Exploring convolutional neural networks with transfer learning for diagnosing Lyme disease from skin lesion images.

BACKGROUND AND OBJECTIVE: Lyme disease which is one of the most common infectious vector-borne diseases manifests itself in most cases with erythema migrans (EM) skin lesions. Recent studies show that convolutional neural networks (CNNs) perform well to identify skin lesions from images. Lightweight CNN based pre-scanner applications for resource-constrained mobile devices can help users with early diagnosis of Lyme disease and prevent the transition to a severe late form thanks to appropriate antibiotic therapy. Also, resource-intensive CNN based robust computer applications can assist non-expert practitioners with an accurate diagnosis. The main objective of this study is to extensively analyze the effectiveness of CNNs for diagnosing Lyme disease from images and to find out the best CNN architectures considering resource constraints. METHODS: First, we created an EM dataset with the help of expert dermatologists from Clermont-Ferrand University Hospital Center of France. Second, we benchmarked this dataset for twenty-three CNN architectures customized from VGG, ResNet, DenseNet, MobileNet, Xception, NASNet, and EfficientNet architectures in terms of predictive performance, computational complexity, and statistical significance. Third, to improve the performance of the CNNs, we used custom transfer learning from ImageNet pre-trained models as well as pre-trained the CNNs with the skin lesion dataset HAM10000. Fourth, for model explainability, we utilized Gradient-weighted Class Activation Mapping to visualize the regions of input that are significant to the CNNs for making predictions. Fifth, we provided guidelines for model selection based on predictive performance and computational complexity. RESULTS: Customized ResNet50 architecture gave the best classification accuracy of 84.42% ±1.36, AUC of 0.9189±0.0115, precision of 83.1%±2.49, sensitivity of 87.93%±1.47, and specificity of 80.65%±3.59. A lightweight model customized from EfficientNetB0 also performed well with an accuracy of 83.13%±1.2, AUC of 0.9094±0.0129, precision of 82.83%±1.75, sensitivity of 85.21% ±3.91, and specificity of 80.89%±2.95. All the trained models are publicly available at https://dappem.limos.fr/download.html, which can be used by others for transfer learning and building pre-scanners for Lyme disease. CONCLUSION: Our study confirmed the effectiveness of even some lightweight CNNs for building Lyme disease pre-scanner mobile applications to assist people with an initial self-assessment and referring them to expert dermatologist for further diagnosis.

The Adjuvanted Recombinant Zoster Vaccine Confers Long-Term Protection Against Herpes Zoster: Interim Results of an Extension Study of the Pivotal Phase 3 Clinical Trials ZOE-50 and ZOE-70.

BACKGROUND: This ongoing follow-up study evaluated the persistence of efficacy and immune responses for 6 additional years in adults vaccinated with the glycoprotein E (gE)-based adjuvanted recombinant zoster vaccine (RZV) at age ≥50 years in 2 pivotal efficacy trials (ZOE-50 and ZOE-70). The present interim analysis was performed after ≥2 additional years of follow-up (between 5.1 and 7.1 years [mean] post-vaccination) and includes partial data for year (Y) 8 post-vaccination. METHODS: Annual assessments were performed for efficacy against herpes zoster (HZ) from Y6 post-vaccination and for anti-gE antibody concentrations and gE-specific CD4[2+] T-cell (expressing ≥2 of 4 assessed activation markers) frequencies from Y5 post-vaccination. RESULTS: Of 7413 participants enrolled for the long-term efficacy assessment, 7277 (mean age at vaccination, 67.2 years), 813, and 108 were included in the cohorts evaluating efficacy, humoral immune responses, and cell-mediated immune responses, respectively. Efficacy of RZV against HZ through this interim analysis was 84.0% (95% confidence interval [CI], 75.9-89.8) from the start of this follow-up study and 90.9% (95% CI, 88.2-93.2) from vaccination in ZOE-50/70. Annual vaccine efficacy estimates were >84% for each year since vaccination and remained stable through this interim analysis. Anti-gE antibody geometric mean concentrations and median frequencies of gE-specific CD4[2+] T cells reached a plateau at approximately 6-fold above pre-vaccination levels. CONCLUSIONS: Efficacy against HZ and immune responses to RZV remained high, suggesting that the clinical benefit of RZV in older adults is sustained for at least 7 years post-vaccination. Clinical Trials Registration. NCT02723773.

Nasopharyngeal swab-induced pain for SARS-CoV-2 screening: A randomised controlled trial of conventional and self-swabbing.

BACKGROUND: Massive screening campaigns for SARS-CoV-2 are currently carried out throughout the world, relying on reverse-transcriptase-polymerase chain reaction (RT-PCR) following nasopharyngeal swabbing performed by a healthcare professional. Yet, due to the apprehension of pain induced by nasopharyngeal probing, poor adhesion to those screening campaigns can be observed. To enhance voluntary participation and to avoid unnecessary exposition to SARS-CoV-2, self-swabbing could be proposed. To date, no data have been published concerning pain induced by conventional- or self-swabbing. Thus, the primary objective of the present study was to evaluate pain induced with the conventional swabbing method and compare it to self-swabbing. Secondary objectives focused on swabbing-induced discomfort and acceptability of the two methods. METHODS: The study was conducted in Clermont-Ferrand medical school (France). Overall, 190 students were randomised into two groups and experienced either self- or conventional-swabbing. Each subject had to rate pain, discomfort and acceptability of such swabbing on a 0-10 numeric rating scale. RESULTS: No significant difference was found between the two methods. The mean pain level was 2.5 ± 1.9, 28% rating pain as ≥4/10. Discomfort was 4.8 ± 2.2, 66% indicating significant (≥4/10) discomfort. Higher pain and discomfort were associated with female sex. Acceptability was ≥8/10 for 89.0% of the subjects and all would have accepted to undergo a new test with the same technique if necessary. CONCLUSION: Both conventional and self-swabbing induce low levels of pain for most young healthy volunteers whereas discomfort is very frequent. Nonetheless, both methods are indifferently well-accepted in medical students. Future studies amongst symptomatic subjects are awaited. SIGNIFICANCE: Using the thinnest available swabs, procedural pain induced by nasopharyngeal swabbing for SARS-CoV-2 screening is very low for most subjects and should not limit voluntary participation in screening campaigns. Self-swabbing does not lead to more pain or discomfort compared to conventional swabbing, is well-accepted, and could be proposed to optimize screening campaigns, at least in healthcare professionals.

High Prevalence of Headaches During Covid-19 Infection: A Retrospective Cohort Study.

OBJECTIVES: To document the prevalence of new headaches in patients with Covid-19 infection and the potential association with other neuro-sensorial symptoms (anosmia and ageusia). The persistence of these symptoms 1 month after recovery was also documented. BACKGROUND: Headaches are a very common symptom of viral infections. Surprisingly, early Chinese studies reported a relatively low prevalence (12-15%) of headaches associated with Covid-19. METHODS: All the patients with laboratory-confirmed or chest-CT-confirmed Covid-19 infection, diagnosed between February 27th and April 15th , 2020 in the dedicated laboratory of Clermont-Ferrand University Hospital were followed for 1 month after recovery. RESULTS: A total of 139 consecutive patients (mean [SD] age, 48.5 [15.3] years; 87 women [62.6%]) were interviewed 1 month after disappearance of fever and dyspnea (semi-structured phone interview). Overall, 59.0% (82/139) of people with Covid-19 had mild disease, 36.7% (51/139) had severe disease, and 4.3% (6/139) had critical illness. Eighty-two (59.0%; 95% CI: 50.3 to 67.3) reported new headaches during the acute phase and 3.6% (5/139) had persistent headaches 1 month after fever and dyspnea remission. Anosmia and ageusia were also very common, occurring in 60.4% (84/139) and 58.3% (81/139) of the patients, respectively. These 2 symptoms persisted in 14.4% (20/139) and 11.5% (16/139) of Covid-19 patients 1 month after recovery. Headaches were neither clearly associated with anosmia, nor with ageusia, and were not associated with disease severity (ie, requiring hospitalization or intensive care unit). CONCLUSION: This specific study highlights the high prevalence of new headaches during Covid-19 infection in French patients. Further studies are needed to refine the characterization of patients with Covid-19-associated headaches.

Skin diseases in internationally adopted children.

Internationally adopted children often present diseases contracted in the country of origin. Skin diseases are common in new arrivals, and diagnosis may prove challenging for GPs or even dermatologists if they are inexperienced in the extensive geographic and ethnic diversity of international adoptees. To analyse the frequency and characteristics of skin diseases in international adoptees. In total, 142 adoptees were evaluated for a cross-sectional cohort study. The most frequent diseases observed at arrival were dermatological conditions. Of the adoptees, 70% presented at least one skin disease, of which 57.5% were infectious; Tinea capitis being the most frequent (n = 42). The recovery rate of Tinea capitis was 89% (n = 32/36). Ten cases of scabies were diagnosed. Other diseases included viral skin infection (n = 22), with 16 cases of Molluscum contagiosum and bacterial infection. Skin diseases are very common in internationally adopted children. There is a need for close collaboration between dermatologists and paediatricians to diagnose such infections, as well as clear guidelines to treat them.

Staphylococcus aureus-Related Diabetic Osteomyelitis: Medical or Surgical Management? A French and Spanish Retrospective Cohort.

Staphylococcus aureus is the main cause of diabetic foot osteomyelitis (DFO) and can be treated medically or by surgery. We investigated the outcome of consecutive patients with a diagnosis of S aureus DFO retrospectively in 4 hospitals according to the type of management, medical (including debridement at bedside) or surgical. The outcome was classified as either favorable or failure (relapse, impaired wound healing, or amputation). Seventy-four patients with S aureus DFO, including 26 with methicillin-resistant S aureus, were included with a mean duration of follow-up of 21 ± 1 months. As part of the initial treatment, 47% underwent bone surgery followed with a short course of antibiotic. Others were treated with antibiotic therapy alone with bedside debridement. The outcome was favorable for 84% of these patients, with similar rates in the surgical and medical groups (80% vs 87%, P > .05). Patients in the medical group were less frequently hospitalized (49% vs 94%, P < .001) and had a shorter length of hospital stay (17 ± 3 vs 50 ± 12 days, P = .004). Patients in the surgery group received a shorter course of antibiotic therapy (10 ± 2 vs 11 ± 1 weeks, P = .001) with fewer side effects (9% vs 33%, P = .01). The type of management was not associated with subsequent new episode of noncontiguous DFO, which developed in 32% of cases. In conclusion, except significant differences in duration of hospitalization and antibiotic therapy, medical and surgical management of S aureus DFO had similar outcomes with a cure rate >80%.

Suppressive therapy using azithromycin in 2 rare cases of recurrent staphylococcal infections.

Recurrent staphylococcal skin and soft tissue infections may recur despite decontamination and multiple courses of antibiotic therapy and may dramatically impair the patient's quality of life. We report successful use of long-term azithromycin prophylaxis in a recurrent laryngitis and a scalp folliculitis due to methicillin-susceptible Staphylococcus aureus.

Populations at risk for alveolar echinococcosis, France.

During 1982-2007, alveolar echinococcosis (AE) was diagnosed in 407 patients in France, a country previously known to register half of all European patients. To better define high-risk groups in France, we conducted a national registry-based study to identify areas where persons were at risk and spatial clusters of cases. We interviewed 180 AE patients about their way of life and compared responses to those of 517 controls. We found that almost all AE patients lived in 22 départements in eastern and central France (relative risk 78.63, 95% CI 52.84-117.02). Classification and regression tree analysis showed that the main risk factor was living in AE-endemic areas. There, most at-risk populations lived in rural settings (odds ratio [OR] 66.67, 95% CI 6.21-464.51 for farmers and OR 6.98, 95% CI 2.88-18.25 for other persons) or gardened in nonrural settings (OR 4.30, 95% CI 1.82-10.91). These findings can help sensitization campaigns focus on specific groups.

[The French Committee for the prevention and control of influenza and the 2009 influenza pandemic: Lessons learnt]. / Comité de lutte contre la grippe et la pandémie 2009 : retour d'expérience.

The Committee for the Prevention and Control of Influenza (Comité de lutte contre la Grippe - CLCG) is an advisory committee to the French Health Minister for a medical and scientific collective expertise on the measures to be implemented to control or to reduce the impact of an epidemic or a pandemic of influenza. Appointed by decree, the CLCG consists of ex-officio members; representatives of French Agencies strongly involved by influenza and qualified personalities, representing various fields of expertise. Collective expertise is based on consensus after thorough collective discussion. A notice is drafted in reply to every official question and passed on either to the Chief Medical Officer, or, when the question concerns vaccines, to the Technical Committee of the vaccinations for which the CLCG acted as a working group. The CLCG was extremely active throughout the pandemic. The objective of this article is to describe in a factual way its output throughout this period of sanitary crisis. This article presents and compare chronologically and in a factual way the state of the scientific knowledge about influenza due to the A(H1N1)pdm09 virus and the CLCG notices. Between the alert launched by the WHO the 24th of April and the 31st of December 2009, CLCG met on 40 occasions. Its work dealt in particular with patient care, recommendations on medical treatment (antivirals, seasonal and pandemic vaccines), and on virological diagnosis. Whatever the defects of its expertise delivered in a context of urgency, which was a difficult exercise, the CLCG fulfilled its advisory to the health authorities. However, the pandemic experience showed that this expertise must be improved by insuring the recognition and the visibility of the advisory committee and by defining their exact position in the chain of decision.

Health care support issues for internationally adopted children: a qualitative approach to the needs and expectations of families.

BACKGROUND: Families of internationally adopted children may face specific problems with which general practitioners (GPs) may not be familiar. The aim of the study was to explore problems faced by families before, during and after the arrival of their internationally adopted child and to assess the usefulness of a specific medical structure for internationally adopted children, which could be a resource for the GP. METHODOLOGY/PRINCIPAL FINDINGS: We conducted a qualitative study using individual semistructured guided conversations and interviewed 21 families that had adopted a total of 26 children internationally in the Puy de Dome department, France, in 2003. Quantitative data were used to describe the pathologies diagnosed and the investigations performed.Our study showed that the history of these families, from the start of the adoption project to its achievement, is complex and warrants careful analysis. Health-care providers should not only consider the medical aspects of adoption, but should also be interested in the histories of these families, which may play a role in the forming of attachments between the adoptee and their adoptive parents and prevent further trouble during the development of the child. We also showed that adoptive parents have similar fears or transient difficulties that may be resolved quickly by listening and reassurance. Most such families would support the existence of a specific medical structure for internationally adopted children, which could be a resource for the general practitioner. However, the health-care providers interviewed were divided on the subject and expressed their fear that a special consultation could be stigmatizing to children and families. CONCLUSIONS/SIGNIFICANCE: A specific consultation with well-trained and experienced practitioners acting in close collaboration with GPs and paediatricians may be of help in better understanding and supporting adopted children and their families.

Clinical features and evolution of alveolar echinococcosis in France from 1982 to 2007: results of a survey in 387 patients.

BACKGROUND & AIMS: Alveolar echinococcosis (AE) is a rare disease in humans, caused by the larval stage of the fox tapeworm Echinococcus multilocularis. METHODS: We present here 387 detailed AE cases diagnosed in France from 1982 to 2007 actively identified by a retrospective survey performed in 1997-1998 and prospectively thereafter. RESULTS: Male:female ratio was 1.03 and mean age 57.8 years at time of diagnosis. Among the 362 complete files (including 347 non dead-out and 15 dead-out lesions), 73% of the patients were symptomatic at first admittance. Among them, 83% presented with clinical patterns evocative either of a digestive or a hepatic disorder. Other symptomatic patients presented with erratic clinical pictures, generally due to metastasis or extra-hepatic location of the parasite. Except for a few patients with particularly severe AE who died shortly after the diagnosis, most patients were treated using benzimidazoles. Their mortality tends to merge with that of the general French population, matched by sex, age, and calendar year. This study also highlights an unexpectedly high frequency of blood-tied family cases (13% of patients submitted to a specific questionnaire). CONCLUSIONS: Even though the broad set of clinical features provoked by E. multilocularis makes AE a potential diagnostic trap for many physicians, our study revealed an improvement of its prognosis. However, as shown by our findings about the frequency of family cases, there is still a need for studies aimed at better describing this uncommon parasitic disease.

Antibodies to tetanus, diphtheria and pertussis among healthy adults vaccinated according to the French vaccination recommendations.

In this sero-epidemiological study, we investigated humoral immunity to three vaccine-preventable diseases--tetanus, diphtheria and pertussis--among 331 adults (aged 18-60 years) attending vaccination centres for travellers and who had been vaccinated according to national recommendations in France. Serological results showed that the percentage of subjects with antibodies to diphtheria and tetanus decreases with age. Results also confirmed surveillance data on vaccination in France, with 7.6% of the study population (13.4% of those aged 18-29 years) having recently acquired a pertussis infection. These results confirm the importance of following French recommendations for regular boosters for tetanus and diphtheria among adults. They also indicate the need for better implementation of the current recommendations for pertussis-vaccine boosters in adults.

Safety of Tdap-IPV given one month after Td-IPV booster in healthy young adults: a placebo-controlled trial.

BACKGROUND: In France, the only vaccines available for use as a pertussis booster in adults are combined vaccines containing adsorbed tetanus, diphtheria (adult formulation), acellular pertussis and inactivated poliovirus (Tdap-IPV). Adults may require a pertussis booster relatively soon after having received vaccines containing tetanus-diptheria antigens (Td) (occupational or familial circumstances such as new job, childbirth in recent past or future), although the safety of Tdap-IPV when administered soon after vaccination with Td is undocumented. METHODS: In this randomized, double-blind, multi-centre study, we assessed the safety of Tdap-IPV administered one month after vaccination with tetanus, diphtheria (adult formulation), inactivated poliovirus vaccination (Td-IPV) in healthy adults vaccinated according to the French vaccination calendar (seven tetanus-diphtheria vaccinations by age 18 years). Subjects received either Td-IPV (n = 249) or placebo (n = 251) followed 1 month later by Tdap-IPV. Any adverse events (AEs) were recorded. RESULTS: The safety of Tdap-IPV was similar when Tdap-IPV vaccine was administered one month after either Td-IPV or placebo: at seven days, 85.1% versus 93.4% subjects reported at least one reaction at the injection site, mainly pain (82.6% versus 92.1%); 40.5% versus 45.0%, at least one systemic AE (mainly headache: 26.4% versus 26.0%); fever concerned 1.7% of both groups. No serious vaccine-related AEs were reported. Both safety profiles corresponded to documented product characteristics. CONCLUSIONS: Tdap-IPV may be administered to adults one month after Td-IPV without exacerbating post-vaccination side-effects.

Methicillin-susceptible, doxycycline-resistant Staphylococcus aureus, Côte d'Ivoire.

We report 2 outbreaks of Panton-Valentine leukocidin-positive, doxycycline-resistant, methicillin-susceptible Staphylococcus aureus infections in French soldiers operating in Côte d'Ivoire. In a transssectional survey, nasal carriage of this strain was found in 2.9% of 273 soldiers about to be sent to Côte d'Ivoire and was associated with prior malaria prophylaxis with doxycycline.

[Emergence of monomicrobial methicillin-resistant Staphylococcus aureus infections in diabetic foot osteomyelitis (retrospective study of 48 cases)]. / Emergence des infections monomicrobiennes à staphylocoque doré méticilline-résistant dans les ostéites du pied diabétique. Etude rétrospective de 48 cas.

OBJECTIVE: Describe the clinical appearance, microorganisms involved, and prognosis of diabetic foot osteomyelitis. METHOD: Retrospective study of 48 patients seen in 2004 for presumed osteomyelitis (exposed bone or suggestive radiographic or clinical picture). Specimens for culture came from swabs of wound discharge, needle aspiration and bone biopsy. RESULTS: Forty-eight patients with diabetes and contiguous osteomyelitis of the foot were followed for a year. The principal microorganisms isolated were Staphylococcus aureus (58%) and Gram-negative bacilli (29%); 58% of the infections were monomicrobial, 31% of the microorganisms multidrug-resistant, and 85% of the patients were hospitalized, for a median duration of 30 days. Healing occurred in 40 patients, although 15 required amputation first, and 18 had a new infection at a different site (11 involving osteomyelitis) in the year after antibiotic treatment ended. PERSPECTIVES: Diabetic foot osteomyelitis is a serious disease in view of its site and the microorganisms involved, which are often multidrug-resistant. There is a clear predominance of S. aureus. Medical treatment has an increasingly important role in its management and requires that samples be properly collected for bacteriological testing. The prognosis for these infections, which remains grim in view of the amputation rate and the high risk of new infection, could be improved by reinforcing prevention measures.

[Vancomycin-resistant Enterococcus in an epidemic situation: screening at admission for patients at risk of carriage]. / Entérocoques résistant aux glycopeptides dans un contexte endémo-épidémique. Stratégie d'isolement àl'admission des patients à risque.

OBJECTIVES: To evaluate a strategy based on screening and isolation at admission to a department of infectious diseases during an epidemic of vancomycin-resistant Enterococcus (VRE) at the University Hospital of Clermont-Ferrand. METHODS: Systematic screening for VRE by anal swabs began on November 15, 2004. Patients were isolated on admission if (a) they had been hospitalized more than 24 h in an at-risk department of our hospital or (b) they had received a course of wide-spectrum antimicrobial therapy for longer than 48 h in the three months preceding admission. Patients hospitalized in our department were screened weekly if they were treated with wide-spectrum antibiotics, had a urinary catheter left in place for one week, or were neutropenic. RESULTS: Through May 15, 2005, 12 (3.5%) of 341 swabs were found to be positive for VRE: eight were detected on admission and four during hospitalization. In all, 81 patients were isolated on admission. A case-control study confirmed that the criteria for patient isolation were indeed risk factors for VRE. Isolation was well accepted when it was clearly explained. No new case has been detected since March 2005. CONCLUSION: An isolation strategy based on known risk factors for VRE with systematic screening on admission appears to be an effective way to control an outbreak of VRE, perhaps in part because it helps to keep the medical staff alert to this problem. Isolation is well tolerated as long as it is explained clearly.

Whole body leucine flux in HIV-infected patients treated with or without protease inhibitors.

The present study was carried out to assess the effects of protease inhibitor (PI) therapy on basal whole body protein metabolism and its response to acute amino acid-glucose infusion in 14 human immunodeficiency virus (HIV)-infected patients. Patients treated with PIs (PI+, 7 patients) or without PIs (PI-, 7 patients) were studied after an overnight fast during a 180-min basal period followed by a 140-min period of amino acid-glucose infusion. Protein metabolism was investigated by a primed constant infusion of l-[1-(13)C]leucine. Dual-energy X-ray absorptiometry for determination of fat-free mass (FFM) and body fat mass measured body composition. In the postabsorptive state, whole body leucine balance was 2.5 times (P < 0.05) less negative in the PI+ than in the PI- group. In HIV-infected patients treated with PIs, the oxidative leucine disposal during an acute amino acid-glucose infusion was lower (0.58 +/- 0.09 vs. 0.81 +/- 0.07 micromol x kg FFM(-1) x min(-1) using plasma [(13)C]leucine enrichment, P = 0.06; or 0.70 +/- 0.10 vs. 0.99 +/- 0.08 micromol x kg FFM(-1) x min(-1) using plasma [(13)C]ketoisocaproic acid enrichment, P = 0.04 in PI+ and PI- groups, respectively) than in patients treated without PIs. Consequently, whole body nonoxidative leucine disposal (an index of protein synthesis) and leucine balance (0.50 +/- 0.10 vs. 0.18 +/- 0.06 micromol x kg FFM x (-1) x min(-1) in PI+ and PI- groups respectively, P < 0.05) were significantly improved during amino acid-glucose infusion in patients treated with PIs. However, whereas the response of whole body protein anabolism to an amino acid-glucose infusion was increased in HIV-infected patients treated with PIs, any improvement in lean body mass was detected.