Volume 9 (2016): Issue 2 (December 2016)

Health technology assessment (HTA) isaprocess, which should answer the question“Isagiven health technology/medication worth its price for the value it provides?” In the spirit of the amendments to the Bulgarian Health Insurance Act and institutionalization of HTA, our team prepared this situational evaluation aiming to throw light on the practices and approaches to HTAin European countries. As awhole,we can identify two types of agencies that perform it: those servicing the population of an entire nation oraregion, and those working at the level of hospitals oranetwork of hospitals. All the agencies studied have two common characteristics. First, they were created withanon-profit purpose and second, all of them are financed by public funds inavariety of ways. It also becomes clear from the comparative analysis performed that the ways HTAis conducted in Europe differ from country to country. Irrespective of the variations, the common aspiration is that the value forapatient, to which the approved health technologies contribute, should be greater than the price to be paid for them. Bulgaria is may be the last EUstate to implement HTAin its domestic legislation and this also gives the advantage of having and using the experience of the other countries. Establishing an independent structure, which is appointed to prepare local health technologies assessment would result in transparent decision-making, participation of all concerned parties and optimization of the budget for medicines regarding the effectiveness/benefit ratio, as well as expenses.

The study aimed to assess the inhalation technique of patients with bronchial asthma/chronic obstructive pulmonary disease (COPD) via an objective method and to evaluate the effect of training in patients with incorrect technique. Тhe inhalation technique of 120 patients with obstructive pulmonary disease was tested. The patients were divided into two groups: using metered dose inhalers (MDI) - 34 patients (28%) and dry powered inhalers (DPI) - 86 patients (72%). The most frequent mistakes in the MDIgroup were short duration of the inhalation (55.88%) and bad synchronization between activating the canister and the inhalation (29.41%). For the DPIgroup, the inhalation was not forceful enough (48.84%) and the short duration of the inhalation (12.79%). Patients claiming to have good inhalation technique accounted for 97%of those in the MDIgroup, and 96.5%of those in the DPIgroup. There were two patients (5.88%) with correct inhalation technique in the MDIgroup at their first attempt, and 31 patients (36.05%) in the DPIgroup. We found that in the MDIgroup there wasasignificant reduction in the number of mistakes (p<0.001). In the DPIgroup, such correlation was not found but during visit 2 there were no patients with more than 1 mistake. Correcting poor inhalation technique led to reduction of the number of mistakes during inhalation.

Matrix metalloproteinases (MMPs) areagroup of proteases containing Zn ions asacofactor, which are involved in degrading ofalarge number of extracellular matrix proteins, and bioactive molecules. They also playamajor role in processes such as cell proliferation, cell migration, differentiation and apoptosis. Very little is known about the expression and function of MMPs in the male reproductive tract. Occurrence of MMP-2 and MMP-9 activity in human seminal plasma has been previously reported but their origin and function are still not fully understood. The aim of this study was to examine the presence of MMP-2 and MMP-9 in normal and abnormal human sperm samples and find if any correlation existed between the levels of expression of MMPs and fertilization potential of the spermatozoa. Human spermsamples were examined for the presence of MMP-2 and MMP-9 by gel zymography and western blot analysis. A DNAfragmentation test was performed. The samples were divided into two groups - samples with normozoospermia and teratozoospermia. The gelatin zymography showed gelatinolytic bands with molecular weight 64 and 72 k Da corresponding to active and inactive form of MMP-2. MMP-9 was not detected. The MMP-2 enzymatic activity appeared to be much higher in samples with compromised sperm morphology as compared to the normozoospermic samples. The mean DNAfragmentation index (DFI) of the group with teratozoospermia was relatively higher (22.16%) and over the upper reference limits, compared to the normozoospermic group, in which it was within the normal range (17.26%).

Immune thrombocytopenia (ІTP) is one of the most common causes of clinically overt hemorrhage. Despite the progress made in recent years in clarifying the pathogenesis of the disease, the exact unlockmechanisms still remain unclear. The aim of the study was to correlate the oxidative stress markers and the severity of immune thrombocytopenia in adults and to investigate their predictive value of transforming the acute formof ITPinto chronicІTP.We studiedatotal of 58 subjects (14 patients with newly diagnosedІTP, 13 patients with chronic form ofІTR, and 31 controls). The plasma levels of human pantetheinase ( vanin-1) and lipid hydroperoxides were measured using commercial assay kits.We found that the form of the disease was not significantly related to the plasma vanin-1 levels (p=0.120). Asignificant difference in the vanin-1concentrations was observed between newly diagnosed IPTand the controls (p=0.046). Further studies with larger and more homogenous groups of patients and including more indicators of oxidative stress are needed to be able to draw statistically valid conclusions about the role of oxidative biomarkers in diagnosing and treatment ofІTP.

Breast cancer is the most common cancer in women worldwide. The standard for detecting it includes clinical exam, mammography and fine-needle aspiration cytology. Our aim was to establish the role of the tru-cut biopsy in the diagnosis of malignant breast lesions. We provideatwo-year retrospective clinical study defining 98.67%sensitivity, 100%specificity, 100%positive predictive value, 80%negative predictive value and an overall diagnostic accuracy of 98.73%. In 89.1%of the malignant lesions, the sample was adequate to define the receptor status. Therefore, tru-cut biopsy is an easy, cheap, safe and accurate alternative to fine-needle aspiration cytology in the diagnosis of breast lesions.

In the past two decades, the demographic crisis in Bulgaria has been widely debated. According to the National Statistical Institute (NSI), the proportion of people aged 65 and over is increasing, despite the general population decline in the country. To investigate whether the age structure of patients operated on has changed during the past 10 years and assess the need to reorganize the training of anesthetists,aretrospective study in the anesthesia electronic database of the University Hospital in Rouse was carried out. The data of anesthesia performed by anesthesiologists in 2005, 2010 and 2015 in patients aged 65 and over were summarized. The distribution of these patients by ASA Physical Classification System and frequency of complications during anesthesia were analyzed. The average annual number of anaesthesias for the three years was almost unchanged and amounted to about 5500. The proportion of patients aged 65 and over increased from 30.54%in 2005 to 35.72%in 2010, and 37.81%in 2015. The distribution of patients in according to the ASA Classification changed significantly: the percentage of patients ASAI-IIdropped from 36.19%in 2005 to 11.85%in 2015. The patients in the ASA III-IVgroups for the three analyzed years was 41.86%, 58.66%and 65.30%, respectively, and this was mainly due to the increase in the ASAIVpatients. It is necessary to build multidisciplinary teams and prepare specialized protocols for behavior in geriatric patients. It is imperative that anesthesiologists possess specialized knowledge about age-related organ changes and their effects on anesthesia.

Human papillomaviruses (HPVs) are associated with the most common sexually transmitted infections. It is well documented that high-risk (HR)-HPVtypes are etiologically associated with some cancers. The aim of the study was to investigate HPV16-DNApositivity and prevalence of Ig Gantibody against HPV16 in patients with laryngeal carcinoma and precancerous lesions of cervix uteri in Pleven region, Bulgaria. Material/Methods: We performedacross-sectional study and investigated clinical materials. Attached is real-time PCR-analysis for detection of HPV16-DNA. HPVspecific antibody response by enzyme-linked immunosorbent assay (ELISA) test for detection and quantification of specific Ig Gantibodies in serum were used. Results: For the six-month period, 30 samples were collected and tested. Fourteen of them were found in patients with carcinoma of the larynx and sixteen - in patients with various lesions of cervix uteri.We found that six patients (42.8%) in the first group and eight patients (50%) in the second group were HPV16-DNA-positive. Different age groups were affected. The sera analyzed in this study showed that seven patients (50%) with carcinoma of the larynx were seropositive of whom four (57%) were males. Fourteen of the females with dysplasia (88%) were seropositive. Matching DNApositivity and antibody response were found in 29%of the patients with laryngeal cancer. The match was found in 50%of the females with cervical dysplasia. Conclusions: Real-time PCRisarapid, cost-effective method for detection of HPVs.Ahigh level of seropositivity was found in the two groups of patients.

Asthma and allergic rhinitis are common in childhood. Establishing sensitization to aeroallergens is crucial to effectively prevent exacerbation of these respiratory allergic diseases. The study aimed to evaluate sensitization to the most common aeroallergens in children with asthma and allergic rhinitis.We establishedacorrelation between patients sensitized to indoor, outdoor and simultaneously to both allergens. The study population consisted of 276 patients (168 boys and 108 girls) ages 4 to 16 years with asthma (A) and allergic rhinitis (AR). Skin prick tests were performed with 21 commercial allergen extracts: pollens, mites, epithelia and insects, and molds. We found that 217 patients were sensitized to at least one aeroallergen: 117 patients hadapositive result to mites, 92 to pollens, 72 to epithelia and insects, and 63 - to mold allergens. Dermatophagoides pteronyssinus was the most prevalent aeroallergen. Sensitized only to indoor allergens were 104 patients, 60 - only to outdoor allergens, and 53 were sensitized to both. Mites were the most frequent aeroallergens in children with Aand AR. Lately there has been foundasignificant increase in rates of sensitization to mold allergens, especially to Alternaria alternata. Our study has confirmed the dominant role of indoor allergens in children with respiratory allergic diseases.

Prostate cancer (PC) is the most common type of cancer in men inanumber of countries. The choice of surgical technique for radical prostatectomy (RP) concerns both patients and urologists. The choice is not easy to make, since data is still limited due to the lack of large multicentric randomized research trials. For three years (2011-2014), 244 patients with limited prostate cancer were operated in the Urology Clinic of the University Hospital in Pleven. Robot-assisted radical prostatectomy (RARP) was performed on 35 patients (14%), open retropubic radical prostatectomy (ORP) - on 199 patients (81%), and laparoscopic RP - on 12 patients (5%). The preoperative and post-op results from the first two groups were compared. For the follow-up period of 12 months, functional results in 82 patients of the ORPgroup were compared to the results in the 35 patients of the RARPgroup. The operative time was significantly longer in the RARPgroup, and blood loss was lower. The catheter stay was shorter in patients with RARP. The percentage of significant postoperative complications was 0%in the patients with RARPand 3%in the patients with an ORP. RARPpatients demonstrated better continence: 91%vs. 87%and erectile function46%vs.40%at 12 months.

Cancer of the cervix causes internal, external compression or both of the upper urinary tract in 50-60%of patients in advanced stages. Retrograde stenting is the most widely used technique for desobstruction of the upper urinary tract in urology practice. Diversion of urine flow is an alternative, achieved by nephrostomy of one or both kidneys.We studied retrospectively 33 women with upper urinary tract obstruction caused by carcinoma of the uterine cervix operated on between March 2014 and March 2015 in the urology clinic at the University Hospital in Pleven, Bulgaria. Apercutaneous nephrostomy (PNS) was placed in 17 patients, and 11 patients hadaretrograde catheterization with ureteral stent type JJ. Five patients were treated with both methods. Placement ofa JJstent was the first choice procedure for all patients since it providesabetter quality of life. PNSimproves renal function faster than retrograde JJstenting. Therefore, the first method of choice for patients with an untreated primary cervical, uterine cancer is the placement of PNS. Retrograde JJstenting is the method of choice in patients who undergo surgery and radiation therapy withoutarelapse of the disease.

Acne vulgaris is among the commonest inflammatory skin diseases affecting pilosebaceous units. It occurs mainly in puberty and affects adolescents at the age of 14-19 years both females and males, in relation to sebum production of hair follicles under the action of sex hormones. Clinically the disease is presented with comedones, papules, pustules, nodules and scars in some cases. Seborrheic areas face, chest and back are affected. Recent epidemiologic studies have shown significant number of female patients aged over 25 years with acne and the term Adult onset acne (AOA)was established.The latter is manifested clinically in the lower third of the face. Primary etiological cause of AOAisahormonal imbalance, mainly hyperandrogenemia. Acase ofa25-year-old woman with adult acne and elevated levels of testosterone and prolactine is presented in this paper.

Acute appendicitis due to Enterobius vermicularis, usually known as pinworm, is very rare and affects mostly children.According to different authors, it is controversial whether pinworms cause inflammation of the appendix or appendiceal colic only.We presentacase ofa14-year-old female with three subsequent hospitalizations in 1 month due to abdominal pain in the right lower abdomen, with rebound tenderness, normal CTscan and laboratory findings. During the last hospitalization, laparoscopic appendectomy was performed. Intraoperatively multiple pinworms were found in the appendix. These were trapped byastercolith in the appendicular base inanoninflamed and histologically normal appendix. Two oral doses of mebendazole were administered postoperatively. Uneventful postoperative period and postoperative follow-up showed lack of symptoms six months after the operation. Despite the widespread idea that acute appendicitis due to Enterobius vermicularis is very rare, it should always be considered in young female patients with repeated abdominal pain in the right lower abdomen with normal laboratory and radiologic findings.

Psoriasis isachronic autoimmune multisystem disease, mainly affecting the skin and joints. Its origin is related to both environmental and genetic factors. The condition affects 1-3%of the population worldwide. Psoriasis is also associated with cardiovascular risk factors, atherothrombotic events, and markers of hypercoagulation (platelet activation and hyperhomocysteinemia). Venous thromboembolism (VTE) isawidespread severe disease. Both VTEand psoriasis are connected with risk factors for cardiovascular disorders (obesity and hypertension). The incidence of VTEevents in patients with psoriasis is higher. Patients with psoriasis should be checked for risk factors (metabolic disorders and cardiovascular diseases).We reportacase of a 53-year old man, diagnosed with plaque psoriasis 20 years ago, andafive year history of hypertension. In 2006, he hadastroke, and in 2011 ‒aheart attack. In 2013 he was diagnosed with thrombophlebitis. The patient was recently diagnosed with Type IIdiabetes, dyslipidemia and metabolic syndrome. The DNAanalysis revealed that the patient wasahomozygous carrier of 4G/4G (rs1799889) polymorphism in plasminogen activator inhibitor 1 (PAI-1) -a risk factor for thrombophilia. This case is important because of the major comorbidities, more particularly thrombotic events in combination withaprothrombotic mutation.