12 research outputs found
Epidemiological and clinical features of patients hospitalized due to Clostridium difficile - associated diarrhea
UVOD: Dijareja uzrokovana bakterijom Clostridium difficile je jedna od ÄeÅ”Äih neželjenih posljedica primjene antibiotske terapije, no malo se zna o odnosu epidemioloÅ”kih okolnosti razbolijevanja i kliniÄke težine bolesti te ishoda lijeÄenja. ----- CILJ: Opisati epidemioloÅ”ka i kliniÄka obilježja bolesti te utvrditi odnos epidemioloÅ”kih okolnosti razbolijevanja i kliniÄke težine bolesti i ishoda lijeÄenja u bolesnika s Clostridium difficile infekcijom (CDI). ----- BOLESNICI I METODE: Radi se o retrospektivnom deskriptivnom istraživanju provedenom na bolesnicima oba spola i svih dobi hospitalno lijeÄenim zbog dijareje uzrokovane laboratorijski potvrÄenom CDI u razdoblju od 2013. ā 2016. godine u Klinici za infektivne bolesti āDr. Fran MihaljeviÄā, Zagreb. U statistiÄkoj obradi podataka koriÅ”tena je metoda linearne regresije, hi-kvadrat test, studentov t-test i njegove neparametarske inaÄice u sluÄaju odstupanja podataka od normalne distribucije. ----- REZULTATI: Od 776 bolesnika s CDI njih je 76% imalo CDI povezanu sa zdravstvenom skrbi, 16% je imalo izvanbolniÄki steÄenu infekciju, a u 8% bolesnika se epidemioloÅ”ke okolnosti razbolijevanja nisu mogle utvrditi. Udio bolesnika s CDI povezanom sa zdravstvenom skrbi je u promatranom razdoblju znaÄajno rastao u odnosu na bolesnike s izvanbolniÄki steÄenom CDI (p=0.0395). Bolesnici s CDI povezanom sa zdravstvenom skrbi su imali statistiÄki znaÄajno veÄe vrijednosti maksimalne tjelesne temperature (prosjek 37,99 vs. 37,21), veÄi broj stolica u 24 sata (prosjek 9,14 vs. 5,83), ÄeÅ”Äu pojavu renalne insuficijencije (19,2 vs. 5,7%) i ÄeÅ”Äe prisutne ostale komplikacije (8,2 vs. 2,5%). Ti su bolesnici imali statistiÄki znaÄajno veÄe vrijednosti leukocita u perifernoj krvi (prosjek 15,51 vs. 13,64), niže vrijednosti albumina (prosjek 28,29 vs. 32,82) te su u njih vrijednosti kreatinina ÄeÅ”Äe bile veÄe od 1,5x u odnosu na bazalne vrijednosti (33,2 vs. 15,1%). U njih je bio znaÄajno veÄi McCabe skor (1.57 vs. 1.13) i ATLAS skor (4.05 vs. 1.85). TakoÄer, navedeni bolesnici su bili statistiÄki znaÄajno duže hospitalizirani (prosjek 14,83 vs. 10,13 dana) te je kod njih smrtni ishod bio znaÄajno ÄeÅ”Äi (11,7 vs. 3,3%) u odnosu na bolesnike s izvanbolniÄki steÄenom CDI. ----- ZAKLJUÄAK: U promatranom razdoblju je meÄu hospitalno lijeÄenim bolesnicima zabilježen znaÄajan trend rasta udjela pacijenata koji su imali C. difficile infekciju povezanu sa zdravstvenom skrbi u periodu od 2013. ā 2016. Bolesnici s CDI povezanom sa zdravstvenom skrbi su imali kliniÄki težu bolest i loÅ”iji ishod od bolesnika s izvanbolniÄkom CDI.BACKGROUND: Clostridium difficile-associated diarrhea is one of the most common unintended consequences of the administration of antibiotics and the correlation between epidemiological circumstances of acquisition and severity of illness and its outcome is not well known. ----- OBJECTIVE: To determine epidemiological and clinical features of C. difficile infection (CDI) and to assess the relationship between the epidemiological circumstances of acquisition and severity of illness and its outcome. ----- PATIENTS AND METHODS: This is a retrospective descriptive study that includes patients of both genders and all age groups hospitalized and treated for CDI with laboratory detected infection from 2013 to 2016 at University Hospital for Infectious Diseases āDr. Fran MihaljeviÄā, Zagreb. Linear regression analysis, Chi-square test, Student t-test are used to compare mean values and non-parametric tests are used if distribution is not normal. ----- RESULTS: Of 776 patients 76% had healthcare-associated C. difficile infection, 16% had community-associated C. difficile infection and 8% had undetermined association. Proportion of the patients with healthcare-associated C. difficile infection significantly increased compared to proportion of patients with community-associated infection over the study period (p=0.0395). Patients with healthcare-associated C. difficile infection had significantly higher maximum body temperature (mean 37,99 vs. 37,21), more stools in 24 hours (mean 9,14 vs. 5,83), had more often renal impairment (19,2% vs. 5,7%) and had more often other complications (8,2 vs. 2,5%). Patients with healthcare-associated C. difficile infection had significantly more elevated leukocyte count (mean 15,51 vs. 13,64), lower serum albumin (mean 28,29 vs. 32,82) and had more often Ė50% increase in baseline serum creatinine level (33,2 vs. 15,1%). Patients with healthcare-associated CDI had significantly higher McCabe score (1.57 vs. 1.13) and ATLAS score (4.05 vs. 1.85). Also, they had longer length of stay in hospital (mean 14,83 vs. 10,13 days) and higher mortality rates (11,7 vs. 3,3%) when compared to patients with community-associated C. difficile infection. ----- CONCLUSIONS: There is a significant increase in proportion of healthcare-associated C. difficile cases from 2013 ā 2016. Patients with healthcare-associated CDI had more severe illness and worse outcome than patients with community-associated CDI
Epidemiological and clinical features of patients hospitalized due to Clostridium difficile - associated diarrhea
UVOD: Dijareja uzrokovana bakterijom Clostridium difficile je jedna od ÄeÅ”Äih neželjenih posljedica primjene antibiotske terapije, no malo se zna o odnosu epidemioloÅ”kih okolnosti razbolijevanja i kliniÄke težine bolesti te ishoda lijeÄenja. ----- CILJ: Opisati epidemioloÅ”ka i kliniÄka obilježja bolesti te utvrditi odnos epidemioloÅ”kih okolnosti razbolijevanja i kliniÄke težine bolesti i ishoda lijeÄenja u bolesnika s Clostridium difficile infekcijom (CDI). ----- BOLESNICI I METODE: Radi se o retrospektivnom deskriptivnom istraživanju provedenom na bolesnicima oba spola i svih dobi hospitalno lijeÄenim zbog dijareje uzrokovane laboratorijski potvrÄenom CDI u razdoblju od 2013. ā 2016. godine u Klinici za infektivne bolesti āDr. Fran MihaljeviÄā, Zagreb. U statistiÄkoj obradi podataka koriÅ”tena je metoda linearne regresije, hi-kvadrat test, studentov t-test i njegove neparametarske inaÄice u sluÄaju odstupanja podataka od normalne distribucije. ----- REZULTATI: Od 776 bolesnika s CDI njih je 76% imalo CDI povezanu sa zdravstvenom skrbi, 16% je imalo izvanbolniÄki steÄenu infekciju, a u 8% bolesnika se epidemioloÅ”ke okolnosti razbolijevanja nisu mogle utvrditi. Udio bolesnika s CDI povezanom sa zdravstvenom skrbi je u promatranom razdoblju znaÄajno rastao u odnosu na bolesnike s izvanbolniÄki steÄenom CDI (p=0.0395). Bolesnici s CDI povezanom sa zdravstvenom skrbi su imali statistiÄki znaÄajno veÄe vrijednosti maksimalne tjelesne temperature (prosjek 37,99 vs. 37,21), veÄi broj stolica u 24 sata (prosjek 9,14 vs. 5,83), ÄeÅ”Äu pojavu renalne insuficijencije (19,2 vs. 5,7%) i ÄeÅ”Äe prisutne ostale komplikacije (8,2 vs. 2,5%). Ti su bolesnici imali statistiÄki znaÄajno veÄe vrijednosti leukocita u perifernoj krvi (prosjek 15,51 vs. 13,64), niže vrijednosti albumina (prosjek 28,29 vs. 32,82) te su u njih vrijednosti kreatinina ÄeÅ”Äe bile veÄe od 1,5x u odnosu na bazalne vrijednosti (33,2 vs. 15,1%). U njih je bio znaÄajno veÄi McCabe skor (1.57 vs. 1.13) i ATLAS skor (4.05 vs. 1.85). TakoÄer, navedeni bolesnici su bili statistiÄki znaÄajno duže hospitalizirani (prosjek 14,83 vs. 10,13 dana) te je kod njih smrtni ishod bio znaÄajno ÄeÅ”Äi (11,7 vs. 3,3%) u odnosu na bolesnike s izvanbolniÄki steÄenom CDI. ----- ZAKLJUÄAK: U promatranom razdoblju je meÄu hospitalno lijeÄenim bolesnicima zabilježen znaÄajan trend rasta udjela pacijenata koji su imali C. difficile infekciju povezanu sa zdravstvenom skrbi u periodu od 2013. ā 2016. Bolesnici s CDI povezanom sa zdravstvenom skrbi su imali kliniÄki težu bolest i loÅ”iji ishod od bolesnika s izvanbolniÄkom CDI.BACKGROUND: Clostridium difficile-associated diarrhea is one of the most common unintended consequences of the administration of antibiotics and the correlation between epidemiological circumstances of acquisition and severity of illness and its outcome is not well known. ----- OBJECTIVE: To determine epidemiological and clinical features of C. difficile infection (CDI) and to assess the relationship between the epidemiological circumstances of acquisition and severity of illness and its outcome. ----- PATIENTS AND METHODS: This is a retrospective descriptive study that includes patients of both genders and all age groups hospitalized and treated for CDI with laboratory detected infection from 2013 to 2016 at University Hospital for Infectious Diseases āDr. Fran MihaljeviÄā, Zagreb. Linear regression analysis, Chi-square test, Student t-test are used to compare mean values and non-parametric tests are used if distribution is not normal. ----- RESULTS: Of 776 patients 76% had healthcare-associated C. difficile infection, 16% had community-associated C. difficile infection and 8% had undetermined association. Proportion of the patients with healthcare-associated C. difficile infection significantly increased compared to proportion of patients with community-associated infection over the study period (p=0.0395). Patients with healthcare-associated C. difficile infection had significantly higher maximum body temperature (mean 37,99 vs. 37,21), more stools in 24 hours (mean 9,14 vs. 5,83), had more often renal impairment (19,2% vs. 5,7%) and had more often other complications (8,2 vs. 2,5%). Patients with healthcare-associated C. difficile infection had significantly more elevated leukocyte count (mean 15,51 vs. 13,64), lower serum albumin (mean 28,29 vs. 32,82) and had more often Ė50% increase in baseline serum creatinine level (33,2 vs. 15,1%). Patients with healthcare-associated CDI had significantly higher McCabe score (1.57 vs. 1.13) and ATLAS score (4.05 vs. 1.85). Also, they had longer length of stay in hospital (mean 14,83 vs. 10,13 days) and higher mortality rates (11,7 vs. 3,3%) when compared to patients with community-associated C. difficile infection. ----- CONCLUSIONS: There is a significant increase in proportion of healthcare-associated C. difficile cases from 2013 ā 2016. Patients with healthcare-associated CDI had more severe illness and worse outcome than patients with community-associated CDI
Allergic rhinitis: a cross-sectional survey assessing the knowledge and therapeutic approach among final year medical students, pharmacy students, general practitioners and community pharmacists in Croatia
Objectives. To assess the current knowledge of allergic rhinitis (AR) among final year medical and pharmacy students, general practitioners (GPs) and community pharmacists in Croatia.
Methods: Data were collected from September 2017 to November 2017 through an online questionnaire. Final year medical and pharmacy students (N=201), GPs and pharmacists from Croatia (N=127) were included. The two factor structured questionnaire was formed regarding general knowledge and treatment of AR. T-test and chi-square tests were used for statistical analysis.
Results: Overall knowledge of AR was low among respondents (mean score among GPs: 11.4/20, pharmacists: 11.3/20, pharmacy students: 10.8/20, medical students: 10.3/20). With reference to treatment mean scores were also low; GPs 5.1/10, pharmacists: 4.9/10, pharmacy students: 4.3/10 and medical students: 4.1/10. GPs were significantly better than medical students in reference to treatment approach (p<.001) and overall knowledge (p=0.004). Pharmacists\u27 knowledge of treatment was better than pharmacy students\u27 (p=0.029), and the overall knowledge was insignificantly higher (p=0.210). The overall knowledge was insignificantly different among GPs and pharmacists (p=0.911), as was knowledge of treatment approach (p=0.335). The overall knowledge and knowledge of AR treatment was insignificantly better among pharmacy vs. medical students (p=0.252, p=0.583 respectively).
Conclusion: This study indicates an inadequate level of knowledge of AR among participants. Even though GPs and pharmacistsā knowledge on therapy of AR was better than among students, it was still unsatisfying. It would be advisable to introduce the changes to curriculum regarding AR, with more emphasis on treatment approach and to organize additional education for GPs and pharmacists
Allergic rhinitis: a cross-sectional survey assessing the knowledge and therapeutic approach among final year medical students, pharmacy students, general practitioners and community pharmacists in Croatia
Objectives. To assess the current knowledge of allergic rhinitis (AR) among final year medical and pharmacy students, general practitioners (GPs) and community pharmacists in Croatia.
Methods: Data were collected from September 2017 to November 2017 through an online questionnaire. Final year medical and pharmacy students (N=201), GPs and pharmacists from Croatia (N=127) were included. The two factor structured questionnaire was formed regarding general knowledge and treatment of AR. T-test and chi-square tests were used for statistical analysis.
Results: Overall knowledge of AR was low among respondents (mean score among GPs: 11.4/20, pharmacists: 11.3/20, pharmacy students: 10.8/20, medical students: 10.3/20). With reference to treatment mean scores were also low; GPs 5.1/10, pharmacists: 4.9/10, pharmacy students: 4.3/10 and medical students: 4.1/10. GPs were significantly better than medical students in reference to treatment approach (p<.001) and overall knowledge (p=0.004). Pharmacists\u27 knowledge of treatment was better than pharmacy students\u27 (p=0.029), and the overall knowledge was insignificantly higher (p=0.210). The overall knowledge was insignificantly different among GPs and pharmacists (p=0.911), as was knowledge of treatment approach (p=0.335). The overall knowledge and knowledge of AR treatment was insignificantly better among pharmacy vs. medical students (p=0.252, p=0.583 respectively).
Conclusion: This study indicates an inadequate level of knowledge of AR among participants. Even though GPs and pharmacistsā knowledge on therapy of AR was better than among students, it was still unsatisfying. It would be advisable to introduce the changes to curriculum regarding AR, with more emphasis on treatment approach and to organize additional education for GPs and pharmacists
FarmakoloÅ”ko lijeÄenje koronavirusne bolesti 19 (COVID-19): gdje smo sada?
Since the first cases of COVID-19 were reported from China the disease became pandemic within a few months. The viral genome was sequenced soon after the outbreak of COVID-19 which enabled development of diagnostic tests and therapeutic options. As the knowledge of SARS-CoV-2 virology increased, many potential drugs appeared. At this moment (January 12th 2021), 4426 studies of COVID-19 are registered, and more than 2680 studies are investigating therapeutic options. This is a short narrative review of currently available evidence on pharmacological treatment of COVID-19.U roku nekoliko mjeseci od pojave prvih sluÄajeva COVID-19 u Kini, bolest je poprimila pandemijske razmjere. Virusni genom je sekvencioniran ubrzo nakon pojave COVID-19 Å”to je omoguÄilo razvoj dijagnostiÄkih testova i terapije. Kako su pristizala saznanja o samom virusu SARS-CoV-2, pojavljivali su se razni potencijalni lijekovi. U ovom trenutku (12. sijeÄnja 2021.) registrirano je 4426 studija o COVID-19, a viÅ”e od 2680 studija se bavi istraživanjem terapijskih opcija. U ovom preglednom radu prikazana su sadaÅ”nja saznanja o farmakoloÅ”kom lijeÄenju COVID-19
Successful treatment of genotype 3 hepatitis C infection in a noncirrhotic HIV infected patient on chronic dialysis with the combination of sofosbuvir and velpatasvir
RATIONALE:
Data on anti-HCV therapy in patients on dialysis is still evolving. Sofosbuvir is mainly eliminated through the renal route and there is controversy about its use in these patients. -----
PATIENT CONCERNS:
We describe a 53-year-old male patient with HCV genotype 3 and human immunodeficiency type 1 (HIV) infection on chronic dialysis. HIV infection was diagnosed in 1987 and since July 2007 the patient was compliant with his antiretroviral therapy (ART) and had an undetectable plasma HIV viral load on all follow-up measurements. The patient was known to have HCV infection since 1997 but has never been treated for chronic hepatitis C. Because of progressive renal impairment dialysis started in 2005. -----
DIAGNOSIS:
Before anti-HCV treatment commenced the patient liver transient elastography (FibroScan) indicated F3 fibrosis (stiffness, 11.6 kPa) and his HCV RNA viral load was 320,798āIU/mL (Abbott RealTime HCV assay). -----
INTERVENTION:
Fixed dose combination of sofosbuvir/velpatasvir (400āmg/100āmg) for 11 weeks. -----
OUTCOMES:
Twelve weeks after treatment cessation HCV RNA was undetectable, hence the patient achieved a sustained virologic response. The drugs were well tolerated and the patient did not report any side effects. -----
LESSONS:
Sofosbuvir/velpatasvir may be an option for HCV genotype 3 infection in patients coinfected with HIV on long-term dialysis
Epidemiological and clinical features of patients hospitalized due to Clostridium difficile - associated diarrhea
UVOD: Dijareja uzrokovana bakterijom Clostridium difficile je jedna od ÄeÅ”Äih neželjenih posljedica primjene antibiotske terapije, no malo se zna o odnosu epidemioloÅ”kih okolnosti razbolijevanja i kliniÄke težine bolesti te ishoda lijeÄenja. ----- CILJ: Opisati epidemioloÅ”ka i kliniÄka obilježja bolesti te utvrditi odnos epidemioloÅ”kih okolnosti razbolijevanja i kliniÄke težine bolesti i ishoda lijeÄenja u bolesnika s Clostridium difficile infekcijom (CDI). ----- BOLESNICI I METODE: Radi se o retrospektivnom deskriptivnom istraživanju provedenom na bolesnicima oba spola i svih dobi hospitalno lijeÄenim zbog dijareje uzrokovane laboratorijski potvrÄenom CDI u razdoblju od 2013. ā 2016. godine u Klinici za infektivne bolesti āDr. Fran MihaljeviÄā, Zagreb. U statistiÄkoj obradi podataka koriÅ”tena je metoda linearne regresije, hi-kvadrat test, studentov t-test i njegove neparametarske inaÄice u sluÄaju odstupanja podataka od normalne distribucije. ----- REZULTATI: Od 776 bolesnika s CDI njih je 76% imalo CDI povezanu sa zdravstvenom skrbi, 16% je imalo izvanbolniÄki steÄenu infekciju, a u 8% bolesnika se epidemioloÅ”ke okolnosti razbolijevanja nisu mogle utvrditi. Udio bolesnika s CDI povezanom sa zdravstvenom skrbi je u promatranom razdoblju znaÄajno rastao u odnosu na bolesnike s izvanbolniÄki steÄenom CDI (p=0.0395). Bolesnici s CDI povezanom sa zdravstvenom skrbi su imali statistiÄki znaÄajno veÄe vrijednosti maksimalne tjelesne temperature (prosjek 37,99 vs. 37,21), veÄi broj stolica u 24 sata (prosjek 9,14 vs. 5,83), ÄeÅ”Äu pojavu renalne insuficijencije (19,2 vs. 5,7%) i ÄeÅ”Äe prisutne ostale komplikacije (8,2 vs. 2,5%). Ti su bolesnici imali statistiÄki znaÄajno veÄe vrijednosti leukocita u perifernoj krvi (prosjek 15,51 vs. 13,64), niže vrijednosti albumina (prosjek 28,29 vs. 32,82) te su u njih vrijednosti kreatinina ÄeÅ”Äe bile veÄe od 1,5x u odnosu na bazalne vrijednosti (33,2 vs. 15,1%). U njih je bio znaÄajno veÄi McCabe skor (1.57 vs. 1.13) i ATLAS skor (4.05 vs. 1.85). TakoÄer, navedeni bolesnici su bili statistiÄki znaÄajno duže hospitalizirani (prosjek 14,83 vs. 10,13 dana) te je kod njih smrtni ishod bio znaÄajno ÄeÅ”Äi (11,7 vs. 3,3%) u odnosu na bolesnike s izvanbolniÄki steÄenom CDI. ----- ZAKLJUÄAK: U promatranom razdoblju je meÄu hospitalno lijeÄenim bolesnicima zabilježen znaÄajan trend rasta udjela pacijenata koji su imali C. difficile infekciju povezanu sa zdravstvenom skrbi u periodu od 2013. ā 2016. Bolesnici s CDI povezanom sa zdravstvenom skrbi su imali kliniÄki težu bolest i loÅ”iji ishod od bolesnika s izvanbolniÄkom CDI.BACKGROUND: Clostridium difficile-associated diarrhea is one of the most common unintended consequences of the administration of antibiotics and the correlation between epidemiological circumstances of acquisition and severity of illness and its outcome is not well known. ----- OBJECTIVE: To determine epidemiological and clinical features of C. difficile infection (CDI) and to assess the relationship between the epidemiological circumstances of acquisition and severity of illness and its outcome. ----- PATIENTS AND METHODS: This is a retrospective descriptive study that includes patients of both genders and all age groups hospitalized and treated for CDI with laboratory detected infection from 2013 to 2016 at University Hospital for Infectious Diseases āDr. Fran MihaljeviÄā, Zagreb. Linear regression analysis, Chi-square test, Student t-test are used to compare mean values and non-parametric tests are used if distribution is not normal. ----- RESULTS: Of 776 patients 76% had healthcare-associated C. difficile infection, 16% had community-associated C. difficile infection and 8% had undetermined association. Proportion of the patients with healthcare-associated C. difficile infection significantly increased compared to proportion of patients with community-associated infection over the study period (p=0.0395). Patients with healthcare-associated C. difficile infection had significantly higher maximum body temperature (mean 37,99 vs. 37,21), more stools in 24 hours (mean 9,14 vs. 5,83), had more often renal impairment (19,2% vs. 5,7%) and had more often other complications (8,2 vs. 2,5%). Patients with healthcare-associated C. difficile infection had significantly more elevated leukocyte count (mean 15,51 vs. 13,64), lower serum albumin (mean 28,29 vs. 32,82) and had more often Ė50% increase in baseline serum creatinine level (33,2 vs. 15,1%). Patients with healthcare-associated CDI had significantly higher McCabe score (1.57 vs. 1.13) and ATLAS score (4.05 vs. 1.85). Also, they had longer length of stay in hospital (mean 14,83 vs. 10,13 days) and higher mortality rates (11,7 vs. 3,3%) when compared to patients with community-associated C. difficile infection. ----- CONCLUSIONS: There is a significant increase in proportion of healthcare-associated C. difficile cases from 2013 ā 2016. Patients with healthcare-associated CDI had more severe illness and worse outcome than patients with community-associated CDI
Clostridioides difficile infection treatment guidelines adherence and comparison of treatment outcomes of the first, non-severe disease episode between oral metronidazole and vancomycin group: a single tertiary center retrospective study
Hepatitis A Outbreak in Men Who Have Sex with Men Using Pre-Exposure Prophylaxis and People Living with HIV in Croatia, January to October 2022
The hepatitis A virus (HAV) is a highly hepatotropic virus transmitted mainly via the fecalāoral route. The purpose of this study is to describe a prolonged HAV outbreak in HIV-infected men who have sex with men (MSM) and pre-exposure prophylaxis (PrEP) users in Croatia in 2022. Croatia has a centralized system of HIV care and the PrEP service is only available at the University Hospital for Infectious Diseases (UHID), Zagreb. We reviewed all MSM living with HIV and MSM PrEP users at UHID and identified those diagnosed with HAV between January and October 2022. During this period, a total of 1036 MSM living with HIV and 361 PrEP users were followed, and 45 (4.4%) and 32 (8.9%) were diagnosed with HAV, respectively. Most cases were diagnosed in mid-February. A total of 70.1% (726/1036) MSM living with HIV and 82.3% (297/361) PrEP users were susceptible to HAV. Sequencing information was available for 34 persons; in all cases the HAV subtype IA was found. Our findings indicate that both MSM living with HIV and HIV-uninfected PrEP users are vulnerable to HAV infection and might be a potential source for a more widespread HAV epidemic