PCSK9 inhibition: from effectiveness to cost-effectiveness.

Dyslipidaemia is a complex disorder characterised by abnormal lipid levels in the blood, including cholesterol and triglycerides, and plays an important role in the development of atherosclerotic cardiovascular disease. Most risk factors for cardiovascular disease are modifiable, and dyslipidaemia is a key factor among them. It can result from a combination of genetic and environmental factors. A distinction is made between primary dyslipidaemia, which is mainly caused by inherited genetic changes, and secondary dyslipidaemia, which is due to underlying diseases or certain medications. The treatment of dyslipidaemia has evolved over the years. In the past, statins were the first choice, but newer drugs, such as proprotein convertase subtilisin-kexin type 9 (PCSK9) inhibitors, have gained prominence due to their effectiveness in lowering lipids. Although recent guidelines recommend PCSK9 inhibitors for high-risk patients and patients who cannot tolerate statins, their widespread use is limited because of cost. Several meta-analyses have confirmed the efficacy and safety of PCSK9 inhibitors and have shown a significant reduction in low-density lipoprotein (LDL) cholesterol levels. However, the long-term side effects and interactions with other risk factors for cardiovascular disease remain uncertain. In addition, cost-effectiveness analyses have shown mixed results, with some countries considering PCSK9 inhibitors to be cost-effective for certain patient groups, while others consider them less economical. Meanwhile, initial data from patients using PCSK9 inhibitors support the results of the clinical trials. To summarise, PCSK9 inhibitors represent a revolutionary solution for lowering LDL cholesterol, but their cost-effectiveness remains controversial. Despite the controversy, they offer clear benefits for high-risk patients and should therefore be considered in the treatment of dyslipidaemia.

Using a combination of three clinical tests for detecting meniscal tears increases the accuracy of the clinical examination.

BACKGROUND: Recent studies indicate that using combination of two or more clinical tests for detecting meniscal tear gets a higher sensitivity and specificity than any clinical test performed individually. METHODS: The study involved 84 participants who were divided into two groups: the "OP group" consisting of participants diagnosed with a meniscal tear and who consequently underwent arthroscopic meniscectomy, and the "CN group" comprising of healthy participants with no history of knee injury. Two independent observers (orthopedic surgeons) recorded the results of six clinical tests: Thessaly Test, joint line tenderness, McMurray Test, Ege Test, Steinmann I Test, and atrophy of the thigh muscles. The tests were grouped into two combinations of three tests each. The first combination included Thessaly Test, joint line tenderness and McMurray Test, while the second combination comprised of remaining three tests. Cochran's Q Test was used to calculate interobserver variability for both combinations of clinical tests and for each test performed individually. RESULTS: First combination of three clinical tests when considering the combination positive if two tests are positive had high sensitivity of 95%, specificity of 90.9%, and an overall accuracy of 92.9%. Furthermore, when compared to clinical tests performed individually, the combination demonstrated superior results. CONCLUSIONS: This study shows that using a combination of three clinical tests for detection of meniscal tear (Thessaly Test, joint line tenderness, McMurray Test), when considering the combination positive if two tests are positive, has greater accuracy than six clinical tests performed individually. There were no statistically significant differences between observers.

Maternal diaphragmatic hernia in pregnancy: A systematic review with a treatment algorithm.

BACKGROUND: Diaphragmatic hernia (DH) is extremely rarely described during pregnancy. Due to the rarity, there is no diagnostic or treatment algorithm for DH in pregnancy. AIM: To summarize and define the most appropriate diagnostic methods and therapeutic options for DH in pregnancy based on scarce literature. METHODS: Literature search of English-, German-, Spanish-, and Italian-language articles were performed using PubMed (1946-2021), PubMed Central (1900-2021), and Google Scholar. The PRISMA protocol was followed. The search terms included: Maternal diaphragmatic hernia, congenital hernia, pregnancy, cardiovascular collapse, mediastinal shift, abdominal pain in pregnancy, hyperemesis, diaphragmatic rupture during labor, puerperium, hernie diaphragmatique maternelle, hernia diafragmática congenital. Additional studies were identified by reviewing reference lists of retrieved studies. Demographic, imaging, surgical, and obstetric data were obtained. RESULTS: One hundred and fifty-eight cases were collected. The average maternal age increased across observed periods. The proportion of congenital hernias increased, while the other types appeared stationary. Most DHs were left-sided (83.8%). The median number of herniated organs declined across observed periods. A working diagnosis was correct in 50%. DH type did not correlate to maternal or neonatal outcomes. Laparoscopic access increased while thoracotomy varied across periods. Presentation of less than 3 days carried a significant risk of strangulation in pregnancy. CONCLUSION: The clinical presentation of DH is easily confused with common chest conditions, delaying the diagnosis, and increasing maternal and fetal mortality. Symptomatic DH should be included in the differential diagnosis of pregnant women with abdominal pain associated with dyspnea and chest pain, especially when followed by collapse. Early diagnosis and immediate intervention lead to excellent maternal and fetal outcomes. A proposed algorithm helps manage pregnant women with maternal DH. Strangulated DH requires an emergent operation, while delivery should be based on obstetric indications.

New Assessment Tool-Postpartum Functional Assessment Questionnaire.

Background and Objectives: Functional status of the mother after delivery is crucial for performing activities of daily living and caring for the newborn. It is important to assess functional abilities after childbirth in order to improve the quality of postpartum care. The aim of this study is to determine the psychometric properties of the questionnaire and assess the functional abilities after childbirth. Materials and Methods: This study is observational. Postpartum Functional Assessment Questionnaire includes eleven items. 301 women after childbirth, 234 after vaginal birth and 67 after caesarean section participated in the study. An assessment of pain intensity and functional abilities was performed on the first and third day after childbirth. The Factor and Cronbach's alpha analyses were performed to determine the factor structure and internal consistency. Results: The analysis reveals two factors, with seven items loading on factor 1 and four on factor 2. Cronbach's alpha for construct I (Mobility) at the first day was 0.927 and at the third day was 0.913; and for Factor II (Self-care) at the first day was 0.846 and at the third day was 0.894. All between-group differences in pain intensity and functional abilities were highly statistically significant (p < 0.001). Differences between the first and third postpartum day were statistically significant for all variables and all subgroups (p < 0.001). Conclusions: Postpartum Functional Assessment Questionnaire has good psychometric properties and is a valuable tool for use in clinical practice.

Ankle Arthroscopy Without Tourniquet: A Mid-Term Follow-Up.

Ankle arthroscopy is a surgical technique still most commonly performed with a tourniquet. In 2017, we published a randomized controlled trial comparing anterior ankle arthroscopy with and without the tourniquet use. The results showed feasibility of performing the anterior ankle arthroscopy without the tourniquet, as well as comparable functional outcomes at 3- and 6-month follow-up visits, regardless of the tourniquet use. The aim of the current study was to evaluate mid-term functional outcomes after a 5-year period and to document patient satisfaction with the surgery. All 49 available patients from the original study were asked to attend examination at the 60-month follow-up visit. Patients were assessed with the same functional scores, as well as with additional Munich Ankle Questionnaire (MAQ) to assess the postoperative subjective and objective outcome and Abdelatif questionnaire to evaluate patient satisfaction. Any new complications were noted. At the 60-month follow-up visit, 39 (79.6%) patients were available for examination. No significant difference was found between the groups regarding the functional outcomes or the MAQ. In comparison with the 3- and 6-month follow-up visits, no further improvement or decline of functional outcomes was present. High patient satisfaction was found in both groups. No new complications were noted during the follow-up period. Similar improvement in both groups reveals that the anterior ankle arthroscopy can be performed without the tourniquet with no negative impact on mid-term functional outcomes. In addition, high patient satisfaction can be expected even after 5 years from surgery, regardless of the tourniquet use.

TRENDS IN PROSTATE CANCER DIAGNOSIS DURING THE COVID-19 PANDEMIC: SINGLE-INSTITUTION EXPERIENCE.

The aim of this study was to compare the number of biopsy and surgical procedures on prostate, as well as the number of newly diagnosed, histologically confirmed cases of prostate cancer during the COVID-19 pandemic at Zagreb University Hospital Center (UHC). We retrospectively collected and processed a total of 1344 histopathologic findings of the prostate at the Zagreb UHC. Our results show that during the COVID-19 pandemic, there was a statistically significant decrease in the absolute number of biopsy and surgical procedures on prostate at Zagreb UHC, and so was the number of newly diagnosed, histologically confirmed cases of prostate cancer. During the observed time of the pandemic (March 19, 2020 to December 31, 2020), there was a 37.5% decrease in the absolute number of newly diagnosed prostate cancer cases compared to the same period of the previous year (March 19, 2019 to December 31, 2019). To our knowledge, this is the first study of this kind that is based on the number of prostate cancer diagnoses in Croatia. By observing the early period of the pandemic, our results provide important guidelines for monitoring and understanding the long-term consequences of the pandemic on the prostate cancer morbidity and mortality.

UROTHELIAL CARCINOMA BEFORE AND DURING THE COVID-19 PANDEMIC IN CROATIA - A SINGLE-CENTER STUDY.

The aim of this study was to compare the number of newly diagnosed, histopathologically confirmed cases of urothelial carcinoma before and during the COVID-19 pandemic at the Zagreb University Hospital Center. We retroactively collected and analyzed 300 histopathologically confirmed urothelial carcinoma between January 1, 2019, and December 31, 2020, at the Department of Pathology and Cytology, Zagreb University Hospital Center. Our results showed that during the COVID-19 pandemic, there was a statistically significant decrease (p=0.001; χ2-test) in the number of newly diagnosed, histopathologically confirmed cases of urothelial carcinoma at the Zagreb University Hospital Center. There was a decrease in the absolute number of newly diagnosed urothelial carcinoma by 25.8% in the observed time of the pandemic (March 19, 2020 to December 31, 2020) as compared to the same period of the previous year (March 19, 2019 to December 31, 2019). Our study is the first study of this type based on the number of newly diagnosed urothelial carcinoma in Croatia. Observing the early period of the pandemic, our results provide important foundation for future monitoring and long-term consequences of the pandemic on the morbidity and mortality of urothelial carcinoma.

The effect of multistrain probiotics on functional constipation in the elderly: a randomized controlled trial.

BACKGROUND AND OBJECTIVES: Constipation is one of the most common gastrointestinal conditions, particularly among older individuals. This study aimed to evaluate the efficacy and safety of selected multistrain probiotics on functional constipation and laboratory blood parameters in the elderly living in a nursing home. SUBJECTS AND METHODS: Sixty participants (42 females and 18 males) aged 77.9 ± 8.84 years with functional constipation, who met the eligibility criteria, completed the study. In a double-blind, placebo-controlled, parallel design, each participant was randomized to receive either the selected probiotic mixture (N = 28) or placebo (N = 32) for 12 weeks as an adjunct to their usual diet and medications. The liquid probiotic formulation containing Bifidobacterium animalis subsp. lactis BLC1, Lactobacillus acidophilus LA3 and Lactobacillus casei BGP93 was tested for the first time. RESULTS: Supplementation of selected probiotics resulted in a slight but nonsignificant increase in cumulative stool frequency compared with placebo. However, after the 71st day of the treatment, the cumulative number of stools was significantly higher in the probiotic group (P < 0.05) when the influence of laxative was excluded. The trend towards an increase in the difference between the two groups, which began 1 week after the probiotic intervention, pointed out to their prolonged effect. There were no significant dependent or independent effects of treatment and time on most of the 27 laboratory blood parameters tested. CONCLUSIONS: Multistrain probiotic supplementation was found to be efficacious, safe and well tolerated in the elderly with functional constipation.

The Role of Seawater and Saline Solutions in Treatment of Upper Respiratory Conditions.

The history of saline nasal irrigation (SNI) is indeed a long one, beginning from the ancient Ayurvedic practices and gaining a foothold in the west at the beginning of the 20th century. Today, there is a growing number of papers covering the effects of SNI, from in vitro studies to randomized clinical trials and literature overviews. Based on the recommendations of most of the European and American professional associations, seawater, alone or in combination with other preparations, has its place in the treatment of numerous conditions of the upper respiratory tract (URT), primarily chronic (rhino)sinusitis, allergic rhinitis, acute URT infections and postoperative recovery. Additionally, taking into account its multiple mechanisms of action and mounting evidence from recent studies, locally applied seawater preparations may have an important role in the prevention of viral and bacterial infections of the URT. In this review we discuss results published in the past years focusing on seawater preparations and their use in clinical and everyday conditions, since such products provide the benefits of additional ions vs. saline, have an excellent safety profile and are recommended by most professional associations in the field of otorhinolaryngology.

Choline elevation in amygdala region at recovery indicates longer survival without depressive episode: a magnetic resonance spectroscopy study.

RATIONALE: Depression, with variable longitudinal patterns, recurs in one third of patients. We lack useful predictors of its course/outcome, and proton magnetic resonance spectroscopy (1H-MRS) of brain metabolites is an underused research modality in finding outcome correlates. OBJECTIVES: To determine if brain metabolite levels/changes in the amygdala region observed early in the recovery phase indicate depression recurrence risk in patients receiving maintenance therapy. METHODS: Forty-eight patients on stable-dose antidepressant (AD) maintenance therapy were analyzed from recovery onset until (i) recurrence of depression or (ii) start of AD discontinuation. Two 1H-MRS scans (6 months apart) were performed with a focus on amygdala at the beginning of recovery. N-acetylaspartate (NAA), choline-containing metabolites (Cho), and Glx (glutamine/glutamate and GABA) were evaluated with regard to time without recurrence, and risks were assessed by Cox proportional hazard modeling. RESULTS: Twenty patients had depression recurrence, and 23 patients reached AD discontinuation. General linear model repeated measures analysis displayed three-way interaction of measurement time, metabolite level, and recurrence on maintenance therapy, in a multivariate test, Wilks' lambda = 0.857, F(2,40) = 3.348, p = 0.045. Cho levels at the beginning of recovery and subsequent changes convey the highest risk for earlier recurrence. Patients experiencing higher amygdala Cho after recovery are at a significantly lower risk for depression recurrence (hazard ratio = 0.32; 95% confidence interval 0.13-0.77). CONCLUSION: Cho levels/changes in the amygdala early in the recovery phase correlate with clinical outcome. In the absence of major NAA fluctuations, changes in Cho and Glx may suggest a shift towards reduction in (previously increased) glutamatergic neurotransmission. Investigation of a larger sample with greater sampling frequency is needed to confirm the possible predictive role of metabolite changes in the amygdala region early in the recovery phase.

Gram-negative bacteria as causative agents of ventilator-associated pneumonia and their respective resistance mechanisms.

Ventilator-associated pneumonia (VAP) is a serious and common complication in patients admitted to intensive care unit (ICU) and contributes to mortality. Multidrug Gram-negative bacteria such as Acinetobacter baumannii, Pseudomonas aeruginosa, and Klebsiella pneumoniae are frequently associated with VAP in ICU. A prospective study was set up in three ICUs of the University Hospital Center Zagreb and one ICU in General Hospital Pula from September 2017 to March 2018. Antibiotic susceptibility was determined by broth microdilution method. Production of extended-spectrum ß-lactamases (ESBLs) was determined by double-disk synergy test and carbapenemases by Hodge and carbapenem inactivation method (CIM). The genes encoding ESBLs, carbapenemases of class A, B and D and qnr genes were determined by PCR. In total 97 Gram-negative bacteria isolates were analyzed. P. aeruginosa demonstrated high resistance rates for imipenem and meropenem with 74% and 68% of resistant strains, respectively. Moderate resistance rates were observed for ceftazidime andpiperacillin/tazobactam, ciprofloxacin and gentamicin (44%). All except three A. baumannii isolates, were resistant to carbapenems and to all other antibiotics apart from colistin and amikacin. Eight A. baumannii isolates were positive for blaOXA-23 and 12 for blaOXA-24 genes. Four K. pneumoniae and two E. cloacae strains were ESBL positive and harboured group 1 of CTX-M ß-lactamases. Three P. mirabilis strains were positive for plasmid-mediated ampC ß-lactamase of CMY family. Two carbapenem-resistant K. pneumoniae harboured OXA-48 and one carbapenem-resistant E. cloacae VIM-1. A high proportion of multidrug-resistant P. aeruginosa, K. pneumoniae and extensively resistant A. baumannii was reported. Acquired resistance mechanisms, mainly production of carbapenemases and ESBLs were dominant in A. baumannii and K. pneumoniae, respectively. Resistance of P. aeruginosa isolates was more likely due to upregulation of efflux pumps or porin loss. A marked diversity of ß-lactamases was identified in Enterobacteriaceae.

Incidence and Geographical Variability of Pediatric Inflammatory Bowel Disease in Croatia: Data From the Croatian National Registry for Children With Inflammatory Bowel Disease.

The aim of this study was to determine the annual incidence and geographic distribution of pediatric inflammatory bowel disease (IBD) in Croatia. This is a prospective, cohort, multicenter observational study based on the data obtained from the Croatian national registry for children with IBD. Children and adolescents younger than 18 years diagnosed with IBD, in time period between June 1, 2016, and May 31, 2017, were recruited. In total, 51 new cases were identified; 19 Crohn's disease, 28 ulcerative colitis, and 8 IBD-unclassified. Male preponderance of all 3 types of the disease was noticed. The median age at diagnosis was 14.8 years. The calculated annual incidence of pediatric IBD per 100 000 persons per year was 7.05 (2.63 for Crohn's disease, 3.87 for ulcerative colitis, and 0.55 for IBD-unclassified). A north to south gradient was observed with almost 2 times higher incidence in the northern region of the country.

IBD phenotype at diagnosis, and early disease-course in pediatric patients in Croatia: data from the Croatian national registry.

BACKGROUND: Pediatric inflammatory bowel disease (IBD) presents with extensive phenotype. The aim of this study was to determine the phenotype of pediatric IBD patients in Croatia at diagnosis and follow-up. METHODS: Children were prospectively recruited into Croatian IBD national registry. Data on diagnostic evaluation, therapy and 1-year follow-up were collected. RESULTS: A total of 51 newly diagnosed patients were recruited (19 Crohn's disease (CD), 28 ulcerative colitis (UC) and 4 IBD-unclassified (IBD-U)). Most common location in CD was ileocolonic disease (52.6%), and pancolitis in UC (53.6%). The recommended complete diagnostic algorithm was performed only in 29.4% of patients. First-line therapy used in CD was exclusive enteral nutrition for remission induction (84.2%) and azathioprine for maintenance (73.7%). In patients with UC, aminosalicylates were the most common drug used (89.3%). By the end of the first year 41.2% of CD and 53.9% of UC patients had one or more relapses and required treatment escalation. CONCLUSION: Our data confirm extensive intestinal involvement in pediatric IBD and relatively high relapse rate during the first year of follow-up. More effort should be invested on the national level to implement more stringent adherence to the current European guidelines. IMPACT: The key message of our article is that pediatric IBD in Croatia shows extensive intestinal involvement with high relapse rates in first year of follow-up. It is the first cohort study reporting on the phenotype of pediatric IBD in Croatia, but also investigates adherence to diagnostic and therapeutic European guidelines which is not commonly reported. The study is national based, thus having the greatest impact on Croatian health care,stressing out that more effort should be invested on the national level to implement more stringent adherence to the current European guidelines.