Immune responses against group B Streptococcus monovalent and pentavalent capsular polysaccharide tetanus toxoid conjugate vaccines in Balb/c mice.

Immunization of pregnant women with Group B Streptococcus (GBS) capsular polysaccharide (CPS) conjugate vaccine (CV) could protect young infants against invasive GBS disease. We evaluated the immunogenicity of investigational five GBS monovalent (serotypes Ia, Ib, II, III, and V) CPS-tetanus toxoid (TT)-CV with adjuvant and GBS pentavalent CPS-TT-CV with adjuvant (GBS5-CV-adj) and without adjuvant (GBS5-CV-no-adj), in Balb/c mice. Aluminum phosphate was the adjuvant in the formulations, where included. The homotypic immunoglobulin G (IgG) geometric mean concentration (GMC) and opsonophagocytic activity (OPA) geometric mean titer (GMT) did not differ after the third dose of the GBS5-CV-adj vaccine compared with the monovalent counterparts for all five serotypes. The GBS5-CV-adj induced higher post-vaccination serotype-specific IgG GMCs and OPA GMTs compared to GBS5-CV-no_adj. The GBS5-CV with and without adjuvant should be considered for further development as a potential vaccine for pregnant women to protect their infants against invasive GBS disease.

Beware the recurrent 'benign' multinodular goitre.

BACKGROUND: The diagnosis of follicular carcinoma is often difficult to make on pathological analysis, as the histological distinction from follicular adenoma rests solely on the presence of capsular or vascular invasion. Even on retrospective review of the histopathology after the disease biology has declared itself as malignant, the pathological diagnosis of malignancy may not be possible to make. METHODS: We report three cases in which patients were initially diagnosed with benign follicular lesions, but re-presented with locally recurrent disease and a subsequent malignant disease course. RESULTS: We describe a rare entity of follicular thyroid carcinoma that demonstrates a locally recurrent and eventually metastatic disease phenotype, despite persistently benign pathological findings. CONCLUSION: We highlight that if local recurrence occurs in discrete anatomical tissue planes, or in the thyroid bed following open total thyroidectomy for 'benign multinodular goitre', the possibility of this rare presentation of follicular thyroid carcinoma should be considered.

Outcomes of live renal donors with a history of nephrolithiasis; A systematic review.

The clinical outcomes of kidney donors with a prior history of nephrolithiasis are poorly defined. We conducted a systematic review assessing the post-donation clinical outcomes of kidney donors with a history of nephrolithiasis. Electronic databases (Ovid and Embase) were searched between 1960 and 2021 using key terms and Medical Subject Headings (MeSH) - nephrolithiasis, renal stones, renal transplantation and renal graft. Articles included conference proceedings and journal articles and were not excluded based on patient numbers. Primary outcome was donor stone-related event. Secondary outcomes were renal function upon follow-up or post-operative nephrectomy complications. In summary, 340 articles were identified through database search. We identified 14 studies (16 cohorts) comprising 432 live donors followed up for a median of 26 months post live kidney donation. Six donors donated the stone-free kidney whilst 23 live donors had bilateral stones. Mean stone size was 4.2 ± 1.4 mm (1-16) with average follow up duration of 21.1 months (1-149). Twelve studies provided primary outcome (n = 138 patients) and eight (n = 348) for secondary outcomes. One donor had a stone-related event upon follow up. A total of 195 patients had eGFR <60 upon follow up. However, they were not significantly different when compared to renal function of live donors that didn't have pre-donation nephrolithiasis. Many of the studies couldn't provide long term follow up, coupled with limited data regarding the nature of the pre-donation stone disease. In conclusion, this systematic review shows that we have very limited information upon which to base recommendation regarding pre-donation risk of post-donation complications. Longer term follow up is required and lifelong follow up with live donor registries will aid further understanding.

Transplant Outcomes From Deceased Donors Dying With Burns Injury, a Systematic Review.

AIM: The ever-expanding organ supply and demand gap necessitates alternate sources of organ donors. Initially thought to be a contraindication, organ procurement from nonsurvivable burns patients is possibly an additional organ donor source. We aimed to conduct a systematic review investigating the prevalence and outcomes of the use of burn victims as a source of organ donation for transplantation. METHODS: Medline and EMBASE were searched between 1990 and 2020, using the following keywords: organ procurement, organ donation, organ transplantation, and burns. Studies were not excluded based on patient numbers and included both published abstracts/conference proceeding and journal articles. Studies were excluded if specific organs were not identified or if posttransplant outcomes were not recorded. Primary and secondary outcomes of interest were post-transplantation organ function and complications respectively. RESULTS: Six manuscripts met study inclusion criteria. Fourteen burns donors were identified, including both donation after circulatory death and donation after brain death pathways. The total body surface area of burn ranged from 4% to 90%. A total of 4 hearts, 2 lungs, 8 livers, 1 pancreas, and 24 kidneys were transplanted with varying duration of follow-up and outcomes. CONCLUSION: A very small number of studies have reported the posttransplant outcomes of organs derived from victims of burn injury, including very limited information regarding graft function in the short or long term. Hence, recommendations for the utilization of organs from victims of burn injury should remain guarded and subject to surveillance.

Hypoglycaemia due to insulin therapy for the management of hyperkalaemia in hospitalised adults: A scoping review.

INTRODUCTION: Hyperkalaemia is a very common electrolyte disorder encountered in hospitalised patients. Although hypoglycaemia is a frequent complication of insulin therapy, it is often under-appreciated. We conducted a scoping review of this important complication, and of other adverse effects, of the treatment of hyperkalaemia in hospitalised adults to map existing research on this topic and to identify any knowledge gaps. MATERIALS AND METHODS: We followed the PRISMA-ScR guidelines. Studies were eligible for inclusion if they reported on any adverse effects in hospitalised patients ≥18-years-old, with hyperkalaemia receiving treatment that included insulin. All eligible research from 1980 to 12 October 2021 were included. We searched Medline (PubMed), Embase (Ovid), the Cochrane Library, CINHAL, Africa-Wide Information, Web of Science Core Collection, LILACS and Epistemonikos. The protocol was prospectively registered with the Open Science Framework (https://osf.io/x8cs9). RESULTS: Sixty-two articles were included. The prevalence of hypoglycaemia by any definition was 17.2% (95% CI 16.6-17.8%). The median timing of hypoglycaemia was 124 minutes after insulin administration (IQR 102-168 minutes). There were no differences in the prevalence of hypoglycaemia when comparing insulin dose (<10 units vs. ≥10 units), rate of insulin administration (continuous vs. bolus), type of insulin (regular vs. short-acting) or timing of insulin administration relative to dextrose. However, lower insulin doses were associated with a reduced prevalence of severe hypoglycaemia (3.5% vs. 5.9%, P = 0.02). There was no difference regarding prevalence of hypoglycaemia by dextrose dose (≤25 g vs. >25 g); however, prevalence was lower when dextrose was administered as a continuous infusion compared with bolus administration (3.3% vs. 19.5%, P = 0.02). The most common predictor of hypoglycaemia was the pre-treatment serum glucose concentration (n = 13 studies), which ranged from < 5.6-7.8 mmol/L. CONCLUSION: This is the first comprehensive review of the adverse effects following insulin therapy for hyperkalaemia. Hypoglycaemia remains a common adverse effect in hospitalised adults. Future randomised trials should focus on identifying the optimal regimen of insulin therapy to mitigate the risk of hypoglycaemia.

Development and Validation of a Discriminative Dissolution Medium for a Poorly Soluble Nutraceutical Tetrahydrocurcumin

Objectives: The present study aimed to develop and validate a discriminative dissolution method for tetrahydrocurcumin (THC), a Biopharmaceutical Classification System class II drug, by a simple ultraviolet (UV) spectrophotometric analysis. The final dissolution medium composition was selected based on the solubility and stability criteria of the drug. Materials and Methods: As a prerequisite for this, the solubility of the drug was assessed in media of different pH (1.2-7.4), and surfactant concentrations of 0.5-1.5% (w/v) sodium lauryl sulfate (SLS) in water, and pH 7.4 phosphate buffer. The dissolved drug concentration in each medium was quantified by UV analysis at 280 nm wavelength. Results: The drug solubility was found to be high at a pH of 1.2 and 7.4. The media with surfactant enhanced solubility of the drug by approximately 17-fold and exhibited better sink conditions. The discriminative power of the developed dissolution medium (i.e., 1% w/v SLS in pH 7.4) was determined by performing in vitro dissolution studies of the prepared THC tablets and comparing their release profiles using fit factors (f1 and f2). The results of the fit factor comparisons made between the dissolution profiles of THC tablets proved the discriminative ability of the medium. The validation of the developed dissolution method was performed by international guidelines and the method showed specificity, linearity, accuracy, and precision within the acceptable range. Conclusion: The proposed dissolution method was found to be adequate for the routine quality control analysis of THC, as there is no specified dissolution method for the drug in the pharmacopoeia.

Contemporary evaluation of adverse outcome risks associated with 'did not wait' emergency department presentations.

OBJECTIVE: Did not wait (DNW) is a frequently cited ED key performance indicator. We conducted a network-based observational study of consecutive DNW presentations. METHODS: Prospective cohort study of Western Sydney Local Health District with a primary outcome measure of reported 30-day all-cause mortality and secondary outcomes of demographic characteristics and representation risk. For re-presenting patients who were subsequently admitted, a manual review of electronic records and incident report systems based on a priori plan assessed each case for the length of stay and adverse outcomes. RESULTS: During the study window, there were 1114 DNW presentations with 172 (15.4%) re-presentation within 72 h. The analysis of re-presented patients did not reveal adverse outcomes or prolonged length of stay. A review of available outcomes data revealed one DNW patient died within 30 days but had a previous palliative plan for terminal illness. CONCLUSION: While a proportion of DNW patients re-presented within 72 h, an excess prevalence of poor outcomes were not observed.

Willingness of community based health insurance uptake and associated factors among urban residents of Oromia regional state, Oromia, Ethiopia, a cross-sectional study.

BACKGROUND: Globally, Millions of people cannot use health services because of the fear of payment for the service at the time of service delivery. From the agenda of transformation and the current situation of urbanization as well as to ensure universal health coverage implementing this program to the urban resident is mandatory. The aim of this study is to assess the willingness of community-based health insurance (CBHI) uptake and associated factors among urban residents of Oromia regional state, Oromia, Ethiopia, 2018. METHODS: A community-based cross-sectional study was conducted. From the total of eighteen towns; six towns which account for 33% of the total were selected randomly for the study. One population proportion formula was employed to get a total of 845 households. A pre-tested, semi-structured interviewer-administered questionnaire was used to collect the required data. Double-Bounded Dichotomous Choice Variant of the contingent valuation method was used to assess the maximum willingness to pay for the scheme, and a multiple logistic regression model was used to determine the effect of various factors on the willingness to join and willingness to pay for the households. RESULT: About 839 (99.3%) of the respondents participated. The mean ages of the respondents were 40.44(SD ± 11.12) years. 621 (74.1%) ever heard about CBHI with 473 (56.3%) knowing the benefits package. Out of 839, 724 (86.3%) were willing to uptake CBHI of which 704 (83.9%) were willing to pay if CBHI established in their town. CONCLUSION: If CBHI established about 86.3% of the households would enroll in the scheme. Having education, with a family size between 3 & 6, having difficulty in paying for health care and less than 20mins it took to reach the nearest health facility were the independent predictors of the willingness of CBHI uptake. The Oromia and Towns Health Bureau should consider the availability of health facilities near to the community and establishing CBHI in the urban towns.

Treatment for displaced Tillaux fractures in adolescent age group.

BACKGROUND: Around age 11-15 years, a forced external rotation of the foot in a supination or a medial rotation of the leg on the fixed foot usually is responsible for an avulsion injury to the anterolateral epiphysis, known as Tillaux fracture. Ligamentous injuries are rare in children because ligaments are stronger than is the growth plate that frequently is injured. OBJECTIVE: The aim of this study was to present the clinical outcome until the end of growth after surgical treatment for displaced adolescent Tillaux fractures. PATIENTS AND METHODS: 13 patients with Tillaux fractures in the adolescent age group. Patient`s age ranged (12-17 years) with an average 13.4 years. Of those 13 patients, there were 9 females and 4 males. RESULTS: Fracture union was obtained in all cases (100%) and was assed radiologically when X-ray check-ups in all projections showed the significant presence of trabeculation crossing the fracture, without pain and functionally using the American Orthopedic Foot and Ankle Society (AOFAS) score of the ankle joint. Overall average score was 97 ranged 95-100. There was no recorded post-operative complication. CONCLUSION: The plain radiographs of patients with an avulsion injury of anterolateral tubercle (Tillaux fragment) should be carefully examined for evidence of syndesmotic widening. If there is any doubt, CT scans is helpful. If fracture displacement was greater than 2 mm, a surgical intervention is recommended to restore the normal anatomy of the ankle joint. Anatomically reduced Tillaux fractures at adolescent age group either by closed or opened means, followed by post-operative plaster cast immobilization will lead to excellent results.

Correction to: Long-term effect of high-intensity laser therapy in the treatment of patients with chronic low back pain: a randomized blinded placebo-controlled trial.

After publication of this paper, the authors determined that the name of the author Tamer Mohamed Shosha was incorrectly spelled. The correct presentation should be Tamer Mohamed Shousha.

Long-Term Effect of Pulsed Nd:YAG Laser in the Treatment of Patients with Rotator Cuff Tendinopathy: A Randomized Controlled Trial.

OBJECTIVE: The purpose of the present study was to investigate the long-term effect of pulsed Nd:YAG laser on the treatment of rotator cuff tendinopathy. METHODS: Sixty patients with rotator cuff tendinopathy participated and completed the study. The mean age was 50.2 ± 3.6 years. Participants were randomly assigned to one of two groups: the control group and the treatment group. Both groups were treated with an exercise program, in addition to the pulsed Nd:YAG laser received by the treatment group and the "sham" laser received by the control group, both for three sessions per week for 4 weeks. Outcome measures included pain, assessed by the visual analog scale, and range of motion (ROM), assessed using a traditional goniometer, while the shoulder pain and disability index were used to evaluate the functional recovery of the shoulder joint. Evaluation was carried out before treatment, immediately after treatment, 3 months posttreatment, and 6 months posttreatment. Statistical analyses were used to investigate the effect of interventions and to compare the study groups' pretreatment, posttreatment, and at follow-up points. The significance level was set to p < 0.05. RESULTS: Pain was significantly decreased after treatment and at follow-up points, while ROM and shoulder functions were significantly improved after treatment and at follow-up intervals in both groups. The improvement was more significant in the treatment group than in the control group posttreatment and at follow-up intervals. CONCLUSIONS: Pulsed Nd:YAG laser combined with an exercise program seems to be more effective in the treatment of patients with rotator cuff tendinopathy than a sham laser with exercises.

Endoscopic Plantar Fasciotomy Through Two Medial Portals for the Treatment of Recalcitrant Plantar Fasciopathy.

Plantar fasciopathy is a common cause of heel pain. Endoscopic plantar fasciotomy has the advantage of less surgical trauma and rapid recovery. The aim of the present prospective study was to delineate the results of endoscopic plantar fascia release through 2 medial portals. The present study included 2 groups. The first group included 27 feet in 25 patients that had undergone endoscopic plantar fascia release followed up for 19.7 (range 12 to 33) months. The second group, the control group, included 20 feet in 16 patients treated conservatively and followed up for 16.4 (range 12 to 24) months. The results of endoscopic plantar fascia release were superior to the conservative methods. The surgically treated group experienced significantly less pain, activity limitations, and gait abnormality. The presence of a calcaneal spur had no effect on the final postoperative score. In conclusion, endoscopic plantar fascia release through 2 medial portals is an effective procedure for treatment of resistant plantar fasciopathy that fails to respond to conservative management options.

Efficacy of Multiwave Locked System Laser on Pain and Function in Patients with Chronic Neck Pain: A Randomized Placebo-Controlled Trial.

BACKGROUND: Multiwave locked system (MLS) laser therapy utilizes the synchronized emission of an 808 nm continuous laser and a 905 nm pulsed laser. It is postulated that MLS enables greater penetration and therapeutic benefit than single-wavelength low-level laser therapy (LLLT). OBJECTIVE: The aim of this research was to evaluate the efficacies of MLS laser therapy and the 830 nm laser in the treatment of patients with chronic neck pain (CNP). MATERIALS AND METHODS: Seventy-five patients with CNP (mean age 46.28 ± 5.89, weight 83.78 ± 5.65 kg, height 1.72 ± 4.96 m, and duration of illness of 5.98 ± 1.44 months). They were randomized into three groups. Group I received MLS laser therapy and exercises, Group II received LLLT and exercises, and Group III received placebo laser therapy plus exercises (PL + EX). Neck pain levels and neck function were measured using the visual analogue scale (VAS) and neck disability index (NDI), respectively. RESULTS: Both VAS and NDI were significantly reduced post-treatment for all treatment groups. After 6 weeks of treatment, MLS plus exercise showed a significantly greater decrease in pain and disability scores {Δ VAS (6.68) and Δ NDI (39.84)} compared to both LLLT plus exercise group {Δ VAS (5.72) and Δ NDI (37.88)} and PL + EX {Δ VAS (4.84) and Δ NDI (36.68)}. CONCLUSIONS: MLS laser therapy in conjunction with exercises decreased pain and increased functional activity following 6 months of therapy. MLS laser therapy in combination with exercises is a more effective therapy for CNP compared to exercise plus LLLT or exercise alone.

Laparoscopic splenectomy in children with benign hematological diseases: Leaving nothing behind policy.

CONTEXT: Laparoscopic splenectomy (LS) is considered the standard approach for the treatment of children with nonmalignant hematological diseases due to the advances in the minimal invasive surgery over the conventional splenectomy (CS). Different techniques are involved in the operation to secure the hilum. AIM: The use of (Ligasure™) is a safe, effective, less time consuming and with less complications rate. MATERIALS AND METHODS: Sixty children (33 with thalassemia, 20 with immune thrombocytopenic purpura [ITP] and seven with spherocytosis) were operated during the period from June 2007 to December 2014. These children had undergone LS using (Ligasure™). Three ports were used in small-sized spleens while four ports were used in large spleens. RESULTS: There were 60 children (37 girls and 23 boys) with a mean age of 10.2 years had LS using Ligasure™ with mean operative time of 85 min for cases of ITP and 120 min for other cases. There was no mortality. Two cases were converted to CS. CONCLUSIONS: Use of Ligasure™ alone was safe, less time consuming with less complications rates.

"ORIF" for displaced intra-articular calcaneal fractures in children.

BACKGROUND: Calcaneal fractures in children are rare injuries, and those with displaced intra-articular fracture patterns are found even less frequently. Recent data in the adult literature have suggested operative treatment of displaced intra-articular calcaneal fractures leads to a more favorable outcome. OBJECTIVE: The aim of this study is to analyze the outcomes of displaced intra-articular calcaneal fractures in children treated by open reduction and internal fixation. METHODS: Ten displaced intra-articular calcaneal fractures in 10 patients were treated by open reduction and internal fixation. Mean age was 10.2 (6-12 years). According to Sanders' classification, there were 8 patients who had Sanders' Type II fractures, and 2 children sustained Type III fracture. All patients were followed up with a mean 20.3 months (range 6-30). Clinical score according to the (AOFAS) was 95.8 (range 78-100). CONCLUSION: The characteristics of intra-articular calcaneal fractures in children are similar to those in adults and, from our experience, operative treatment of these fractures, to restore calcaneal anatomical alignment yields good short-term results.

Solid lipid nanoparticles of diethylcarbamazine citrate for enhanced delivery to the lymphatics: in vitro and in vivo evaluation.

OBJECTIVES: The major objective is to target diethylcarbamazine citrate (DEC) to the lymphatics and to increase its retention time. The effect of various excipients on the physicochemical characteristics of the nanoparticles was also studied. MATERIALS AND METHODS: Solid lipid nanoparticles (SLNs) of DEC were prepared by ultrasonication by varying the concentrations of compritol 888 ATO, poloxamer 188 and soya lecithin. The SLNs were evaluated for size, shape, texture, surface charge, physical nature of the entrapped drug, entrapment efficiency and in vitro drug release. In vivo animal studies were carried out to estimate the pharmacokinetic parameters in blood and drug concentration in lymph after oral administration. RESULTS: The size of the spherical particles was in the range of 27.25 ± 3.43 nm to 179 ± 3.08 nm and a maximum entrapment efficiency of 68.63 ± 1.53% was observed. In vitro release studies in pH 7.4 PBS displayed a rapid release and the maximum time taken for the complete drug to release was 150 min. In vivo studies indicated an enhancement in the amount of drug that reached lymphatics when administered via SLNs. CONCLUSION: Targeting of DEC to the lymphatics is possible through SLNs and the retention time in the lymphatics can also be enhanced.

High-intensity versus low-level laser therapy in the treatment of patients with knee osteoarthritis: a randomized controlled trial.

The aim of this randomized controlled study was to compare the effects of low-level laser therapy (LLLT) and high-intensity laser therapy (HILT) on pain relief and functional improvement in patients with knee osteoarthritis (KOA). A total of 53 male patients participated in this study, with a mean (SD) age of 54.6 (8.49) years. Patients were randomly assigned into three groups and treated with HILT and exercise (HILT + EX), LLLT and exercise (LLLT + EX), and placebo laser plus exercise (PL + EX) in groups 1, 2, and 3, respectively. The outcomes measured were pain level measured by visual analog scale (VAS) and knee function measured by Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC). Statistical analyses were performed to compare the differences between baseline and posttreatment measurements. The level of statistical significance was set as P < 0.05. The result showed that HILT and LLLT combined with exercise were effective treatment modalities in decreasing the VAS and WOMAC scores after 6 weeks of treatment. HILT combined with exercises was more effective than LLLT combined with exercises, and both treatment modalities were better than exercises alone in the treatment of patients with KOA.

Long-term effect of high-intensity laser therapy in the treatment of patients with chronic low back pain: a randomized blinded placebo-controlled trial.

The aim of this study was to compare the effect of high-intensity laser therapy (HILT), alone or combined with exercise, in the treatment of chronic low back pain (CLBP). A total of 72 male patients participated in this study, with a mean (SD) age of 32.81 (4.48) years. Patients were randomly assigned into three groups and treated with HILT plus exercise (HILT + EX), placebo laser plus exercise (PL + EX), and HILT alone in groups 1, 2, and 3, respectively. The outcomes measured were lumbar range of motion (ROM), pain level by visual analog scale (VAS), and functional disability by both the Roland Disability Questionnaire (RDQ) and the Modified Oswestry Disability Questionnaire (MODQ). Statistical analyses were performed to compare the differences between baseline and post-treatment measurements. The level of statistical significance was set as P < 0.05. ROM significantly increased after 4 weeks of treatment in all groups, then significantly decreased after 12 weeks of follow-up, but was still significantly more than the baseline value in groups 1 and 2. VAS, RDQ, and MODQ results showed significant decrease post-treatment in all groups, although the RDQ and MODQ results were not significantly different between groups 2 and 3. HILT combined with exercise appears to be more effective in patients with CLBP than either HLLT alone or placebo laser with exercise.

Bifunctional inhibition of human immunodeficiency virus type 1 reverse transcriptase: mechanism and proof-of-concept as a novel therapeutic design strategy.

Human immunodeficiency virus type 1 reverse transcriptase (HIV-1 RT) is a major target for currently approved anti-HIV drugs. These drugs are divided into two classes: nucleoside and non-nucleoside reverse transcriptase inhibitors (NRTIs and NNRTIs). This study illustrates the synthesis and biochemical evaluation of a novel bifunctional RT inhibitor utilizing d4T (NRTI) and a TMC-derivative (a diarylpyrimidine NNRTI) linked via a poly(ethylene glycol) (PEG) linker. HIV-1 RT successfully incorporates the triphosphate of d4T-4PEG-TMC bifunctional inhibitor in a base-specific manner. Moreover, this inhibitor demonstrates low nanomolar potency that has 4.3-fold and 4300-fold enhancement of polymerization inhibition in vitro relative to the parent TMC-derivative and d4T, respectively. This study serves as a proof-of-concept for the development and optimization of bifunctional RT inhibitors as potent inhibitors of HIV-1 viral replication.