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The COVID-19 pandemic requires urgent decisions regarding treatment policy in the face of rapidly evolving evidence. In response, the South African Essential Medicines List Committee established a subcommittee to systematically review and appraise emerging evidence, within very short timelines, in order to inform the National Department of Health COVID-19 treatment guidelines. To date, the subcommittee has reviewed 14 potential treatments, and made recommendations based on local context, feasibility, resource requirements and equity. Here we describe the rapid review and evidence-to-decision process, using remdesivir and dexamethasone as examples. Our experience is that conducting rapid reviews is a practical and efficient way to address medicine policy questions under pandemic conditions.

A series of tris(pyrazolyl)borate mono-, di- and trinuclear complexes, [Tp 2 Ln] n X (Ln = Eu, Tb, Gd, Dy, X n- = various mono-, bis- and tris(β-diketonates) has been prepared. The Tb 3+ and Dy 3+ complexes are luminescent single molecular magnets (SMM) and exhibit luminescence quantum efficiencies up to 73% for the Tb 3+ and 4.4% for the Dy 3+ compounds. Similar Eu 3+ complexes display bright emission only at lower temperatures. The Dy 3+ and Tb 3+ complexes possess SMM behavior in a non-zero dc field at low temperatures, while the polynuclear Dy 3+ complexes also show slow magnetic relaxation even in zero dc field up to 8 K. U eff -values determined from dynamic magnetic measurements were up to 31 and 6 cm -1 for the Dy 3+ and Tb 3+ complexes, respectively. It was found that within a series of Dy 3+ and Tb 3+ compounds, U eff and luminescence quantum yields decreased with increasing nuclearity of the compounds and a shortening of the intramolecular Ln-Ln distance. Δ Orbach -values estimated from low-temperature luminescence spectra were significantly higher than those obtained from ac magnetic data, which may be due to involvement of additional processes in the relaxation mechanism (quantum tunneling, Raman, direct) reducing the energy barrier. Some of the Tb 3+ -compounds also display metal-centred electroluminescence, giving them potential as emitting layers in LEDs.

Background: Of the different types of pneumonia, community acquired pneumonia (CAP), has been identified as the leading cause of infectious morbidity and mortality in the western and developing countries. To eradicate the bacterial cause of CAP, medical doctors) often tend to prescribe a differing cocktail of medicine which may be costly for the health care system. Aim: To analyze the cost of oral and/or intravenous antibiotic medicine use in different treatment approaches for treating CAP in adult inpatients from the health care system perspective. Settings: This study was undertaken at Piggs Peak Government Hospital, a 220 bed tertiary hospital located in the rural northern Hhohho region of Swaziland. Method: Seventy-one ( n = 71) medical records of adult patients, hospitalized and diagnosed with CAP at Piggs Peak Government Hospital from July 2014 to June 2015, were retrieved and entered into the database once confirmed as having met the selection criteria. Only direct antibiotic medicine(s) costs were considered. The total cost per treatment option was calculated by multipling the unit cost of the medicine by the administration frequency and the length of hospital stay. The Kruskal-Wallis test was used to compare the cost difference between more than two treatment options. Results: Medical doctors at Piggs Peak Government Hosptial use a range of antibiotics to treat community acquire pneumonia. Furthermore, doctors prefer using dual antibiotics combination as first line treatment of CAP in adult inpatients. The cost of treating community acquire pneumonia at the hospital ranged from ZAR 70.98 to ZAR 467.60 per adult inpatient admitted into care. A statistically significant difference in the cost of the different treatment approaches used for treating CAP was noted. Conclusion: This cost-exploratory study has highlighted a significant difference in the monetary cost of the differing approaches used for treating CAP at the hospital. It is evident therefore that the use of different treatment approaches in treating CAP significantly influences the cost of CAP treatment. There is therefore need for cost minimization measure to be put in place at the facility.

Background: The 4Kscore combines measurement of four kallikreins in blood with clinical information as a measure of the probability of significant (Gleason ≥7) prostate cancer (PCa) before prostate biopsy., Objective: To perform the first prospective evaluation of the 4Kscore in predicting Gleason ≥7 PCa in the USA., Design, Setting, and Participants: Prospective enrollment of 1012 men scheduled for prostate biopsy, regardless of prostate-specific antigen level or clinical findings, was conducted at 26 US urology centers between October 2013 and April 2014., Intervention: The 4Kscore., Outcome Measurements and Statistical Analysis: The primary outcome was Gleason ≥7 PCa on prostate biopsy. The area under the receiver operating characteristic curve, risk calibration, and decision curve analysis (DCA) were determined, along with comparisons of probability cutoffs for reducing the number of biopsies and their impact on delaying diagnosis., Results and Limitations: Gleason ≥7 PCa was found in 231 (23%) of the 1012 patients. The 4Kscore showed excellent calibration and demonstrated higher discrimination (AUC 0.82) and net benefit compared to a modified Prostate Cancer Prevention Trial Risk Calculator 2.0 model and standard of care (biopsy for all men) according to DCA. A possible reduction of 30-58% in the number biopsies was identified with delayed diagnosis in only 1.3-4.7% of Gleason ≥7 PCa cases, depending on the threshold used for biopsy. Pathological assessment was performed according to the standard of care at each site without centralized review., Conclusion: The 4Kscore showed excellent diagnostic performance in detecting significant PCa. It is a useful tool in selecting men who have significant disease and are most likely to benefit from a prostate biopsy from men with no cancer or indolent cancer., Patient Summary: The 4Kscore provides each patient with an accurate and personalized measure of the risk of Gleason ≥7 cancer to aid in decision-making regarding the need for prostate biopsy., (Copyright © 2014 European Association of Urology. Published by Elsevier B.V. All rights reserved.)

Objective: We report the largest known series of vesicoureteral reflux (VUR) in children with urachal anomalies (UA)., Methods: Two institutions' records were reviewed for children with UA (1951‒2007)., Results: Of 30 girls and 36 boys with UA (34 urachal cysts, 14 patent urachus, 10 urachal diverticula, 7 urachal sinuses, and 1 unknown), 57 (86%) underwent surgical resection or drainage. A voiding cystourethrogram was obtained in 22 (33%). VUR was demonstrated in 14 of the 22 children (64%), and rates were similar among the various types of UA. The median age with versus without VUR was not different (1.3 vs 1.7 years, P=0.97). Of 24 refluxing renal units, classification was grade≤3 in 71%, 4‒5 in 12%, and unspecified in 17%. Four children (26%) underwent ureteroneocystostomy and 10 observed patients resolved spontaneously., Conclusion: To our knowledge, this is the first series of VUR associated with UA. The increased incidence of VUR (64%) in this small subset of patients warrants prospective studies to determine if there is a positive correlation with UA. We believe thorough genitourinary and family histories are important when evaluating children with UA to help detect clinically significant VUR., (Copyright © 2011. Published by Elsevier Ltd.)

Purpose: Prognostic information is limited on children with congenital anterior urethral valves or a diverticulum. We reviewed the literature and examined our clinical database to identify clinical features predicting a poor renal outcome, defined as azotemia, renal failure or death., Materials and Methods: We reviewed 97 English language studies of patients 18 years old or younger. Seven patients from our institutions were also included in analysis. After data abstraction we used multivariate models to define factors associated with outcomes of interest., Results: We identified 239 male patients with anterior urethral valves, of whom 139 had adequate data available for study inclusion. Of these patients 108 (78%) had normal renal function after treatment. On bivariate analysis vesicoureteral reflux (OR 22.4, p <0.0001), pretreatment azotemia (OR 17.1, p <0.0001), urinary tract infection (OR 3.3, p = 0.006), hydronephrosis (OR 10.0, p = 0.0004) and bladder trabeculation (OR 7.3, p = 0.01) were associated with renal failure or death while treatment method (p = 0.9), obstruction type (valve vs diverticulum, p = 0.4) and valve location (p = 0.6) were not. After adjusting for other factors only pretreatment azotemia (p = 0.0005) and vesicoureteral reflux (p = 0.01) remained associated with renal failure and/or death with a trend toward significance for urinary tract infection (p = 0.06). When all 3 factors were present, the odds of a poor renal outcome increased 25-fold (p = 0.005)., Conclusions: Congenital anterior urethral obstruction in children has a generally good prognosis but may occasionally result in a poor renal outcome. The combination of pretreatment azotemia, vesicoureteral reflux and urinary tract infection is highly predictive of a poor renal outcome., (Copyright © 2010 American Urological Association Education and Research, Inc. Published by Elsevier Inc. All rights reserved.)

Less than 100 cases of prostate carcinosarcoma have been described in published studies. Most of these cases describe symptoms due to bladder outlet obstruction that typically results in transurethral resection of the prostate. Our patient presented with tenesmus and stranguria due to prostate carcinosarcoma that developed years after being treated with external radiation and androgen deprivation for prostate adenocarcinoma. Because of the patient's escalating symptoms, a pelvic exenteration with creation of urinary and fecal diversions was performed. Despite the dismal survival associated with prostate carcinosarcoma, palliative surgical extirpation can be successful in patients with debilitating pain.

Cystic dysplasia of the testis (CDT) is a rare entity that typically does not present with orchalgia in affected patients. Most patients with CDT are asymptomatic and have ipsilateral renal malformations. Our patient with CDT was referred because of prolonged unilateral orchalgia. Computed tomography demonstrated an ipsilateral atrophic kidney and hydro-ureter traveling posterior to the bladder. Orchalgia resolved with resection of the dysplastic kidney and ectopic ureter, which drained to an enlarged seminal vesicle. Atypical symptoms associated with CDT, such as chronic orchalgia, should prompt additional investigation to rule out concomitant malformations. This is the first report of an ectopic ureter associated with CDT.

Background and Purpose: The recent literature has questioned the infectious risk of natural orifice translumenal endoscopic surgery (NOTES). The need for a clean portal of entry may be important to minimize peritoneal contamination after NOTES. Our study examines the resultant microbial contamination of the human peritoneum after transvesical incision and exposure of the abdomen to bladder contents during robot-assisted laparoscopic prostatectomy (RALP) to better understand the potential for infection in transvesical NOTES., Patients and Methods: Sixty consecutive men undergoing RALP for clinically localized prostate adenocarcinoma from January to May 2008 were prospectively studied as part of a database approved by an Institutional Review Board. The patient's preoperative urine microscopy values, complete blood cell count, and prostate-specific antigen (PSA) levels were recorded, along with the total length of time the cystotomy was open to the peritoneum. Intraoperative samplings of peritoneal fluid were collected before and after transvesical incision and sent for anaerobic, aerobic and fungal cultures., Results: Patients undergoing RALP had peritoneal exposure after transvesical incision for an average of 118 minutes. Five of 60 (8.3%) patients had evidence of novel aerobic bacterial contamination of the peritoneum after RALP. No patient had a positive anaerobic culture or fungal culture from the peritoneum. Preoperative serum leukocyte and PSA levels were elevated in patients with peritoneal contamination (P < 0.05). Remaining clinicopathologic features, total operative time, or open cystotomy time did not predict peritoneal contamination., Conclusion: Prolonged peritoneal exposure to bladder contents demonstrates minimal contamination of the abdominal cavity and is without postoperative infectious significance. This study may overestimate bacterial contamination via the bladder during RALP, because the specific bacteria seen may have originated from the seminal or prostatic fluid during prostatectomy. Transvesical incision would effectively be a clean portal of entry for NOTES with its low rate of peritoneal contamination.

Disseminated candidiasis occurs almost exclusively in leukemic patients recovering from neutropenia. Although renal involvement can be a sequela of disseminated candidiasis, acute renal infarction secondary to Candida invading the renal vasculature has not previously been reported. Our patient, who was being treated for acute myelogenous leukemia, developed complete obstruction of the right renal vessels during the course of 36 hours as documented by serial renal ultrasound scans with Doppler investigation of the vasculature. Histopathologic examination of the nephrectomy specimen revealed complete infarction of the kidney secondary to Candida spp. infiltrating the parenchyma and occluding the hilar vessels.

Objectives: To detail a percutaneous technique of sacral nerve neuromodulation (SN) that eliminates the first-stage incisions and the need for second-stage fluoroscopy. Our group has previously described the results of SN in children with medically refractory dysfunctional elimination syndrome. The drawbacks to SN include the use of fluoroscopy and the need to reopen recent skin incisions during the second stage. This results in increased radiation exposure, poor cosmesis, and possible wound infection., Methods: The incisionless first stage consisted of percutaneously tunneling the temporary external appliance to the contralateral axillary line at the buttock after localization of the S3 nerve root and placement of a quadripolar tined lead under fluoroscopic guidance. A subcutaneous bolus of methylene blue marked the lead connector site, obviating the need for later fluoroscopic localization to place the implantable pulse generator at the second stage., Results: A total of 27 children with refractory dysfunctional elimination syndrome underwent SN using the InterStim device. Of the 27 patients, 19 underwent our modified technique. The operative time for our modified tunneling and placement technique was < or = 2 minutes. The mean hospital stay was 0.6 day, with no patient requiring postoperative intravenous narcotics. At a mean follow-up of 35.9 months, no wound infections had occurred in the incisionless cohort compared with 1 postoperative wound infection requiring device explantation in the conventional lead placement group., Conclusions: The incisionless technique of SN device implantation is technically simple, quick to perform, and results in decreased radiation exposure, excellent pain control, and improved cosmesis without compromising the outcomes.

Purpose: Testicular tumor of the adrenogenital syndrome is a rare clinical entity found in young men with endocrine disorders. Histologically it resembles Leydig cell tumor. We 1) reviewed the clinical features of testicular tumor of the adrenogenital syndrome and 2) determined if special histopathological features of the tumor and synaptophysin reactivity could distinguish testicular tumor of the adrenogenital syndrome from Leydig cell tumor., Materials and Methods: We reviewed the medical and pathological records for all patients with testicular tumor of the adrenogenital syndrome seen at our institution from 1978 to 2004. These tumors were examined by histological and immunophenotypic methods for comparison to Leydig cell tumor., Results: A total of 14 males with an endocrine disorder had pathological evidence of testicular tumor of the adrenogenital syndrome. These tumors were often bilateral (93% or 13 of 14 cases), associated with pain (92% or 12 of 13) and refractory to medical management with high dose exogenous steroids (93% or 13 of 14). Testicular tumor of the adrenogenital syndrome was managed by tumor enucleation in 7 patients (54%) and by radical orchiectomy in 6 (46%). All patients had resolution of pain at 3-month followup. Upon histological review features found to be more common to testicular tumor of the adrenogenital syndrome compared with Leydig cell tumor were nuclear pleiomorphism, low mitotic activity, extensive fibrosis, lymphoid aggregates, adipose metaplasia and prominent lipochrome pigment. Synaptophysin (ICN, Costa Mesa, California) reactivity was strong in testicular tumor of the adrenogenital syndrome but rarely observed in Leydig cell tumor., Conclusions: In our series medical treatment failed in patients with testicular tumor of the adrenogenital syndrome and conservative surgical therapy was possible in select individuals. We identified special histopathological and immunophenotypic features, including synaptophysin staining, which distinguish testicular tumor of the adrenogenital syndrome from Leydig cell tumor.

Background and Purpose: The classic standard for surgical repair of ureteropelvic junction (UPJ) obstruction has been open pyeloplasty, with a 95% success rate. Antegrade endopyelotomy is a less-invasive option with a slightly lower success rate. However, recent data call into question the long-term durability of UPJ repair. We present the long-term success of treatment of UPJ obstruction comparing these two modalities., Patients and Methods: We reviewed the medical records of patients undergoing percutaneous antegrade endopyelotomy or open and laparoscopic pyeloplasty for UPJ repair in our practice from 1988 to 2004. Success was defined as both radiographic and symptomatic improvement. We evaluated the impact of preoperative factors, including prior surgical repair, crossing vessels, renal function, and calculi, on success., Results: The estimated 3-, 5-, and 10-year recurrence-free survival rates for the endopyelotomy group (N = 182) were 63%, 55%, and 41%, respectively, compared with 85%, 80%, and 75% for the pyeloplasty group (N = 175; P < 0.001). Of the failed endopyelotomies undergoing salvage open repair, 8 of 26 (31%) had crossing vessels. Poor renal function and previous failed pyeloplasty decreased success in the pyeloplasty group. Variation from standard cold-knife incision adversely affected endopyelotomy success., Conclusions: Long-term success rates after both endopyelotomy and pyeloplasty are worse than previously reported. Although most failures in both groups occurred within 2 years, failures continue to appear after 5 and 10 years, and patients should be followed accordingly. In view of these results of endopyelotomy, laparoscopic pyeloplasty may prove to be the preferred minimally invasive approach to repair UPJ obstruction.

A healthy 31-year-old male abstinent from drug abuse during his recent incarceration developed slurred speech, a severe headache, and left-sided hemiparesis prior to his eventual death 9.5 hours after inhalation of methamphetamine. On postmortem examination, inspection of the brain revealed bilateral subarachnoid hemorrhage, with a prominent intralobar hemorrhage centered within the right frontal cerebral hemisphere. No evidence of vasculitis, infarction, intraventricular hemorrhage, or ruptured aneurysm could be observed. While this is not the first report of a methamphetamine-related stroke, this report describes the autopsy findings of an intracerebral hemorrhage secondary to methamphetamine abuse on autopsy and compares the findings and antemortem history to previously reported methamphetamine cerebral vascular deaths.

A patient with a history of ingesting large quantities of an over-the-counter stimulant developed renal calculi that on further analysis, after stone passage, revealed increased amounts of ephedrine. Over the course of 7 months, all of the patient's ephedrine stones were managed successfully by alkalinization. Similar to previously reported ephedrine calculi, these stones were radiolucent on x-ray imaging, but their course was monitored on serial nonenhanced computed tomography scans. We believe this to be the first reported use of alkaline therapy for the dissolution of renal stones containing ephedrine.

A patient who had developed a persistent fistula between the urethra and bladder neck after its surgical closure in the construction of a continent urinary pouch and Mitrofanoff nipple was successfully treated by antegrade periurethral injection of a newly approved injectable bulking agent for stress urinary incontinence (Durasphere) to occlude the bladder neck. We believe this to be the first reported use of Durasphere for such treatment.