Erythromycin, retapamulin, pyridoxine, folic acid, and ivermectin inhibit cytopathic effect, papain-like protease, and MPRO enzymes of SARS-CoV-2.

Background: Although tremendous success has been achieved in the development and deployment of effective COVID-19 vaccines, developing effective therapeutics for the treatment of those who do come down with the disease has been with limited success. To repurpose existing drugs for COVID-19, we previously showed, qualitatively, that erythromycin, retapamulin, pyridoxine, folic acid, and ivermectin inhibit SARS-COV-2-induced cytopathic effect (CPE) in Vero cells. Aim: This study aimed to quantitatively explore the inhibition of SARS-CoV-2-induced CPE by erythromycin, retapamulin, pyridoxine, folic acid, and ivermectin and to determine the effect of these drugs on SARS-CoV-2 papain-like protease and 3CL protease (MPRO) enzymes. Methods: Neutral red (3-amino-7-dimethylamino-2-methyl-phenazine hydrochloride) cell viability assay was used to quantify CPE after infecting pre-treated Vero cells with clinical SARS-Cov-2 isolates. Furthermore, SensoLyte® 520 SARS-CoV-2 papain-like protease and SensoLyte® 520 SARS-CoV-2 MPRO activity assay kits were used to evaluate the inhibitory activity of the drugs on the respective enzymes. Results: Erythromycin, retapamulin, pyridoxine, folic acid, and ivermectin dose-dependently inhibit SARS-CoV-2-induced CPE in Vero cells, with inhibitory concentration-50 (IC50) values of 3.27 µM, 4.23 µM, 9.29 µM, 3.19 µM, and 84.31 µM, respectively. Furthermore, erythromycin, retapamulin, pyridoxine, folic acid, and ivermectin dose-dependently inhibited SARS-CoV-2 papain-like protease with IC50 values of 0.94 µM, 0.88 µM, 1.14 µM, 1.07 µM, and 1.51 µM, respectively, and inhibited the main protease (MPRO) with IC50 values of 1.35 µM, 1.25 µM, 7.36 µM, 1.15 µM, and 2.44 µM, respectively. Conclusion: The IC50 for all the drugs, except ivermectin, was at the clinically achievable plasma concentration in humans, which supports a possible role for the drugs in the management of COVID-19. The lack of inhibition of CPE by ivermectin at clinical concentrations could be part of the explanation for its lack of effectiveness in clinical trials.

Paucity of Health Data in Africa: An Obstacle to Digital Health Implementation and Evidence-Based Practice.

Background: Among the numerous challenges that Africa faces in improving its healthcare systems, the paucity of health data stands out as paramount. This study aims to examine the challenges related to the paucity of health data in Africa and its impact on the implementation of digital health and evidence-based practice. The findings of the study reveal that health data availability in Africa is both limited and frequently of poor quality. Several factors contribute to this concerning situation, encompassing inadequate infrastructure, a shortage of resources, and cultural barriers. Furthermore, the available data, despite its limitations, is often underutilized due to a lack of capacity and expertise in data analysis and interpretation. Policy Options and Recommendations: To improve healthcare delivery in Africa, we recommend implementing novel strategies for data collection. It's important to recognize that effective information technology service is crucial for enhancing healthcare delivery, and a holistic approach is necessary to achieve this. Conclusion: This brief presents information to help policymakers develop long-term solutions to Africa's health data poverty. Taking action based on this evidence can assist in addressing the problem.

Prevalence and pattern of adverse events following COVID 19 vaccination among adult population in Sokoto metropolis, northwest, Nigeria

BackgroundCOVID-19 still poses a major public health challenge worldwide and vaccination remains one of the major interventions to control the disease. Different types of vaccines approved by the World Health Organization (WHO) are currently in use across the world to protect against the disease. As all vaccines are associated with some adverse reactions (ARs), this study assessed the prevalence and pattern of adverse events following immunization (AEFI) after receiving COVID-19 vaccine among the adult population in Sokoto metropolis, North-west, Nigeria MethodsWe conducted a cross-sectional study among 230 adults in Sokoto metropolis who received COVID-19 vaccine. Data was collected using a structured questionnaire administered via personal phone calls to respondents who were selected via a systematic sampling technique. For data analysis, IBM SPSS version 25.0 was used. ResultsThe Majority of the participants [183 (79.7%)] experienced AEFI. The most common adverse events were body weakness [157(85%)], fever [111(60.3%)] and headache [103(56%)]. Up to half of the respondents that experienced AEFI said it occurred within minutes and a few hours, whereas 75 (40.8%) said it was within 2-3 days. Up to 66.3 of the adverse reactions were mild and lasted between a few hours (37.5%) and one day (31.5%); however, 15.2% of the respondents had severe reactions of which 22.7% were admitted to a health facility. The development of AEFI was linked to the absence of an underlying medical condition, a previous history of AEFI, and a history of drug reaction. ConclusionThe majority of respondents reported adverse events following COVID-19 vaccination, with body weakness, fever, and headache being the most common AEFIs. The underlying medical condition as well as a history of adverse drug reactions were predictors of the development of adverse reactions following COVID-19 vaccination. Service providers at each COVID-19 vaccination point should always take the time to explain to vaccine recipients that adverse reactions are possible; however, they should reassure them that most ARs resolve within a few hours to a few days.

Inhibition of Trypanosoma evansi Protein-Tyrosine Phosphatase by Myristic Acid Analogues Isolated from Khaya senegalensis and Tamarindus indica.

BACKGROUND: Trypanosome infections still pose severe health and economic consequences, especially in the endemic regions of Sub-Saharan Africa. Trypanosome differentiation to the procyclic forms which lack the immune evasion mechanisms for survival in the bloodstream is prevented by tyrosine dephosphorylation which is catalyzed by protein-tyrosine phosphatase; thereby promoting survival of the parasites in the host. Inhibition of Protein-tyrosine phosphatase is a strategic therapeutic target that could attenuate trypanosomiasis. This study investigated the in vitro inhibitory effect of stem bark extracts of Khaya senegalensis and Tamarindus indica on the enzymatic activity of protein-tyrosine phosphatase. METHODS: All determinations were carried out following standard procedures for analytical experiments. The analogues of myristic acid that inhibited the enzymatic activity of protein-tyrosine phosphatase were isolated by bioassay-guided fractionation of stem bark extracts of Khaya senegalensis and Tamarindus indica. RESULTS: Analogues of myristic acid proved to be potent inhibitors of protein-tyrosine phosphatase. Double reciprocal (Lineweaver-Burk) plots of the initial velocity data indicated non-competitive inhibition with Ki of 0.67 mg/mL for Khaya senegalensis and 2.17 mg/mL for Tamarindus indica. The kinetic parameters for the cleavage of para-nitrophenylphosphate by the enzyme showed a KM of 3.44 mM and Vmax of 0.19 µmol/min. Sodium orthovanadate, the enzymes' specific inhibitor, inhibited the enzyme competitively with Ki of 0.20 mg/mL. Gas chromatography-mass spectrometry analysis of the stem bark bioactive fractions of Khaya senegalensis and Tamarindus indica revealed the presence of myristic acid analogues. CONCLUSION: Analogues of myristic acid are potent inhibitors of protein-tyrosine phosphatase that could be developed as trypanocide to inhibit the enzymatic activity of protein-tyrosine phosphatase in order to prevent transmission of trypanosomes.

Prospective Observational Study on acute Appendicitis Worldwide (POSAW).

Background: Acute appendicitis (AA) is the most common surgical disease, and appendectomy is the treatment of choice in the majority of cases. A correct diagnosis is key for decreasing the negative appendectomy rate. The management can become difficult in case of complicated appendicitis. The aim of this study is to describe the worldwide clinical and diagnostic work-up and management of AA in surgical departments. Methods: This prospective multicenter observational study was performed in 116 worldwide surgical departments from 44 countries over a 6-month period (April 1, 2016-September 30, 2016). All consecutive patients admitted to surgical departments with a clinical diagnosis of AA were included in the study. Results: A total of 4282 patients were enrolled in the POSAW study, 1928 (45%) women and 2354 (55%) men, with a median age of 29 years. Nine hundred and seven (21.2%) patients underwent an abdominal CT scan, 1856 (43.3%) patients an US, and 285 (6.7%) patients both CT scan and US. A total of 4097 (95.7%) patients underwent surgery; 1809 (42.2%) underwent open appendectomy and 2215 (51.7%) had laparoscopic appendectomy. One hundred eighty-five (4.3%) patients were managed conservatively. Major complications occurred in 199 patients (4.6%). The overall mortality rate was 0.28%. Conclusions: The results of the present study confirm the clinical value of imaging techniques and prognostic scores. Appendectomy remains the most effective treatment of acute appendicitis. Mortality rate is low.

Complicated intra-abdominal infections worldwide: the definitive data of the CIAOW Study.

The CIAOW study (Complicated intra-abdominal infections worldwide observational study) is a multicenter observational study underwent in 68 medical institutions worldwide during a six-month study period (October 2012-March 2013). The study included patients older than 18 years undergoing surgery or interventional drainage to address complicated intra-abdominal infections (IAIs). 1898 patients with a mean age of 51.6 years (range 18-99) were enrolled in the study. 777 patients (41%) were women and 1,121 (59%) were men. Among these patients, 1,645 (86.7%) were affected by community-acquired IAIs while the remaining 253 (13.3%) suffered from healthcare-associated infections. Intraperitoneal specimens were collected from 1,190 (62.7%) of the enrolled patients. 827 patients (43.6%) were affected by generalized peritonitis while 1071 (56.4%) suffered from localized peritonitis or abscesses. The overall mortality rate was 10.5% (199/1898). According to stepwise multivariate analysis (PR = 0.005 and PE = 0.001), several criteria were found to be independent variables predictive of mortality, including patient age (OR = 1.1; 95%CI = 1.0-1.1; p < 0.0001), the presence of small bowel perforation (OR = 2.8; 95%CI = 1.5-5.3; p < 0.0001), a delayed initial intervention (a delay exceeding 24 hours) (OR = 1.8; 95%CI = 1.5-3.7; p < 0.0001), ICU admission (OR = 5.9; 95%CI = 3.6-9.5; p < 0.0001) and patient immunosuppression (OR = 3.8; 95%CI = 2.1-6.7; p < 0.0001).

2013 WSES guidelines for management of intra-abdominal infections.

Despite advances in diagnosis, surgery, and antimicrobial therapy, mortality rates associated with complicated intra-abdominal infections remain exceedingly high.The 2013 update of the World Society of Emergency Surgery (WSES) guidelines for the management of intra-abdominal infections contains evidence-based recommendations for management of patients with intra-abdominal infections.

Complicated intra-abdominal infections in a worldwide context: an observational prospective study (CIAOW Study).

Despite advances in diagnosis, surgery, and antimicrobial therapy, mortality rates associated with complicated intra-abdominal infections remain exceedingly high. The World Society of Emergency Surgery (WSES) has designed the CIAOW study in order to describe the clinical, microbiological, and management-related profiles of both community- and healthcare-acquired complicated intra-abdominal infections in a worldwide context. The CIAOW study (Complicated Intra-Abdominal infection Observational Worldwide Study) is a multicenter observational study currently underway in 57 medical institutions worldwide. The study includes patients undergoing surgery or interventional drainage to address complicated intra-abdominal infections. This preliminary report includes all data from almost the first two months of the six-month study period. Patients who met inclusion criteria with either community-acquired or healthcare-associated complicated intra-abdominal infections (IAIs) were included in the study. 702 patients with a mean age of 49.2 years (range 18-98) were enrolled in the study. 272 patients (38.7%) were women and 430 (62.3%) were men. Among these patients, 615 (87.6%) were affected by community-acquired IAIs while the remaining 87 (12.4%) suffered from healthcare-associated infections. Generalized peritonitis was observed in 304 patients (43.3%), whereas localized peritonitis or abscesses was registered in 398 (57.7%) patients.The overall mortality rate was 10.1% (71/702). The final results of the CIAOW Study will be published following the conclusion of the study period in March 2013.

Management of AIDS-associated Kaposi's sarcoma in Nigerian children: a case series and review of literature.

INTRODUCTION: There is a paucity of published studies on the management and outcome of AIDS-associated Kaposi's sarcoma (AAKS) in African children. In this study, we reviewed the management and literature of AAKS in Nigerian children. PATIENTS AND METHODS: A prospective review of children aged 1 to 14 years and adolescents aged 15 to 18 years who presented with AAKS. Following clinical evaluation and resuscitation, patients were treated with highly active antiretroviral therapy (HAART). Stable patients were further treated with chemotherapy consisting of vincristine, doxorubicin, and bleomycin. Patients were monitored until death or loss to follow-up. RESULTS: There were 9 patients: 6 children and 3 adolescents. Three children had vertical transmission of HIV infection. Kaposi's sarcoma was the AIDS-defining disease in 5 patients. One patient was on HAART at the time of diagnosis. There were multiple skin lesions in all patients, and cervical lymph nodes and oropharynx were frequently affected. The CD4 counts at the time of AAKS diagnosis ranged 78 to 601 cells/ uL, mean of 317. Five patients had best palliative care. Three had anticancer chemotherapy, of which 2 were alive 4 years after diagnosis. Three patients died at the initial hospitalization 2 to 6 weeks after diagnosis. CONCLUSION: Children and adolescents with AAKS presented with generalized skin lesions and lymphadenopathy, which facilitated the diagnosis. The majority of the patients presented with advanced disease that was rapidly fatal. However, patients with good immunity may have a prolonged control of symptoms if treated with HAART and appropriate anticancer chemotherapy.

Management and outcomes of male breast cancer in zaria, Nigeria.

Male breast cancer is an uncommon disease accounting for only 1% of all breast cancers. We present the evaluation, treatment and outcome of male patients seen with breast cancer in our institution. Male patients that had histological diagnosis of breast cancer from 2001 to 2010 were retrospectively evaluated. After evaluation patients were treated with modified radical mastectomy. Combination chemotherapy was given to patients with positive axillary lymph nodes. Radiotherapy and hormonal therapy were also employed. There were 57 male patients with breast cancer which accounted for 9% of all breast cancers seen during the study period. Their mean age was 59 ± 2.3 years. The mean tumor diameter was 13 ± 2.5 cm. Fifty three (93%) patients presented with advanced disease including 15 with distant metastasis. Four patients with stage II disease were treated with modified radical mastectomy, chemotherapy and tamoxifen. Of the 30 patients with sage III disease that had modified radical mastectomy, complete axillary clearance and tumor free margins were achieved in 25. Overall 21 (36.8%) patients were tumor free at one year. Overall 5-year survival was 22.8%. In conclusion, male patients with breast cancer present with advanced disease which is associated with poor outcome of treatment.

Hand-held cow horn: resurgence of an old arm or a potential terrorist weapon.

A 23 year old man presented with intestinal evisceration from stab injury to the left side of the abdomen with a hand-held cow horn at a local night party. He complained of severe abdominal pain and bleeding at the site of injury. He was hemodynamically stable. At emergency exploration, the eviscerated bowel was viable with no adjacent mesenteric tear. Other intra abdominal organs were normal. The eviscerated bowel was lavaged and reduced into the abdomen through the 7 cm anterior abdominal wall laceration. The laceration was repaired and abdomen closed in layers. Post operative recovery was uneventful. The hand-held cow horn can easily be concealed and may pass through security checks undetected. It should be added to the ever increasing list of weapons of small scale terror.

Spontaneous rupture of umbilical hernia in pregnancy: a case report.

A 28 year old woman presented with a spontaneous rupture of an umbilical hernia in her seventh month of pregnancy. She had four previous unsupervised normal deliveries. There was no history of trauma or application of herbal medicine on the hernia. The hernia sac ruptured at the inferior surface where it was attached to the ulcerated and damaged overlying skin. There was a gangrenous eviscerated small bowel. The patient was resuscitated and the gangrenous small bowel was resected and end to end anastomosis done. The hernia sac was excised and the 12 cm defect repaired. Six weeks later, she had spontaneous vaginal delivery of a live baby. We advocate that large umbilical hernias should be routinely repaired when seen in women of child bearing age.

Achalasia: what is the best treatment?

BACKGROUND: Achalasia is an infrequent primary motility disorder of the esophagus. Because of uncertain etiology, treatment is only palliative and is directed at decreasing lower esophageal sphincter pressure, improving esophageal emptying and relieving the symptoms of achalasia. Current treatment options include pharmacological, endoscopic and surgical. We undertook a systematic literature review of the management strategies currently available for achalasia. METHOD: A Medline, PubMed and Cochrane database search was conducted using reference manager 11. Original articles and reviews published in the English literature on the management of achalasia were reviewed. Emphasis was placed on articles published in the last ten years on randomized controlled trials comparing the various forms of treatment. RESULTS: Esophageal manometry is the standard diagnostic evaluation for achalasia. Accurate diagnosis can also be made based on clinical findings and barium esophagogram. Medical treatment with nitrates or calcium channel blockers has variable results in alleviating the symptoms of achalasia but long-term results are disappointing because of tolerance and side effects. Intrasphincteric injection of botulinum toxin, pneumatic dilatation and surgical myotomy are variably effective at controlling the symptoms of achalasia but each modality has specific strength and weaknesses which make their choice suitable in a particular group of patients. While pneumatic dilatation is superior to botulinum toxin injection surgical myotomy provides the best long-term control of symptoms in patients with achalasia. CONCLUSION: Laparoscopic myotomy should be the initial treatment for most patients with achalasia. Pneumatic dilatation is the most cost-effective alternative but its long-term efficacy is less than that of surgical myotomy. Endoscopic botulinum toxin injection can be considered when other forms of treatment are contraindicated.

Childhood circumcision: a planned approach.

We prospectively reviewed 3824 boys circumcised during two circumcision festivities. The boys were circumcised in their respective houses under aseptic conditions by teams of nurses, midwives and surgical aids locally trained for that purpose. Complications were seen in 2.3% of the boys, the commonest being infection that was easily controlled by local wound care.

Removal of selected fracture fixation implants under local anaesthesia.

AIMS AND OBJECTIVES: This study was undertaken to evaluate the feasibility and tolerability of fracture fixation implants (FFI) removal under local anaesthesia. MATERIALS AND METHODS: We reviewed 176 patients who had osteosynthetic materials inserted for the treatment of fractures and whose implants were removed under local anaesthesia. Pain and tolerance were determined using a pain severity score determined by the patients. About 60% of the implants were Kuntcher nails while 31% were Krischner wires. In 171 (97.2% ) patients the implants were removed under local anaesthesia while in 5 (2.8% ) patients with Kuntcher nails the procedures were difficult and painful which necessitated the use of intravenous ketamine. RESULTS: About 89% of patients felt no pain during the procedures while 8.5% felt mild to moderate pain, which was easily tolerated. CONCLUSION: The use of local anaesthesia for fracture fixation implants removal is recommended because it is simple and safe and reduced the cost and complications of treatment.