Nevin Manimala

Therapie. 2022 Oct 20:S0040-5957(22)00177-9. doi: 10.1016/j.therap.2022.10.008. Online ahead of print.

ABSTRACT

Evidence-based medicine is the cornerstone of shared-decision making in healthcare today. The public deserves clear, transparent and trust-worthy information on drug efficacy. Yet today, many drugs are prescribed and used without solid evidence of efficacy. Clinical trials and randomized clinical trials (RCTs) are the best method to evaluate drug efficacy and side effects. In a shared medical decision-making approach, general practitioners need drug assessment to be based on patient-important outcomes. The aim of project rebuild the evidence base (REB) is to bridge the gap between the data needed in clinical practice and the data available from clinical research. The drugs will be assessed on clinical patient important outcomes and for a population. Using the Cochrane tools, we propose to analyse for each population and outcome: 1) a meta-analysis based on RCTs with a low risk of bias overall; 2) an evaluation of results of confirmatory RCTs; 3) a statistical analysis of heterogeneity between RCTs, and 4) an analysis of publication bias. Depending on the results of these analyses, the evidence will be categorized in 4 different levels: firm evidence, evidence (to be confirmed), signal or absence of evidence. Project REB proposes a method for reading and interpreting randomized clinical trials and their meta-analysis to produce quality data for general practitioners to focus on benefit-risk assessment in the interest of patients. If this data does not exist, it could enable clinical research to better its aim.

PMID:36371260 | DOI:10.1016/j.therap.2022.10.008

Orphanet J Rare Dis. 2022 Nov 12;17(1):412. doi: 10.1186/s13023-022-02562-9.

ABSTRACT

BACKGROUND: X-linked hypophosphatemia (XLH) is characterized by increased serum concentrations of fibroblast growth factor 23 (FGF23), hypophosphatemia and insufficient endogenous synthesis of calcitriol. Beside rickets, odonto- and osteomalacia, disproportionate short stature is seen in most affected individuals. Vitamin D analogs and phosphate supplements, i.e., conventional therapy, can improve growth especially when started early in life. Recombinant human growth hormone (rhGH) therapy in XLH children with short stature has positive effects, although few reports are available. Newly available treatment (burosumab) targeting increased FGF23 signaling leads to minimal improvement of growth in XLH children. So far, we lack data on the growth of XLH children treated with concomitant rhGH and burosumab therapies.

RESULTS: Thirty-six patients received burosumab for at least 1 year after switching from conventional therapy. Of these, 23 received burosumab alone, while the others continued rhGH therapy after switching to burosumab. Children treated with burosumab alone showed a minimal change in height SDS after 1 year (mean ± SD 0.0 ± 0.3 prepubertal vs. 0.1 ± 0.3 pubertal participants). In contrast, rhGH clearly improved height during the first year of treatment before initiating burosumab (mean ± SD of height gain 1.0 ± 0.4); patients continued to gain height during the year of combined burosumab and rhGH therapies (mean ± SD height gain 0.2 ± 0.1). As expected, phosphate serum levels normalized upon burosumab therapy. No change in serum calcium levels, urinary calcium excretion, or 25-OHD levels was seen, though 1,25-(OH)₂D increased dramatically under burosumab therapy.

CONCLUSION: To our knowledge, this is the first study on growth under concomitant rhGH and burosumab treatments. We did not observe any safety issue in this cohort of patients which is one of the largest in Europe. Our data suggest that continuing treatment with rhGH after switching from conventional therapy to burosumab, if the height prognosis is compromised, might be beneficial for the final height.

PMID:36371259 | DOI:10.1186/s13023-022-02562-9

J Transl Med. 2022 Nov 12;20(1):527. doi: 10.1186/s12967-022-03731-x.

ABSTRACT

BACKGROUND: The role of the inflammatory milieu in prostate cancer progression is not well understood. Differences in inflammatory signaling between localized and metastatic disease may point to opportunities for early intervention.

METHODS: We modeled PCa disease progression by analyzing RNA-seq of localized vs. metastatic patient samples, followed by CIBERSORTx to assess their immune cell populations. The VHA CDW registry of PCa patients was analyzed for anti-TNF clinical outcomes.

RESULTS: We observed statistically significant opposing patterns of IL-6 and TNFα expression between localized and metastatic disease. IL-6 was robustly expressed in localized disease and downregulated in metastatic disease. The reverse was observed with TNFα expression. Metastatic disease was also characterized by downregulation of adhesion molecule E-selectin, matrix metalloproteinase ADAMTS-4 and a shift to M2 macrophages whereas localized disease demonstrated a preponderance of M1 macrophages. Treatment with anti-TNF agents was associated with earlier stage disease at diagnosis.

CONCLUSIONS: Our data points to clearly different inflammatory contexts between localized and metastatic prostate cancer. Primary localized disease demonstrates local inflammation and adaptive immunity, whereas metastases are characterized by immune cold microenvironments and a shift towards resolution of inflammation and tissue repair. Therapies that interfere with these inflammatory networks may offer opportunities for early intervention in monotherapy or in combination with immunotherapies and anti-angiogenic approaches.

PMID:36371231 | DOI:10.1186/s12967-022-03731-x

BMC Endocr Disord. 2022 Nov 12;22(1):277. doi: 10.1186/s12902-022-01198-x.

ABSTRACT

BACKGROUND: The interplay between HCV, DM, and DAA therapy is poorly understood. We compared HCV infection characteristics, treatment uptake, and treatment outcomes in patients with and without DM. METHODS: A retrospective cohort study was conducted using data from The Ottawa Hospital Viral Hepatitis Program. Statistical comparisons between diabetes and non-diabetes were made using χ² and t-tests. Logistic regression analyses were performed to assess predictors of DM and SVR.

RESULTS: One thousand five hundred eighty-eight HCV patients were included in this analysis; 9.6% had DM. Patients with DM were older and more likely to have cirrhosis. HCC and chronic renal disease were more prevalent in the DM group. Treatment uptake and SVR were comparable between groups. Regression analysis revealed that age and employment were associated with achieving SVR. Post-SVR HCC was higher in DM group.

CONCLUSION: The high prevalence of DM in our HCV cohort supports screening. Further assessment is required to determine if targeted, early DAA treatment reduces DM onset, progression to cirrhosis and HCC risk. Further studies are needed to determine if optimization of glycemic control in this population can lead to improved liver outcomes.

PMID:36371200 | DOI:10.1186/s12902-022-01198-x

BMC Musculoskelet Disord. 2022 Nov 12;23(1):979. doi: 10.1186/s12891-022-05940-3.

ABSTRACT

BACKGROUND: Postoperative fever (POF) is a common problem after total joint arthroplasty (TJA). The goal of this research is to analyze the characteristics and risk factors of fever following TJA.

METHODS: We retrospectively investigated 2482 patients who had primary total knee arthroplasty (TKA) or total hip arthroplasty (THA) surgery at our institution between January 2020 and December 2020. Those patients were divided into TKA group and THA group. The patients’ axillary temperatures were measured. POF was defined as a body temperature greater than 38 °C. Then patients in the TKA and THA groups were respectively divided into afebrile group and febrile group based on their body temperatures. Temperature changing characteristics of the patients in the febrile group were analyzed and recorded. According to the number of patients in the febrile group, we randomly selected a corresponding number of patients from the afebrile group at a ratio of 1:2 to establish a control group. Gender, hypertension, diabetes, anesthesia, surgical time, and some laboratory data were analyzed between the febrile group and the afebrile group.

RESULTS: Three percent of TKA patients (N = 45) had febrile, and in the febrile group of TKA group, 38% (N = 17) had fever and maximum body temperature on postoperative day 2(POD2). Six percent of THA patients (N = 46) had fever, and in the febrile group of THA group, 65% (N = 30) of the patients had fever and maximum body temperature on POD1. In TKA group, compared with afebrile group, febrile group has higher C-reactive protein (mg/L) (CRP) after surgery. In THA group, compared with the afebrile group, the patients in the febrile group had larger fall in hemoglobin (g/L), and higher C-reactive protein (mg/L) (CRP) after surgery, so there were statistically significant differences between the two groups (P < 0.05).

CONCLUSION: The POF rate of TKA is 3%, and the first fever and maximum body temperature most commonly appear on the POD2. THA has a 6% POF rate, and the first fever and the maximum body temperature most commonly appear on the POD1. In both groups, high C-reactive protein is a risk factor for postoperative fever. In addition, the fall in hemoglobin is also related to postoperative fever in the THA group.

PMID:36371192 | DOI:10.1186/s12891-022-05940-3

BMC Oral Health. 2022 Nov 12;22(1):486. doi: 10.1186/s12903-022-02505-7.

ABSTRACT

OBJECTIVES: This in vivo study aims to assess the accuracy of the digital intraoral implant impression technique, the conventional closed-tray impression technique, and open-tray impression techniques in a standardized method of data segmentation along with the best-fit algorithm to overcome the inconsistency of results of previous studies regarding implant impression techniques.

MATERIALS AND METHODS: Sixteen implants were placed in eight patients. Each patient has undergone four impression techniques: direct intraoral scanning of the stock abutment, intraoral scanning using a scan body, conventional closed tray impression technique, and the conventional open tray impression technique. The conventional impressions were poured into stone casts with analogues and stock abutments and scanned using a desktop scanner. In intraoral scanning of the scan body, computer-aided design software was used for the replacement of the scan body with a custom-made abutment that is identical to the stock abutment, allowing comparison with the other impression techniques. The deviation in implant position between the groups was measured using special 3D inspection and metrology software. Statistical comparisons were carried out between the studied groups using a one-way analysis of variance (ANOVA) test.

RESULTS: The total deviation between groups was compared to the reference group represented by the intraoral scanning of the abutment. The total deviation was statistically significantly different (P = 0.000) among the different studied groups. The mean deviation was recorded as 21.45 ± 3.3 μm, 40.04 ± 4.1 μm, and 47.79 ± 4.6 μm for the intraoral scanning of the scan body, the conventional closed, and open tray, respectively.

CONCLUSION: For implant impressions in partially edentulous patients, intraoral oral scanning using a scan body significantly improves scanning and overall accuracy. Regarding conventional impressions, the closed-tray impression techniques showed more accuracy than conventional open-tray impressions.

CLINICAL RELEVANCE: Intraoral digital implant impression using scan body offers more accuracy than conventional implant impression techniques for recording posterior implant position in free-end saddle partially edentulous patients.

PMID:36371189 | DOI:10.1186/s12903-022-02505-7

BMC Bioinformatics. 2022 Nov 12;23(1):476. doi: 10.1186/s12859-022-04992-5.

ABSTRACT

The rapid evolution of image processing equipment and techniques ensures the development of novel picture analysis methodologies. One of the most powerful yet computationally possible algebraic techniques for measuring the topological characteristics of functions is persistent homology. It’s an algebraic invariant that can capture topological details at different spatial resolutions. Persistent homology investigates the topological features of a space using a set of sampled points, such as pixels. It can track the appearance and disappearance of topological features caused by changes in the nested space created by an operation known as filtration, in which a parameter scale, in our case the intensity of pixels, is increased to detect changes in the studied space over a range of varying scales. In addition, at the level of machine learning there were many studies and articles witnessing recently the combination between homological persistence and machine learning algorithms. On another level, prostate cancer is diagnosed referring to a scoring criterion describing the severity of the cancer called Gleason score. The classical Gleason system defines five histological growth patterns (grades). In our study we propose to study the Gleason score on some glands issued from a new optical microscopy technique called SLIM. This new optical microscopy technique that combines two classic ideas in light imaging: Zernike’s phase contrast microscopy and Gabor’s holography. Persistent homology features are computed on these images. We suggested machine learning methods to classify these images into the corresponding Gleason score. Machine learning techniques applied on homological persistence features was very effective in the detection of the right Gleason score of the prostate cancer in these kinds of images and showed an accuracy of above 95%.

PMID:36371184 | DOI:10.1186/s12859-022-04992-5

Psychiatr Pol. 2022 Apr 15:1-15. doi: 10.12740/PP/OnlineFirst/145884. Online ahead of print.

ABSTRACT

The source literature points to the increasing number of crimes committed by people with mental diseases. Based on international data, it is estimated that the incidence of mental disorders among inmates is increasing at a disproportionate rate in prisons around the world. It is estimated that even every fourth convict may have a diagnosis of mental illness. It is worth noting that repeat offence rates among mentally ill people are also higher than in the general population of repeat offenders. The repeat offence rate among offenders with a diagnosis of mental illness ranges from 60% to 80%. This paper is intended to describe the situation of people diagnosed with mental illness in Poland, with reference to the available statistical data and international research.

PMID:36370438 | DOI:10.12740/PP/OnlineFirst/145884

Psychiatr Pol. 2022 May 25:1-14. doi: 10.12740/PP/OnlineFirst/147733. Online ahead of print.

ABSTRACT

OBJECTIVES: The aim of the study was to assess the predictors quality of life (QoL) in women with postmenopausal osteoporosis.

METHODS: The study was an outpatient, questionnaire-based poll, carried out from June 2018 to May 2019. The study included a group of 198 women, aged 72.31 ± 8.59 years, with diagnosed postmenopausal osteoporosis, treated in two osteoporosis clinics in the city of Lodz (Poland). The inclusion criteria were as follows: a diagnosed osteoporosis in the patients’ medical records according to the ICD-10 – M81.0 and no chronic diseases which would require systematic treatment. The paper utilized the following tools: the Polish version of the QUALEFFO-41 quality of life scale, the visual analogue scale (VAS) and the author’s own survey. The data were analyzed with the use of the multiple linear regression. Statistical analysis was performed using Statistica 13.0 software.

RESULTS: The average result of the QUALEFFO-41 was 40.26 ± 16.92 points. An analysis of particular QUALEFFO-41 domains revealed the lowest quality of life in the mental function domain (48.49 ± 18.06 points). The domain of activities of daily living was assessed twice as well compared to the domain of mental functions. Marital status, education and financial situation had a statistically significant impact on the quality of life (p <0.05). The analysis showed that the pain expressed on the VAS scale, pain waking from sleep, taking sleeping pills, and older age of the respondents deteriorate the quality of life.

CONCLUSIONS: The analysis showed that Polish women with postmenopausal osteoporosis enjoy an average quality of life. The quality of life of chronically ill patients and pain severity on the VAS scale are not routinely or commonly assessed in Poland.

PMID:36370434 | DOI:10.12740/PP/OnlineFirst/147733

J Cosmet Dermatol. 2022 Nov 12. doi: 10.1111/jocd.15493. Online ahead of print.

ABSTRACT

BACKGROUND: It has been proven that there is an increase in intestinal permeability in some autoimmune diseases. In our study, we purposed to assess intestinal permeability in vitiligo disease by looking at zonulin levels. At the same time, we aimed to examine the correlation of inflammatory cytokines and lipopolysaccharide (LPS) levels with zonulin.

METHODS: Forty-one patients and 41 healthy participants were involved in our study. Blood samples were taken from all patients and controls, and the levels of zonulin, tumor necrosis factor (TNF)-α, interleukin (IL)-6 and LPS were examined.

RESULTS: The mean of zonulin in the patient group was found to be statistically higher than the control group (p < 0.05). A positive correlation was found between zonulin level and IL-6, TNF-α, and LPS levels (p < 0.05). TNF-α and LPS levels in the vitiligo group were significantly higher than in the control group, but there was no such significance in terms of IL-6 levels.

CONCLUSION: We think that serum zonulin level increases and intestinal permeability increases in vitiligo disease.

PMID:36370419 | DOI:10.1111/jocd.15493