ABSTRACT
BACKGROUND: Irrational medicine use is a global problem that may potentiate antimicrobial resistance. AIM: This study aims to assess prescribing practices and the effect of a prescription audit and feedback coupled with small-group education intervention on prescribing indicators. SETTING: The study was conducted in public-sector healthcare facilities in Eswatini. METHODS: A cluster quasi-randomised controlled study was conducted from 2016 to 2019 using the World Health Organization/ International Network for Rational Use of Drugs (WHO/INRUD) prescribing indicators at baseline, post-intervention and post-follow-up. A 6-month unblinded intervention was tested in 32 healthcare facilities, randomly allocated to intervention (16) and control (16) arms. Prescribing practices were assessed post-intervention, and 6 months after the intervention, through an audit of 100 randomly selected prescriptions from each facility. Comparisons of WHO or INRUD prescribing indicators were conducted using the intention-to-treat analysis at the two times. RESULTS: At baseline, in both arms, rational prescribing standards were met by the number of medicines per prescription and the use of injections. Antibiotic use was above 50% in both arms. After adjustment for baseline antibiotics use, region and level of care, there were no significant differences in all prescribing indicators between the two arms, post-intervention and at 6 months follow-up. CONCLUSION: In a lower middle-income setting with a high prevalence of irrational prescribing practices, a prescription audit, feedback and small-group education intervention had no benefits in improving rational prescribing.Contribution: Multifaceted strategies, strengthening of pharmacy and therapeutics committees, and holistic monitoring of medicine use are recommended to promote rational medicine use.
Subject(s)
Pharmaceutical Services , Pharmacies , Humans , Anti-Bacterial Agents/therapeutic use , Practice Patterns, Physicians' , World Health Organization , Random AllocationABSTRACT
AIMS: To evaluate comparative outcomes of fenestrating and reconstituting subtotal cholecystectomy (STC) in patients with difficult gallbladder. METHODS: A systematic search of electronic data sources and bibliographic reference lists were conducted. All comparative studies reporting outcomes of laparoscopic fenestrating and reconstituting STC were included and their risk of bias were assessed using ROBINS-I tool. RESULTS: Seven comparative studies were included enrolling 590 patients undergoing laparoscopic STC using either fenestrating (n = 353) or reconstituting (n = 237) approaches. Although fenestrating STC was associated with a significantly higher rate of bile leak (OR: 2.47, p = 0.007) compared to reconstituting STC, both approaches were comparable in terms of resolution of bile leak without (RD: -0.02, p = 0.86) or with (OR: 1.84, p = 0.40) postoperative ERCP. Moreover, there was no significant difference in development of bile duct injury (RD: -0.02, p = 0.16), need for postoperative ERCP (OR: 1.36, p = 0.49), wound infection (RD: 0.03, p = 0.27), re-operation (OR: 0.95, p = 0.95), gallbladder remnant cholecystitis (OR: 0.21, p = 0.09) or need for completion cholecystectomy (RD: 0.01, p = 0.59) between two groups. CONCLUSIONS: Fenestrating STC is associated with a higher risk of bile leak than the reconstructing technique. This issue can be mitigated by routine use of drains, delayed drain removal, and in selected cases endoscopic therapy. We encourage the fenestrating approach considering trends in improved short- and long-term outcomes.
Subject(s)
Cholecystectomy, Laparoscopic , Cholecystitis , Laparoscopy , Humans , Cholecystectomy/adverse effects , Cholecystectomy/methods , Cholecystectomy, Laparoscopic/adverse effects , Cholecystitis/surgeryABSTRACT
AIMS: To evaluate comparative outcomes of laparoscopic spleen-preserving distal pancreatectomy (LSPDP) and laparoscopic distal pancreatectomy with splenectomy (LDPS). METHODS: A systematic search of multiple electronic data sources and bibliographic reference lists were conducted. Comparative studies reporting outcomes of LSPDP and LDPS were considered followed by evaluation of the associated risk of bias according to ROBINS-I tool. Perioperative complications, clinically important postoperative pancreatic fistula (POPF), infectious complications, blood loss, conversion to open, operative time and duration of hospital stay were the investigated outcome parameters. RESULTS: Nineteen studies were identified enrolling 3739 patients of whom 1860 patients underwent LSPDP and the remaining 1879 patients had LDPS. The patients in the LSPDP and LDPS groups were of comparable age (p = 0.73), gender (p = 0.59), and BMI (p = 0.07). However, the patient in the LDPS group had larger tumour size (p = 0.0004) and more malignant lesions (p = 0.02). LSPDP was associated with significantly lower POPF (OR:0.65, p = 0.02), blood loss (MD:-28.30, p = 0.001), and conversion to open (OR:0.48, p < 0.0001) compared to LDPS. Moreover, it was associated with significantly shorter procedure time (MD: -22.06, p = 0.0009) and length of hospital stay (MD: -0.75, p = 0.005). However, no significant differences were identified in overall perioperative (OR:0.89, p = 0.25) or infectious (OR:0.67, p = 0.05) complications between two groups. CONCLUSIONS: LSPDP seems to be associated with lower POPF, bleeding and conversion to open compared to LDPS in patients with small-sized benign tumours. Moreover, it may be quicker and reduce hospital stay. Nevertheless, such advantages are of doubtful merit about large-sized or malignant tumours. The available evidence is subject to confounding by indication.
Subject(s)
Laparoscopy , Pancreatic Neoplasms , Humans , Laparoscopy/adverse effects , Length of Stay , Pancreatectomy/adverse effects , Pancreatectomy/methods , Pancreatic Fistula/etiology , Pancreatic Neoplasms/surgery , Pancreatic Neoplasms/pathology , Postoperative Complications/epidemiology , Postoperative Complications/etiology , Postoperative Complications/surgery , Retrospective Studies , Spleen/pathology , Spleen/surgery , Splenectomy/adverse effects , Treatment OutcomeABSTRACT
AIMS: To evaluate short-term clinical and long-term survival outcomes of pancreatic resection for pancreatic metastasis from renal cell carcinoma (RCC). METHODS: A retrospective evaluation of patients undergoing pancreatic resection for metastasis from RCC over a 12-years period was conducted. Furthermore, a systematic search of electronic data sources and bibliographic reference lists were conducted to identify studies investigating the same clinical question. Short-term clinical and long-term survival outcomes were evaluated. Kaplan-Meier survival plots were constructed for survival outcomes. Cox-proportional regression analysis was performed to determine factors associated with survival. Finally, meta-analysis of survival outcomes was conducted using random-effects modelling. RESULTS: Eighteen patients underwent pancreatic resections for RCC pancreatic metastasis within the study period. The mean age of the included patients was 63.8 ± 8.0 years. There were 10(55.6 %) male and 8(44.4 %) female patients. Pancreatectomy was associated with 4(25.0 %) Clavien-Dindo (C-D) I, 5(31.3 %) C-D II, and 7(43.7 %) C-D III complications, 7(38.8 %) pancreatic fistula, 3(16.7 %) post-pancreatectomy acute pancreatitis, 1(5.6 %) delayed gastric emptying, and 1(5.6 %) chyle leak. The mean length of hospital stay was 18 ± 16.3 days. The median survival was 64 months (95 % CI 60-78). The 3-and 5-year disease-free survival rates were 83.3 % and 55.5 %, respectively. The 3-and 5-year survival rates were 100 % and 55.6 %, respectively. The pooled analyses of 553 patients demonstrated 3-and 5-year survival rates of 77.6 % and 60.7 %, respectively. CONCLUSIONS: Pancreatectomy for RCC metastasis is associated with acceptable short-term clinical and promising long-term survival outcomes. Considering the rarity of the entity, escalation of level of evidence in this context is challenging.
Subject(s)
Carcinoma, Renal Cell , Kidney Neoplasms , Pancreatic Neoplasms , Pancreatitis , Humans , Male , Female , Middle Aged , Aged , Pancreatectomy/adverse effects , Carcinoma, Renal Cell/surgery , Carcinoma, Renal Cell/secondary , Retrospective Studies , Acute Disease , Pancreatitis/etiology , Pancreatic Neoplasms/pathology , Kidney Neoplasms/surgery , Treatment OutcomeABSTRACT
BACKGROUND: To evaluate comparative outcomes of pancreatic cancer resection with or without adjuvant chemotherapy in patients with stage I pancreatic cancer. METHODS: A systematic search of MEDLINE, CENTRAL, and Web of Science and bibliographic reference lists were conducted. All comparative studies reporting outcomes of pancreatic cancer resection for stage I cancer with or without adjuvant chemotherapy were included, and their risk of bias was assessed using the Risk Of Bias In Non-randomized Studies-of Interventions tool. Survival outcomes were analyzed using the hazard ratio and odds ratio for the time-to-event and dichotomous outcomes, respectively. RESULTS: We included 6 comparative studies reporting a total of 6,874 patients with resected stage 1 pancreatic cancer, of whom 3,951 patients had no adjuvant chemotherapy, and the remaining 2,923 patients received adjuvant chemotherapy. The use of adjuvant chemotherapy was associated with significantly higher overall survival (hazard ratio 0.71, 95% confidence interval 0.62-0.82, P < .00001) and 2-year survival (65.1% vs 57.4%, odds ratio 1.99; 95% confidence interval 1.01-1.41, P = .04) compared to no use of adjuvant chemotherapy. However, there was no statistically significant difference in 1-year (86.8% vs 78.4%, odds ratio 1.60; 95% confidence interval 0.72-3.57, P = .25), 3-year (46.0% vs 44.0%, odds ratio 1.07; 95% confidence interval 0.90-1.29, P = .43), or 5-year survival (24.8% vs 23.3%, odds ratio 1.03; 95% confidence interval 0.80-1.33, P = .81) between the 2 groups. CONCLUSION: Meta-analysis of best available evidence (level 2a with low to moderate certainty) demonstrates that adjuvant chemotherapy may confer survival benefits for stage I pancreatic cancer when compared to the use of surgery alone. Randomized control trials are required to escalate the level of evidence and confirm these findings with consideration of contemporary chemotherapy agents and regimens.
Subject(s)
Neoplasm Staging , Pancreatic Neoplasms , Humans , Chemotherapy, Adjuvant/statistics & numerical data , Pancreatic Neoplasms/mortality , Pancreatic Neoplasms/surgery , Pancreatic Neoplasms/drug therapy , Pancreatic Neoplasms/pathology , Pancreatic Neoplasms/therapy , Pancreatectomy , Treatment OutcomeABSTRACT
Normothermic machine perfusion (NMP) enables pretransplant assessment of high-risk donor livers. The VITTAL trial demonstrated that 71% of the currently discarded organs could be transplanted with 100% 90-day patient and graft survivals. Here, we report secondary end points and 5-year outcomes of this prospective, open-label, phase 2 adaptive single-arm study. The patient and graft survivals at 60 months were 82% and 72%, respectively. Four patients lost their graft due to nonanastomotic biliary strictures, one caused by hepatic artery thrombosis in a liver donated following brain death, and 3 in elderly livers donated after circulatory death (DCD), which all clinically manifested within 6 months after transplantation. There were no late graft losses for other reasons. All the 4 patients who died during the study follow-up had functioning grafts. Nonanastomotic biliary strictures developed in donated after circulatory death livers that failed to produce bile with pH >7.65 and bicarbonate levels >25 mmol/L. Histological assessment in these livers revealed high bile duct injury scores characterized by arterial medial necrosis. The quality of life at 6 months significantly improved in all but 4 patients suffering from nonanastomotic biliary strictures. This first report of long-term outcomes of high-risk livers assessed by normothermic machine perfusion demonstrated excellent 5-year survival without adverse effects in all organs functioning beyond 1 year (ClinicalTrials.gov number NCT02740608).
Subject(s)
Liver Transplantation , Aged , Humans , Constriction, Pathologic/etiology , Liver/surgery , Liver Transplantation/adverse effects , Organ Preservation , Perfusion , Prospective Studies , Quality of LifeABSTRACT
INTRODUCTION: Increasingly, Fourier-transform infrared (FTIR) spectroscopy is being used as a harm reduction tool to provide people who use drugs real-time information about the contents of their substances. However, FTIR spectroscopy has been shown to have a high detection limit for fentanyl and interpretation of results by a technician can be subjective. This poses concern, given that some synthetic opioids can produce serious toxicity at sub-detectable levels. The objective of this study was to develop a neural network model to identify fentanyl and related analogues more accurately in drug samples compared to traditional analysis by technicians. METHODS: Data were drawn from samples analyzed point-of-care using combination FTIR spectroscopy and fentanyl immunoassay strips in British Columbia between August 2018 and January 2021. We developed neural network models to predict the presence of fentanyl based on FTIR data. The final model was validated against the results from immunoassay strips. Prediction performance was assessed using F1 score, accuracy, and area under the receiver-operating characteristic curve (AUROC), and was compared to results obtained from analysis by technicians. RESULTS: A total of 12,684 samples were included. The neural network model outperformed results from those analyzed by technicians, with an F1 score of 96.4% and an accuracy of 96.4%, compared to 78.4% and 82.4% with a technician, respectively. The AUROC of the model was 99.0%. Fentanyl positive samples correctly detected by the model but not by the technician were typically those with low fentanyl concentrations (median: 2.3% quantity by weight; quartile 1-3: 0.0%-4.6%). DISCUSSION: Neural network models can accurately predict the presence of fentanyl and related analogues using FTIR data, including samples with low fentanyl concentrations. Integrating this tool within drug checking services utilizing FTIR spectroscopy has the potential to improve decision making to reduce the risk of overdose and other negative health outcomes.
Subject(s)
Drug Overdose , Fentanyl , Humans , Analgesics, Opioid , British Columbia , Neural Networks, ComputerABSTRACT
OBJECTIVES: To evaluate the ability of the c-reactive protein-to-albumin ratio (CAR) in predicting outcomes in patients undergoing pancreatic cancer resection. METHODS: A systematic search of electronic information sources and bibliographic reference lists was conducted. Survival outcomes and perioperative morbidity were the evaluated outcome parameters. RESULTS: Eight studies reporting a total of 1056 patients undergoing pancreatic cancer resection were identified. The median cut-off value for CAR was 0.05 (range 0.0003-0.54). Using multivariate analysis, all studies demonstrated that a higher CAR value was an independent and significant predictor of poor overall survival in patients undergoing pancreatic cancer resection. The estimated hazard ratio (HR) ranged from 1.4 to 3.6. Although there was a positive correlation between the reported cut-off values for CAR and HRs for overall survival, it was weak and non-significant (r = 0.36, n = 6, p = 0.480). There was significant between-study heterogeneity. CONCLUSIONS: Preoperative CAR value seems to be an important prognostic score in predicting survival outcomes in patients undergoing pancreatic cancer resection. However, the current evidence does not allow the determination of an optimal cut-off value for CAR, considering the heterogeneous reporting of cut-off values by the available studies and the lack of knowledge of their sensitivity and specificity. Future research is required.
ABSTRACT
BACKGROUND: Recent growth in the market share of higher priced branded generic medicines in low- and middle-income countries (LMICs) has raised concerns around affordability and access. We examined consumer willingness to pay (WTP) for branded versus unbranded generic non-communicable disease (NCD) medicines in Kenya. METHODS: We randomly assigned NCD patients to receive a hypothetical offer for either a Novartis Access-branded medicine or for an unbranded generic equivalent. We then analysed WTP data captured using a bidding game methodology. RESULTS: We found that WTP for Novartis Access medicines was on average 23% higher than for unbranded generic equivalents (p = 0.009). The WTP brand premium was driven almost entirely by wealthier patients. CONCLUSIONS: Our findings suggest that the dominance of branded generics in LMICs like Kenya reflect in part consumer preferences for these medicines. Governments and other health sector actors may be justified in intervening to improve access to these medicines and equivalent non-branded generics, particularly for the poorest patients who appear to have no preference for branded medicines.
Subject(s)
Drugs, Generic , Noncommunicable Diseases , Humans , Costs and Cost Analysis , Drugs, Generic/economics , Drugs, Generic/therapeutic use , KenyaABSTRACT
Background: Research on the impact of the PEPFAR transition in South Africa (SA) in 2012 found varying results in retention in care (RIC) of people living with HIV (PLWH). Objectives: We investigated the factors that impacted RIC during the U.S. President's Emergency Plan for AIDS Relief (PEPFAR) transition in Western Cape, South Africa in 2012. Methods: We used aggregate data from 61 facilities supported by four non-governmental organizations from to 2007-2015. The main outcome was RIC at 12-months after antiretroviral therapy initiation for two time periods. We used quantile regression to estimate the effect of the PEPFAR pull-out and other predictors on RIC. The models were adjusted for various covariates. Results: Regression models (50th quantile) for 12-month RIC showed a 4.6% (95%CI: -8.4, -0.8%) decline in RIC post direct service. Facilities supported by Anova/Kheth'impilo fared worst post PEFPAR; a decline in RIC of (-5.8%; 95% CI: -9.7, -1.8%), while that'sit fared best (6.3% increase in RIC; 95% CI:2.5,10.1%). There was a decrease in RIC when comparing urban to rural areas (-5.8%; 95% CI: -10.1, -1.5%). City of Cape town combined with Western Cape Government Health facilities showed a substantial decrease (-9.1%; 95% CI: -12.3, -5.9%), while community health clinic (vs. primary health clinic) declined slightly (-4.4; 95% CI: -9.6, 0.9%) in RIC. We observed no RIC difference by facility size and a slight increase when two or more human resources transitioned from PEPFAR to the government. Conclusions: When PEPFAR funding decreased in 2012, there was a decrease in RIC. To ensure the continuity of HIV care when a major funder withdraws sufficient and stable transition resources, investment in organizations that understand the local context, joint planning, and coordination are required.
ABSTRACT
Progress in high-resolution nuclear magnetic resonance (NMR) instrumentation has enabled fast and accurate acquisition of quantitative 1 H NMR (qNMR) data, but analyzing complex forensic drug samples in the presence of significant peak overlap remains challenging. This limitation has hampered the adoption of 1 H NMR in areas such as traditional medicine and law enforcement. We present the NMRquant algorithm, which can detect and quantitate compounds of interest within forensic mixed drug samples even when there is overlap between chemical shift regions. Our algorithm is robust against variations in chemical shift resulting from temperature, concentration, and inter-analyte interactions. We have integrated these desirable features into an automated workflow, enabling routine unattended proton qNMR analysis of forensic drug samples.
Subject(s)
Magnetic Resonance Imaging , Protons , Magnetic Resonance Spectroscopy/methodsABSTRACT
In situ normothermic regional perfusion (NRP) and ex situ normothermic machine perfusion (NMP) aim to improve the outcomes of liver transplantation (LT) using controlled donation after circulatory death (cDCD). NRP and NMP have not yet been compared directly. In this international observational study, outcomes of LT performed between 2015 and 2019 for organs procured from cDCD donors subjected to NRP or NMP commenced at the donor center were compared using propensity score matching (PSM). Of the 224 cDCD donations in the NRP cohort that proceeded to asystole, 193 livers were procured, resulting in 157 transplants. In the NMP cohort, perfusion was commenced in all 40 cases and resulted in 34 transplants (use rates: 70% vs. 85% [p = 0.052], respectively). After PSM, 34 NMP liver recipients were matched with 68 NRP liver recipients. The two cohorts were similar for donor functional warm ischemia time (21 min after NRP vs. 20 min after NMP; p = 0.17), UK-Donation After Circulatory Death risk score (5 vs. 5 points; p = 0.38), and laboratory Model for End-Stage Liver Disease scores (12 vs. 12 points; p = 0.83). The incidence of nonanastomotic biliary strictures (1.5% vs. 2.9%; p > 0.99), early allograft dysfunction (20.6% vs. 8.8%; p = 0.13), and 30-day graft loss (4.4% vs. 8.8%; p = 0.40) were similar, although peak posttransplant aspartate aminotransferase levels were higher in the NRP cohort (872 vs. 344 IU/L; p < 0.001). NRP livers were more frequently allocated to recipients suffering from hepatocellular carcinoma (HCC; 60.3% vs. 20.6%; p < 0.001). HCC-censored 2-year graft and patient survival rates were 91.5% versus 88.2% (p = 0.52) and 97.9% versus 94.1% (p = 0.25) after NRP and NMP, respectively. Both perfusion techniques achieved similar outcomes and appeared to match benchmarks expected for donation after brain death livers. This study may inform the design of a definitive trial.
Subject(s)
Carcinoma, Hepatocellular , End Stage Liver Disease , Liver Neoplasms , Liver Transplantation , Aspartate Aminotransferases , End Stage Liver Disease/surgery , Graft Survival , Humans , Liver Transplantation/methods , Organ Preservation/methods , Perfusion/methods , Severity of Illness IndexABSTRACT
AIMS: To describe and compare the health system responses for type 1 diabetes in Kyrgyzstan, Mali, Peru and Tanzania. METHODS: The Rapid Assessment Protocol for Insulin Access, a multi-level assessment of the health system, was implemented in Kyrgyzstan, Mali, Peru and Tanzania using document reviews, site visits and interviews to assess the delivery of care and access to insulin. RESULTS: Despite the existence of noncommunicable or diabetes strategies and Universal Health Coverage policies including diabetes-related supplies, this has not necessarily translated into access to insulin or diabetes care for all. Insulin and related supplies were often unavailable and unaffordable. Across the four countries test strips and insulin, when paid for by the individual, represented respectively 48-82% and 25-36% of total costs. Care was mainly delivered at tertiary-level hospitals by specialists. Only Kyrgyzstan had data collection systems integrated into the Ministry of Health structure. In addition, issues with healthcare worker training and education and empowerment of people with diabetes were present in these health systems. CONCLUSIONS: People with type 1 diabetes in these countries face different barriers, including the cost of insulin and care. Given the renewed attention to diabetes on the global health agenda tailored health system responses for type 1 diabetes are needed. Insulin should be prioritized as it is the foundation of type 1 diabetes care, but other elements of care and support need to be fostered by different actors.
Subject(s)
Diabetes Mellitus, Type 1 , Developing Countries , Diabetes Mellitus, Type 1/epidemiology , Diabetes Mellitus, Type 1/therapy , Humans , Insulin/therapeutic use , Kyrgyzstan/epidemiology , Mali/epidemiology , Peru , Tanzania/epidemiologyABSTRACT
OBJECTIVES: This study aims to describe trends and estimate impact of county-level universal health coverage expansion in Kenya on household availability of non-communicable disease medicines, medicine obtainment at public hospitals and proportion of medicines obtained free of charge. METHODS: Data from phone surveillance of households in eight Kenyan counties between December 2016 and September 2019 were used. Three primary outcomes related to access were assessed based on patient report: availability of non-communicable disease medicines at the household; non-communicable disease medicine obtainment at a public hospital versus a different outlet; and non-communicable disease medicine obtainment free of cost versus at a non-zero price. Mixed models adjusting for fixed and random effects were used to estimate associations between outcomes of interest and UHC exposure. RESULTS: The 197 respondents with universal health coverage were similar on all demographic factors to the 415 respondents with no universal health coverage. Private chemists were the most popular place of purchase throughout the study. Adjusting for demographic factors, county and time fixed effects, there was a significant increase in free medicines (aOR 2.55, 95% CI 1.73, 3.76), significant decrease in medicine obtainment at public hospitals (aOR 0.68, 95% CI 0.47, 0.97), and no impact on the availability of non-communicable disease medicines in households (aß -0.004, 95% CI -0.058, 0.050) with universal health coverage. CONCLUSIONS: Access to universal health coverage caused a significant increase in free non-communicable disease medicines, indicating financial risk protection. Interestingly, this is not accompanied with increases in public hospitals purchases or household availability of non-communicable disease medicines, with public health centers playing a greater role in supply of free medicines. This raises the question as to the status of supply-side investments at the public hospitals, to facilitate availability of quality-assured medicines.
Subject(s)
Drugs, Essential , Noncommunicable Diseases , Health Services Accessibility , Humans , Kenya , Noncommunicable Diseases/drug therapy , Noncommunicable Diseases/epidemiology , Time Factors , Universal Health CareSubject(s)
Liver Transplantation , Hepatocytes , Humans , Liver , Living Donors , Necrosis , PerfusionABSTRACT
BACKGROUND: National and county governments in Kenya have introduced various health insurance schemes to protect households against financial hardship as a result of large health expenditure. This study examines the relationship between health insurance and medicine expenditure in eight counties in Kenya. METHODS: A cross-sectional study of collected primary data via household survey in eight counties was performed. Three measures of medicine expenditure were analysed: the probability of any out-of-pocket expenditure (OOPE) on medicines in the last 4 weeks; amount of OOPE on medicines; and OOPE on medicines as a proportion of total OOPE on health. RESULTS: Out of the 452 individuals, those with health insurance (n = 225) were significantly different from individuals without health insurance (n = 227): overall, they were older, had a higher level of educational attainment and possessed more assets. Adjusting for covariates, individuals with health insurance had a reduced probability of OOPE on medicines (0.40, CI95% 0.197-0.827) and spent proportionally less on medicines out of total health expenditure (0.50, CI95% 0.301-0.926). CONCLUSIONS: Kenya has made great strides to scale up Universal Health Coverage including access to medicines. Prioritising enrollment of low-income individuals with non-communicable diseases can accelerate access to medicines and financial protection.
Subject(s)
Health Expenditures , Insurance, Health , Cross-Sectional Studies , Humans , Kenya , ProbabilityABSTRACT
Normothermic machine perfusion (NMP) allows objective assessment of donor liver transplantability. Several viability evaluation protocols have been established, consisting of parameters such as perfusate lactate clearance, pH, transaminase levels, and the production and composition of bile. The aims of this study were to assess 3 such protocols, namely, those introduced by the teams from Birmingham (BP), Cambridge (CP), and Groningen (GP), using a cohort of high-risk marginal livers that had initially been deemed unsuitable for transplantation and to introduce the concept of the viability assessment sensitivity and specificity. To demonstrate and quantify the diagnostic accuracy of these protocols, we used a composite outcome of organ use and 24-month graft survival as a surrogate endpoint. The effects of assessment modifications, including the removal of the most stringent components of the protocols, were also assessed. Of the 31 organs, 22 were transplanted after a period of NMP, of which 18 achieved the outcome of 24-month graft survival. The BP yielded 94% sensitivity and 50% specificity when predicting this outcome. The GP and CP both seemed overly conservative, with 1 and 0 organs, respectively, meeting these protocols. Modification of the GP and CP to exclude their most stringent components increased this to 11 and 8 organs, respectively, and resulted in moderate sensitivity (56% and 44%) but high specificity (92% and 100%, respectively) with respect to the composite outcome. This study shows that the normothermic assessment protocols can be useful in identifying potentially viable organs but that the balance of risk of underuse and overuse varies by protocol.
Subject(s)
Liver Transplantation , Graft Survival , Humans , Liver , Liver Transplantation/adverse effects , Liver Transplantation/methods , Living Donors , Organ Preservation/methods , Perfusion/methodsABSTRACT
North America has been contending with an unregulated street drug supply in which opioids are often adulterated with illicitly manufactured fentanyl. The unpredictability of composition may result in an increased risk of overdose due to unexpected elevated concentrations of the high-potency drug. Using data from a community-based drug-checking project, we evaluated trends in fentanyl concentration of illicit opioids in the context of an overdose epidemic. Using a quantification model for fentanyl hydrochloride, historical Fourier-transform infrared spectra from opioid drug-checking samples were analyzed to determine fentanyl concentrations. Median monthly fentanyl concentrations were plotted, and polynomial and autoregressive time-series analyses were performed to examine trends over time. A total of 3,621 fentanyl-positive samples were included in the study, spanning November 2017 to December 2019. Monthly median fentanyl concentrations ranged from 4.5% to 10.4%. Time-series analyses indicated that a third-degree polynomial model fit the data well (R2 = 0.639), suggesting a cyclical pattern in median concentration over time. Notably, absolute variance in fentanyl concentration decreased by an average 0.1% per month (P < 0.001). Future research should explore the relationship between fentanyl concentration and overdose to identify potential targeted harm-reduction interventions that can respond to changes in observed fentanyl concentration.
Subject(s)
Analgesics, Opioid/chemistry , Drug Contamination , Fentanyl/analysis , Illicit Drugs/chemistry , Canada , Humans , Time FactorsABSTRACT
Colorectal cancer is a prevalent disease worldwide, with more than 50% of patients developing metastases to the liver. Despite advances in improving resectability, most patients present with non-resectable colorectal liver metastases requiring palliative systemic therapy and locoregional disease control strategies. There is a growing interest in the use of liver transplantation to treat non-resectable colorectal liver metastases in well selected patients, leading to a surge in the number of studies and prospective trials worldwide, thereby fuelling the emerging field of transplant oncology. The interdisciplinary nature of this field requires domain-specific evidence and expertise to be drawn from multiple clinical specialities and the basic sciences. Importantly, the wider societal implication of liver transplantation for non-resectable colorectal liver metastases, such as the effect on the allocation of resources and national transplant waitlists, should be considered. To address the urgent need for a consensus approach, the International Hepato-Pancreato-Biliary Association commissioned the Liver Transplantation for Colorectal liver Metastases 2021 working group, consisting of international leaders in the areas of hepatobiliary surgery, colorectal oncology, liver transplantation, hepatology, and bioethics. The aim of this study was to standardise nomenclature and define management principles in five key domains: patient selection, evaluation of biological behaviour, graft selection, recipient considerations, and outcomes. An extensive literature review was done within the five domains identified. Between November, 2020, and January, 2021, a three-step modified Delphi consensus process was undertaken by the workgroup, who were further subgrouped into the Scientific Committee, Expert Panel, and Transplant Centre Representatives. A final consensus of 44 statements, standardised nomenclature, and a practical management algorithm is presented. Specific criteria for clinico-patho-radiological assessments with molecular profiling is crucial in this setting. After this, the careful evaluation of biological behaviour with bridging therapy to transplantation with an appropriate assessment of the response is required. The sequencing of treatment in synchronous metastatic disease requires special consideration and is highlighted here. Some ethical dilemmas within organ allocation for malignant indications are discussed and the role for extended criteria grafts, living donor transplantation, and machine perfusion technologies for non-resectable colorectal liver metastases are reviewed. Appropriate immunosuppressive regimens and strategies for the follow-up and treatment of recurrent disease are proposed. This consensus guideline provides a framework by which liver transplantation for non-resectable colorectal liver metastases might be safely instituted and is a meaningful step towards future evidenced-based practice for better patient selection and organ allocation to improve the survival for patients with this disease.