Adjuvant Nivolumab versus Placebo in Muscle-Invasive Urothelial Carcinoma.

BACKGROUND: The role of adjuvant treatment in high-risk muscle-invasive urothelial carcinoma after radical surgery is not clear. METHODS: In a phase 3, multicenter, double-blind, randomized, controlled trial, we assigned patients with muscle-invasive urothelial carcinoma who had undergone radical surgery to receive, in a 1:1 ratio, either nivolumab (240 mg intravenously) or placebo every 2 weeks for up to 1 year. Neoadjuvant cisplatin-based chemotherapy before trial entry was allowed. The primary end points were disease-free survival among all the patients (intention-to-treat population) and among patients with a tumor programmed death ligand 1 (PD-L1) expression level of 1% or more. Survival free from recurrence outside the urothelial tract was a secondary end point. RESULTS: A total of 353 patients were assigned to receive nivolumab and 356 to receive placebo. The median disease-free survival in the intention-to-treat population was 20.8 months (95% confidence interval [CI], 16.5 to 27.6) with nivolumab and 10.8 months (95% CI, 8.3 to 13.9) with placebo. The percentage of patients who were alive and disease-free at 6 months was 74.9% with nivolumab and 60.3% with placebo (hazard ratio for disease recurrence or death, 0.70; 98.22% CI, 0.55 to 0.90; P<0.001). Among patients with a PD-L1 expression level of 1% or more, the percentage of patients was 74.5% and 55.7%, respectively (hazard ratio, 0.55; 98.72% CI, 0.35 to 0.85; P<0.001). The median survival free from recurrence outside the urothelial tract in the intention-to-treat population was 22.9 months (95% CI, 19.2 to 33.4) with nivolumab and 13.7 months (95% CI, 8.4 to 20.3) with placebo. The percentage of patients who were alive and free from recurrence outside the urothelial tract at 6 months was 77.0% with nivolumab and 62.7% with placebo (hazard ratio for recurrence outside the urothelial tract or death, 0.72; 95% CI, 0.59 to 0.89). Among patients with a PD-L1 expression level of 1% or more, the percentage of patients was 75.3% and 56.7%, respectively (hazard ratio, 0.55; 95% CI, 0.39 to 0.79). Treatment-related adverse events of grade 3 or higher occurred in 17.9% of the nivolumab group and 7.2% of the placebo group. Two treatment-related deaths due to pneumonitis were noted in the nivolumab group. CONCLUSIONS: In this trial involving patients with high-risk muscle-invasive urothelial carcinoma who had undergone radical surgery, disease-free survival was longer with adjuvant nivolumab than with placebo in the intention-to-treat population and among patients with a PD-L1 expression level of 1% or more. (Funded by Bristol Myers Squibb and Ono Pharmaceutical; CheckMate 274 ClinicalTrials.gov number, NCT02632409.).

Treatment of muscle-invasive urothelial cancer with nivolumab (CheckMate 274 study): a plain language summary.

WHAT IS THIS SUMMARY ABOUT?: This is a summary of a paper published in a medical journal that describes the results of a study called CheckMate 274. This study looked at a new treatment for muscle-invasive urothelial cancer, a type of cancer found in the urinary tract that has spread from the inner lining of the urinary tract or bladder and into the surrounding muscle wall where it can then spread to other parts of the body. The standard treatment for muscle-invasive urothelial cancer is surgery to remove affected parts of the urinary tract. However, cancer returns in more than half of people after this surgery. Adjuvant therapy is given to people after surgery with muscle-invasive urothelial cancer with a goal to reduce the risk of the cancer coming back; however, at the time this study started, there was no standard adjuvant treatment. WHAT HAPPENED IN THE STUDY?: In the CheckMate 274 study, researchers compared nivolumab with a placebo as an adjuvant treatment for people with muscle-invasive urothelial cancer. The aim of the study was to understand how well nivolumab worked to reduce the chance of the cancer returning after surgery. The study also looked at what side effects (unwanted or unexpected results or conditions that are possibly related to the use of a medication) people had with treatment. WHAT DO THE RESULTS MEAN?: The results showed that people who received nivolumab versus placebo: Survived longer before the cancer was detected again, including people who had programmed death ligand-1 (shortened to PD-L1) on their cancer cells. Survived longer before a secondary cancer outside of the urinary tract was detected. Experienced no differences in health-related quality of life (the impact of the treatment on a person's mental and physical health). Had similar side effects to the people who received nivolumab in other studies. Clinical Trial Registration: NCT02632409 (ClinicalTrials.gov).

Adjuvant nivolumab versus placebo following radical surgery for high-risk muscle-invasive urothelial carcinoma: a subgroup analysis of Japanese patients enrolled in the phase 3 CheckMate 274 trial.

BACKGROUND: The phase 3 CheckMate 274 trial demonstrated superiority of adjuvant nivolumab over placebo after radical surgery in patients with high-risk muscle-invasive urothelial carcinoma. However, the efficacy and safety of adjuvant nivolumab in Japanese patients with muscle-invasive urothelial carcinoma have not been clarified. METHODS: Patients with muscle-invasive urothelial carcinoma were randomized to adjuvant nivolumab 240 mg or placebo (every 2 weeks via intravenous infusion) up to 120 days after radical surgery in CheckMate 274. RESULTS: Of 49 patients in the Japanese subgroup, 27 and 22 patients were randomized to nivolumab and placebo, respectively. Eleven and 8 patients, respectively, had tumor PD-L1 expression level of 1% or more. The median disease-free survival times in the nivolumab and placebo groups were 29.67 months (95% confidence interval 7.79-not reached) and 9.72 months (95% confidence interval 4.73-not reached), respectively (hazard ratio 0.77, 95% confidence interval 0.35-1.69). The corresponding values in patients with tumor PD-L1 expression level of 1% or more were 29.67 months (95% confidence interval 2.63-not reached) and 25.95 months (95% confidence interval 5.59-not reached) (hazard ratio 1.10, 95% confidence interval 0.31-3.92), respectively. Treatment-related adverse events of Grade 3-4 occurred in 25.9 and 13.6% of patients in the nivolumab and placebo groups, respectively. The most common treatment-related adverse events in the nivolumab group were lipase increased, amylase increased and diarrhea. The changes in quality of life scores from baseline over time were similar in both groups. CONCLUSIONS: The efficacy and safety results in the Japanese subgroup were consistent with the overall population of CheckMate 274.

Multi-country clinical practice patterns, including use of biomarkers, among physicians' treatment of BCG-unresponsive non-muscle invasive bladder cancer (NMIBC).

BACKGROUND: Intravesical bacillus Calmette-Guérin (BCG) fails in a considerable proportion of non-muscle invasive bladder cancer (NMIBC) patients despite treatment per recommended protocol. This real-world study aimed to understand the current patterns of treatment and disease management for the broad BCG-unresponsive NMIBC patient population, alongside collecting sufficient data on patients who do not undergo cystectomy. METHODS: This was a multicenter, retrospective survey of physicians treating BCG-unresponsive NMIBC patients. Data were collected in eight countries - France, Germany, Spain, Italy, United Kingdom, United States, China, and Japan - between January and May 2019. The study consisted of a short online physician survey and a retrospective chart review of eligible BCG-unresponsive NMIBC patients. Physicians abstracted chart data for the last 10 (five patients in Japan) eligible BCG-unresponsive NMIBC patients meeting the inclusion criteria, and the data were analysed for all countries combined using descriptive statistics. Country-specific analyses were also carried out, as appropriate. RESULTS: Overall, 508 physicians participated in the study. Almost one-quarter (22.9%) of physicians' current NMIBC patient caseload was BCG-unresponsive, whereby BCG therapy was no longer considered an option. Half of physicians (49.4%) did not regularly use biomarker tests in their practice, with particularly few physicians undertaking biomarker testing in Spain and Japan. Biomarker testing varied considerably, with the proportions of physicians selecting 'none' ranging from 11.4% in China to 70.3% in Japan. Physicians reported transurethral resection of the bladder tumor (TURBT) and BCG as the most common current treatments received by their patients. Chemotherapy and anti-PD-L1 treatment options were considered impactful new therapies by 94.7% and 90.0% of physicians surveyed in this study, respectively. CONCLUSIONS: The most common treatments received by patients in this study were TURBT and BCG. Emerging new treatments are driven by exploring biomarkers, but in real-world clinical practice only half of physicians or fewer regularly tested their NMIBC patients for biomarkers; PD-1/PD-L1 was the most common biomarker test used. Most physicians reported that, in addition to chemotherapy, anti-PD-L1 was an impactful new therapy.

Effectiveness of in-service training plus the collaborative improvement strategy on the quality of routine malaria surveillance data: results of a pilot study in Kayunga District, Uganda.

BACKGROUND: Surveillance data are essential for malaria control, but quality is often poor. The aim of the study was to evaluate the effectiveness of the novel combination of training plus an innovative quality improvement method-collaborative improvement (CI)-on the quality of malaria surveillance data in Uganda. METHODS: The intervention (training plus CI, or TCI), including brief in-service training and CI, was delivered in 5 health facilities (HFs) in Kayunga District from November 2015 to August 2016. HF teams monitored data quality, conducted plan-do-study-act cycles to test changes, attended periodic learning sessions, and received CI coaching. An independent evaluation was conducted to assess data completeness, accuracy, and timeliness. Using an interrupted time series design without a separate control group, data were abstracted from 156,707 outpatient department (OPD) records, laboratory registers, and aggregated monthly reports (MR) for 4 time periods: baseline-12 months, TCI scale-up-5 months; CI implementation-9 months; post-intervention-4 months. Monthly OPD register completeness was measured as the proportion of patient records with a malaria diagnosis with: (1) all data fields completed, and (2) all clinically-relevant fields completed. Accuracy was the relative difference between: (1) number of monthly malaria patients reported in OPD register versus MR, and (2) proportion of positive malaria tests reported in the laboratory register versus MR. Data were analysed with segmented linear regression modelling. RESULTS: Data completeness increased substantially following TCI. Compared to baseline, all-field completeness increased by 60.1%-points (95% confidence interval [CI]: 46.9-73.2%) at mid-point, and clinically-relevant completeness increased by 61.6%-points (95% CI: 56.6-66.7%). A relative - 57.4%-point (95% confidence interval: - 105.5, - 9.3%) change, indicating an improvement in accuracy of malaria test positivity reporting, but no effect on data accuracy for monthly malaria patients, were observed. Cost per additional malaria patient, for whom complete clinically-relevant data were recorded in the OPD register, was $3.53 (95% confidence interval: $3.03, $4.15). CONCLUSIONS: TCI improved malaria surveillance completeness considerably, with limited impact on accuracy. Although these results are promising, the intervention's effectiveness should be evaluated in more HFs, with longer follow-up, ideally in a randomized trial, before recommending CI for wide-scale use.

Screening in Maternity to Ascertain Tuberculosis Status (SMATS) study.

BACKGROUND: Diagnosis of tuberculosis is difficult among pregnant women because the signs and symptoms of the disease, such as fatigue, shortness of breath, sweating, cough, and mild fever are similar to some manifestations of pregnancy. It is particularly challenging among HIV-infected women as symptoms are often masked or atypical. Currently, WHO recommends a standard four-symptom screening tool for pregnant and lactating women. There is evidence from South Africa that this screening tool (which, despite complex symptomology in this population, recommends identification of patients with weight loss, fever, current cough and night sweats), may be missing true active TB cases. However there exist several laboratory and clinical procedures that have the potential to improve the sensitivity and specificity of this screening tool. METHODS: This study will evaluate the sensitivity and specificity of the current TB screening tool for pregnant and lactating women, both HIV positive and negative. We will also assess several different enhanced screening algorithm using LAM, IGRA, TST and chest radiography and clinical/laboratory procedures and tests. The study will use a cross-sectional analytical study design involving pregnant and lactating women up to six months post-delivery attending antenatal or postnatal care, respectively in one of three selected public health units in Swaziland. Participants will be consecutively enrolled and will be in one of four groups of interest: HIV infected pregnant women, non-HIV infected pregnant women, HIV infected lactating women and non-HIV infected lactating women. DISCUSSION: We expect in conducting all procedures on all participants regardless of result of the symptom screening we may experience a high refusal rate. However, this risk will be mitigated by the long data collection period of five or more months.

Cost-effectiveness of implementing the chronic care model for HIV care in Uganda.

OBJECTIVE: The chronic care model (CCM) is an integrated, population-based approach for treating those with chronic diseases that involves patient self-management, delivery system design and decision support for clinicians to ensure evidence-based care. We sought to determine effectiveness and cost-effectiveness of implementing the CCM for HIV care in Uganda. DESIGN: This controlled, pre/post-intervention study used difference-in-differences analysis to evaluate effectiveness of the CCM to improve patient adherence to antiretroviral therapy (ART) and CD4 counts. SETTING: One district hospital and two smaller facilities each in one intervention and one control district in Uganda. PARTICIPANTS: About 46 randomly sampled patients receiving HIV services at three control sites and 56 patients from three intervention sites. INTERVENTION: Two group training sessions and monthly coaching visits from improvement experts over 1 year, implementing the CCM. MAIN OUTCOME MEASURE(S): Patient adherence to ART prescriptions (pill counts) and CD4 counts were measured at baseline and en dline. RESULTS: The odds of increased CD4 in the intervention group was 3.2 times higher than controls (P = 0.022). Clinician-reported ART adherence was 60% (P = 0.001) higher in the intervention group. The intervention cost $11 740 and served 7016 patients ($1.67 per patient). Incremental cost-effectiveness ratios of the intervention compared to business-as-usual was $6.90 per additional patient with improved CD4 and $3.40 per additional ART patient with stable or improved adherence. CONCLUSION: For modest expenditure, it is possible to improve indicators of HIV care quality using the CCM. We recommended implementing the CCM in Uganda; it may be applicable in similar settings in other countries.

Effectiveness, Safety, and Patterns of Real-World Isavuconazole Use in Europe (2015-2019).

INTRODUCTION: Real-world data from multinational observational studies are required to better understand the role and performance of isavuconazole in real-world practice in Europe. METHODS: A retrospective medical record review was conducted at 16 sites in Europe (France, Germany, Italy, Spain, and the United Kingdom). Eligible records were from patients aged ≥ 18 years at the time of isavuconazole initiation and received at least one dose of isavuconazole for suspected or confirmed invasive aspergillosis (IA) or invasive mucormycosis (IM) during the eligibility period (October 15, 2015 to June 30, 2019). Data were descriptively analysed. Success rates, overall survival, and times to these events were descriptively analysed. RESULTS: Data were abstracted from 218 patients (201, IA; 17, IM) who received isavuconazole as monotherapy (initiated as infusion, 52%; oral, 46%). Isavuconazole was initiated as primary therapy in 92 patients (42.2%) and salvage therapy in 121 patients (55.5%) (unknown for five patients). Mean (standard deviation) age was 56.8 (15.6) years, 66% were men and 62% had at least three comorbidities, most frequently haematologic malignancy (62%). Estimated clinical response rate at week 24 was 54.5% (95% confidence interval [CI], 38.2-66.5%) for primary treatment and 73.5% (95% CI, 62.7-81.1%) for salvage therapy. Overall, 45 patients (21%) experienced at least one adverse event (AE). Serious AEs were experienced by 37 patients (17%), with seven related to isavuconazole; five patients (2.3%) discontinued isavuconazole monotherapy due to the serious AE. A total of 137 patients (63%) died, with 17 deaths (12.4%) related to their invasive fungal infection, 11 of whom initiated isavuconazole as salvage therapy. CONCLUSIONS: This study adds to the growing body of evidence that whether used as first-line therapy or after the failure of other antifungal therapies, isavuconazole appears to have a promising clinical response and a good safety profile as an antifungal agent in patients with varied underlying conditions.

The cost-savings of implementing kangaroo mother care in Nicaragua.

OBJECTIVE: To examine the costs of implementing kangaroo mother care (KMC) in a referral hospital in Nicaragua, including training, implementation, and ongoing operating costs, and to estimate the economic impact on the Nicaraguan health system if KMC were implemented in other maternity hospitals in the country. METHODS: After receiving clinical training in KMC, the implementation team trained their colleagues, wrote guidelines for clinicians and education material for parents, and ensured adherence to the new guidelines. The intervention began September 2010 The study compared data on infant weight, medication use, formula consumption, incubator use, and hospitalization for six months before and after implementation. Cost data were collected from accounting records of the implementers and health ministry formularies. RESULTS: A total of 46 randomly selected infants before implementation were compared to 52 after implementation. Controlling for confounders, neonates after implementation had lower lengths of hospitalization by 4.64 days (P = 0.017) and 71% were exclusively breastfed (P < 0.001). The intervention cost US$ 23 113 but the money saved with shorter hospitalization, elimination of incubator use, and lower antibiotic and infant formula costs made up for this expense in 1 - 2 months. Extending KMC to 12 other facilities in Nicaragua is projected to save approximately US$ 166 000 (based on the referral hospital incubator use estimate) or US$ 233 000 after one year (based on the more conservative incubator use estimate). CONCLUSIONS: Treating premature and low-birth-weight infants in Nicaragua with KMC implemented as a quality improvement program saves money within a short period even without considering the beneficial health effects of KMC. Implementation in more facilities is strongly recommended.

Cost-effectiveness of a quality improvement collaborative for obstetric and newborn care in Niger.

PURPOSE: The purpose of this paper is to describe a quality improvement collaborative conducted in 33 Nigerian facilities to improve maternal and newborn care outcomes by increasing compliance with high-impact, evidence-based care standards. Intervention costs and cost-effectiveness were examined and costs to the Niger Health Ministry (MoH) were estimated if they were to scale-up the intervention to additional sites. DESIGN/METHODOLOGY/APPROACH: Facility-based maternal care outcomes and costs from pre-quality improvement collaborative baseline monitoring data in participating facilities from January to May 2006 were compared with outcomes and costs from the same facilities from June 2008 to September 2008. Cost data were collected from project accounting records. The MoH costs were determined from interviews with clinic managers and quality improvement teams. Effectiveness data were obtained from facilities' records. FINDINGS: The average delivery-cost decreased from $35 before to $28 after the collaborative. The USAID/HCI project's incremental cost was $2.43/delivery. The collaborative incremental cost-effectiveness was $147/disability-adjusted life year averted. If the MoH spread the intervention to other facilities, substantive cost-savings and improved health outcomes can be predicted. PRACTICAL IMPLICATIONS: The intervention achieved significant positive health benefits for a low cost. The Niger MoH can expect approximately 50 per cent return on its investment if it implements the collaborative in new facilities. The improvement collaborative approach can improve health and save health care resources. ORIGINALITY/VALUE: This is one of the first studies known to examine collaborative quality improvement and economic efficiency in a developing country.

Real-world treatment patterns and clinical outcomes among patients with advanced urothelial carcinoma in the United States.

INTRODUCTION: This large-scale, US-based study characterized real-world treatment patterns and clinical outcomes in patients with advanced or metastatic urothelial carcinoma (aUC). METHODS: This retrospective cohort analysis included patients with stage IV or node-positive aUC between January 1, 2011, and August 31, 2020, from an electronic health record-derived, de-identified database (Flatiron Health). Baseline characteristics and treatment patterns were assessed by first-line (1L) systemic treatment received and cisplatin eligibility status. Overall survival (OS) and progression-free survival (PFS) were evaluated. RESULTS: Of 8,183 patients included, 5,855 (71.6%) received systemic 1L therapy and 2,328 (28.4%) did not. Median (range) follow-up from aUC diagnosis was 9.7 (0.2-116.6) months. Of patients who received 1L systemic therapy, 30.1% were cisplatin-eligible, 39.2% were cisplatin-ineligible, 10.5% did not receive cisplatin despite qualifying ECOG PS and renal function, and cisplatin eligibility was unknown in 20.2%. Of those treated, 74.8% received 1L chemotherapy and 23.0% received 1L immuno-oncology-based monotherapy. Median OS (95% CI) was 14.5 (14.0-15.2) months in patients who received 1L systemic therapy and 6.8 (6.2-7.3) months in those who did not. Of those treated, cisplatin-ineligible patients had worse OS and PFS outcomes vs. other subgroups. Among cisplatin-ineligible patients, 1L immuno-oncology monotherapy (n = 865) was associated with worse OS and PFS outcomes than 1L chemotherapy (n = 1,369). CONCLUSIONS: More than 25% of aUC patients did not receive 1L systemic therapy; of patients who were treated, most received chemotherapy, with less than 25% receiving immuno-oncology-based monotherapy. Overall, these results highlight the substantial unmet need in this population, specifically among cisplatin-ineligible patients.

Treatment and disease management patterns for bacillus Calmette-Guérin unresponsive nonmuscle invasive bladder cancer in North America, Europe and Asia: A real-world data analysis.

Background: This study examined real-world treatment and management of bacillus Calmette-Guérin (BCG)-unresponsive patients across 3 continents, including patients unable or unwilling to undergo cystectomy. Materials and methods: Physicians actively involved in managing patients with nonmuscle invasive bladder cancer completed online case report forms for their 5 consecutive patients from the broad BCG-unresponsive population and a further 5 consecutive BCG-unresponsive patients who did not undergo cystectomy (in Japan, physicians provided a total of 5 patients across both cohorts). Results: Most patients had received 1 (37%) or 2 (24%) maintenance courses of BCG. Five or more maintenance BCG courses were received by patients in Japan (59%) and China (31%), while in Germany 76% of patients received only 1 course. Most patients became BCG-unresponsive during their first (44%) or second (22%) treatment course; in Germany, 77% became BCG-unresponsive during their first treatment course. Most countries did not provide another course of BCG after a patient first became unresponsive, whereas unresponsive patients in Japan and China were most likely to be retreated with BCG. "Untreated - on watch and wait" was the main treatment/management approach received post-BCG treatment for 42% or more of patients in most countries except China (39%) and the United States (36%). "Following treatment guidelines" was consistently the top reason for post-BCG treatment selection across all treatment options. Conclusions: This study confirmed the global unmet need for patients with nonmuscle invasive bladder cancer, and found that many patients experienced periods of no treatment after not responding to BCG therapy.

Health-related Quality of Life with Adjuvant Nivolumab After Radical Resection for High-risk Muscle-invasive Urothelial Carcinoma: Results from the Phase 3 CheckMate 274 Trial.

BACKGROUND: The programmed death-1 (PD-1) inhibitor nivolumab prolongs disease-free survival in patients with muscle-invasive urothelial carcinoma (MIUC). OBJECTIVE: To evaluate the effects of nivolumab on health-related quality of life (HRQoL) after radical resection in patients with MIUC. DESIGN, SETTING, AND PARTICIPANTS: We used data from 709 patients in CheckMate 274 (NCT02632409; 282 with programmed death ligand 1 [PD-L1] expression ≥1%), an ongoing randomized, double-blind, placebo-controlled phase 3 trial of adjuvant nivolumab. INTERVENTION: Intravenous injection of nivolumab (240 mg) or placebo every 2 wk for ≤1 yr. OUTCOME MEASUREMENTS AND STATISTICAL ANALYSIS: HRQoL was assessed using the European Organisation for Research and Treatment of Cancer Quality of Life Questionnaire (EORTC QLQ-C30) and the EQ-5D-3L. Linear mixed-effect models for repeated measures were used to compare nivolumab and placebo on changes in HRQoL. Time to confirmed deterioration (TTCD) of HRQoL was analyzed by Cox proportional hazards regression. RESULTS AND LIMITATIONS: In the full HRQoL evaluable population, no clinically meaningful deterioration of HRQoL was observed in either treatment arm. Moreover, nivolumab was noninferior to placebo on changes from baseline for all main outcomes. The median TTCD for fatigue was 41.0 wk for nivolumab and 44.3 wk for placebo (hazard ratio [HR]: 1.11, 95% confidence interval [CI], 0.89-1.39). For the visual analog scale, the median TTCD was not reached for nivolumab and it was 57.6 wk for placebo (HR: 0.78, 95% CI, 0.61-1.00). The median TTCD for the other main outcomes was not reached in either treatment arm. The findings were similar for patients with PD-L1 expression ≥1%. CONCLUSIONS: These results demonstrate that nivolumab did not compromise the HRQoL of patients with MIUC in CheckMate 274. PATIENT SUMMARY: Nivolumab is being researched as a new treatment for patients with bladder cancer (urothelial carcinoma). We found that nivolumab maintained quality of life while increasing the time until cancer returns in patients whose bladder cancer had spread or grown and who had unsuccessfully tried platinum-containing chemotherapy.

Validity of self-assessment in a quality improvement collaborative in Ecuador.

OBJECTIVE: Health care quality improvement (QI) efforts commonly use self-assessment to measure compliance with quality standards. This study investigates the validity of self-assessment of quality indicators. DESIGN: Cross sectional. SETTING: A maternal and newborn care improvement collaborative intervention conducted in health facilities in Ecuador in 2005. PARTICIPANTS: Four external evaluators were trained in abstracting medical records to calculate six indicators reflecting compliance with treatment standards. INTERVENTIONS: About 30 medical records per month were examined at 12 participating health facilities for a total of 1875 records. The same records had already been reviewed by QI teams at these facilities (self-assessment). MAIN OUTCOME MEASURES: Overall compliance, agreement (using the Kappa statistic), sensitivity and specificity were analyzed. We also examined patterns of disagreement and the effect of facility characteristics on levels of agreement. RESULTS: External evaluators reported compliance of 69-90%, while self-assessors reported 71-92%, with raw agreement of 71-95% and Kappa statistics ranging from fair to almost perfect agreement. Considering external evaluators as the gold standard, sensitivity of self-assessment ranged from 90 to 99% and specificity from 48 to 86%. Simpler indicators had fewer disagreements. When disagreements occurred between self-assessment and external valuators, the former tended to report more positive findings in five of six indicators, but this tendency was not of a magnitude to change program actions. Team leadership, understanding of the tools and facility size had no overall impact on the level of agreement. CONCLUSIONS: When compared with external evaluation (gold standard), self-assessment was found to be sufficiently valid for tracking QI team performance. Sensitivity was generally higher than specificity. Simplifying indicators may improve validity.

Cost-effectiveness of improving pediatric hospital care in Nicaragua.

OBJECTIVE: To determine the costs and cost-effectiveness of an intervention to improve quality of care for children with diarrhea or pneumonia in 14 hospitals in Nicaragua, based on expenditure data and impact measures. METHODS: Hospital length of stay (LOS) and deaths were abstracted from a random sample of 1294 clinical records completed at seven of the 14 participating hospitals before the intervention (2003) and 1505 records completed after two years of intervention implementation ("post-intervention"; 2006). Disability-adjusted life years (DALYs) were derived from outcome data. Hospitalization costs were calculated based on hospital and Ministry of Health records and private sector data. Intervention costs came from project accounting records. Decision-tree analysis was used to calculate incremental cost-effectiveness. RESULTS: Average LOS decreased from 3.87 and 4.23 days pre-intervention to 3.55 and 3.94 days post-intervention for diarrhea (P = 0.078) and pneumonia (P = 0.055), respectively. Case fatalities decreased from 45/10 000 and 34/10 000 pre-intervention to 30/10 000 and 27/10 000 post-intervention for diarrhea (P = 0.062) and pneumonia (P = 0.37), respectively. Average total hospitalization and antibiotic costs for both diagnoses were US$ 451 (95% credibility interval [CI]: US$ 419-US$ 482) pre-intervention and US$ 437 (95% CI: US$ 402-US$ 464) post-intervention. The intervention was cost-saving in terms of DALYs (95% CI: -US$ 522- US$ 32 per DALY averted) and cost US$ 21 per hospital day averted (95% CI: -US$ 45- US$ 204). CONCLUSIONS: After two years of intervention implementation, LOS and deaths for diarrhea decreased, along with LOS for pneumonia, with no increase in hospitalization costs. If these changes were entirely attributable to the intervention, it would be cost-saving.

Higher hospital costs and lengths of stay associated with quinolone-resistant Salmonella enterica infections in Hong Kong.

OBJECTIVES: The study sought to determine the differences in lengths of stay and medical costs between patients admitted to hospital with non-typhoidal salmonellosis that were either quinolone resistant (QR) or quinolone susceptible (QS). DESIGN: We examined medical records of all patients 1 year of age or older admitted to a Hong Kong hospital between 2003 and 2008 with confirmed salmonellosis diagnosis. Data were collected on length of stay, age, sex, comorbidities, antibiotics and other medication use, diagnostic tests completed, serotype and susceptibility characteristics of isolated and the circumstances of discharge from hospital. We used Cox proportional regression to determine the differences in lengths of stay and quantile regression for differences in hospital costs. RESULTS: Median duration of hospitalization among QR salmonellosis patients was 1 day (33%; 95% CI: 13-47%) longer than those with QS salmonellosis, adjusting for confounders. Adjusted median costs were US $399 (35%) and 75th percentile costs were US $760 (43%) higher in the QR group than those in the QS group, indicating a greater difference among sicker patients. CONCLUSION: The finding of substantially longer stays and higher costs associated with QR indicates that interventions that decrease QR prevalence will lead to significant savings for the health system in the management of hospitalized salmonellosis cases.

Detecting tuberculosis in pregnant and postpartum women in Eswatini.

BACKGROUND: Tuberculosis diagnosis in pregnancy is complex because tuberculosis symptoms are often masked by physiological symptoms of pregnancy. Untreated tuberculosis in pregnant and postpartum women may lead to maternal morbidity and low birth weight. Tuberculosis in HIV-positive pregnant women increases the risk of maternal and infant mortality. OBJECTIVE: This study aimed to determine tuberculosis prevalence stratified by HIV status and identify screening algorithms that maximise detection of active tuberculosis among pregnant and postpartum women in Eswatini. METHODS: Women were enrolled at antenatal and postnatal clinics in Eswatini for tuberculosis screening and diagnostic investigations from 01 April to 30 November 2015 in a cross-sectional study. Sputum samples were collected from all participants for tuberculosis diagnostic tests (smear microscopy, GeneXpert, MGIT culture). Blood and urine samples were collected from HIV-positive women for cluster-of-differentiation-4 cell count, interferon gamma release assay and tuberculosis lateral flow urine lipoarabinomannan tests. RESULTS: We enrolled 990 women; 52% were pregnant and 47% were HIV-positive. The prevalence of tuberculosis among HIV-positive pregnant women was 5% (95% confidence interval [CI]: 2-7) and among postpartum women it was 1% (95%CI: -1-3). Tuberculosis prevalence was 2% (95%CI: 0-3) in HIV-negative pregnant women and 1% (95%CI: -1-2) in HIV-negative postpartum women. The national tuberculosis symptom screening tool failed to identify women who tested tuberculosis-culture positive. CONCLUSION: Routine tuberculosis symptom screening alone is insufficient to rule out tuberculosis in pregnant and postpartum women. Only sputum culture maximised the detection of tuberculosis, indicating a need to balance access and cost in developing countries.

Prevalence of antibiotic-resistant Salmonella in fish in Guangdong, China.

INTRODUCTION: This study examines fish from freshwater aquaculture operations in Guangdong Province, China, to determine the prevalence of antibiotic-resistant Salmonella isolates. This information can help identify risks of human exposure to Salmonella and guide decisions of whether to include farmed fish samples in routine food surveillance for Salmonella. METHODS: One hundred live freshwater-farmed finfish were sampled from several stalls at two wholesale and four retail markets in Guangzhou from June to July 2008. Isolation and antibiotic sensitivity testing was done according to the U.S. FDA Bacteriological Analytical Manual. Antibiotic sensitivity testing was done using the Kirby Bauer disk diffusion method. RESULTS: All five Salmonella isolates were susceptible to neomycin, cefotaxime, and cefepime and resistant to erythromycin and penicillin. The most resistant isolate was susceptible to 7 of the 16 antibiotics tested. DISCUSSION: The estimated prevalence of Salmonella is 5% (95% CI: 2-11%) in live finfish from markets in Guangzhou, China. All five isolates were not susceptible to three or more antibiotics. Three of the five isolates had decreased susceptibility to nitrofurantoin, suggesting illegal use of nitrofurans in food animal production, and surveillance of resistance to this class of antibiotics is warranted. We suggest aquaculture-producing countries where there may be high antibiotic use to add farmed fish products to the list of foods they include in Salmonella surveillance. This would help evaluate human health risks posed by antibiotic-resistant bacteria in farmed fish products.

The cost-effectiveness of three methods of disseminating information to improve medical male circumcision in Uganda.

BACKGROUND: Uganda is working to increase voluntary medical male circumcision (VMMC) to prevent HIV infection. To support VMMC quality improvement, this study compared three methods of disseminating information to facilities on how to improve VMMC quality: M-providing a written manual; MH-providing the manual plus a handover meeting in which clinicians shared advice on implementing key changes and participated in group discussion; and MHC-manual, handover meeting, and three site visits to the facility in which a coach provided individualized guidance and mentoring on improvement. We determined the different effects these had on compliance with indicators of quality of care. METHODS: This controlled pre-post intervention study randomized health facility groups to receive M, MH, or MHC. Observations of VMMCs performance determined compliance with quality indicators. Intervention costs per patient receiving VMMC were used in a decision-tree cost-effectiveness model to calculate the incremental cost per additional patient treated to compliance with indicators of informed consent, history taking, anesthesia administration, and post-operative instructions. RESULTS: The most intensive method (MHC) cost $28.83 per patient and produced the biggest gains in history taking (35% improvement), anesthesia administration (20% improvement), and post-operative instructions (37% improvement). The least intensive method (M; $1.13 per patient) was most efficient because it produced small gains for a very low cost. The handover meeting (MH) was the most expensive among the three interventions but did not have a corresponding positive effect on quality. CONCLUSION: Health workers in facilities that received the VMMC improvement manual and participated in the handover meeting and coaching visits showed more improvement in VMMC quality indicators than those in the other two intervention groups. Providing the manual alone cost the least but was also the least effective in achieving improvements. The MHC intervention is recommended for broader implementation to improve VMMC quality in Uganda.