Factors related to prehospital delay and decision delay among acute stroke patients in a district hospital, Malaysia.

INTRODUCTION: Time is the greatest challenge in stroke management. This study aimed to examine factors contributing to prehospital delay and decision delay among stroke patients. MATERIALS AND METHODS: A cross-sectional study involving acute stroke patients admitted to Seri Manjung Hospital was conducted between August 2019 and October 2020 via faceto- face interview. Prehospital delay was defined as more than 120 minutes taken from recognition of stroke symptoms till arrival in hospital, while decision delay was defined as more than 60 minutes taken from recognition of stroke symptoms till decision was made to seek treatment. RESULTS: The median prehospital delay of 102 enrolled patients was 364 minutes (IQR 151.5, 1134.3) while the median for decision delay was 120 minutes (IQR 30.0, 675.0). No history of stroke (adj. OR 4.15; 95% CI 1.21, 14.25; p=0.024) and unaware of thrombolysis service (adj. OR 17.12; 95% CI 1.28, 229.17; p=0.032) were associated with higher odds of prehospital delay, while Indian ethnicity (adj. OR 0.09; 95% CI 0.02, 0.52; p=0.007) was associated with lower odds of prehospital delay as compared to Malay ethnicity. On the other hand, higher National Institutes of Health Stroke Scale (NIHSS) score (adj. OR 0.86; 95% CI 0.78, 0.95; p=0.002) was associated with lower odds of decision delay. CONCLUSION: Public awareness is crucial to shorten prehosital delay and decision delay for better patients' outcomes in stroke. Various public health campaigns are needed to improve the awareness for stroke.

Some Additional Data That Might Be Useful for Diastasis Recti Assessment.

Background: Diastasis recti (DR) is characterized by separation of both rectus muscles and protrusion of the median bulging, but besides median bulging DR can also entail global abdominal bulging. On other note, DR classification is based on the width of divarication, but measurement values are different at rest and at effort due to muscle contraction. Aim of the study is to provide additional features concerning the type of bulging and the width of divarication. Methods: Findings were retrospectively drawn from the data prospectively collected in the records of a continuous cohort of 105 patients (89 females, 16 males) referred for diastasis and concomitant ventral hernia repair. Results: There was a median bulging alone in 45 (42.9%) cases, a global bulging alone in 18 (17.1%) cases, both types combined in 37 (35.2%) cases and no bulging in 5 (4.8%). On 55 patients with a global bulging, 51 were females. Tape measurements values of DR width were closer to the values measured on the CT scan at leg raise than at rest. The differences were significant at rest as well as at leg raise. Though the difference at rest was highly significant (p = 0.000), the difference at effort was not far from being not significant (p = 0.049). Conclusion: Besides median bulging, presence or absence of the global bulging should be included in DR assessment. The difference between width of divarication at rest and on exertion raises the question of which value should be used for DR classification. The question is worth being debated.

Health utilities for non-melanoma skin cancers and pre-cancerous lesions: A systematic review.

Background: Non-melanoma skin cancers (NMSCs) are common and consume many healthcare resources. A health utility is a single preference-based value for assessing health-related quality of life, which can be used in economic evaluations. There are scarce data on health utilities for NMSCs. Objectives: Using a systematic review approach, we synthesized the current data on NMSC-related health utilities. Methods: A systematic review of studies of NMSC-related health utilities was conducted in Medline, Embase, and Cochrane databases. Data were extracted based on the protocol and a quality assessment was performed for each study. Results: The protocol resulted in 16 studies, involving 121 621 participants. Mean utility values across the studies ranged from 0.56 to 1 for undifferentiated NMSC, 0.84 to 1 for actinic keratosis, 0.45 to 1 for squamous cell carcinoma, and 0.67 to 1 for basal cell carcinoma. There was considerable variability in utilities by type of cancer, stage of diagnosis, time to treatment, treatment modality, and quality of life instrument or method. Utility values were predominantly based on the EuroQol 5-dimension instrument and ranged from 0.45 to 0.96, while other measurement methods produced values ranging from 0.67 to 1. Lower utility values were observed for advanced cancers and for the time period during and immediately after treatment, after which values gradually returned to pre-treatment levels. Conclusions: Most utility values clustered around relatively high values of 0.8 to 1, suggesting small decrements in quality of life associated with most NMSCs and their precursors. Variability in utilities indicates that careful characterization is required for measures to be used in economic evaluations.

Encorafenib and binimetinib for the treatment of BRAF-mutated metastatic melanoma in the setting of combined hepatic and renal impairment.

Inhibitors of BRAF, a gene coding a protein called B-raf, with or without inhibitors of MEK (MAPK/extracellular signal-regulated kinase) are often used as palliative treatment in BRAF-mutated metastatic melanoma. Recent data show improved progression-free survival with encorafenib with binimetinib, a newer BRAF/MEK inhibitor combination, compared with older agents, but there have been no reports of this treatment in the setting of renal and liver failure. We report a patient with disease-induced transaminitis and renal failure requiring dialysis who was successfully treated with encorafenib and binimetinib. His transaminitis improved and he was able to stop dialysis without any significant adverse effects during treatment, suggesting encorafenib with binimetinib may be used safely and effectively even in patients with end organ damage.

[Inguinal hernia. What techniques are available for the surgeon? Theoretical and practical advantages and disadvantages]. / Hernie inguinale. De quelles techniques dispose le chirurgien? Avantages et inconvénients théoriques et pratiques.

There are many hernia repair techniques. Among the most popular, the Shouldice Hospital method was the most widely used in the 1980s. Since then, methods employing prosthetic mesh have taken over, mainly because they are tension-free and therefore seem to lead to less recurrence and cause less postoperative pain. There are several ways of placing the prosthesis, which differ according to the approach used and the superficial or deep situation of the prosthesis. The Lichtenstein technique consists of placing and fixing the prosthesis on the posterior wall of the inguinal canal through an inguinal incision: it is currently the most widely used procedure because of its simplicity. The concept of placing the prosthesis in the subperitoneal space was developed by the French school (Rives, Stoppa). Initially the operation was performed through an inguinal (Rives) or midline (Stoppa) incision. These techniques are no longer adapted to the minimally invasive concept of surgery that prevails today and therefore are less used. The laparoscopic approach places the prosthesis through the trocars instead of through a large incision. The transabdominal approach opens the preperitoneal space through the abdominal cavity, breaching the peritoneum. The extraperitoneal approach consists of direct penetration of the preperitoneal space without violating the peritoneum, as in the Stoppa technique. This is undoubtedly the most elegant laparoscopic technique, but more difficult to perform. Other, simpler methods can also reinforce the posterior wall with a preperitoneal prosthesis. The Polysoft prosthesis, placed through an inguinal incision and inguinal ring, is a modern substitute for the Rives technique, but can be performed under local or locoregional anesthesia. Other types of prostheses, consisting of two, both superficial and deep, components are available: the Prolene Hernia System, for instance, is composed of two circular plates, linked together by a central stalk; there are also several types of plugs. As for anesthesia, there are several evidence-based arguments that indicate that local anesthesia is best.

Effects of Genotype by Environment Interaction on Genetic Gain and Genetic Parameter Estimates in Red Tilapia (Oreochromis spp.).

The extent to which genetic gain achieved from selection programs under strictly controlled environments in the nucleus that can be expressed in commercial production systems is not well-documented in aquaculture species. The main aim of this paper was to assess the effects of genotype by environment interaction on genetic response and genetic parameters for four body traits (harvest weight, standard length, body depth, body width) and survival in Red tilapia (Oreochromis spp.). The growth and survival data were recorded on 19,916 individual fish from a pedigreed population undergoing three generations of selection for increased harvest weight in earthen ponds from 2010 to 2012 at the Aquaculture Extension Center, Department of Fisheries, Jitra in Kedah, Malaysia. The pedigree comprised a total of 224 sires and 262 dams, tracing back to the base population in 2009. A multivariate animal model was used to measure genetic response and estimate variance and covariance components. When the homologous body traits in freshwater pond and cage were treated as genetically distinct traits, the genetic correlations between the two environments were high (0.85-0.90) for harvest weight and square root of harvest weight but the estimates were of lower magnitudes for length, width and depth (0.63-0.79). The heritabilities estimated for the five traits studied differed between pond (0.02 to 0.22) and cage (0.07 to 0.68). The common full-sib effects were large, ranging from 0.23 to 0.59 in pond and 0.11 to 0.31 in cage across all traits. The direct and correlated responses for four body traits were generally greater in pond than in cage environments (0.011-1.561 vs. -0.033-0.567 genetic standard deviation units, respectively). Selection for increased harvest body weight resulted in positive genetic changes in survival rate in both pond and cage culture. In conclusion, the reduced selection response and the magnitude of the genetic parameter estimates in the production environment (i.e., cage) relative to those achieved in the nucleus (pond) were a result of the genotype by environment interaction and this effect should be taken into consideration in the future breeding program for Red tilapia.

Novel CagA ELISA exhibits enhanced sensitivity of Helicobacter pylori CagA antibody.

AIM: To develop a novel Helicobacter pylori (H. pylori) CagA antibody enzyme-linked immunosorbent assay (ELISA) suitable for detecting serum anti-CagA antibodies with high sensitivity. METHODS: Recombinant East Asian-type CagA protein was purified and immobilized for ELISA. Serum samples from 217 Vietnamese individuals (110 H. pylori-infected and 107 uninfected individuals) were applied. Conventional ELISA from Western-type CagA and our East Asian-type CagA ELISA were evaluated by comparing 38 subjects with the Western-type genotype and 72 subjects with the East Asian-type cagA genotype. Histological scores of the gastric mucosa were determined using the updated Sydney System to examine the relationship with anti-CagA antibody titers. RESULTS: Recombinant 70-100 kDa fragments were immobilized on the ELISA plate. In ROC analysis, the area under the curve of our East Asian-type CagA ELISA was comparable to that of conventional CagA ELISA. The sensitivity of the two ELISAs differed depending on the cagA genotype. The sensitivity of East Asian-type CagA ELISA was higher for subjects infected with East Asian-type cagA H. pylori (P < 0.001), and the sensitivity of the conventional CagA ELISA tended to be higher for subjects infected with Western cagA H. pylori (P = 0.056). The titer of anti-CagA antibody tended to correlate with monocyte infiltration scores (r = 0.25, P = 0.058) and was inversely correlated with H. pylori density (r = -0.26, P = 0.043). CONCLUSION: The novel ELISA is useful to detect anti-CagA antibodies in East Asian countries, and the titer may be a marker for predicting chronic gastritis.

[Subperitoneal inguinal hernioplasty by anterior approach, using a memory-ring patch. Preliminary results]. / Hernioplastie inguinale sous-péritonéale par voie antérieure, à l'aide d'une prothèse à mémoire de forme. Résultats préliminaires.

OBJECTIVE: Incidence of chronic pain is lower following laparoscopic hernioplasty than open surgery, probably due to the location of the patch in the preperitoneal space. But since laparoscopy is more demanding, the rates of complications and recurrences are higher. The aim of this study was to evaluate the results of a procedure consisting of placement of a patch, endowed with some memory of shape, provided by a thin peripheral memory ring, in the preperitoneal space, by inguinal incision, through the hernia orifice, under spinal or local anesthesia. METHODS: The study was carried out in two stages. The first study consisted of evaluating the results of a prosthesis made of a polypropylene mesh endowed with a memory-ring made of a PDS cord (Ethicon SAS, 92787 Issy-les-Moulineaux). The second study evaluated the results of the Polysoft patch manufactured by Bard C degrees (Bard France, 78960 Voisins-le-Bretonneux), according to this concept. RESULTS: The first study involved 129 hernias operated on 126 patients of mean age 60 years (27-84). There were 3 (2.3%) benign complications. With a median follow-up of 24.5 months (12-42), 124 hernias (96%) were evaluated. There were 2 recurrences (1.6%) and 7 cases (5.6%) of chronic pain. The second series involved 150 hernias operated on 139 patients of mean age 60 years (21-94). Four (2.7%) benign complications occurred. The median length of surgery was 36 min (20-60), the median postoperative hospital stay was 1 day (0-5), the median time to return to normal activity was 3 days (0-8) and the median time off work was 18 days (1(30). The patients took paracetamol for 3 days (0-10) and the total units number was 8 (0-28). CONCLUSION: These results suggest that the method, easily reproducible, provides a low rate of complications and recurrences, as well as a low level of postoperative and chronic pain. They are worth being confirmed by a randomised comparison to the laparoscopic and Lichtenstein techniques.

Ambulatory groin and ventral hernia repair.

OBJECTIVE: Ambulatory surgery is not commonly practiced in France today. The aim of this study was to prospectively evaluate the feasibility of ambulatory hernia repair in a consecutive series of unselected patients. PATIENTS AND METHODS: From June 2008 to October 2009, 257 patients (238 men and 19 women, median age 65 years) were treated in a same-day surgery unit for 270 hernias (244 groin hernias, 25 ventral hernias and one Spiegelian hernia). RESULTS: For groin hernia, the techniques included the totally extraperitoneal repair (TEP) in 108 cases, the transinguinal preperitoneal (TIPP) approach in 106 cases and other alternative techniques in 30 cases; for ventral hernias, the technique was an open suture in 20 cases, an open prosthetic repair in four cases and laparoscopic repair in one case. Anesthesia was general in 145 cases, local in 121 cases and spinal in four cases. Repair was completed in a same-day surgery setting in 242 (89.6%) cases; hospital stay greater than 23 hours was planned for 21 (7.8%) patients while non-programmed hospitalizations were necessary for seven (2.6%) patients. There were two (0.7%) readmissions and nine (3.3%) benign postoperative complications. CONCLUSION: These results suggest that groin and ventral hernia repair can be performed in an outpatient setting in nearly 90% of unselected patients.

Paediatric acute asthma management in Australia and New Zealand: practice patterns in the context of clinical practice guidelines.

OBJECTIVES: To compare clinical practice guideline (CPG) recommendations and reported physician management of acute paediatric asthma in the 11 largest paediatric emergency departments, all of which have CPGs, in Australia (n = 9) and New Zealand (n = 2). All 11 sites participate in the Paediatric Research in Emergency Departments International Collaborative (PREDICT) research network. METHODS: (a) A review of CPGs for acute childhood asthma from all PREDICT sites. (b) A standardised anonymous survey of senior emergency doctors at PREDICT sites investigating management of acute childhood asthma. RESULTS: CPGs for mild to moderate asthma were similar across sites and based on salbutamol delivery by metered dose inhaler with spacer and oral prednisolone. In severe to critical asthma, differences between sites were common and related to recommendations for: ipratropium use; metered-dose inhaler versus nebulised delivery of salbutamol in severe asthma; use of intravenous aminophylline, intravenous magnesium and dosing of intravenous salbutamol in critical asthma. The questionnaire (78 of 83 doctors responded) also revealed significant differences between doctors in the treatment of moderate to severe asthma. Ipratropium was used for moderate asthma by 42%. For severe to critical asthma, nebulised delivery of salbutamol was preferred by 79% of doctors over metered dose inhalers. For critical asthma, doctors reported using intravenous aminophylline in 45%, intravenous magnesium in 55%, and intravenous salbutamol in 87% of cases. Thirty-nine different dosing regimens for intravenous salbutamol were reported. CONCLUSIONS: CPG recommendations and reported physician practice for mild to moderate paediatric asthma management were broadly similar across PREDICT sites and consistent with national guidelines. Practice was highly variable for severe to critical asthma and probably reflects limitations of available evidence. Areas of controversy, in particular the comparative efficacy of intravenous bronchodilators, would benefit from multi-centre trials. Collaborative development of CPGs should be considered.

Effects of the 21-aminosteroid U74389G in a model of chronic myocardial infarction in the rat.

21-Aminosteroids are a group of new synthetic compounds developed as antiperoxidants. Although several studies have demonstrated their cardioprotective properties in acute ischemic models, none has assessed their long-term benefits after chronic myocardial infarction. In this investigation, we examined the cardioprotective effects of U74389G, a novel 21-aminosteroid, in a model of chronic myocardial infarction in the rat. After permanent ligation of the proximal branch of the left coronary artery, the experimental animals were treated daily by gavage with U74389G (10 mg/kg) for 21 days. After the study period, harvested hearts were perfused ex vivo and submitted to cold cardioplegia with 90-min global ischemia and 30-min reperfusion (surgical stress). Myocardial function and coronary endothelial (bradykinin, 1 microM) and smooth muscle (sodium nitroprusside, 1 microM) reactivity were assessed before and after exposure to the surgical stress. Percentage infarct size of the left ventricle was computed as the ratio of infarct area (mg)/total left ventricle (mg) x 100. During or immediately after surgery, there were eight deaths, which were considered technical failures. No further deaths occurred during the follow-up period (21 days). Compared with vehicle-treated rats, long-term administration of U74389G elicited a significant reduction of infarct size (percentage of left ventricle, 9 +/- 5% in the U74389G-treated group vs. 32 +/- 5% in the vehicle-treated group; p < 0.01). Ex vivo heart-perfusion studies showed no significant difference in baseline coronary flow, left ventricular developed pressure, and heart rate between normal and chronic infarcted hearts treated with the vehicle or with U74389G. However, a reduced endothelium-dependent coronary dilator response was observed in infarcted hearts from vehicle-treated controls but not in those from U74389G-treated rats. When cardioplegia and global myocardial ischemia/reperfusion were added, most of the benefits from U74389G were lost. These results indicate that 21-aminosteroids can reverse oxygen-derived free radicals and lipid peroxidation-induced myocardial and coronary dysfunction associated with chronic myocardial infarction. However, additive protective measures are required when an acute ischemic stress is superimposed.

Structural and functional effects of endometrial photodynamic therapy in a rat model.

OBJECTIVE: Our purpose was to determine the optical dose required for irreversible endometrial destruction and prevention of implantation by photodynamic therapy with topical 5-aminolevulinic acid. STUDY DESIGN: Three hours after drug application 74 female Sprague-Dawley rats received varying doses of 630 nm of light delivered by an intrauterine cylindric diffusing fiber. RESULTS: A 64 J/cm2 in situ optical dose resulted in long-term irreversible endometrial destruction; 43 J/cm2 damaged endometrial stroma and myometrium but not glandular epithelium 1 day after photodynamic therapy. At this lower light dose endometrium regenerated to full thickness within 3 weeks; however, implantation sacs were significantly reduced. CONCLUSIONS: Photodynamic destruction of glandular epithelium accompanies irreversible endometrial ablation, whereas isolated stromal damage leads to reproductive impairment only. The optical dose required for endometrial ablation is approximately 1.5-fold higher than for reproductive impairment (functional damage) because of differential cell photosensitivity.

Discovery and initial structure-activity relationships of trisubstituted ureas as thrombin receptor (PAR-1) antagonists.

Thrombin is the most potent agonist of platelet activation, and its effects are predominantly mediated by platelet thrombin receptors. Therefore, antagonists of the thrombin receptor have potential utility for the treatment of thrombotic disorders. Screening of combinatorial libraries revealed 2 to be a potent antagonist of the thrombin receptor. Modifications of this structure produced 11k, which inhibits thrombin receptor stimulated secretion and aggregation of platelets.