Relapses in Illicit Drug Use Among Probationers: Results in a Risk Group of Public Health Services in Bavaria.

Objective: We aimed to identify in this study time trends of relapses in the illicit consumption of narcotics in a special at-risk population of former drug users under a public health perspective. Methods: In a pooled dataset of 14 consecutive calendar years (2006-2019), the use of seven different narcotic substances was studied in 380 persons with a total of 2,928 urine samples which were analyzed using a valid marker system for narcotic residues. Results: During the entire observation period, the relapse rate for cannabinoids and opiates was the highest despite abstinence requirements. It was noticeable that the relapses across all narcotics groups occurred primarily during the first 3 years of the probation period (90%) with a decrease in illegal consumption during the following years of the observation period. Conclusion: Special attention should be paid to probationers at the beginning of the probation period to develop more effective prevention strategies for substance abstinence by all involved actors in public health services.

Detection of two SNPs of the LIPE gene in Holstein-Friesian cows with divergent milk production.

The LIPE gene (lipase E, hormone-sensitive type), also known as hormone-sensitive lipase, acts as a primary regulator of lipid metabolism during lactation in cows. We studied a total of two hundred Holstein-Friesian cows and performed sequencing analysis that revealed two synonymous nucleotide changes within the LIPE gene: a transition change, c.276 T > C in exon 2 (g.50631651 T > C; position 351 of GenBank: ON638900) and a transversion change, c.219C > A in exon 6 (g.50635369C > A; position 1070 of GenBank: ON638901). The observed genotypes were TC and CC for the c.276 T > C SNP and CC and CA for the c.219C > A SNP. Notably, the heterozygous TC genotype of the T351C SNP exhibited a significant association with high milk yield. Furthermore, the T351C SNP displayed significant associations with various milk parameters, including temperature, freezing point, density and the percentages of fat, protein, lactose, solids and solids-not-fat, with the homozygous CC genotype showing higher values. The c.219C > A SNP also demonstrated a significant association with milk composition, with heterozygous genotypes (CA) exhibiting higher percentages of fat, protein, and lactose compared to homozygous genotypes (CC). This effect was consistent among both high and low milk producers for fat and lactose percentages, while high milk producers exhibited a higher protein percentage than low milk producers. These findings highlight the importance of considering the detected SNPs in marker-assisted selection and breeding programs for the identification of high milk-producing Holstein-Friesian cows and potentially other breeds. Moreover, this study strongly supports the fundamental role of the LIPE gene in milk production and composition in lactating animals.

Role of endoscopy in suspicion of atrophic gastritis with and without intestinal metaplasia in comparison to histopathology.

Background and study aims: Atrophic gastritis (AG) and intestinal metaplasia (IM) are established premalignant gastric lesions. Many studies documented a poor correlation between esophagogastroduodenoscopy (EGD) and histopathological (HP) findings of precancerous gastric lesions. The aim was to bridge the gap between endoscopy and HP in detection of chronic gastritis, AG and IM. Patients and methods: a prospective single-center study involved 150 patients with endoscopic criteria of gastric lesions with upper gastrointestinal symptoms referred for upper GI endoscopy met the endoscopic criteria and classified according to HP of biopsies from targeted gastric lesions into chronic gastritis (GI), AG(GII) or IM(GIII). We correlated the endoscopic criteria of the 3 groups with the HP results. Results: (73 males & 75 females) with ages ranged17-75 years and mean± SD was 41.96 ± 15.95. GI, GII & GIII were [42 patients (28%),82 patients (54.7%) and 26 patients (17.3%)], respectively. Diffuse gastric mottling was more common in GI (74.3%, P<0.001), visible submucosal vessels, gastric atrophy predominated in GII (75.6, 82.3 & 73.1% (P 0.005,0.4 & <0.01)), respectively. Whitish raised lesions were more specific in GIII (85.7%) (P<0.001). The sensitivity and specificity of endoscopic suspicion of chronic gastritis were (86&88% in GI), (87&85% in GII) and (54% & 100% in GIII) (p-0.001). The logistic regression model for risk factors was χ2= 25.74 and 49.32, p < 0.001. Conclusion: Conventional endoscopy has high sensitivity and specificity for suspicion of chronic gastritis and AG, but low sensitivity and very high specificity for IM. Targeted biopsies may be valuable with image enhanced techniques.

A systematic review and meta-analysis of the safety and efficacy of fistula laser closure.

BACKGROUND: Fistula laser closure (FiLaC) is a novel sphincter-saving technique for the treatment of fistula-in-ano. The aim of this study was to assess the safety and efficacy of the FiLaC procedure. METHODS: Databases including PubMed/Medline, Scopus, Web of Science, and Embase were searched for articles assessing FiLaC. All studies including case series and comparative studies reporting the outcome of FiLaC in the treatment of fistula-in-ano were considered eligible. The main outcomes were healing rates of fistula laser closure, postoperative complications including incontinence, technical aspects of the procedure and failure of healing. RESULTS: Seven studies were included. There were a total of 454 patients, 69.1% with a transsphincteric fistula-in-ano and 35% with recurrent disease. The median age of the patients was 43 years (range 18-83 years). The median operation time was 18.3 min (range 6-32 min). With a median follow-up of 23.7 months, the weighed mean rate of primary healing was 67.3% and the overall success when FiLaC was reused was 69.7%. The weighted mean rate of complications was 4%, all of them were minor complications and the weighted mean rate of continence affection was 1% in the form of minor soiling. CONCLUSIONS: FiLaC may be considered an effective and safe sphincter-saving technique for the treatment of fistula-in-ano with an acceptable, low, complication rate. However, well-designed randomized control trials comparing FiLaC with other techniques are required to substantiate the promising outcomes reported in this review.

Intracorporeal versus extracorporeal anastomosis in minimally invasive right colectomy: an updated systematic review and meta-analysis.

BACKGROUND: Minimally invasive colectomy has become the standard for treatment of colonic disease in many centers. Restoration of bowel continuity following resection can be achieved by intracorporeal (IC) or extracorporeal (EC) anastomosis. The aim of this systematic review was to assess the outcomes of IC compared to EC anastomosis in minimally invasive right colectomy. METHODS: A Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA)-compliant systematic literature search for studies assessing the outcome of IC and EC anastomosis in laparoscopic and robot-assisted right colectomy was conducted. The primary outcome of this review was postoperative complications. Secondary outcomes included operative time, blood loss, length of stay, conversion to open surgery, and bowel recovery. RESULTS: Twenty-five studies including 4450 patients were evaluated. 47.7% of patients had IC anastomosis and 52.3% had EC anastomosis. The weighted mean length of extraction site incision in the IC group was shorter than the EC group. The EC group had significantly higher odds of conversion to open surgery (OR 1.87, 95% CI 1-3.45, p = 0.046), total complications (OR 1.54, 95% CI 1.05-2.11, p = 0.007), anastomotic leakage (AL) (OR 1.95, 95% CI 1.4-2.7, p = 0.003), surgical site infection (SSI) (OR 1.69, 95% CI 1.4-2.6, p = 0.002), and incisional hernia (OR 3.14, 95% CI 1.85-5.33, p < 0.001) compared to the IC group. Both groups had similar rates of ileus, small bowel obstruction, bleeding, and intra-abdominal infection. CONCLUSION: IC anastomosis was associated with significantly shorter extraction site incisions, earlier bowel recovery, fewer complications, and lower rates of conversion, AL, SSI, and incisional hernia than has the EC anastomosis.

Systematic review of endoluminal vacuum-assisted therapy as salvage treatment for rectal anastomotic leakage.

Background: Endoluminal vacuum-assisted therapy (EVT) has been introduced recently to treat colorectal anastomotic leakage. The aim of this study was to evaluate the safety and efficacy of EVT in the treatment of anastomotic leakage and rectal stump insufficiency after Hartmann's procedure. Methods: A systematic search of MEDLINE, Scopus and Cochrane databases was performed using search terms related to EVT and anastomotic leakage or rectal stump insufficiency in line with the PRISMA checklist. Observational studies, RCTs and case series studies published to July 2017 were included. Primary outcomes of the review were the success of EVT, defined as complete or partial healing of the anastomotic defect and associated cavity, and the rate of stoma reversal after EVT. Secondary outcomes included the duration of treatment to complete healing, complications of treatment and the need for further intervention. A meta-analysis was conducted. The potential effect of clinical confounders on the failure of EVT was investigated using the random-effects meta-regression model. Results: Of 476 articles identified, 17 studies reporting on 276 patients were ultimately included. The weighted mean rate of success was 85·3 (95 per cent c.i. 80·1 to 90·5) per cent, with a median duration from inception of EVT to complete healing of 47 (range 40-105) days. The weighted mean rate of stoma reversal across the studies was 75·9 (64·6 to 87·2) per cent. Twenty-five patients (9·1 per cent) required additional interventions after EVT. Thirty-eight patients (13·8 per cent) developed complications. The weighted mean complication rate across the studies was 11·1 (6·0 to 16·2) per cent. Variables significantly associated with failure included preoperative radiotherapy, absence of diverting stoma, complications and male sex. Conclusion: EVT is associated with a high rate of complete healing of anastomotic leakage and stoma reversal. It is an effective option in appropriately selected patients with anastomotic leakage.

Management of acute uncomplicated diverticulitis without antibiotics: a systematic review, meta-analysis, and meta-regression of predictors of treatment failure.

BACKGROUND: Diverticulitis is a common complication of diverticular disease of the colon. While complicated diverticulitis often warrants intervention, acute uncomplicated diverticulitis (AUD) is usually managed conservatively. The aim of the present review was to evaluate the efficacy and safety of conservative treatment of AUD without antibiotics compared to standard antibiotic treatment. METHODS: A systematic literature review in compliance with PRISMA guidelines was conducted. Electronic databases including PubMed/Medline, Scopus, Embase and Cochrane central register of controlled trials were searched. Studies that assessed efficacy and safety of treatment of AUD without antibiotics were included. Outcome parameters were rates of treatment failure, recurrence of diverticulitis, complications and mortality, readmission to hospital, and need for surgery. RESULTS: Nine studies including 2565 patients were included to the review. Of these patients, 65.1% were treated conservatively without antibiotics. Treatment failure was observed in 5.1% of patients not-given-antibiotic treatment versus 3.4% of those given antibiotic treatment. Recurrent diverticulitis occurred in 9.3% of patients in the non-antibiotic group versus 12.1% of patients in the antibiotic group. On meta-analysis of the studies, there were no significant differences between non-antibiotic and antibiotic treatment groups regarding rates of treatment failure (OR = 1.5, p = 0.06), recurrence of diverticulitis (OR = 0.81, p = 0.2), complications (OR = 0.56, p = 0.25), readmission rates (OR = 0.97, p = 0.91), need for surgery (OR = 0.59, p = 0.28), and mortality (OR = 0.64, p = 0.47). The only variable that was significantly associated with treatment failure in the non-antibiotic treatment group was associated comorbidities (standard error (SE) = - 0.07, 95% CI - 0.117 - 0.032; p < 0.001). CONCLUSIONS: Treatment of AUD without antibiotics is feasible, safe, and effective. Adding broad-spectrum antibiotics to the treatment regimen did not serve to decrease treatment failure, recurrence, complications, hospital readmissions, and need for surgery significantly compared to non-antibiotic treatment.

91-Year-Old Allograft: Oldest Surviving Donor Heart Still Going: A Case Report.

For patients with end-stage heart failure, heart transplantation remains one of the most successful therapies with excellent long-term survival rates. However, over the past few decades, there has been a worsening supply/demand mismatch given the rising epidemic of heart failure and the relatively fixed availability of donor hearts. In this case report, we describe the case of a 30-year-old woman who underwent transplantation with a 68-year-old donor heart and who has survived for 23 years without any major cardiac problems. To our knowledge, this patient has one of the oldest surviving donor hearts (91-year-old heart). Review of the latest guidelines and recent studies have demonstrated a gradual expansion of donor criteria to meet this critical shortage of donor organs.

Efficacy of laparoscopically assisted high ligation of patent processus vaginalis in children.

INTRODUCTION: Laparoscopic hernia repairs have been proven to be efficient and safe for children, despite the slightly higher recurrence rate compared with the classic surgical repair. They have the advantage of easy and precise identification of the type of defect and its correction, both in ipsilateral and contralateral sides. OBJECTIVES: The objectives of this study were to evaluate the efficacy, safety and outcome of the laparoscopically assisted piecemeal high ligation of a patent processus vaginalis (PPV) in children. METHODS: A total of 40 children were enrolled into this prospective study; they were aged ≥ 6 months and had an inguinal hernia. The peritoneal cavity, including the contralateral side, was inspected for the possibility of bilateral hernias using a 3-mm 30° telescope. Another 3-mm port was introduced through the same infra-umbilical incision. The hernia was manually reduced or with the aid of a working infra-umbilical grasper. A prolene or vicryl 2/0 or 3/0 suture on a curved semicircle round-bodied taper-ended 25-30 mm needle was introduced through a very small inguinal skin-crease incision. It was passed through the abdominal wall layers to the peritoneum and was manipulated by the laparoscopic grasper to pick up the peritoneum in piecemeal all around the internal ring. The needle was then pushed to the outside near to the entrance site, thus forming a semicircle around the internal ring. The suture was then tied and the knot was subcutaneously buried. The primary outcome of the procedure was the incidence of intraoperative diagnosis and surgical repair of contralateral hernias in pre-operatively diagnosed unilateral cases. The secondary outcomes were defined as the incidence of complications and hernia recurrence. DISCUSSION: The exploratory laparoscopy found contralateral patent processus vaginalis (CPPV) with a detection rate of 28.1%. Chan et al., Esposito et al., Toufique et al. and Niyogi et al. reported similar figures for laparoscopic contralateral hernia detection rates of 28%, 39%, 39.7% and 29.2%, respectively. The limitations of this study were the small sample size, plus the risk factors and clinical significance for CPPV. CONCLUSION: Laparascopically assisted piecemeal closure of the internal inguinal ring in children is a safe and effective procedure. It helps in detecting a contralateral hernia without prolonging the operative time.

Characterization of Streptomyces isolates causing colour changes of mural paintings in ancient Egyptian tombs.

Paintings in ancient Egyptian tombs often suffer colour changes due to microbial growth and colonization. Streptomyces strains were isolated from mural paintings of Tell Basta and Tanis tombs (East of Nile Delta, Egypt) and were identified using biochemical and molecular methods. The16S rDNA sequences data indicated that isolated strains were closely related to S. coelicolor, S. albidofuscus, S. ambofaciens, S. canarius, S. parvullus, S. corchorusii, S. albidofuscus and S. nigrifaciens. It could be shown that Streptomyces strains are involved on a large scale in the colour changes of paintings and stone support by producing a wide range of metabolites such as acids (oxalic, citric and sulphuric acids), biopigments of melanin, carotenoids, and hydrogen sulphide.

Buccal versus lingual mucosal graft urethroplasty for complex hypospadias repair.

OBJECTIVES: To compare surgical outcomes and donor site complications of buccal and lingual mucosa used as ventral onlay graft for complex hypospadias cases. PATIENTS & METHODS: Forty four cases with complex hypospadias after failed previous surgery were prospectively included. All had severely scarred penile skin with reasonable residual urethral plate. Cases were categorized into two groups: Group I (23) where buccal mucosal graft [BMG] was used and group II (21) where lingual mucosal graft [LMG] was used. Donor site complications as well as functional and esthetic outcomes were recorded for each group. RESULTS: Mean follow up was 20.8 months (range 12-24). Average graft harvesting time was 24 min for BMG and 19 min for LMG. Donor site pain was reported with both techniques but recovery was earlier with LMG. Slurred speech and difficult tongue protrusion were reported with lingual but not buccal grafts; however mouth tightness, peri-oral numbness and persistent oral discomfort were reported only with buccal grafts. Successful urethroplasty was obtained in 78.2% of BMG compared to 76.1% of LMG. CONCLUSION: Surgical outcomes of LMG urethroplasty were comparable to those of BMG in complex hypospadias cases. Compared to buccal mucosa, LMG is easy to harvest, with minimal donor site complications.

A clinico-radiological study of the contralateral ear in acquired unilateral cholesteatoma.

OBJECTIVE: Clinico-audiological and CT scan assessments of the contralateral ear in patients with unilateral cholesteatoma can be a good predictive method for the fate of these ears. MATERIAL AND METHODS: Fifty patients with unilateral cholesteatoma and 25 control subjects with bilateral normal ears were subjected to otomicroscopical and audiological assessment. Axial and coronal computed tomography (CT) for the mastoid bone at 1 mm slice thickness was done for all ears. A simplified method was used to find out the surface area (SA) of the air cells at each individual section and semi-automatically calculate the total volume of the matstoid air cells. RESULTS: Otomicroscopically, 72% of the contralateral ears showed signs of retraction pockets, granulation tissues and other signs of chronicity. Audiologically 20% of the control ears showed moderate to severe conductive hearing loss while 10% showed mixed hearing loss. As regards mastoid pneumatization, the mean air cell volumes were 6.1, 12.68 and 29.92 CC in cholesteatomatous, contralateral and control ears respectively. This indicates a highly significant difference in the mean air cell volume between the control ears and the other two groups. CONCLUSION: It can be concluded that continuous follow up of the contralateral ear in cholesteatomatous ears is mandatory to detect subtle pathological changes and manage them early. Volumetry of contralateral ear using the applied simple method can lead to a reduction in major surgery and can affect the choice of the surgical approach.

Poly(dimethylsiloxane) coatings for controlled drug release--polymer modifications.

Modifications of endhydroxylated poly(dimethylsiloxane) (PDMS) formulations were studied for their ability to be applied onto tablet cores in a spray-coating process and to control drug release in zero-order fashion. Modifications of the crosslinker from the most commonly used tetraethylorthosilicate (TEOS) to the trifunctional 3-(2,3-epoxypropoxy)propyltrimethoxysilane (SIG) and a 1:1 mixture of the two were undertaken. Addition of methylpolysiloxane-copolymers were studied. Lactose, microcrystalline cellulose (MCC) and polyethylene glycol 8000 (PEG) were the channeling agents applied. The effects on dispersion properties were characterized by particle size distribution and viscosity. Mechanical properties of resulting free films were studied to determine applicability in a pan-coating process. Release of hydrochlorothiazide (marker drug) was studied from tablets coated in a lab-size conventional coating pan. All dispersions were found suitable for a spray-coating process. Preparation of free films showed that copolymer addition was not possible due to great decline in mechanical properties. Tablets coated with formulations containing PEG were most suitable to control drug release, at only 5% coating weight. Constant release rates could be achieved for formulations with up to 25% PEG; higher amounts resulted in a non-linear release pattern. Upon adding 50% PEG, a drug release of 63% over 24 h could be achieved.

Influence of methacrylic acid and hydroxypropylmethyl cellulose on the tablet properties and in vitro release of dextromethorphan hydrobromide.

The release of dextromethorphan hydrobromide from matrices containing hydroxypropylmethyl cellulose (HPMC K100LV) and methacrylic acid copolymer (Eudragit L100-55) has been evaluated at different ratios of the polymers. The physicochemical properties (including weight, thickness, crushing strengh, friability and disintegration time) were also determined at 1000, 2000 and 4000 p compression forces. No significant differences in weight uniformity and thickness values were observed between the different formulations. The crushing strength of the tablets increased with increasing compression force and it reached a constant level at 4000 p. The formulations containing only HPMC K100LV resulted in an extended release pattern, however, Eudragit L100-55 alone could not effectively prolong the drug release. A combination of HPMC K100LV and Eudragit L100-55 in a 1:1 ratio at the 40% level provided an almost similar drug release profile than the marketed product.

Effect of drug proportion and mixing time on the content uniformity of a low dose drug in a high shear mixer.

The purpose of this study was to investigate the effect of reducing drug proportion and mixing time on the content uniformity of a low dose drug. Buspirone hydrochloride was used as a model drug and was mixed with other ingredients in two different concentrations (0.5% w/w and 5% w/w) in a T. K. Fielder high shear mixer at a high impeller speed (522 rpm) and a high chopper speed (3600 rpm) up to 32 min. Samples were withdrawn from nine locations in the mixer at specific time points using a side-sampling thief probe. The final blends at 32 min were compressed using an instrumented tablet press. Tablets were sampled at the beginning, middle, and end of the compression run. The statistical results indicated that the drug proportion had a significant effect on the content uniformity of the powder blend and the corresponding tablets. For this study, the optimum time to mix the 0.5% w/w formulation was after 8 min while it was only 1 min for the 5% w/w formulation. The RSD of buspirone hydrochloride contents of tablets decreased as the compression run was toward its end. Uniformly mixed blends produced tablets that met the USP XXIV content uniformity requirements.

A comparative multidose pharmacokinetic study of buspirone extended-release tablets with a reference immediate-release product.

Buspirone is disclosed in U.S. Patent No. 3,717,634 as a pharmaceutically active compound that has been found to be effective for the treatment of anxiety disorders and depression. In this randomized, two-treatment, two-period, multidose crossover study, the pharmacokinetics of a once-daily extended-release (ER)formulation of buspirone was compared with that of an immediate-release (IR) formulation of commercially available buspirone. A total of 30 mg of the ER formulation was administered to 36 healthy volunteers once daily for 7 days, and 15 mg of the IR formulation was administered twice daily for 7 days. Pharmacokinetic profiles of buspirone and its metabolite, 1-pyrimidinylpiperazine (1-PP), were obtained at steady state. The bioavailability of buspirone from the ER formulation was more than three times higher than that from the IR formulation at steady state, and that of 1-PP was about 25% less. The mean steady-state Cmax of buspirone from the ER formulation was 46% higher than that from the IR formulation (p < 0.05), and that for 1-PP was lower by 29% (p < 0.05). The mean apparent half-life of buspirone from the ER formulation (9.04 hours) was considerably longer than that observed for the IR formulation (3.06 hours). The median 1-PP/buspirone AUC ratio was much higher for the IR formulation at steady state (24.4) than for the ER formulation (6.44). There were no significant differences in average pharmacokinetic metrics observed in men and women. Based on these observations of the potential benefits of once-daily dosing with the ER product in terms of prolonged buspirone plasma concentrations, a significant increase in the ratio of buspirone to 1-PP concentration with a lower intersubject variation could be achieved that should provide an improvement in the desired therapeutic effects of buspirone.

Application of multiple response optimization technique to extended release formulations design.

The purpose of the present study was to apply response surface methodology and multiple response optimization utilizing superimposed contour diagrams to design extended release formulations with a preplanned release profile. Bumetanide solution was layered on sugar pellets followed by coating with various coating formulations according to a central composite statistical design using a Glatt GPCG 1 Wurster Fluid Bed. The coated pellets were tested for their release profiles and the percent of drug released after 1, 4 and 8 h were used to describe and optimize the release process. Statistical models describing the percent bumetanide released after 1, 4 and 8 h were developed and the corresponding contour diagrams were superimposed to predict the coating formulation parameters expected to produce target release profile. The pellets coated with the designed coating formulation were tested for their release profiles in comparison to the target profile. According to the model-independent approach using similarity factor (F2), the dissolution profile of the designed formulation and the expected target profile were found to be similar. It was concluded that response surface methodology and multiple response optimization could be successfully used to design and optimize extended release formulations with desired preplanned release profile.

Effect of anionic polymers on the release of propranolol hydrochloride from matrix tablets.

Anionic polymers, namely Eudragit S, Eudragit L 100-55, and sodium carboxymethylcellulose, were incorporated into hydroxypropylmethylcellulose (HPMC K100M) to modify the drug release from HPMC matrices. The effects of changing the ratio of HPMC to anionic polymers were examined in water and in media with different pH. The dissolution profiles were compared according to release rates. The interaction between propranolol hydrochloride and anionic polymers was confirmed using the UV difference spectra method. The drug release was controlled with the type of anionic polymer and the interaction between propranolol hydrochloride and anionic polymers. The HPMC-anionic polymer ratio also influenced the drug release. The matrix containing HPMC-Eudragit L 100-55 (1:1 ratio) produced pH-independent extended-release tablets in water, 0.1 N HCl, and pH 6.8 phosphate buffer.