Early Outcomes of Interwoven Nitinol Wire Stent Placement versus Endarterectomy for the Treatment of Atherosclerotic Disease of the Common Femoral Artery.

PURPOSE: To compare the clinical outcomes of common femoral artery (CFA) atherosclerotic disease treated with either surgical endarterectomy or an interwoven nitinol wire stent system. MATERIALS AND METHODS: A retrospective review was conducted of all patients with chronic, de novo atherosclerotic CFA disease treated with surgical endarterectomy (CFAE) or stent placement between July 2019 and March 2022. Outcome measures assessed up to 12 months after procedure included clinical improvement, primary restenosis, target vessel revascularization (TVR), major adverse limb events (MALEs), and all-cause mortality. RESULTS: Thirty-nine stents were deployed in 33 patients, and 56 CFAEs were performed in 55 patients. No differences were noted in the rate of primary patency (95.5% vs 94.4%, P = .618), TVR (2.9% vs 1.8%, P = .777), MALE (5.1% vs 5.4%, P = .949), and all-cause mortality (14.1% vs 3.6%, P = .076) between the stent and CFAE groups up to 12 months after procedure. There was greater improvement in median clinical severity in the stent group than in the CFAE group (Rutherford score change of 3.0 vs 1.5, P = .013). The median length of stay was less for the stent group (3 vs 7 days, P = .002), and there was a lower likelihood of severe or disabling adverse events in the stent group (0 vs 9 cases, P = .010). CONCLUSIONS: Patients treated with an interwoven nitinol wire stent had patency rates comparable to those treated with CFAE while having a lower incidence of severe adverse events and a shorter length of hospital stay than those who underwent CFAE.

Confirmation of the presence of Anopheles stephensi among internally displaced people's camps and host communities in Aden city, Yemen.

BACKGROUND: Declines in global malaria cases and deaths since the millennium are currently challenged by multiple factors including funding limitations, limits of, and resistance to vector control tools, and also recent spread of the invasive vector species, Anopheles stephensi-especially into novel urban settings where malaria rates are typically low. Coupled with general increases in urbanization and escalations in the number of conflicts creating rapid and unplanned population displacement into temporary shelter camps within host urban areas, particularly in the Middle East and sub-Saharan Africa, increased urban malaria is a major threat to control and elimination. METHODS: Entomological monitoring surveys (targeting Aedes aegypti) of water containers across urban areas hosting internally displaced people (IDP) communities in Aden city, Yemen, were performed by The MENTOR Initiative, a non-governmental organisation. As part of these surveys in 2021 23 larvae collected and raised to adults were morphologically identified as An. stephensi. Twelve of the samples were sent to Liverpool School of Tropical Medicine for independent morphological assessment and genetic analysis by sequencing the ribosomal ITS2 region and the mitochondrial COI gene. RESULTS: All twelve samples were confirmed morphologically and by sequence comparison of the single ITS2 and COI haplotype detected to the NCBI BLAST database as An. stephensi. Phylogenetic analysis with comparable COI sequences indicated close relationship to haplotypes found in Djibouti and Ethiopia. CONCLUSION: The study results confirm the presence of An. stephensi in Yemen. Confirmation of the species in multiple urban communities hosting thousands of IDPs living in temporary shelters with widescale dependency on open water containers is of particular concern due to the vulnerability of the population and abundance of favourable breeding sites for the vector. Proactive monitoring and targeted integrated vector management are required to limit impacts in this area of typically low malaria transmission, and to prevent further the spread of An. stephensi within the region.

Durable wall lining for malaria control in Liberia: results of a cluster randomized trial.

BACKGROUND: Malaria control in Liberia depends upon universal coverage with pyrethroid-impregnated long-lasting insecticidal nets (LLINs). Despite regular mass distribution, LLIN coverage and usage is patchy. Pyrethroid resistance in malaria vectors may further reduce LLIN efficacy. Durable Wall Lining (DWL), a novel material treated with two non-pyrethroid class insecticides, was designed to be installed onto the surface of inner walls, and cover openings and ceiling surfaces of rural houses. OBJECTIVES: AIM: To determine the malaria control efficacy of DWL. PRIMARY OBJECTIVE: To determine if DWL has an additional protective effect in an area of pyrethroid resistance. SECONDARY OBJECTIVES: To compare surface bio-availability of insecticides and entomological effectiveness over the study duration. DESIGN: A cluster randomized trial. PARTICIPANTS: Children aged 2-59 months. CONTROL ARM: 50 houses per 20 clusters, all of which received LLIN within the previous 12 months. ACTIVE ARM: 50 houses per 20 experimental clusters, all of which received LLINs with the previous 12 months, and had internal walls and ceilings lined with DWL. RANDOMISATION: Cluster villages were randomly allocated to control or active arms, and paired on 4 covariates. MAIN OUTCOME MEASURES: PRIMARY MEASURE: Prevalence of infection with P. falciparum in children aged 2 to 59 months. SECONDARY MEASURE: Surface bioavailability and entomological effectiveness of DWL active ingredients. RESULTS: Plasmodium falciparum prevalence in active clusters after 12 months was 34.6% compared to 40.1% in control clusters (p = 0.052). The effect varied with elevation and was significant (RR = 1.3, p = 0.022) in 14 pairs of upland villages. It was not significant (RR = 1.3, p = 0.344) in 6 pairs of coastal villages. Pooled risk ratio (RR) was calculated in SAS (Cary, NC, USA) using the Cochran-Mantel-Haenszel (CMH) test for upland and coastal cluster pairs. DWL efficacy was sustained at almost 100% for 12 months. CONCLUSIONS: Findings indicate that DWL is a scalable and effective malaria control intervention in stable transmission areas with pyrethroid-resistant vectors, where LLIN usage is difficult to achieve, and where local housing designs include large gable and eve openings. Trial registration ClinicalTrials.gov identifier: NCT02448745 (19 May 2015): https://clinicaltrials.gov/ct2/show/NCT02448745.

Erratum: Strong constraints on aerosol-cloud interactions from volcanic eruptions.

This corrects the article DOI: 10.1038/nature22974.

Strong constraints on aerosol-cloud interactions from volcanic eruptions.

Aerosols have a potentially large effect on climate, particularly through their interactions with clouds, but the magnitude of this effect is highly uncertain. Large volcanic eruptions produce sulfur dioxide, which in turn produces aerosols; these eruptions thus represent a natural experiment through which to quantify aerosol-cloud interactions. Here we show that the massive 2014-2015 fissure eruption in Holuhraun, Iceland, reduced the size of liquid cloud droplets-consistent with expectations-but had no discernible effect on other cloud properties. The reduction in droplet size led to cloud brightening and global-mean radiative forcing of around -0.2 watts per square metre for September to October 2014. Changes in cloud amount or cloud liquid water path, however, were undetectable, indicating that these indirect effects, and cloud systems in general, are well buffered against aerosol changes. This result will reduce uncertainties in future climate projections, because we are now able to reject results from climate models with an excessive liquid-water-path response.

Accuracy and Reliability of Peripheral Artery Calcium Scoring Systems Using an Intravascular Ultrasound Reference Standard.

BACKGROUND: Peripheral artery calcium scoring systems are commonly used in clinical trials to categorize calcium severity but there are little data on their accuracy and reliability. The purpose of this study was to investigate the accuracy and reliability of these systems. METHODS: Angiographic, computed tomography angiography, and intravascular ultrasound (IVUS) imaging were obtained from 47 consecutive cases sourced from a prospectively collected database of patients undergoing femoropopliteal artery endovascular intervention. Two independent blinded readers graded calcium severity using the Peripheral Arterial Calcium Scoring System, Peripheral Academic Research Consortium, and Fanelli calcium scoring systems. IVUS maximum arc of calcium and calcium length were compared between severity grades for each scoring system. The diagnostic accuracy of each scoring system for identifying severe calcium was calculated using the reference standard of an IVUS maximum calcium arc ≥ 180°. Agreement testing was performed between scoring systems and between and within observers for each system. RESULTS: IVUS identified calcium in 85% (42/47) of cases, compared to 68% (32/47) of cases with angiography. There were no differences in IVUS calcium parameters between grades of calcium for any of the scoring systems. Severe calcium was detected by IVUS in 30 cases, in 23 cases by Peripheral Arterial Calcium Scoring System (sensitivity: 73%, specificity: 33%, positive predictive value [PPV]: 83%, negative predictive value [NPV]: 22%), in 12 cases by Peripheral Academic Research Consortium (sensitivity: 42%, specificity: 83%, PPV: 92%, NPV: 25%), and in 10 cases by Fanelli (sensitivity: 39%, specificity: 100%, PPV: 100%, NPV: 27%). Agreement between scoring systems was weak to moderate (range: k = 0.55-0.74). Interobserver agreement was weak (k = 0.41-0.54) and intraobserver agreement was highly variable ranging from k = 0.41 to k = 0.92. CONCLUSIONS: The poor diagnostic accuracy and weak-to-moderate reliability of calcium scoring systems raise doubts about the use of current calcium scoring systems for use in clinical trials.

Percutaneous Cholecystostomy Tube for Acute Cholecystitis: Quantifying Outcomes and Prognosis.

BACKGROUND: Percutaneous cholecystostomy tubes (PCT) are utilized in the management of acute cholecystitis in patients deemed unsuitable for surgery. However, the drive for these decisions and the outcomes remain understudied. We sought to characterize the practices and utilization of PCT and evaluate associated outcomes at an urban medical center. METHODS: Patients undergoing PCT placement over a 12-y study period ending May 2019 were reviewed. Demographics, clinical presentation, labs, imaging studies, and outcomes were abstracted. The primary and secondary outcomes were 30-d mortality and interval cholecystectomy, respectively. RESULTS: Two hundred and four patients met inclusion criteria: 59.3% were male with a median age of 67.5 y and a National Surgical Quality Improvement Program (NSQIP) risk of serious complication of 8.0%. Overall, 57.8% of patients were located in an intensive care unit setting. The majority (80.9%) had an ultrasound and 48.5% had a hepatobiliary iminodiacetic acid scan. The overall 30-d mortality was 31.9%: 41.5% for intensive care unit and 18.6% for ward patients (P < 0.01). Of patients surviving beyond 30 d (n = 139), the PCT was removed from 106 (76.3%), and a cholecystectomy was performed in 55 (39.6%) at a median interval of 58.0 d. A forward logistic regression identified total bilirubin (Adjusted Odds Ratio: 1.12, adjusted P < 0.01) and NSQIP risk of serious complication (Adjusted Odds Ratio: 1.16, adjusted P < 0.01) as the only predictors for 30-d mortality. CONCLUSIONS: Patients selected for PCT placement have a high mortality risk. Despite subsequent removal of the PCT, the majority of surviving patients did not undergo an interval cholecystectomy. Total bilirubin and NSQIP risk of serious complication are useful adjuncts in predicting 30-d mortality in these patients.

Comparison of Angiographic Dissection Classification Systems in the Femoropopliteal Arteries Using IVUS Validation and Reliability Testing.

PURPOSE: Objective assessment of dissection severity is difficult. Recognition of this has led to the creation of classification systems. This study investigated the performance of the National Heart Lung and Blood Institute (NHLBI) and Kobayashi systems at differentiating severity of femoropopliteal dissection using intravascular ultrasound (IVUS) as the reference standard. Comparison between the 2 systems and the inter- and intra-observer reliability were also investigated. MATERIALS AND METHODS: Angiographic and IVUS imaging was assessed in 51 cases sourced from a RCT investigating the use of IVUS in femoropopliteal disease. A total of 2 readers independently scored the angiography images according to NHLBI and Kobayashi dissection classification systems and a consensus score was obtained for each system in each case. The NHLBI classification was condensed into 3 grades of dissection to allow comparison between systems. Dissection length, dissection arc, minimum lumen area, and lumen area stenosis were obtained from the IVUS imaging. IVUS parameters were compared between grades of severity for both systems. Agreement in grading between the systems was assessed and IVUS parameters for each level of dissection severity were compared between systems. Inter and intra-observer agreement tested for each system. RESULTS: Dissection was present on IVUS in 92.2% (47/51) of cases and angiography identified 78.7% (37/47) of these. No difference was present in any IVUS parameters between mild and severe dissections with either classification system. No difference in IVUS findings was present for the same grades of dissection between systems. The 2 systems agreed on severity grade in 47 of 51 cases. The inter-observer agreement was for NHLBI was k=0.549 and k=0.627 for Kobayashi. Intra-observer agreement for NHLBI was k=0.633 and k=0.633 and for Kobayashi was k=0.657 and k=0.297. CONCLUSION: The lack of difference in IVUS parameters between mild and severe dissection for the NHLBI and Kobayashi systems raises doubts about their ability to effectively differentiate dissection severity. Weak to moderate reliability suggests that variability in interpreting dissection may be higher than acceptable. IVUS imaging is more sensitive for detecting dissection than angiography and research is required to establish the value of adding IVUS to dissection classification systems.

Outcomes Following Percutaneous Cholecystostomy Tube Placement for Acalculous Versus Calculous Cholecystitis.

BACKGROUND: Acute acalculous cholecystitis (AAC) is often diagnosed in critically ill patients. Percutaneous cholecystostomy tube (PCT) placement facilitates less invasive gallbladder decompression in patients who are poor surgical candidates. Specific guidelines for optimal management of AAC patients following PCT placement remain to be defined. We hypothesize that AAC patients are at lower risk of recurrent cholecystitis than acute calculous cholecystitis (ACC) patients and do not require cholecystectomy after PCT placement. METHODS: A retrospective review of patients who underwent PCT placement for AAC or ACC between 6/1/2007 and 5/31/2019 was performed. Primary outcome was recurrent cholecystitis and interval cholecystectomy for patients surviving 30 days after PCT placement. Secondary outcome was 30 day mortality. A cox regression model calculated the adjusted hazard ratio (AHR) for the outcomes. RESULTS: Eighty-four AAC and 85 ACC patients underwent PCT placement. Compared to ACC patients, more AAC patients were male (72.6 vs. 48.2%; p < 0.01), younger (median age 62 vs. 73 years; p < 0.01), and required intensive care (69.0 vs. 52.9%; p = 0.04), with lower median Charlson Comorbidity Index (4.0 vs. 6.0; p < 0.01). 30 day mortality was higher among AAC patients than ACC patients (45.2 vs. 21.2%; p < 0.01). 2/24 (8.3%) AAC patients and 5/31 (16.1%) ACC patients developed recurrent cholecystitis at a median 208.0 days (IQR:64.0-417.0) after PCT placement and 115.0 days (IQR:7.0-403.0) following PCT removal. Cox regression analysis demonstrated that AAC patients had lower likelihood of interval cholecystectomy compared to ACC patients (AHR 2.35; 95% CI:1.11,4.96). CONCLUSION: Recurrent cholecystitis is rare in patients surviving 30 days following PCT placement. When compared with ACC patients, fewer AAC patients require cholecystectomy.

Identification of micro-channels within chronic total occlusions using contrast-enhanced ultrasound.

BACKGROUND: Vascular micro-channels within chronic total occlusions (CTO) have been identified in histopathology and animal studies. They have been proposed as a potential path for achieving endovascular crossing via the lumen. There are currently no noninvasive means of imaging these structures. The aim of this study was to investigate whether contrast-enhanced ultrasound (CEUS) examination can identify micro-channels within CTO in humans. METHODS: CTO within the femoropopliteal arteries were imaged with CEUS examination in 38 patients. Segments containing micro-channels were identified and their length measured. The proportion of occlusion length containing micro-channels was assessed for each case. Micro-channel appearances including linear or tortuous configuration, crossing of occlusion caps, and connections to vasa vasorum were recorded. RESULTS: The median CTO length was 17.0 cm (interquartile range [IQR], 6.9-27.9 cm) and median age of CTO was 12 months (IQR, 6-16 months). Micro-channels were identified in 92.1% of cases (35/38). The median length within a lesion containing micro-channels was 6.4 cm (IQR, 2.4-14.3 cm) and median proportion of CTO containing micro-channels was 47.9% (IQR, 1.7%-28.5%). A linear micro-channel configuration was seen in 84.2% of cases and a tortuous configuration was seen in 57.9% of cases. Micro-channel connections through the cap were seen in 50% (19/38 cases) and connections to the vasa vasorum in 71.1% (27/38 cases). No association was found between the proportion of each lesion containing micro-channels and CTO age, lesion length or calcification severity. There were no adverse effects related to contrast use. CONCLUSIONS: CEUS can be used to detect micro-channels in CTO in human femoropopliteal arteries. This imaging technique is safe and minimally invasive and may represent a practical method for selection of occlusion crossing method. Further work is required to determine whether identification of micro-channels can be used to improve treatment decision-making and provide a better understanding of the natural history of femoropopliteal CTO.

Towards advancing scientific knowledge of climate change impacts on short-duration rainfall extremes.

A large number of recent studies have aimed at understanding short-duration rainfall extremes, due to their impacts on flash floods, landslides and debris flows and potential for these to worsen with global warming. This has been led in a concerted international effort by the INTENSE Crosscutting Project of the GEWEX (Global Energy and Water Exchanges) Hydroclimatology Panel. Here, we summarize the main findings so far and suggest future directions for research, including: the benefits of convection-permitting climate modelling; towards understanding mechanisms of change; the usefulness of temperature-scaling relations; towards detecting and attributing extreme rainfall change; and the need for international coordination and collaboration. Evidence suggests that the intensity of long-duration (1 day+) heavy precipitation increases with climate warming close to the Clausius-Clapeyron (CC) rate (6-7% K-1), although large-scale circulation changes affect this response regionally. However, rare events can scale at higher rates, and localized heavy short-duration (hourly and sub-hourly) intensities can respond more strongly (e.g. 2 × CC instead of CC). Day-to-day scaling of short-duration intensities supports a higher scaling, with mechanisms proposed for this related to local-scale dynamics of convective storms, but its relevance to climate change is not clear. Uncertainty in changes to precipitation extremes remains and is influenced by many factors, including large-scale circulation, convective storm dynamics andstratification. Despite this, recent research has increased confidence in both the detectability and understanding of changes in various aspects of intense short-duration rainfall. To make further progress, the international coordination of datasets, model experiments and evaluations will be required, with consistent and standardized comparison methods and metrics, and recommendations are made for these frameworks. This article is part of a discussion meeting issue 'Intensification of short-duration rainfall extremes and implications for flash flood risks'.

Comparing clinical outcomes of image-guided percutaneous transperitoneal and transhepatic cholecystostomy for acute cholecystitis.

BACKGROUND: Percutaneous cholecystostomy is performed by interventional radiologists for patients with calculous/acalculous cholecystitis who are poor candidates for cholecystectomy. Two anatomical approaches are widely utilized: transperitoneal and transhepatic. PURPOSE: To compare the clinical outcomes of transperitoneal and transhepatic approaches to cholecystostomy catheter placement. MATERIAL AND METHODS: From December 2007 to August 2015, 165 consecutive patients (97 men, 68 women) underwent either transperitoneal (n = 89) or transhepatic (n = 76) cholecystostomy at a single center. Indications were calculous cholecystitis (n = 21), acalculous cholecystitis (n = 35), hydrops (n = 1), gangrenous cholecystitis (n = 1), and other cholecystitis (n = 107). The most common high-risk co-morbidities were sepsis (n = 53) and cardiac (n = 11). Outcomes were compared using univariate and multivariable analysis. RESULTS: Post-procedure outcomes included tube dislodgement (transperitoneal [n = 6] and transhepatic [n = 3], P = 0.44), bile leak (transperitoneal [n = 5], transhepatic [n = 1], P = 0.14), gallbladder hemorrhage (transperitoneal [n = 2]; transhepatic [n = 3], P = 0.52), duodenal fistula (transperitoneal [n = 0], transhepatic [n = 1], P = 0.27), repeat cholecystostomy (transperitoneal [n = 1], transhepatic [n = 3], P = 0.27), and repeat cholecystitis requiring separate admission (transperitoneal [n = 6], transhepatic [n = 10], P = 0.15). All complications were Common Terminology Criteria for Adverse Events grade <3. Twenty transperitoneal patients underwent post-procedure cholecystectomy: 13 laparoscopic, three open, and four unclear/outside records. The mean time from cholecystostomy to operation was 38 days (range 3-211 days). Twenty-three transhepatic patients underwent cholecystectomy: 14 laparoscopic, eight open, and one unclear/outside records, with the mean time from cholecystostomy being 98 days (range 0-1053 days). One transhepatic and three transperitoneal patients died during admission. CONCLUSION: There were no significant differences in short-term complications after transperitoneal and transhepatic approaches to percutaneous cholecystostomy catheter placement.

Malaria Test, Treat and Track policy implementation in Angola: a retrospective study to assess the progress achieved after 4 years of programme implementation.

BACKGROUND: Malaria is one of the main causes of death in Angola, particularly among children under 5 years of age. An essential means to improve the situation is with strong malaria case management; this includes diagnosing suspected patients with a confirmatory test, either with a rapid diagnostic test (RDT) or microscopy, prompt and correct treatment with artemisinin-based combination therapy (ACT), and proper case registration (track). In 2011, the United States President's Malaria Initiative (PMI) launched a country-wide programme to improve malaria case management through the provision of regular training and supervision at different levels of health care provision. An evaluation of malaria testing, treatment and registration practices in eight provinces, and at health facilities of various capacities, across Angola was conducted to assess progress of the national programme implementation. METHODS: A retrospective assessment analysed data collected during supervision visits to health facilities conducted between 2012 and 2016 in 8 provinces in Angola. The supervision tool used data collected for malaria knowledge, testing, treatment and case registration practices among health workers as well as health facilities stock outs from different levels of health care delivery. Contingency tables with Pearson chi-squared (χ2) tests were used to identify factors associated with "knowledge", "test", "treat" and "track." Multivariable logistic regression models were used to assess factors associated with the defined outcomes. RESULTS: A total of 7156 supervisions were conducted between September 2012 and July 2016. The overall knowledge, testing, treatment and tracking practices among health care workers (HCWs) increased significantly from 2013 to 2016. Health care workers in 2016 were 3.3 times (95% CI: 2.7-3.9) as likely to have a higher knowledge about malaria case management as in 2013 (p < 0.01), 7.4 (95% CI: 6.1-9.0) times as likely to test more suspected cases (p < 0.01), 10.9 (95% CI: 8.6-13.6) times as likely to treat more confirmed cases (p < 0.01) and 3.7 (95% CI: 3.2-4.4) times as likely to report more accurately in the same period (p < 0.01). DISCUSSION: Improvements demonstrated in knowledge about malaria case management, testing with RDT and treatment with artemisinin-based combinations among HCWs is likely associated with malaria case management trainings and supportive supervisions. Gaps in testing and treatment practices are associated with RDT and ACT medicines stock outs in health facilities. Tracking of malaria cases still poses a major challenge, despite training and supervision. Hospitals consistently performed better compared to other health facilities against all parameters assessed; likely due to a better profile of HCWs. CONCLUSION: Significant progress in malaria case management in eight provinces Angola was achieved in the period of 2013-2016. Continued training and supportive supervision is essential to sustain gains and close existing gaps in malaria case management and reporting in Angola.

A new long noncoding RNA (lncRNA) is induced in cutaneous squamous cell carcinoma and down-regulates several anticancer and cell differentiation genes in mouse.

Keratinocyte-derived cutaneous squamous cell carcinoma (cSCC) is the most common metastatic skin cancer. Although some of the early events involved in this pathology have been identified, the subsequent steps leading to tumor development are poorly defined. We demonstrate here that the development of mouse tumors induced by the concomitant application of a carcinogen and a tumor promoter (7,12-dimethylbenz[a]anthracene (DMBA) and 12-O-tetradecanoylphorbol-13-acetate (TPA), respectively) is associated with the up-regulation of a previously uncharacterized long noncoding RNA (lncRNA), termed AK144841. We found that AK144841 expression was absent from normal skin and was specifically stimulated in tumors and highly tumorigenic cells. We also found that AK144841 exists in two variants, one consisting of a large 2-kb transcript composed of four exons and one consisting of a 1.8-kb transcript lacking the second exon. Gain- and loss-of-function studies indicated that AK144841 mainly inhibited gene expression, specifically down-regulating the expression of genes of the late cornified envelope-1 (Lce1) family involved in epidermal terminal differentiation and of anticancer genes such as Cgref1, Brsk1, Basp1, Dusp5, Btg2, Anpep, Dhrs9, Stfa2, Tpm1, SerpinB2, Cpa4, Crct1, Cryab, Il24, Csf2, and Rgs16 Interestingly, the lack of the second exon significantly decreased AK144841's inhibitory effect on gene expression. We also noted that high AK144841 expression correlated with a low expression of the aforementioned genes and with the tumorigenic potential of cell lines. These findings suggest that AK144841 could contribute to the dedifferentiation program of tumor-forming keratinocytes and to molecular cascades leading to tumor development.

Leishmaniasis in Northern Syria during Civil War.

Since the onset of the ongoing civil war in Syria, the governmental surveillance system for leishmaniasis has lost access to provinces of northern Syria. The MENTOR Initiative, an international not-for-profit organization, was commissioned to implement an integrated leishmaniasis control program, providing an opportunity to reassess the epidemiology of leishmaniasis in northern Syria. Epidemiologic data and biologic samples for molecular species diagnostics were collected from collaborating local health centers. Incidence peaked in March 2015 at 7,743 estimated monthly cases. High levels of transmission were observed in traditional endemic regions but extended to previously hypoendemic regions, such as Al-Raqqa and Al-Hasakah. Incidence decreased to 3,209 in July 2015. Data indicate that the prewar trend of increasing incidence of cutaneous leishmaniasis accelerated during the beginning of armed conflict but declined after implementation of the comprehensive control program by the MENTOR Initiative. Molecular analysis revealed a spectrum of Leishmania species and sporadic cases of visceral leishmaniasis.

Malaria case management by community health workers in the Central African Republic from 2009-2014: overcoming challenges of access and instability due to conflict.

BACKGROUND: In the Central African Republic (CAR), decades of armed conflict have crippled the public health system. This has left the population without timely access to life-saving services and therefore vulnerable to the numerous consequences of infectious diseases, including malaria. As a response, in 2008 an international non-governmental organization started a network of community health workers (CHWs) in the highly malaria-endemic region of northwest CAR. The area has experienced years of violent clashes between rebel groups and seen hundreds of thousands of people displaced. METHODS: Data from routine patient registers from 80 CHWs working in Paoua and Markounda sub-prefectures were entered and retrospectively reviewed. The time period covered December 2009-April 2014 and hence different stages of conflict and unrest. Several indicators were measured over time, including malaria rapid diagnostic test (RDT) positivity rates, CHW reporting rates, and malnutrition indicators. RESULTS: Among nearly 200,000 people who consulted a CHW during this period, 81% were found to be positive for malaria parasites by RDT. In total, 98.9% of these positive cases were appropriately treated with artemisinin-based combination therapy (ACT). Only 1.2% of RDT negative cases were incorrectly treated with an ACT. Monthly data from each CHW were regularly reported, with more than 96% of CHWs reporting each month in the first 3 years of the project. However, since the coup d'état in March 2013, the number of CHWs reporting each month decreased as the programme battled the additional constraints of civil war. CONCLUSIONS: Although the political crisis affected the CHWs, the programme showed that it could reach those most vulnerable and continue some level of care at all times. In addition, this programme revealed that surveillance could be maintained in conflict zones. This paper fills a significant gap in the knowledge of malaria control in CAR and this is especially important for agencies which must often decide in a short space of time how to respond effectively to complex emergencies.

The effect of supervised exercise therapy for intermittent claudication on lower limb lean mass.

OBJECTIVE: Supervised exercise is currently recommended for the first-line treatment of intermittent claudication based on improvement in walking capacity. However, the promotion of skeletal muscle atrophy by repetitive ischemia-reperfusion caused by treadmill-based programs remains a concern. Because preservation of skeletal muscle mass (SMM) and lean mass (LM) is integral to functional capacity and longevity, this study measured the effect of standard treadmill-based supervised exercise on SMM and regional lower limb LM in patients with intermittent claudication. METHODS: Patients with calf claudication caused by infrainguinal peripheral artery disease underwent whole-body dual-energy X-ray absorptiometry scanning before and after completion of a 12-week supervised treadmill exercise program. Total body SMM and lower limb LM were measured according to anatomical regions of the lower limb (thigh vs calf) and side of symptoms. Walking performance was assessed using pain-free walking distance and 6-minute walking distance tests. RESULTS: Thirty-six patients with calf claudication completed exercise training and dual-energy X-ray absorptiometry scanning, allowing analysis of 55 symptomatic and 17 asymptomatic lower limbs. No difference in total body SMM (P = .41) or LM of symptomatic (P = .53) or asymptomatic calves (P = .59) was detected after the program. In contrast, a significant decrease in LM was observed in symptomatic (P = .04) and asymptomatic thighs (P = .005). Pain-free walking distance (P = .001) and the 6-minute walking distance both improved significantly (P = .004) but were not associated with changes in LM. CONCLUSIONS: Twelve weeks of standard treadmill-training for intermittent calf claudication did not result in loss of calf LM; however, a significant decrease in bilateral thigh LM was observed, even in patients with unilateral symptoms. Further research on optimum exercise modalities and end points are required to determine the pathophysiology and effects of these changes on function and survival.

The effect of dosing strategies on the therapeutic efficacy of artesunate-amodiaquine for uncomplicated malaria: a meta-analysis of individual patient data.

BACKGROUND: Artesunate-amodiaquine (AS-AQ) is one of the most widely used artemisinin-based combination therapies (ACTs) to treat uncomplicated Plasmodium falciparum malaria in Africa. We investigated the impact of different dosing strategies on the efficacy of this combination for the treatment of falciparum malaria. METHODS: Individual patient data from AS-AQ clinical trials were pooled using the WorldWide Antimalarial Resistance Network (WWARN) standardised methodology. Risk factors for treatment failure were identified using a Cox regression model with shared frailty across study sites. RESULTS: Forty-three studies representing 9,106 treatments from 1999-2012 were included in the analysis; 4,138 (45.4%) treatments were with a fixed dose combination with an AQ target dose of 30 mg/kg (FDC), 1,293 (14.2%) with a non-fixed dose combination with an AQ target dose of 25 mg/kg (loose NFDC-25), 2,418 (26.6%) with a non-fixed dose combination with an AQ target dose of 30 mg/kg (loose NFDC-30), and the remaining 1,257 (13.8%) with a co-blistered non-fixed dose combination with an AQ target dose of 30 mg/kg (co-blistered NFDC). The median dose of AQ administered was 32.1 mg/kg [IQR: 25.9-38.2], the highest dose being administered to patients treated with co-blistered NFDC (median = 35.3 mg/kg [IQR: 30.6-43.7]) and the lowest to those treated with loose NFDC-25 (median = 25.0 mg/kg [IQR: 22.7-25.0]). Patients treated with FDC received a median dose of 32.4 mg/kg [IQR: 27-39.0]. After adjusting for reinfections, the corrected antimalarial efficacy on day 28 after treatment was similar for co-blistered NFDC (97.9% [95% confidence interval (CI): 97.0-98.8%]) and FDC (98.1% [95% CI: 97.6%-98.5%]; P = 0.799), but significantly lower for the loose NFDC-25 (93.4% [95% CI: 91.9%-94.9%]), and loose NFDC-30 (95.0% [95% CI: 94.1%-95.9%]) (P < 0.001 for all comparisons). After controlling for age, AQ dose, baseline parasitemia and region; treatment with loose NFDC-25 was associated with a 3.5-fold greater risk of recrudescence by day 28 (adjusted hazard ratio, AHR = 3.51 [95% CI: 2.02-6.12], P < 0.001) compared to FDC, and treatment with loose NFDC-30 was associated with a higher risk of recrudescence at only three sites. CONCLUSIONS: There was substantial variation in the total dose of amodiaquine administered in different AS-AQ combination regimens. Fixed dose AS-AQ combinations ensure optimal dosing and provide higher antimalarial treatment efficacy than the loose individual tablets in all age categories.