Comparison of statistical methods for the early detection of disease outbreaks in small population settings.

Objectives: This study examines the performance of 6 aberration detection algorithms for the early detection of disease outbreaks in small population settings using syndrome-based early warning surveillance data collected by the Pacific Syndromic Surveillance System (PSSS). Although previous studies have proposed statistical methods for detecting aberrations in larger datasets, there is limited knowledge about how these perform in the presence of small numbers of background cases. Methods: To address this gap a simulation model was developed to test and compare the performance of the 6 algorithms in detecting outbreaks of different magnitudes, durations, and case distributions. Results: The study found that while the Early Aberration Reporting System-C1 algorithm developed by Hutwagner et al. outperformed others, no single approach provided reliable monitoring across all outbreak types. Furthermore, aberration detection approaches could only detect very large and acute outbreaks with any reliability. Conclusion: The findings of this study suggest that algorithm-based approaches to outbreak signal detection perform poorly when applied to settings with small numbers of background cases and should not be relied upon in these contexts. This highlights the need for alternative approaches for accurate and timely outbreak detection in small population settings, particularly those that are resource-constrained.

Cost-effectiveness analysis of well-differentiated thyroid carcinoma surveillance using nuclear medicine procedures

Introduction@#Well-differentiated thyroid carcinoma (WDTC) is the most common type of thyroid cancer with a notable increasing incidence worldwide. It is prevalent among Filipino descent as compared to other nationalities. Its good prognosis and high survival rate predispose patients to lifetime surveillance with incomplete response, instead of death, as outcome measure. This eventually leads to increase in cost of care, utilization, and allocation of medical resources for the survivors of the disease. Thyroglobulin immunoradiometric assay (Tg IRMA) and I-131 diagnostic whole-body scan (dWBS) are two nuclear medicine procedures that are part of WDTC surveillance. Due to their varied availability in Asia-Pacific, most clinicians measure thyroglobulin (Tg) alone due to perceived cost-effectiveness. @*Objective@#This study aims to analyze the cost-effectiveness of two nuclear medicine procedures used in WDTC surveillance, namely thyroglobulin immunoradiometric assay and I-131 diagnostic whole-body scan, in detecting incomplete response. @*Methodology@#Three clinical guidelines on WDTC management were reviewed to identify frequency, total number and expenditure for surveillance, namely from the University of the Philippines-Philippine General Hospital in 2008 (PGH 2008), American Thyroid Association in 2015 (ATA 2015), and the Department of Health (DOH 2021). A Markov model was constructed to simulate a 36-month surveillance with complete and incomplete response to treatment as disease states. Parameter values like rate of incomplete response in WDTC patients, prognostic values per each surveillance test, and other relevant data were collected from literature search and established data. The cost of surveillance was based on the rates offered by Philippine General Hospital (PGH) Radioisotope Laboratory as of November 2022. One-way sensitivity was done to check robustness of results. @*Results@#ATA 2015 incurs the most expenses, amounting to PHP 14,600.00 to 20,450.00 ($ 254.19 – 356.04) for three years of surveillance, followed by DOH 2021 (PHP 11,700.00 – 15,600.00 or $ 203.74 – 271.65), and PGH 2008 (PHP 3,900.00 – 6,825.00 or $ 67.91 – 118.85). The thyroglobulin IRMA arm costs lower (PHP 17,784.00 or $ 309.74) than I-131 dWBS (PHP 271,875.00 or $ 4,735.13) in detecting incomplete response. I-131 dWBS should cost around PHP 570.00 (or $ 9.92) to be as cost-effective as the thyroglobulin IRMA.@*Conclusion@#This study has identified that thyroglobulin IRMA is more cost-effective than I-131 diagnostic whole-body scan in detecting incomplete response in WDTC patients. This supports the perceived cost-effectiveness of thyroglobulin measurement in surveillance, even without diagnostic whole body-scans. This study also identified that the new DOH 2021 guidelines will incur lesser expenditure in using nuclear medicine procedures for surveillance as compared to ATA 2015 guidelines. Local clinicians may also find it easier to follow as it is more suitable to the Philippine setting.

Postoperative surgical complications of lymphadenohysterocolpectomy.

UNLABELLED: Rationale The current standard surgical treatment for the cervix and uterine cancer is the radical hysterectomy (lymphadenohysterocolpectomy). This has the risk of intraoperative accidents and postoperative associated morbidity. Objective The purpose of this article is the evaluation and quantification of the associated complications in comparison to the postoperative morbidity which resulted after different types of radical hysterectomy. METHODS AND RESULTS PATIENTS WERE DIVIDED ACCORDING TO THE TYPE OF SURGERY PERFORMED AS FOLLOWS: for cervical cancer - group A- 37 classic radical hysterectomies Class III Piver - Rutledge -Smith ( PRS ), group B -208 modified radical hysterectomies Class II PRS and for uterine cancer- group C -79 extended hysterectomies with pelvic lymphadenectomy from which 17 patients with paraaortic lymphnode biopsy . All patients performed preoperative radiotherapy and 88 of them associated radiosensitization. Discussion Early complications were intra-abdominal bleeding ( 2.7% Class III PRS vs 0.48% Class II PRS), supra-aponeurotic hematoma ( 5.4% III vs 2.4% II) , dynamic ileus (2.7% III vs 0.96% II) and uro - genital fistulas (5.4% III vs 0.96% II).The late complications were the bladder dysfunction (21.6% III vs 16.35% II) , lower limb lymphedema (13.5% III vs 11.5% II), urethral strictures (10.8% III vs 4.8% II) , incisional hernias ( 8.1% III vs 7.2% II), persistent pelvic pain (18.91% III vs 7.7% II), bowel obstruction (5.4% III vs 1.4% II) and deterioration of sexual function (83.3% III vs 53.8% II). PRS class II radical hysterectomy is associated with fewer complications than PRS class III radical hysterectomy , except for the complications of lymphadenectomy . A new method that might reduce these complications is a selective lymphadenectomy represented by sentinel node biopsy . In conclusion PRS class II radical hysterectomy associated with neoadjuvant radiotherapy is a therapeutic option for the incipient stages of cervical cancer. ABBREVIATIONS: PRS- Piver Rutledge-Smith, II- class II, III- class III.

Thymus vulgaris essential oil: chemical composition and antimicrobial activity.

The study was designed to determine the chemical composition and antimicrobial properties of the essential oil of Thymus vulgaris cultivated in Romania. The essential oil was isolated in a yield of 1.25% by steam distillation from the aerial part of the plant and subsequently analyzed by GC-MS. The major components were p-cymene (8.41%), γ-terpinene (30.90%) and thymol (47.59%). Its antimicrobial activity was evaluated on 7 common food-related bacteria and fungus by using the disk diffusion method. The results demonstrate that the Thymus vulgaris essential oil tested possesses strong antimicrobial properties, and may in the future represent a new source of natural antiseptics with applications in the pharmaceutical and food industry.

Treatment of gastric carcinoids type 1 with the gastrin receptor antagonist netazepide (YF476) results in regression of tumours and normalisation of serum chromogranin A.

BACKGROUND: Patients with chronic atrophic gastritis have long-term gastric hypoacidity, and secondary hypergastrinaemia. Some also develop gastric ECL cells carcinoids (type 1 GC). Most type 1 GC remain indolent, but some metastasise. Patients undergo surveillance, and some are treated with somatostatin analogues, endoscopic resection or surgery. Netazepide (YF476) is a highly selective, potent and orally active gastrin receptor antagonist, which has anti-tumour activity in various rodent models of gastric neoplasia driven by hypergastrinaemia. Netazepide has been studied in healthy volunteers. AIM: To assess the effect of netazepide on type 1 GC. METHODS: Eight patients with multiple type 1 GC received oral netazepide once daily for 12 weeks, with follow-up at 12 weeks in an open-label, pilot trial. Upper endoscopy was performed at 0, 6, 12 and 24 weeks, and carcinoids were counted and measured. Fasting serum gastrin and chromogranin A (CgA) and safety and tolerability were assessed at 0, 3, 6, 9, 12 and 24 weeks. RESULTS: Netazepide was well tolerated. All patients had a reduction in the number and size of their largest carcinoid. CgA was reduced to normal levels at 3 weeks and remained so until 12 weeks, but had returned to pre-treatment levels at 24 weeks. Gastrin remained unchanged throughout treatment. CONCLUSIONS: The gastrin receptor antagonist netazepide is a promising new medical treatment for type 1 gastric carcinoids, which appear to be gastrin-dependent. Controlled studies and long-term treatment are justified to find out whether netazepide treatment can eradicate type 1 gastric carcinoids.

Gastric carcinoids after long-term use of a proton pump inhibitor.

BACKGROUND: Proton pump inhibitors (PPIs) are potent inhibitors of gastric acid secretion and give hypergastrinemia secondary to gastric hypoacidity. PPI treatment therefore induces enterochromaffin-like (ECL) cell hyperplasia. Long-term hypergastrinemia in rodents and man also leads to ECL cell neoplasia. Whether long-term PPI treatment will induce ECL cell neoplasia in man has been disputed. AIM: To describe gastric carcinoids in two patients with a history of long-term PPI use. RESULTS: Two patients had been taking PPI for 12-13 years due to gastro-oesophageal reflux disease. At routine upper gastrointestinal endoscopy a solitary tumour was found in the oxyntic mucosa of both patients. Histology from the tumours showed in both cases a well-differentiated neuroendocrine tumour. Biopsies from flat oxyntic mucosa showed no signs of atrophic gastritis and a normal presence of parietal cells in both cases, but hyperplasia of ECL cells. The tumour in patient 1 was resected endoscopically. After cessation of PPI treatment the tumour regressed in patient 2 and the ECL cell hyperplasia regressed in both patients. In patient 2 serum gastrin and chromogranin A were elevated during PPI treatment, and normalised after cessation of treatment. In patient 1, unfortunately, we had serum only after treatment, and at that time both parameters were normal. CONCLUSION: These cases show that hypergastrinemia secondary to proton pump inhibitors treatment, like other causes of hypergastrinemia, may induce enterochromaffin-like cell carcinoids in man.

Pioglitazone delays proximal tubule dysfunction and improves cerebral vessel endothelial dysfunction in normoalbuminuric people with type 2 diabetes mellitus.

AIM: The renal and cerebral protective effects of pioglitazone were assessed in normoalbuminuric patients with type 2 diabetes mellitus (DM). METHODS: A total of 68 normoalbuminuric type 2 DM patients were enrolled in a one-year open-label randomized controlled trial: 34 patients (pioglitazone-metformin) vs. 34 patients (glimepiride-metformin). All patients were assessed concerning urinary albumin: creatinine ratio (UACR), urinary alpha1-microglobulin, urinary beta2-microglobulin, plasma asymmetric dymethyl-arginine (ADMA), GFR, hsC-reactive protein, fibrinogen, HbA1c; pulsatility index, resistance index in the internal carotid artery and middle cerebral artery, intima-media thickness in the common carotid artery; cerebrovascular reactivity was evaluated through the breath-holding test. RESULTS: At 1 year there were differences between groups regarding ADMA, urinary beta2-microglobulin, urinary alpha1-microglobulin, parameters of inflammation, serum creatinine, GFR, UACR, the cerebral haemodynamic indices. Significant correlations were found between alpha 1-microglobulin-UACR (R(2)=0.143; P=0.001) and GFR (R(2)=0.081; P=0.01); beta2-microglobulin-UACR (R(2)=0.241; P=0.0001) and GFR (R(2)=0.064; P=0.036); ADMA-GFR (R(2)=0.338; P=0.0001), parameters of inflammation, HbA1c, duration of DM, cerebral indices. There were no correlations between ADMA-UACR, urinary alpha1-microglobulin and beta2-microglobulin. CONCLUSION: Proximal tubule (PT) dysfunction precedes albuminuria and is dissociated from endothelial dysfunction in patients with type 2 DM. Pioglitazone delays PT dysfunction and improves cerebral vessels endothelial dysfunction in normoalbuminuric patients with type 2 DM.

Colloidal competences of any polyethyleneglycol conjugates.

The present paper presents research rely on the knowledge of basic colloidal competences (surface tension, critical micelar concentration, HLB value) of certain new structured lipids by accessing "homogeneous" polyoxyethylene chains (n=3-18) (PEGn) monoderivatized R(NF; EH) during processing by cyanoethylation, hydrolysis, and esterification together with fatty acids (R') isolated and characterized from grape seeds (Vitis vinifera) (S), wild chestnut (Aesculus hyppocastanum) (Ca), wild rose (Rosa Canina) (mn), coriander (Coriandri fructus) (Co) in the architecture of the conjugates about foaming and wetting competences. Basic colloidal characterisation aimed at directing future research to optimagrape seed technological directions for agroalimentary and horticultural processing (and not only) among which these structures through synergic cumulus of defining competences of the polyunsaturated fatty acids (1 delta; 2delta; 3delta), of "homogeneous" derivatised polyethyleneoxy chains (PEO) with monitored degree of oligomerization (n=3-18). We thought it useful to access oligomeric chains PEO processed through adapted Williamson synthesis to clearly quantify its role in the global "colloidal fingerprint" of the studied conjugate. On the other hand, polyunsaturated plant lipid residues we selected constitute a variant of valorification by-products from horticultural and/or agroalimentary processing accessible over worldwide geographical areas with differences due to soil and climate conditions and to the cultivars specific to spontaneous and cultivated flora.

[Rectal hemangioma--a pseudoneoplastic form. A case report and review of the literature]. / Hemangiomul rectal--forma pseudoneoplazica. Prezentarea unui caz si revista literaturii.

A patient, 23 years old, is presented. He was admitted on in our clinic for a lower, very bleeding rectal tumor, the macroscopically characters evoking quite sure a malignant neoplasm. Three successive histopathologically examinations remained inconclusive and only the fourth suggested the diagnosis of benign glandular polyp. That conclusion strongly contrasted with all the data obtained by the macroscopically examinations. Nevertheless the therapeutically option was in favor of a sphincter-saving surgery, the practiced operation being a pull-through rectosigmoid resection (Babcock). Recovery of the patient which is in a good condition at present (two years after surgery). The histopathological examination of the operative specimen stipulated like diagnosis: rectal haemangioma with component parts of lymphangioma. Carrying on, the paper presented a review of the literature data referring to the very limited experience of others authors, regarding clinical aspects, diagnostics and therapeutically problems of the rectal haemangioma. In similar cases presenting voluminous rectal (or colonic) possibly benign tumors, haemangioma like, macroscopically diagnostic being difficult or unsure, but also without a certitude for a malignant tumor, it is recommended a sphincter-saving operation, adapted to the general status of the patient. In cases with malignant characters at the final histopathological examination, on the operative specimen, the transformation of the initial intervention in a amputation type surgery may be a possible alternative.