both after the operative procedure and four to six weeks after surgery. RESULTS: Forty-seven participants completed the first interview and 37 (78.7%) the second interview. Thirty-seven (78.7%) cases were procedural sedations and ten were (21.3%) emergency surgeries. Intraoperative awareness occurred in nine (24.3%) participants who underwent procedural sedation and two (20%) who underwent emergency surgery. Twenty-six (55.3%) participants reported dreams during the procedure. Thirty-two (86.5%) participants considered their experience positive, and 35 (95%) would recommend a procedure supported by ketamine to a friend. DISCUSSION: Most patients whose painful procedures and emergency operations were supported by the ESM-Ketamine package when no anaesthetist was available reported favourable experiences.

Correction to: Safety and Feasibility of a Ketamine Package to Support Emergency and Essential Surgery in Kenya when No Anesthetist is Available: An Analysis of 1216 Consecutive Operative Procedures.

The corrected order of the authors is as reflected in this erratum. Sebastian Suarez and Ayla Senay are co-second authors.

Safety and Feasibility of a Ketamine Package to Support Emergency and Essential Surgery in Kenya when No Anesthetist is Available: An Analysis of 1216 Consecutive Operative Procedures.

BACKGROUND: Lack of access to emergency and essential surgery is widespread in low- and middle-income countries. Scarce anesthesia services contribute to this unmet need. The aim of this study was to evaluate the safety and feasibility of the Every Second Matters for Emergency and Essential Surgery-Ketamine (ESM-Ketamine) package for emergency and essential procedures when no anesthetist was available. METHODS: From November 2013 to September 2017, the ESM-Ketamine package was used for patients requiring emergency or life-improving surgeries in fifteen selected facilities across Kenya when no anesthetist was available. A mixed-methods approach was used to assess safety and feasibility of the ESM-Ketamine package, including demand, acceptability, and practicality. The primary outcome was ketamine-related adverse events. Key-informant interviews captured perceptions of providers, hospital administrators, and surgeons/proceduralists. RESULTS: Non-anesthetist mid-level providers used ESM-Ketamine for 1216 surgical procedures across the fifteen study facilities. The median ketamine dose was 2.1 mg/kg. Brief (<30 s) oxygen desaturations occurred in 39 patients (3%), and prolonged (>30 s) oxygen desaturations occurred in seven patients (0.6%). There were 157 (13%) reported cases of hallucinations and agitation which were treated with diazepam. All patients recovered uneventfully, and no ketamine-related deaths were reported. Twenty-seven key-informant interviews showed strong support for the program with four main themes: financial considerations, provision of services, staff impact, and scaling considerations. CONCLUSIONS: The ESM-Ketamine package appears safe and feasible and is capable of expanding access to emergency and essential surgeries in rural Kenya when no anesthetist is available.

Evaluation of a ketamine-based anesthesia package for use in emergency cesarean delivery or emergency laparotomy when no anesthetist is available.

OBJECTIVE: To assess the safety of a ketamine-based rescue anesthesia package to support emergency cesarean delivery and emergency laparotomy when no anesthetist was available. METHODS: A prospective case-series study was conducted at seven sub-county hospitals in western Kenya between December 10, 2013, and January 20, 2016. Non-anesthetist clinicians underwent 5days of training in the Every Second Matters-Ketamine (ESM-Ketamine) program. A database captured preoperative, intraoperative, and postoperative details of all surgeries in which ESM-Ketamine was used. The primary outcome measure was the ability of ESM-Ketamine to safely support emergency operative procedures. RESULTS: Non-anesthetist providers trained on ESM-Ketamine supported 83 emergency cesarean deliveries and 26 emergency laparotomies. Ketamine was administered by 10 nurse-midwives and six clinical officers. Brief oxygen desaturations (<92% for <30s) were recorded among 5 (4.6%) of the 109 patients. Hallucinations occurred among 9 (8.3%) patients. No serious adverse events related to the use of ESM-Ketamine were recorded. CONCLUSION: The ESM-Ketamine package can be safely used by trained non-anesthetist providers to support emergency cesarean delivery and emergency laparotomy when no anesthetist is available.

HIV impact on acute morbidity and pelvic tumor control following radiotherapy for cervical cancer.

OBJECTIVE: To determine the impact of HIV infection on acute morbidity and pelvic tumor control following external beam radiotherapy (EBRT) for cervical cancer. METHOD: 218 patients receiving EBRT who also had HIV testing after informed consent was obtained were evaluated. Acute treatment toxicity was documented weekly during treatment and 1 month post-EBRT. Pelvic tumor control was documented at 4 and 7 months post-EBRT. Clinicians were blinded for HIV results. RESULTS: About 20% of the patients were HIV-positive. Overall, 53.4% of the patients had radiation-related acute toxicity (grade 3-4). HIV infection was associated with a 7-fold higher risk of multisystem toxicity: skin, gastrointestinal tract (GIT) and genitourinary tract (GUT) systems. It was also an independent risk factor for treatment interruptions (adjusted relative risk 2.2). About 19% of the patients had residual tumor at 4 and 7 months post-EBRT. HIV infection was independently and significantly associated with 6-fold higher risk of residual tumor post-EBRT. The hazard ratio of having residual tumor after initial EBRT was 3.1-times larger for HIV-positive than for HIV-negative patients (P = 0.014). CONCLUSION: HIV is associated with increased risk of multisystem radiation-related toxicity; treatment interruptions and pelvic failure (residual tumor) following EBRT. HIV infection is an adverse prognostic factor for outcome of cervical cancer treatment.

Impact of HIV infection on invasive cervical cancer in Kenyan women.

OBJECTIVES: To determine the association between invasive cervical cancer (ICC) and HIV infection in Kenyan women. STUDY DESIGN: Case-control, with ICC patients as cases, and women with uterine fibroids as controls. METHODS: Medical and socio-demographic data were collected from 367 ICC patients, and 226 women with fibroids. After informed consent, HIV testing was done. RESULTS: ICC patients were older than fibroid patients (48 versus 41 years; P < 0.001), with an HIV seroprevalence of 15% and 12% respectively (P > 0.05). However, cases younger than 35 years were 2.6-times more likely to be HIV positive than controls of similar age [35% versus 17%; odds ratio (OR), 2.6; P = 0.043]. ICC HIV-seropositive patients were, on average, 10 years younger than HIV-seronegative patients (40 versus 50 years; P < 0.001). Eighty per cent of HIV-seropositive and 77% of HIV-seronegative ICC patients were in FIGO stage IIb or above. However, the odds of having poorly differentiated tumours was three times higher for HIV-seropositive than for HIV-seronegative ICC patients (77% versus 52%; OR, 3.1; P = 0.038) after adjusting for histological cell type and clinical stage. Mean CD4 cell count was 833 x 10(6) cells/l in ICC and 1025 x 10(6) cells/l in fibroid patients (P = 0.001). CONCLUSION: Young women with ICC were more often HIV infected than women with fibroids of the same age groups. HIV infection was associated with poor histological differentiation of the tumours. These findings suggest an accelerated clinical progression of premalignant cervical lesions to ICC in HIV-infected women.