Protective efficacy and safety of radiation-attenuated and chemo-attenuated Plasmodium Falciparum sporozoite vaccines against controlled and natural malaria infection: a systematic review and meta-analysis of randomized controlled trials.

BACKGROUND AND OBJECTIVE: Despite the significant burden of Plasmodium falciparum (Pf) malaria and the licensure of two vaccines for use in infants and young children that are partially effective in preventing clinical malaria caused by Pf, a highly effective vaccine against Pf infection is still lacking. Live attenuated vaccines using Pf sporozoites as the immunogen (PfSPZ Vaccines) hold promise for addressing this gap. Here we review the safety and efficacy of two of the most promising PfSPZ approaches: PfSPZ Vaccine (radiation attenuated PfSPZ) and PfSPZ-CVac (chemo-attenuated PfSPZ). METHODS: We conducted a systematic review and meta-analysis by searching PubMed, EMBASE, SCOPUS, CENTRAL, and WOS until 22nd December 2021. We included randomized controlled trials (RCTs) of these two vaccine approaches that measured protection against parasitaemia following controlled human malaria infection (CHMI) in malaria-naive and malaria-exposed adults or following exposure to naturally transmitted Pf malaria in African adults and children (primary outcome) and that also measured the incidence of solicited and unsolicited adverse events as indicators of safety and tolerability after vaccination (secondary outcome). We included randomized controlled trials (RCTs) that measured the detected parasitaemia after vaccination (primary outcome) and the incidence of various solicited and unsolicited adverse events (secondary outcome). The quality of the included RCTs using the Cochrane ROB 1 tool and the quality of evidence using the GRADE system were evaluated. We pooled dichotomous data using the risk ratio (RR) for development of parasitemia in vaccinees relative to controls as a measure of vaccine efficacy (VE), including the corresponding confidence interval (CI). This study was registered with PROSPERO (CRD42022308057). RESULTS: We included 19 RCTs. Pooled RR favoured PfSPZ Vaccine (RR: 0.65 with 95% CI [0.53, 0.79], P = 0.0001) and PfSPZ-table (RR: 0.42 with 95% CI [0.27, 0.67], P = 0.0002) for preventing parasitaemia, relative to normal saline placebo. Pooled RR showed no difference between PfSPZ Vaccine and the control in the occurrence of any solicited adverse event (RR: 1.00 with 95% CI [0.82, 1.23], P = 0.98), any local solicited adverse events (RR: 0.73 with 95% CI [0.49, 1.08], P = 0.11), any systemic solicited adverse events (RR: 0.94 with 95% CI [0.75, 1.17], P = 0.58), and any unsolicited adverse event (RR: 0.93 with 95% CI [0.78, 1.10], P = 0.37). CONCLUSION: PfSPZ and PfSPZ-CVacs showed comparable efficacy. Therefore, they can introduce a promising strategy for malaria prophylaxis, but more large-scale field trials are required to sustain efficacy and yield clinically applicable findings.

Fascia iliaca compartment block for postoperative pain after total hip arthroplasty: a systematic review and meta-analysis of randomized controlled trials.

BACKGROUND: Fascia iliaca compartment block (FICB) is one of the regional nerve blocks used to reduce pain after total hip arthroplasty (THA). We aim to assess the efficacy of FICB in reducing post-operative pain and opioid consumption. METHODS: We searched PubMed, Web of Science, Cochrane Library, Embase, and Scopus on February 19, 2023, and we updated our search in august 2023 using relevant search strategy. Studies were extensively screened for eligibility by title and abstract screening, followed by full-text screening. We extracted the data from the included studies, and then pooled the data as mean difference (MD) or odds ratio (OR) with a 95% confidence interval (CI), using Review Manager Software (ver. 3.5). RESULTS: FIBC significantly reduced analgesic consumption at 24 h (MD = -8.75, 95% CI [-9.62, -7.88] P < 0.00001), and at 48 h post-operatively. (MD = -15.51, 95% CI [-26.45, -4.57], P = 0.005), with a significant sensory block of the femoral nerve (P = 0.0004), obturator nerve (P = 0.0009), and lateral femoral cutaneous nerve (P = 0.002). However, FICB was not associated with a significant pain relief at 6, 24, and 48 h postoperatively, except at 12 h where it significantly reduced pain intensity (MD = -0.49, 95% CI [-0.85, -0.12], P = 0.008). FICB was also not effective in reducing post-operative nausea and vomiting (MD = 0.55, 95% CI [0.21, 1.45], P = 0.23), and was associated with high rates of quadriceps muscle weakness (OR = 9.09, % CI [3.70, 22.30], P = < 0.00001). CONCLUSIONS: FICB significantly reduces the total analgesic consumption up to 48 h; however, it is not effective in reducing post-operative pain, nausea and vomiting and it induced postoperative muscle weakness.

Efficacy and safety of triple therapy versus dual therapy for lymphatic filariasis: A systematic review and meta-analysis.

OBJECTIVE: Lymphatic filariasis is a serious public health issue. Recent studies showed that a single dosage of triple therapy (Ivermectin, Diethylcarbamazepine, and Albendazole) is more effective than dual therapy (Ivermectin plus Albendazole or Diethylcarbamazepine plus Albendazole) for clearing microfilaria from the blood. We aimed to evaluate the efficacy and safety of triple therapy versus dual therapy in patients infected with microfilaria and communities endemic to lymphatic filariasis. METHODS: For this systematic review and meta-analysis, we searched MEDLINE, EMBASE, SCOPUS, Cochrane Central Register of Controlled Trials, and Web of Science until 24th June 2021. We included randomized control trials that compared triple with dual therapy given to patients with lymphatic filariasis or endemic communities. This study was registered with PROSPERO (CRD42021266724). RESULTS: We included eight articles after the screening process. Triple therapy caused more clearance of microfilaria in the blood (RR: 1.52; 95% CI: 1.15, 2.02; p = 0.003), while dual therapy caused more clearance of the circulating filariae antigen in the blood (RR: 0.76; 95% CI: 0.65, 0.88; p = 0.0003), both 12 months after drug administration. The triple therapy had a similar adverse effect compared with the dual therapy group. CONCLUSION: Based on the greater efficacy in the clearance of microfilaria and the safety of triple therapy, it constitutes a better strategy for the eradication programs of lymphatic filariasis in endemic regions. However, further studies are needed to confirm our results.

Knowledge, attitudes, practices and perceived barriers towards research in undergraduate medical students of six Arab countries.

BACKGROUND: The involvement of the undergraduates in the research field requires a better view of their potential and the anticipated barriers facing them. This study aims to assess the undergraduates' knowledge, attitudes, practices and perceived barriers towards research in six Arab countries. METHODS: A cross sectional study included medical students from six Arab countries, where a self-administered five-section questionnaire was used to assess the students' demographics, knowledge, attitudes, practices and perceived barriers. The questionnaire was distributed in the online educational platforms of the participating medical schools in the six included countries. RESULTS: The total sample of recruited students was 2989, the majority of students (91.6%) showed poor level of knowledge regarding research. Generally high levels of positive attitudes towards research, research relevance and usefulness were found, with moderate levels of perception of research anxiety and difficulty. 33.7% (n = 1006) participated in an actual research project before with a mean of .5 publications per student. Cross-sectional studies were the most common type of studies conducted by students (38.6%), followed by case reports (23.9%). Lack of access to lab equipment for lab research (68.1%), the priority of education over research (66.8%), and lack of time because of educational tasks (66.1%) were generally the top perceived barriers towards research practice. CONCLUSION: In the current study, the participants showed a poor knowledge level with associated positive attitudes towards research. One third of the students participated in research projects that mostly were cross-sectional studies and case reports. Educational tasks and lack of support were the most prevalent barriers. The students' positive attitudes towards research need to be translated into better knowledge and appropriate practice, which can be done by development of better training systems and more structured mentoring.

The prevalence and presentation patterns of microcystic macular oedema: a systematic review and meta-analysis of 2128 glaucomatous eyes.

We conducted this research to determine the prevalence rate and presentation patterns with microcystic macular oedema (MMO) in glaucoma patients. The protocol was pre-registered on PROSPERO ( CRD42022316367 ). PubMed, Scopus, Web of Science, EMBASE, ProQuest, EBSCOHost, CENTRAL, clinicaltrials.gov, and Google Scholar were searched for articles reporting MMO in glaucoma patients. The primary outcome was the prevalence of MMO, while secondary outcomes included the comparison between MMO and non-MMO in terms of patients' characteristics (age, gender), glaucoma stage, and ocular parameters (axial length (AL), intraocular pressure, mean deviation, spherical equivalent). Data are reported as mean difference (MD) or log odds ratio (logOR) along with their corresponding 95% confidence intervals (CI) for continuous and dichotomous outcomes, respectively. The quality of included studies was assessed using the NIH tool, and the certainty of evidence was assessed using GRADE framework. Ten studies (2128 eyes) were included, revealing an overall prevalence rate of MMO of 8% (95%CI: 5-12%). When compared to non-MMO group, MMO was associated with lower age (MD = -5.91; 95%CI: -6.02: -5.20), greater risk of advanced glaucoma stage (LogOR=1.41; 95%CI: 0.72: 2.09), and lower mean deviation of the visual field (MD = -5.00; 95%CI: -7.01: -2.99). No significant difference was noted between both groups in terms of gender, axial length, or spherical equivalent. Three studies had good quality while seven had poor quality. MMO is a prevalent observation in glaucoma patients and is associated with patients' age and stage of the disease. However, the certainty of evidence remains very low.