Dynamic Assessment of Fluid Responsiveness in Surgical ICU Patients Through Stroke Volume Variation is Associated With Decreased Length of Stay and Costs: A Systematic Review and Meta-Analysis.

Static indices, such as the central venous pressure, have proven to be inaccurate predictors of fluid responsiveness. An emerging approach uses dynamic assessment of fluid responsiveness (FT-DYN), such as stroke volume variation (SVV) or surrogate dynamic variables, as more accurate measures of volume status. Recent work has demonstrated that goal-directed therapy guided by FT-DYN was associated with reduced intensive care unit (ICU) mortality; however, no study has specifically assessed this in surgical ICU patients. This study aimed to conduct a systematic review and meta-analysis on the impact of employing FT-DYN in the perioperative care of surgical ICU patients on length of stay in the ICU. As secondary objectives, we performed a cost analysis of FT-DYN and assessed the impact of FT-DYN versus standard care on hospital length of stay and mortality. We identified all randomized controlled trials (RCTs) through MEDLINE, EMBASE, and CENTRAL that examined adult patients in the ICU who were randomized to standard care or to FT-DYN from inception to September 2017. Two investigators independently reviewed search results, identified appropriate studies, and extracted data using standardized spreadsheets. A random effect meta-analysis was carried out. Eleven RCTs were included with a total of 1015 patients. The incorporation of FT-DYN through SVV in surgical patients led to shorter ICU length of stay (weighted mean difference [WMD], -1.43d; 95% confidence interval [CI], -2.09 to -0.78), shorter hospital length of stay (WMD, -1.96d; 95% CI, -2.34 to -1.59), and trended toward improved mortality (odds ratio, 0.55; 95% CI, 0.30-1.03). There was a decrease in daily ICU-related costs per patient for those who received FT-DYN in the perioperative period (WMD, US$ -1619; 95% CI, -2173.68 to -1063.26). Incorporation of FT-DYN through SVV in the perioperative care of surgical ICU patients is associated with decreased ICU length of stay, hospital length of stay, and ICU costs.

Predictors of mortality and cost among surgical patients requiring rapid response team activation.

Background: Prior studies of rapid response team (RRT) implementation for surgical patients have demonstrated mixed results with respect to reductions in poor outcomes. The aim of this study was to identify predictors of in-hospital mortality and hospital costs among surgical inpatients requiring RRT activation. Methods: We analyzed data prospectively collected from May 2012 to May 2016 at The Ottawa Hospital. We included patients who were at least 18 years of age, who were admitted to hospital, who received either preoperative or postoperative care, and and who required RRT activation. We created a multivariable logistic regression model to describe mortality predictors and a multivariable generalized linear model to describe cost predictors. Results: We included 1507 patients. The in-hospital mortality rate was 15.9%. The patient-related factors most strongly associated with mortality included an Elixhauser Comorbidity Index score of 20 or higher (odds ratio [OR] 3.60, 95% confidence interval [CI] 1.96-6.60) and care designations excluding admission to the intensive care unit and cardiopulmonary resuscitation (OR 3.52, 95% CI 2.25-5.52). The strongest surgical predictors included neurosurgical admission (OR 2.09, 95% CI 1.17-3.75), emergent surgery (OR 2.04, 95% CI 1.37-3.03) and occurrence of 2 or more operations (OR 1.73, 95% CI 1.21-2.46). Among RRT factors, occurrence of 2 or more RRT assessments (OR 2.01, 95% CI 1.44-2.80) conferred the highest mortality. Increased cost was strongly associated with admitting service, multiple surgeries, multiple RRT assessments and medical comorbidity. Conclusion: RRT activation among surgical inpatients identifies a population at high risk of death. We identified several predictors of mortality and cost, which represent opportunities for future quality improvement and patient safety initiatives.

Contexte: Les études sur la mobilisation d'équipes d'intervention rapide (EIR) auprès de patients en chirurgie ont donné des résultats mitigés quant à la réduction des issues négatives. La présente étude visait à déterminer les facteurs prédictifs de coûts pour les hôpitaux et de mortalité chez les patients en chirurgie nécessitant la mobilisation d'une EIR. Méthodes: Nous avons analysé des données recueillies de manière prospective de mai 2012 à mai 2016 à l'Hôpital d'Ottawa. Nous avons inclus les patients hospitalisés de 18 ans et plus qui ont reçu des soins préopératoires ou postopératoires et qui ont nécessité l'intervention d'une EIR. Nous avons ensuite créé un modèle de régression logistique multivariée pour décrire les facteurs prédictifs de mortalité et un modèle linéaire généralisé multivarié pour décrire les facteurs prédictifs de coûts. Résultats: Nous avons retenus 1507 patients. Le taux global de mortalité à l'hôpital était de 15,9 %. Les principaux facteurs de mortalité liés au patient étaient un indice de comorbidité d'Elixhauser supérieur ou égal à 20 (rapport de cotes [RC] 3,60, intervalle de confiance [IC] à 95 % 1,96­6,60) et des objectifs de soins excluant l'admission à l'unité des soins intensifs et la réanimation cardiorespiratoire (RC 3,52, IC à 95 % 2,25­5,52). Les principaux facteurs prédictifs liés aux interventions sont l'admission en neurochirurgie (RC 2,09, IC à 95 % 1,17­3,75), l'intervention chirurgicale d'urgence (RC 2,04, IC à 95 % 1,37­3,03) et le fait d'avoir subi au moins 2 opérations (RC 1,73, IC à 95 % 1,21­2,46). Parmi les facteurs liés aux EIR, la tenue d'au moins 2 évaluations par l'EIR s'accompagnait du mortalité le plus élevé (RC 2,01, IC à 95 % 1,44­2,80). L'augmentation des coûts était étroitement associée au service d'admission, aux interventions chirurgicales multiples, aux évaluations multiples par l'EIR et à la comorbidité médicale. Conclusion: La mobilisation d'EIR auprès de patients en chirurgie permet de mettre en évidence une population à risque élevé de décès. Nous avons découvert plusieurs facteurs prédictifs de mortalité et de coûts, dont on pourra se servir pour améliorer la qualité des soins et la sécurité des patients.

Conditional cash transfers to prevent mother-to-child transmission in low facility-delivery settings: evidence from a randomised controlled trial in Nigeria.

BACKGROUND: Nigeria suffers from the highest burden of mother-to-child transmission worldwide. To increase retention in care and prevention programmes, we piloted and evaluated a conditional cash transfer (CCT) programme for preventing mother-to-child transmission (PMTCT) in Akwa Ibom, Nigeria. METHODS: In a randomised controlled trial, pregnant women testing positive for HIV during antenatal care registration at three public hospitals were randomised to one of two study arms: (1) offered enrolment into the CCT programme or (2) continue in standard care for (PMTCT). In the CCT programme, women could receive a compensation package totaling 33,300 Naira (~US$114) for enroling, delivering at the facility, and obtaining a newborn early infant diagnosis (EID) test. The intent-to-treat (ITT) and per protocol (PP) effects of the programme on the primary outcomes of facility delivery and EID testing and on the secondary outcome of nevirapine administration were estimated with logistic regressions. RESULTS: From August 1, 2015 to April 19, 2017, 554 pregnant women tested positive for HIV; 273 were randomised to standard care and 281 were offered enrolment into the CCT intervention. Women offered the CCT programme were more likely to give birth at the facility (n = 109/263; 41.4%) compared to women in standard care (n = 80/254; 31.5%), an absolute difference of 9.9% (OR = 1.54, 95% CI: 1.07-2.21, p = 0.019). For EID testing there was an absolute difference of 12.8% between those offered the CCT intervention (n = 69/263; 26.2%) and those in standard care (n = 34/254; 13.4%; OR = 2.30, 95% CI 1.46-3.62, p = 0.000). PP results show larger differences for both facility deliveries (16.7% absolute difference; OR = 2.02, 95% CI 1.38-2.98, p = 0.000) and EID testing (18.9% absolute difference; OR = 3.09, 95% CI 1.93-4.94, p = 0.000) among intervention enrolees. Over 86% of the facility-delivered newborns received nevirapine, and ITT and PP estimates were similar to those for facility deliveries. CONCLUSIONS: Results show that CCTs improved the likelihood of HIV-positive women giving birth at a facility, of nevirapine being administered to their newborn, and of undergoing EID testing in Akwa Ibom, Nigeria. Effects are especially large among those who agreed to participate in the CCT intervention. TRIAL REGISTRATION: ClinicalTrials.gov NCT02447159 , May 18, 2015.

Impact of nighttime Rapid Response Team activation on outcomes of hospitalized patients with acute deterioration.

BACKGROUND: Rapid Response Teams (RRTs) are groups of healthcare providers that are used by many hospitals to respond to acutely deteriorating patients admitted to the wards. We sought to identify outcomes of patients assessed by RRTs outside standard working hours. METHODS: We used a prospectively collected registry from two hospitals within a single tertiary care-level hospital system between May 1, 2012, and May 31, 2016. Patient information, outcomes, and RRT activation information were stored in the hospital data warehouse. Comparisons were made between RRT activation during daytime hours (0800-1659) and nighttime hours (1700-0759). The primary outcome was in-hospital mortality, analyzed using a multivariable logistic regression model. RESULTS: A total of 6023 RRT activations on discrete patients were analyzed, 3367 (55.9%) of which occurred during nighttime hours. Nighttime RRT activation was associated with increased odds of mortality, as compared with daytime RRT activation (adjusted OR 1.34, 95% CI 1.26-1.40, P = 0.02). The time periods associated with the highest odds of mortality were 0600-0700 (adjusted OR 1.30, 95% CI 1.09-1.61) and 2300-2400 (adjusted OR 1.34, 95% CI 1.01-1.56). Daytime RRT activation was associated with increased odds of intensive care unit admission (adjusted OR 1.40, 95% CI 1.31-1.50, P = 0.02). Time from onset of concerning symptoms to RRT activation was shorter among patients assessed during daytime hours (P < 0.001). CONCLUSIONS: Acutely deteriorating ward patients assessed by an RRT at nighttime had a higher risk of in-hospital mortality. This work identifies important shortcomings in health service provision and quality of care outside daytime hours, highlighting an opportunity for quality improvement.

Cost of HPV screening at community health campaigns (CHCs) and health clinics in rural Kenya.

BACKGROUND: Cervical cancer is the most frequent neoplasm among Kenyan women, with 4800 diagnoses and 2400 deaths per year. One reason is an extremely low rate of screening through pap smears, at 13.8% in 2014. Knowing the costs of screening will help planners and policymakers design, implement, and scale programs. METHODS: We conducted HPV-based cervical cancer screening via self-collection in 12 communities in rural Migori County, Kenya. Six communities were randomized to community health campaigns (CHCs), and six to screening at government clinics. All HPV-positive women were referred for cryotherapy at Migori County Hospital. We prospectively estimated direct costs from the health system perspective, using micro-costing methods. Cost data were extracted from expenditure records, staff interviews, and time and motion logs. Total costs per woman screening included three activities: outreach, HPV-based screening, and notification. Types of inputs include personnel, recurrent goods, capital goods, and services. We costed potential changes to implementation for scaling. RESULTS: From January to September 2016, 2899 women were screened in CHCs and 2042 in clinics. Each CHC lasted for 30 working days, 10 days each for outreach, screening, and notification. The mean cost per woman screened was $25.00 for CHCs [median: $25.09; Range: $22.06-30.21] and $29.56 for clinics [$28.90; $25.27-37.08]. Clinics had higher costs than CHCs for personnel ($14.27 vs. $11.26) and capital ($5.55 vs. $2.80). Screening costs were higher for clinics at $21.84, compared to $17.48 for CHCs. In contrast, CHCs had higher outreach costs ($3.34 vs. $0.17). After modeling a reduction in staffing, clinic per-screening costs ($25.69) were approximately equivalent to CHCs. CONCLUSIONS: HPV-based cervical cancer screening through community health campaigns achieved lower costs per woman screened, compared to screening at clinics. Periodic high-volume CHCs appear to be a viable low-cost strategy for implementing cervical cancer screening.

Guided Training Relative to Direct Skill Training for Individuals With Cognitive Impairments After Stroke: A Pilot Randomized Trial.

OBJECTIVE: To examine the effects of direct skill training and guided training for promoting independence after stroke. DESIGN: Single-blind randomized pilot study. SETTING: Inpatient rehabilitation facility. PARTICIPANTS: Participants in inpatient rehabilitation with acute stroke and cognitive impairments (N=43). INTERVENTIONS: Participants were randomized to receive direct skill training (n=22, 10 sessions as adjunct to usual inpatient rehabilitation) or guided training (n=21, same dose). MAIN OUTCOME MEASURE: The FIM assessed independence at baseline, rehabilitation discharge, and months 3, 6, and 12. RESULTS: Linear mixed models (random intercept, other effects fixed) revealed a significant intervention by time interaction (F4,150=5.11, P<.001), a significant main effect of time (F4,150=49.25, P<.001), and a significant effect of stroke severity (F1,150=34.46, P<.001). There was no main effect of intervention (F1,150=.07, P=.79). Change in FIM scores was greater for the direct group at rehabilitation discharge (effect size of between-group differences, d=.28) and greater for the guide group at months 3 (d=.16), 6 (d=.39), and 12 (d=.53). The difference between groups in mean 12-month change scores was 10.57 points. CONCLUSIONS: Guided training, provided in addition to usual care, offered a small advantage in the recovery of independence, relative to direct skill training. Future studies examining guided training in combination with other potentially potent intervention elements may further advise best practices in rehabilitation for individuals with cognitive impairments after acute stroke.

Feasibility of a Cognitive Behavioral Intervention to Manage Fatigue in Individuals With Traumatic Brain Injury: A Pilot Study.

OBJECTIVE: To evaluate the feasibility of conducting a randomized clinical trial of an Internet-based manualized intervention to teach individuals with traumatic brain injury to manage their fatigue. SETTING: Community dwelling. PARTICIPANTS: Forty-one participants randomized to Maximizing Energy (MAX) intervention group (n = 20) and Health Education group (n = 21). INTERVENTION: The experimental group (MAX intervention) received an 8-week program that combined education and Problem-Solving Therapy to teach individuals to manage fatigue-related problems. The attention control group received health education. MEASURES: Primary outcome measures pertained to the feasibility of conducting the trial. Secondary outcomes were fatigue impact and fatigue severity assessed at baseline and postintervention. RESULTS: Of the 65 participants referred, 41 were enrolled (63% recruitment rate), of which 3 withdrew (92% retention rate). Participants in the experimental and control groups completed their homework 75% and 85% of the time, respectively, and were equally engaged in the sessions. Participants in the experimental group were able to learn and implement the MAX intervention steps. Effect sizes for all measures ranged from small (-0.17) to medium (-0.58) in favor of the intervention group. CONCLUSION: Findings from the study suggest that the MAX intervention is feasible to administer to individuals with post-traumatic brain injury fatigue.

A comparison of the Functional Movement ScreenTM and the Landing Error Scoring System: A cohort study.

The Functional Movement Screen (FMSTM) is a nonspecific movement pattern assessment while the Landing Error Scoring System (LESS) is a screen for movement patterns associated with lower extremity injury. The purpose of this study was to determine if the LESS and FMSTM are correlated or if they can be used as complementary assessments of preseason injury risk for anterior cruciate ligament injury. METHODS: FMSTM and LESS were used to conduct a cohort study of 126 male National Collegiate Athletic Association Division IA football players. One hundred and eleven players met the criteria for inclusion during data review. At risk and not at risk LESS scores of players and FMSTM exercise score status were compared using Welch's t-test. Associations between FMSTM composites and LESS scores were evaluated using linear regression. RESULTS: The average LESS score was 5.51±1.34, and the average composite FMSTM score was 11.77±2.13 (max=15). A poor FMSTM squat score (≤1 or asymmetry present) was associated with a higher LESS score (P<0.001). No other FMSTM individual exercise score was associated with an at-risk LESS score (P>0.05). Composite FMSTM score was loosely associated with the LESS score (R-squared=0.0677, P=0.006). Prior history of an ACL injury and player position were not associated with LESS score on multivariate regression (P>0.05). CONCLUSIONS: The LESS and FMSTM are not well correlated and may serve as complementary assessments for preseason injury risk. LEVEL OF EVIDENCE: Level III.

Incorporating Laboratory Values Into a Machine Learning Model Improves In-Hospital Mortality Predictions After Rapid Response Team Call.

OBJECTIVES: Machine learning models have been used to predict mortality among patients requiring rapid response team activation. The goal of our study was to assess the impact of adding laboratory values into the model. DESIGN: A gradient boosted decision tree model was derived and internally validated to predict a primary outcome of in-hospital mortality. The base model was then augmented with laboratory values. SETTING: Two tertiary care hospitals within The Ottawa Hospital network. PATIENTS: Inpatients over the age of 18 years who experienced a rapid response team activation between January 1, 2015, and May 31, 2016. INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: A total of 2,061 rapid response team activations occurred during the study period. The in-hospital mortality rate was 29.4%. Patients who died were older (median age, 72 vs 68 yr; p < 0.001), had a longer length of stay (length of stay) prior to rapid response team activation (4 vs 2 d; p < 0.001), and more often had respiratory distress (31% vs 22%; p < 0.001). Our base model without laboratory values performed with an area under the receiver operating curve of 0.71 (95% CI, 0.71-0.72). When the base model was augmented with laboratory values, the area under the receiver operating curve improved to 0.77 (95% CI, 0.77-0.78). Important mortality predictors in the base model were age, estimated ratio of Pao2 to Fio2 (calculated using oxygen saturation and estimated Fio2), length of stay prior to rapid response team activation, and systolic blood pressure. CONCLUSIONS: Machine learning models can identify rapid response team patients at a high risk of mortality and potentially supplement clinical decision making. Incorporating laboratory values into model development significantly improved predictive performance in this study.

Predictors of DMPA-SC continuation among urban Nigerian women: the influence of counseling quality and side effects.

OBJECTIVES: In 2015, private healthcare providers in Nigeria introduced DMPA-SC (depot medroxyprogesterone acetate administered subcutaneously) into the method mix. We aimed to [1] examine the sociodemographic predictors of continued DMPA-SC use after 3 months, and [2] characterize the additional influences of contraceptive counseling quality and experiences of side effects on continuation. STUDY DESIGN: From March to August, 2016, we conducted phone interviews with a convenience sample of women obtaining DMPA-SC from selected providers to survey them about their experience obtaining an initial dose of DMPA-SC. Study coordinators contacted women again about 3 months later after when they were due for reinjection. We used logistic regressions to examine the likelihood of having obtained a subsequent dose of DMPA-SC at follow-up as predicted by sociodemographic characteristics, a quality of counseling indicator based on responses to a 14-item scale, and reports of side effects experienced. RESULTS: Of the 541 DMPA-SC users who completed the first survey, 311 were reached again via phone after 3 months to conduct a second survey. Multivariate results for sociodemographic predictors of continued DMPA-SC use show that those with some college education or more (OR=2.79; 95% CI: 1.09-7.14), and those with four or more children (OR=2.89; 95% CI: 1.09 0 7.67) were more likely to obtain another dose. Our summary quality measure showed that women overall rated the quality of their initial counseling session high. Logistic regressions indicated that higher quality during the initial counseling session is related to the likelihood of getting another dose of DMPA-SC (OR=2.04; 95% CI: 1.12-3.47) whereas experiencing more bleeding reduced the likelihood of continuation after 3 months (OR=0.15; 95% CI: 0.07-0.34). CONCLUSIONS: Among urban Nigerian women, both counseling quality and experiencing side effects were important factors in predicting continued use of DMPA-SC after 3 months. These findings are consistent with previous studies of DMPA and injectable contraception continuation. IMPLICATIONS: New contraceptive methods that are designed for increased access and ease of use, combined with high quality provision, have potential to increase contraceptive use in settings with low levels of contraceptive prevalence. Higher quality counseling can help encourage women's continuation of a new injectable contraceptive method at 3 months.

Bias in Contraceptive Provision to Young Women Among Private Health Care Providers in South West Nigeria.

CONTEXT: Health care providers' biases regarding the provision of contraceptives to adolescent and young adult women may restrict women's access to contraceptive methods. METHODS: Two mystery client visits were made to each of 52 private-sector health care facilities and individual providers in South West Nigeria in June 2016. In one visit, the mystery client portrayed an unmarried, nulliparous adolescent, and in the other, the client portrayed a married adult woman with two children. During subsequent in-depth interviews, providers were read vignettes describing hypothetical clients with these same profiles, and were asked how they would interact with each. Descriptive analyses of mystery client interactions were combined with thematic analyses of the interview data. RESULTS: In greater proportions of married-profile visits than of unmarried-profile visits, mystery clients reported that providers had asked about past contraceptive use and method preference; the opposite was true in regard to providers' using side effects to dissuade clients from practicing contraception. In in-depth interviews, providers expressed concerns about fertility loss among unmarried women who used hormonal contraceptives. Providers more commonly recommended condoms, emergency contraception and the pill for unmarried clients, and longer-acting methods for married clients. The restriction of methods was typically explained by providers of various backgrounds in terms of protecting younger, unmarried clients from damaging their fertility. CONCLUSIONS: Provider bias in the provision of contraceptives to adolescent and young adult women in South West Nigeria may affect quality of care and method choice. Interventions to reduce provider bias should go beyond technical training to address the underlying sociocultural beliefs that lead providers to impose restrictions that are not based on evidence.

Comparison of patient flow and provider efficiency of two delivery strategies for HPV-based cervical cancer screening in Western Kenya: a time and motion study.

BACKGROUND: Improving patient flow and reducing over-crowding can improve quality, promptness of care, and patient satisfaction. Given low utilization of preventive care in low-resource countries, improved patient flows are especially important in these settings. OBJECTIVE: Compare patient flow and provider efficiency between two cervical cancer screening strategies via self-collected human papillomavirus (HPV). METHODS: We collected time and motion data for patients screened for cervical cancer in 12 communities in rural Migori County, Kenya as part of a larger cluster randomized trial. Six communities were randomized to screening in community health campaigns (CHCs) and six to screening at government clinics. We quantified patient flow: duration spent on each active stage of screening and wait times, and the number of patients arriving at CHCs and clinics each hour of the day. In addition, for four CHCs, we collected time and motion data for providers, and measured provider efficiency as a ratio of active (service delivery) time to total time spent at the clinic. RESULTS: Total duration of screening visits, at CHCs and clinics was 42 and 87 minutes, respectively (p < 0.001 for difference). Total active time lasted longer at CHCs, with a mean of 28 minutes per patient versus 15 minutes at clinics, largely due to differences in duration for group education (p < 0.001). Wait time for registration at clinics was 36 minutes, explaining most of the difference between settings, but sometimes incorporated other health services. CONCLUSIONS: There is a substantial difference in patient flow at clinics compared to CHCs. Shorter duration at CHCs suggests that the model is favorable for patients in limiting time spent on screening. Future cervical cancer screening programs designed for scale-up should consider how this advantage may enhance satisfaction and uptake. For clinic-based screening programs, efforts could be made towards reducing registration wait times.

Cost analysis of Omega-3 supplementation in critically ill patients with sepsis.

INTRODUCTION: Nutritional supplement of omega-3 fatty acids have been proposed to improve clinical outcomes in critically ill patients. While previous work have demonstrated that omega-3 supplementation in patients with sepsis is associated with reduced ICU and hospital length of stay, the financial impact of this intervention is unknown. OBJECTIVE: Perform a cost analysis to evaluate the impact of omega-3 supplementation on ICU and hospital costs. METHODS: We extracted data related to ICU and hospital length of stay from the individual studies reported in a recent systematic review. The Cochrane Collaboration tool was used to assess the risk of bias in these studies. Average daily ICU and hospital costs per patient were obtained from a cost study by Kahn et al. We estimated the ICU and hospital costs by multiplying the mean length of stay by the average daily cost per patient in ICU or Hospital. Adjustments for inflation were made according to the USD annual consumer price index. We calculated the difference between the direct variable cost of patients with omega-3 supplementation and patients without omega-3 supplementation. 95% confidence intervals were estimated using bootstrap re-sampling procedures with 1000 iterations. RESULTS: A total of 12 RCT involving 925 patients were included in this cost analysis. Septic patients supplemented with omega-3 had both lower mean ICU costs ($15,274 vs. $18,172) resulting in $2897 in ICU savings per patient and overall hospital costs ($17,088 vs. $19,778), resulting in $2690 in hospital savings per patient. Sensitivity analyses were conducted to investigate the impact of different study methods on the LOS. The results were still consistent with the overall findings. CONCLUSION: Patients with sepsis who received omega-3 supplementation had significantly shorter LOS in the ICU and hospital, and were associated with lower direct variable costs than control patients. The 12 RCTs used in this analysis had a high risk of bias. Large-scaled, high-quality, multi-centered RCTs on the effectiveness of this intervention is recommended to improve the quality of the existing evidence.

Introducing the subcutaneous depot medroxyprogesterone acetate injectable contraceptive via social marketing: lessons learned from Nigeria's private sector.

OBJECTIVES: The subcutaneous depot medroxyprogesterone acetate (DMPA-SC) injectable contraceptive was introduced in South West Nigeria in 2015 through private sector channels. The introduction included community-based distribution and was supported by a social marketing approach. From program monitoring and evaluation, aimed at understanding performance, market reach and other process measures, we identify lessons learned to inform future scale-up efforts. METHODS: We synthesized the findings from a core set of key performance indicators collected through different methods: (1) implementer performance indicators, (2) phone survey of DMPA-SC users (n=541) with a follow-up after 3 months (n=342) and (3) in-depth interviews with 57 providers and 42 users of DMPA-SC. RESULTS: Distribution of DMPA-SC to private providers was concentrated in states with large urban populations. A shift toward focusing on high-volume family planning facilities coincided with a rapid increase in distribution in late 2016. Users reached in the phone survey were generally older and married with children; few were under age 25. Users and providers reported favorable opinions of DMPA-SC. Many users reported choosing DMPA-SC due to recommendations from providers and friends, and the hope of experiencing reduced side effects compared to other methods. While users reported positive experiences interacting with community-based distributors, the delivery model encountered a number of challenges - high turnover, low motivation, lack of an appropriate compensation package and logistical costs - and was ultimately disbanded. CONCLUSIONS: In the DMPA-SC introductory program in Nigeria, distribution was amplified when focused on high-volume contraceptive providers. Although community-based distribution can be one effective service delivery model for reaching underserved populations, more consideration for balancing cost recovery and public health goals through private sector approaches are needed in the context of South West Nigeria. Additional communications and outreach efforts are needed to reach younger, unmarried users with contraceptive services.

Regulation of the orphan nuclear receptor steroidogenic factor 1 by Sox proteins.

Steroidogenic factor 1 (SF-1) is an essential factor in endocrine proliferation and gene expression. Despite the fact that SF-1 expression is restricted to specialized cells within the endocrine system, the only identified regulatory factors of SF-1 are the ubiquitously expressed E-box proteins (upstream stimulatory factors 1 and 2). Sequence examination of the SF-1 proximal promoter revealed a conserved site of AACAAAG (Sox-BS1), which matches exactly the defined consensus Sox protein binding element. Among the approximately 20 known members of the Sox gene family, we focused on Sox3, Sox8, and Sox9, based on their coexpression with SF-1 in the embryonic testis. Indeed, all three of these Sox proteins were capable of binding the proximal Sox-BS1 within the SF-1 promoter (-110 to -104), albeit with differing affinities. Of the three Sox proteins, Sox9 exhibited high-affinity binding to the Sox-BS1 element and consistently activated SF-1 promoter-reporter constructs. Mutating the Sox-BS1 attenuated SF-1 promoter activity in both embryonic and postnatal Sertoli cells, as well as in the adrenocortical cell line, Y1. Our findings, taken together with the overlapping expression profiles of Sox9 and SF-1, and the similar intersex phenotypes associated with both SOX9 and SF-1 human mutations, suggest that Sox9 up-regulates SF-1 and accounts partially for the sexually dimorphic expression pattern of SF-1 observed during male gonadal differentiation.

Prevalence of musculoskeletal and balance disorders in patients enrolled in phase II cardiac rehabilitation.

PURPOSE: To determine the prevalence of musculoskeletal, neurological, and balance problems in patients enrolled in early outpatient (phase II) cardiac rehabilitation. METHODS: Data were assessed retrospectively for 284 consecutive patients who attended the phase II Mayo Clinic Cardiac Rehabilitation program from April 2005 to August 2006. All participants completed a questionnaire that identified the presence of musculoskeletal pain, history of falls, joint replacements, osteoporosis, neurological disorders, and difficulties in performing activities of daily living. Balance assessment was evaluated using the single leg stance and the tandem gait tests. RESULTS: Of the total study population (mean age, 62.1 +/- 12.3 years), 25% reported musculoskeletal pain. A significantly higher prevalence of pain was noted in women than men (37% vs 20%, P = .004) and in those > 65 years than those < or = 65 years (35% vs 17%, P = .001). Back (29%), knee (17%), and hip (8%) pain were the most common symptoms, in order of decreasing frequency. Pain was worse with any activity in 32% of participants while 16% of participants had worsening at night. An abnormality in balance was present in 58% of the study participants and was significantly more common in women (71%) and those > 65 years (83%). Falls or gait instability or both were reported by 11% of participants. CONCLUSION: Musculoskeletal and balance limitations are common in persons enrolled in early outpatient cardiac rehabilitation, particularly in women and patients > 65 years. Cardiac rehabilitation programs should screen patients for musculoskeletal limitations and incorporate adaptations for treatment strategies of such patients.

Stromal regulation of vessel stability by MMP14 and TGFbeta.

Innate regulatory networks within organs maintain tissue homeostasis and facilitate rapid responses to damage. We identified a novel pathway regulating vessel stability in tissues that involves matrix metalloproteinase 14 (MMP14) and transforming growth factor beta 1 (TGFbeta(1)). Whereas plasma proteins rapidly extravasate out of vasculature in wild-type mice following acute damage, short-term treatment of mice in vivo with a broad-spectrum metalloproteinase inhibitor, neutralizing antibodies to TGFbeta(1), or an activin-like kinase 5 (ALK5) inhibitor significantly enhanced vessel leakage. By contrast, in a mouse model of age-related dermal fibrosis, where MMP14 activity and TGFbeta bioavailability are chronically elevated, or in mice that ectopically express TGFbeta in the epidermis, cutaneous vessels are resistant to acute leakage. Characteristic responses to tissue damage are reinstated if the fibrotic mice are pretreated with metalloproteinase inhibitors or TGFbeta signaling antagonists. Neoplastic tissues, however, are in a constant state of tissue damage and exhibit altered hemodynamics owing to hyperleaky angiogenic vasculature. In two distinct transgenic mouse tumor models, inhibition of ALK5 further enhanced vascular leakage into the interstitium and facilitated increased delivery of high molecular weight compounds into premalignant tissue and tumors. Taken together, these data define a central pathway involving MMP14 and TGFbeta that mediates vessel stability and vascular response to tissue injury. Antagonists of this pathway could be therapeutically exploited to improve the delivery of therapeutics or molecular contrast agents into tissues where chronic damage or neoplastic disease limits their efficient delivery.

Dietary patterns using Traditional Chinese Medicine principles in epidemiological studies.

Dietary intake and nutritional factors have been shown to be associated with many chronic diseases, such as heart disease, obesity, diabetes, and cancer. There are many approaches to studying dietary intake in relationship to disease; each approach has its strengths and weaknesses. Examples of different methods of studying dietary patterns will be reviewed. In most cultures, consumed and preferred foods are based on cultural and societal influence. Thus, it is important to consider dietary patterns within the context of culture in addition to the standard nutrients or food groupings approach. Traditional Chinese Medicine (TCM) offers another dimension to food analysis. Our approach classifies dietary intake based on Traditional Chinese Medicine principles of yin and yang, hot and cold, and acidic and alkaline forming food concepts in a case-control study of dietary factors and breast cancer. Our results complement previously reported findings of an increased risk of breast cancer associated with dietary fats in Taiwanese women. Our discussion will focus on the implication of using this dietary pattern research and the challenge of combining this research with culturally sensitive messages to improve health. Our ultimate goal is to design an intervention strategy for disease prevention and health promotion that is culturally appropriate for specific populations.

Predictors of mortality for patients with advanced disease in an HIV palliative care program.

BACKGROUND: Despite advances in treatment, AIDS and its associated comorbidities remain important causes of death. Traditional HIV prognostic markers may be less useful in predicting death in current late-stage patients than in the era before highly active antiretroviral therapy. METHODS: We used standardized baseline and follow-up data to describe causes of death and predictors of mortality in a cohort of patients with advanced disease referred to a specialized HIV palliative care program at a large urban medical center. RESULTS: Of 230 patients, 56% were male with a median age of 43 years; 54% were Hispanic and 39% were African American; 41% had a history of injection drug use; 89% had prior AIDS-defining illnesses; and median baseline values included a CD4 count of 39 cells/mm, HIV viral load of 65,202 copies/mL, Karnofsky score of 30, and 5 impaired activities of daily living (ADL). Over a median follow-up of 126 days (range: 1-823 days), 120 patients died; 54% of these died of late-stage HIV disease and/or bacterial pneumonia or sepsis, 19% of non-AIDS-defining cancers, 13% of liver failure and/or cirrhosis, and 12% of other progressive end-organ disease (eg, cardiac, pulmonary, renal). On multivariate analysis, death was predicted only by age (>65 years), baseline number of ADL impairments, and Karnofsky score (P < 0.0001 for all) and not by any AIDS-specific variables. CONCLUSIONS: For patients with late-stage disease referred to an HIV palliative care program, age and markers of functional status were more predictive of mortality than traditional HIV prognostic variables. Close to half of all deaths were attributable to non-AIDS-specific causes, including cancer and end-organ failure. These findings suggest the need for renewed study of predictors of mortality and prognostic markers in patients with advanced HIV disease and related comorbidities in the HAART era.

Embryonic development of the Drosophila corpus cardiacum, a neuroendocrine gland with similarity to the vertebrate pituitary, is controlled by sine oculis and glass.

We have investigated the development of the Drosophila neuroendocrine gland, the corpus cardiacum (CC), and identified the role of regulatory genes and signaling pathways in CC morphogenesis. CC progenitors segregate from the blastoderm as part of the anterior lip of the ventral furrow. Among the early genetic determinants expressed and required in this domain are the genes giant (gt) and sine oculis (so). During the extended germ band stage, CC progenitor cells form a paired cluster of 6-8 cells sandwiched in between the inner surface of the protocerebrum and the foregut. While flanking the protocerebrum, CC progenitors are in direct contact with the neural precursors that give rise to the pars intercerebralis, the part of the brain whose neurons later innervate the CC. At this stage, the CC progenitors turn on the homeobox gene glass (gl), which is essential for the differentiation of the CC. During germ band retraction, CC progenitors increase in number and migrate posteriorly, passing underneath the brain commissure and attaching themselves to the primordia of the corpora allata (CA). During dorsal closure, the CC and CA move around the anterior aorta to become the ring gland. Signaling pathways that shape the determination and morphogenesis of the CC are decapentaplegic (dpp) and its antagonist short gastrulation (sog), as well as hedgehog (hh) and heartless (htl; a Drosophila FGFR homolog). Sog is expressed in the midventral domain from where CC progenitors originate, and these cells are completely absent in sog mutants. Dpp and hh are expressed in the anterior visceral head mesoderm and the foregut, respectively; both of these tissues flank the CC. Loss of hh and dpp results in defects in CC proliferation and migration. Htl appears in the somatic mesoderm of the head and trunk. Although mutations of htl do not cause direct effects on the early development of the CC, the later formation of the ring gland is highly abnormal due to the absence of the aorta in these mutants. Defects in the CC are also caused by mutations that severely reduce the protocerebrum, including tailless (tll), suggesting that additional signaling events exist between brain and CC progenitors. We discuss the parallels between neuroendocrine development in Drosophila and vertebrates.