Evaluating the feasibility and uptake of a community‐led HIV testing and multi‐disease health campaign in rural Uganda

Introduction: Multi‐disease community health campaigns can be effective for population‐wide HIV testing in a research setting (SEARCH: NCT01864603). We sought to evaluate feasibility and uptake of a community‐led health campaign (CLHC) planned and implemented by village leaders and local clinic workers in Uganda. Methods: Over five months in 2014, locally elected village leaders and Ministry of Health (MoH) clinic staff in a rural parish in Uganda planned a census followed by a CLHC, after training by two SEARCH trial consultants and by leaders from a neighbouring parish that had previously participated in a SEARCH health campaign. We defined feasibility as: (1) elected leaders’ participation in training and implementation of pre‐campaign census and mobilization activities; (2) implementation of all campaign activities by MoH‐funded, local clinic staff; and (3) community participation in the campaign, including point‐of‐care screening for HIV, malaria, hypertension and diabetes, and same‐day referral for male circumcision and family planning (FP). Costing of all salaries and supplies was conducted. Results: Elected leaders from all eight villages in the parish participated in CLHC training. They and local clinic staff met monthly to select and plan CLHC services. Village leaders then leveraged existing volunteer health teams to perform a door‐to‐door census, enumerating 5,202 parish residents over 2 weeks. 2,753 (53%) residents participated in the 6‐day CLHC. Of 1,584 adult participants, 1,474 (93%) tested for HIV: 105/1,474 (7.1%) tested HIV positive. 27% (751/2,753) of participants reported fever and underwent malaria rapid diagnostic testing: 5.3% (40/751) tested positive. Among adults screened, 19% (271/1,452) were hypertensive, and 3% (18/637) had a random blood sugar >11.1 mmol/L. Of 805 men and boys (>10 years), 91 (11%) accepted same‐day clinic referral and underwent medical circumcision. Of 900 women offered same‐day long‐term FP referrals, 25 accepted. The CLHC cost, including census, mobilization and testing services, was $23,597 ($8.57/participant). C onclusions: Elected village leaders successfully planned and conducted a 6‐day multi‐disease health campaign with service provision by local clinic staff that reached over half of a rural Ugandan community. These data suggest it is feasible for local leaders and clinics to adopt a multi‐disease health campaign approach to scale‐up HIV testing in rural Africa.     

Genomic Profiling of Intrahepatic Cholangiocarcinoma: Refining Prognosis and Identifying Therapeutic Targets

Background

The molecular alterations that drive tumorigenesis in intrahepatic cholangiocarcinoma (ICC) remain poorly defined. We sought to determine the incidence and prognostic significance of mutations associated with ICC among patients undergoing surgical resection.

Methods

Multiplexed mutational profiling was performed using nucleic acids that were extracted from 200 resected ICC tumor specimens from 7 centers. The frequency of mutations was ascertained and the effect on outcome was determined.

Results

The majority of patients (61.5 %) had no genetic mutation identified. Among the 77 patients (38.5 %) with a genetic mutation, only a small number of gene mutations were identified with a frequency of >5 %: IDH1 (15.5 %) and KRAS (8.6 %). Other genetic mutations were identified in very low frequency: BRAF (4.9 %), IDH2 (4.5 %), PIK3CA (4.3 %), NRAS (3.1 %), TP53 (2.5 %), MAP2K1 (1.9 %), CTNNB1 (0.6 %), and PTEN (0.6 %). Among patients with an IDH1-mutant tumor, approximately 7 % were associated with a concurrent PIK3CA gene mutation or a mutation in MAP2K1 (4 %). No concurrent mutations in IDH1 and KRAS were noted. Compared with ICC tumors that had no identified mutation, IDH1-mutant tumors were more often bilateral (odds ratio 2.75), while KRAS-mutant tumors were more likely to be associated with R1 margin (odds ratio 6.51) (both P < 0.05). Although clinicopathological features such as tumor number and nodal status were associated with survival, no specific mutation was associated with prognosis.

Conclusions

Most somatic mutations in resected ICC tissue are found at low frequency, supporting a need for broad-based mutational profiling in these patients. IDH1 and KRAS were the most common mutations noted. Although certain mutations were associated with ICC clinicopathological features, mutational status did not seemingly affect long-term prognosis.     

Effects of Odanacatib on Bone Structure and Quality in Postmenopausal Women With Osteoporosis: 5-Year Data From the Phase 3 Long-Term Odanacatib Fracture Trial (LOFT) and its Extension

Odanacatib (ODN), a selective oral inhibitor of cathepsin K, was an investigational agent previously in development for the treatment of osteoporosis. In this analysis, the effects of ODN on bone remodeling/modeling and structure were examined in the randomized, double-blind, placebo-controlled, event-driven, Phase 3, Long-term Odanacatib Fracture Trial (LOFT; NCT00529373) and planned double-blind extension in postmenopausal women with osteoporosis. A total of 386 transilial bone biopsies, obtained from consenting patients at baseline (ODN n = 17, placebo n = 23), month 24 (ODN n = 112, placebo n = 104), month 36 (ODN n = 42, placebo n = 41), and month 60 (ODN n = 27, placebo n = 20) were assessed by dynamic and static bone histomorphometry. Patient characteristics at baseline and BMD changes over 5 years for this subset were comparable to the overall LOFT population. Qualitative assessment of biopsies revealed no abnormalities. Consistent with the mechanism of ODN, osteoclast number was higher with ODN versus placebo over time. Regarding bone remodeling, dynamic bone formation indices in trabecular, intracortical, and endocortical surfaces were generally similar in ODN-treated versus placebo-treated patients after 2 years of treatment. Regarding periosteal modeling, the proportion of patients with periosteal double labels and the bone formation indices increased over time in the ODN-treated patients compared with placebo. This finding supported the observed numerical increase in cortical thickness at month 60 versus placebo. In conclusion, ODN treatment for 5 years did not reduce bone remodeling and increased the proportion of patients with periosteal bone formation. These results are consistent with the mechanism of action of ODN, and are associated with continued BMD increases and reduced risk of fractures compared with placebo in the LOFT Phase 3 fracture trial. © 2020 American Society for Bone and Mineral Research.     

Unravelling animal exposure profiles of human Q fever cases in Queensland,Australia, using natural language processing

Q fever, caused by the zoonotic bacterium Coxiella burnetii, is a globally distributed emerging infectious disease. Livestock are the most important zoonotic transmission sources, yet infection in people without livestock exposure is common. Identifying potential exposure pathways is necessary to design effective interventions and aid outbreak prevention. We used natural language processing and graphical network methods to provide insights into how Q fever notifications are associated with variation in patient occupations or lifestyles. Using an 18‐year time‐series of Q fever notifications in Queensland, Australia, we used topic models to test whether compositions of patient answers to follow‐up exposure questionnaires varied between demographic groups or across geographical areas. To determine heterogeneity in possible zoonotic exposures, we explored patterns of livestock and game animal co‐exposures using Markov Random Fields models. Finally, to identify possible correlates of Q fever case severity, we modelled patient probabilities of being hospitalized as a function of particular exposures. Different demographic groups consistently reported distinct sets of exposure terms and were concentrated in different areas of the state, suggesting the presence of multiple transmission pathways. Macropod exposure was commonly reported among Q fever cases, even when exposure to cattle, sheep or goats was absent. Males, older patients and those that reported macropod exposure were more likely to be hospitalized due to Q fever infection. Our study indicates that follow‐up surveillance combined with text modelling is useful for unravelling exposure pathways in the battle to reduce Q fever incidence and associated morbidity.     

Open Versus Minimally Invasive Resection of Gastric GIST: A Multi-Institutional Analysis of Short- and Long-Term Outcomes

Background

Gastrointestinal stromal tumors (GIST) are the most common mesenchymal tumors of the gastrointestinal tract. Overall surgical experience with minimally invasive surgery (MIS) has increased; however, published reports on MIS resection of GIST are limited to small, single-institution experiences.

Methods

A total of 397 patients who underwent open surgery (n = 230) or MIS (n = 167) for a gastric GIST between 1998 and 2012 were identified from a multicenter database. The impact of MIS approach on recurrence and survival was analyzed using propensity-score matching by comparing clinicopathologic factors between patients who underwent MIS versus open resection.

Results

There were 19 conversions (10 %) to open; the most common reasons for conversion were tumor more extensive than anticipated (26 %) and unclear anatomy (21 %). On multivariate analysis, smaller tumor size and higher body mass index (BMI) were associated with receipt of MIS. In the propensity-matched cohort (n = 248), MIS resection was associated with decreased length of stay (MIS, 3 days vs open, 8 days) and fewer ≥ grade 3 complications (MIS, 3 % vs open, 14 %) compared with open surgery. High rates of R0 resection and low rates of tumor rupture were seen in both groups. After propensity-score matching, there was no difference in recurrence-free or overall survival comparing the MIS and the open group (both p > 0.05).

Conclusions

An MIS approach for gastric GIST was associated with low morbidity and a high rate of R0 resection. The long-term oncological outcome following MIS was excellent, and therefore the MIS approach should be considered the preferred approach for gastric GIST in well-selected patients.     

The impact of brief team communication,leadership and team behavior training on ad hoc team performance in trauma care settings

Background

Communication breakdowns and care coordination problems often cause preventable adverse patient care events, which can be especially acute in the trauma setting, in which ad hoc teams have little time for advanced planning. Existing teamwork curricula do not address the particular issues associated with ad hoc emergency teams providing trauma care.

Methods

Ad hoc trauma teams completed a preinstruction simulated trauma encounter and were provided with instruction on appropriate team behaviors and team communication. Teams completed a postinstruction simulated trauma encounter immediately afterward and 3 weeks later, then completed a questionnaire. Blinded raters rated videotapes of the simulations.

Results

Participants expressed high levels of satisfaction and intent to change practice after the intervention. Participants changed teamwork and communication behavior on the posttest, and changes were sustained after a 3-week interval, though there was some loss of retention.

Conclusions

Brief training exercises can change teamwork and communication behaviors on ad hoc trauma teams.     

Sleep disorders: Serious threats among kidney transplant recipients

In patients with chronic kidney disease (CKD) and kidney transplant recipients who continue to have some degree of CKD, the prevalence of sleep-related disorders is very high. Common sleep disorders in both groups include insomnia, sleep-disordered breathing (SDB), restless legs syndrome (RLS), excessive daytime sleepiness (EDS), and others. Depending on the kidney graft function, some patients see sleep disorders resolve after kidney transplantation, while others continue to have persistent sleep disorders or develop new ones. Kidney transplant recipients (KTRs) are unique patients due to the presence of a single kidney, the use of immunosuppressive medications, and other comorbidities including obesity, a high risk of cardiovascular disease, malignancy, and the anxiety of losing their allograft. All of these factors contribute to the risk for sleep disorders. CKD and sleep disorders have a bidirectional relationship; that is, CKD may increase the risk of sleep disorders and sleep disorders may increase the risk of CKD. Obstructive sleep apnea (OSA) is the most common form of SDB and is known to alter renal hemodynamics. OSA leads to hypoxemia and sleeps fragmentation, which activates the sympathetic nervous system. This activates the renin-angiotensin-aldosterone system and ultimately alters cardiovascular hemodynamics. Sleep disorders may have deleterious effects on the kidney allograft and proper screening and management are important for both graft and patient survival.