METHODS: Patients were divided into two groups according to the type of laser employed [Holmium:YAG (HL) or Thulium fiber laser (TFL)]. Residual fragments (RF) were defined as > 2 mm. Multivariable logistic regression analysis was performed to evaluate factors associated with RF and RF needing further intervention.
RESULTS: 4208 patients from 20 centers were included. In whole series, age, recurrent stones, stone size, lower pole stones (LPS), and multiple stones were predictors of RF at multivariable analysis and LPS and stone size with RF requiring further treatment. HU and TFL were associated with lesser RF and RF requiring an additional treatment. In HU treatment, while LPS and TFL were associated with lesser RF requiring further treatment. In HU ≥ 1000 stones, age, stone size, multiple stones, and LPS were predictors of RF at multivariable analysis, while TFL was less likely associated with RF. Stone size and LPS were predictors of RF requiring further treatment, whereas TFL was associated with RF requiring further treatment.
CONCLUSION: Stone size, LPS, and use of HL are predictors of RF after RIRS for intrarenal stones regardless of stone density. HU should be considered an important parameter in predicting SFR.
METHODS: A decision tree model was developed based on literature and expert inputs. An epidemiological projection model was then added to the decision tree to calculate the target population size. The budget impact of adapting the different enteral nutrition (EN) formulas was calculated by multiplying the population size with the costs of the formula and ICU length of stay (LOS). A one-way sensitivity analysis (OWSA) was conducted to examine the effect each input parameter has on the calculated output.
RESULTS: Replacing SPF with SEF would lower ICU cost by MYR 1059 (USD 216) per patient. The additional cost of increased LOS due to EFI was MYR 5460 (USD 1114) per patient. If the MOH replaces SPF with SEF for ICU patients with high EFI risk (estimated 7981 patients in 2022), an annual net cost reduction of MYR 8.4 million (USD 1.7 million) could potentially be realized in the MOH system. The cost-reduction finding of replacing SPF with SEF remained unchanged despite the input uncertainties assessed via OWSA.
CONCLUSION: Early use of SEF in ICU patients with high EFI risk could potentially lower the cost of ICU care for the MOH system in Malaysia.
METHODS: This multicentre, randomised, placebo-controlled, phase 2b trial was done at 60 hospitals and clinics in 20 countries. Eligible study participants were aged between 12 and 75 years with a documented history of GPP as per the European Rare and Severe Psoriasis Expert Network criteria, with a history of at least two past GPP flares, and a GPP Physician Global Assessment (GPPGA) score of 0 or 1 at screening and random assignment. Patients were randomly assigned (1:1:1:1) to receive subcutaneous placebo, subcutaneous low-dose spesolimab (300 mg loading dose followed by 150 mg every 12 weeks), subcutaneous medium-dose spesolimab (600 mg loading dose followed by 300 mg every 12 weeks), or subcutaneous high-dose spesolimab (600 mg loading dose followed by 300 mg every 4 weeks) over 48 weeks. The primary objective was to demonstrate a non-flat dose-response curve on the primary endpoint, time to first GPP flare.
FINDINGS: From June 8, 2020, to Nov 23, 2022, 157 patients were screened, of whom 123 were randomly assigned. 92 were assigned to receive spesolimab (30 high dose, 31 medium dose, and 31 low dose) and 31 to placebo. All patients were either Asian (79 [64%] of 123) or White (44 [36%]). Patient groups were similar in sex distribution (76 [62%] female and 47 [38%] male), age (mean 40·4 years, SD 15·8), and GPP Physician Global Assessment score. A non-flat dose-response relationship was established on the primary endpoint. By week 48, 35 patients had GPP flares; seven (23%) of 31 patients in the low-dose spesolimab group, nine (29%) of 31 patients in the medium-dose spesolimab group, three (10%) of 30 patients in the high-dose spesolimab group, and 16 (52%) of 31 patients in the placebo group. High-dose spesolimab was significantly superior versus placebo on the primary outcome of time to GPP flare (hazard ratio [HR]=0·16, 95% CI 0·05-0·54; p=0·0005) endpoint. HRs were 0·35 (95% CI 0·14-0·86, nominal p=0·0057) in the low-dose spesolimab group and 0·47 (0·21-1·06, p=0·027) in the medium-dose spesolimab group. We established a non-flat dose-response relationship for spesolimab compared with placebo, with statistically significant p values for each predefined model (linear p=0·0022, emax1 p=0·0024, emax2 p=0·0023, and exponential p=0·0034). Infection rates were similar across treatment arms; there were no deaths and no hypersensitivity reactions leading to discontinuation.
INTERPRETATION: High-dose spesolimab was superior to placebo in GPP flare prevention, significantly reducing the risk of a GPP flare and flare occurrence over 48 weeks. Given the chronic nature of GPP, a treatment for flare prevention is a significant shift in the clinical approach, and could ultimately lead to improvements in patient morbidity and quality of life.
FUNDING: Boehringer Ingelheim.
OBJECTIVES: This study sought to examine the different prognostic effects of revascularization strategies according to the diabetes status from the randomized BEST (Randomized Comparison of Coronary Artery Bypass Surgery and Everolimus-Eluting Stent Implantation in the Treatment of Patients With Multivessel Coronary Artery Disease) trial.
METHODS: Patients (n = 880) with MVD were randomly assigned to undergo PCI with an everolimus-eluting stent vs CABG stratified by diabetics (n = 363) and nondiabetics (n = 517). The primary endpoint was the composite of death, myocardial infarction, or target vessel revascularization during a median follow-up of 11.8 years (IQR: 10.6-12.5 years).
RESULTS: In diabetics, the primary endpoint rate was significantly higher in the PCI group than in the CABG group (43% and 32%; HR: 1.53; 95% CI: 1.12-2.08; P = 0.008). However, in nondiabetics, no significant difference was found between the groups (PCI group, 29%; CABG group, 29%; HR: 0.97; 95% CI: 0.67-1.39; P = 0.86; Pinteraction= 0.009). Irrespective of the presence of diabetes, no significant between-group differences were found in the rate of a safety composite of death, myocardial infarction, or stroke and mortality rate. However, the rate of any repeat revascularization was significantly higher in the PCI group than in the CABG group.
CONCLUSIONS: In diabetics with MVD, CABG was associated with better clinical outcomes than PCI. However, the mortality rate was similar between PCI and CABG irrespective of diabetes status during an extended follow-up. (Ten-Year Outcomes of Randomized Comparison of Coronary Artery Bypass Surgery and Everolimus-Eluting Stent Implantation in the Treatment of Patients With Multivessel Coronary Artery Disease [BEST Extended], NCT05125367; Randomized Comparison of Coronary Artery Bypass Surgery and Everolimus-Eluting Stent Implantation in the Treatment of Patients With Multivessel Coronary Artery Disease [BEST], NCT00997828).
METHODS: Patient and tumor characteristics as well as surgical outcomes from 11 international centers were recorded. All tumors were retrospectively assigned an Orbital Resection by Intranasal Technique (ORBIT) class and stratified based on surgical approach as either exclusively endoscopic or combined (endoscopic and open). Outcomes based on approach were compared using chi-squared or Fisher's exact tests. The Cochrane-Armitage test for trend was used to analyze outcomes by class.
RESULTS: Findings from 110 PBOTs from 110 patients (age 49.0 ± 15.0 years, 51.9% female) were included in the analysis. Higher ORBIT class was associated with a lower likelihood of gross total resection (GTR). GTR was more likely to be achieved when an exclusively endoscopic approach was utilized (p treatment of PBOTs is an effective approach, with favorable short-term and long-term postoperative outcomes as well as low rate of adverse events. The ORBIT classification system is an anatomic-based framework that effectively facilitates high-quality outcomes reporting for all PBOTs.
AIM: The study evaluates the effectiveness and safety of a topical moisturizer containing tocotrienol-rich composition over 12 weeks on patients aged between 1 month and 12 years with mild to moderate AD.
METHODS: We conducted a 12 weeks, prospective, open-label clinical study on the effect of tocotrienol as an adjunct to conventional treatment. This study was approved by the Ethics Committee for Research Involving Human Subject. JKEUPM-2019-274 (NMMR-19-1588-49234).
RESULTS: Thirty AD patients with a mean age of 2.77 ± 3.05 were enrolled in the study. At week-12, significant reduction of investigator global assessment (63.4%), Patient-Oriented Scoring Atopic Dermatitis Index (PO-SCORAD) (65%), and SCORAD (52.3%) was noted (p
METHODS: Subjects were recruited from lipid and cardiac specialist hospitals. FH was clinically diagnosed using the Dutch Lipid Clinic Network Criteria. Patients' medical history was recorded using a standardized questionnaire. LLM prescription history and baseline LDL-C were acquired from the hospitals' database. Blood samples were acquired for the latest lipid profile assay.
RESULTS: A total of 206 patients with FH were recruited. Almost all of them were on LLMs (97.6%). Only 2.9% and 7.8% of the patients achieved the target LDL-C of ＜1.4 and ＜1.8 mmol/L, respectively. The majority of patients who achieved the target LDL-C were prescribed with statin-ezetimibe combination medications and high-intensity or moderate-intensity statins. All patients who were prescribed with ezetimibe monotherapy did not achieve the target LDL-C.
CONCLUSION: The majority of Malaysian patients with FH received LLMs, but only a small fraction achieved the therapeutic target LDL-C level. Further investigation has to be conducted to identify the cause of the suboptimal treatment target attainment, be it the factors of patients or the prescription practice.
OBJECTIVE: This review aimed to answer the following research question: 'Does pulpotomy (partial or full) (I) result in better patient and clinical reported outcomes (O), compared with RCT (C) in permanent teeth with pulpitis characterized by spontaneous pain (P) evaluated at various time intervals?' (T).
METHODS: Two authors independently performed study selection, data extraction and risk of bias assessment. The literature search was conducted in the following electronic databases: Clarivate Analytics' Web of Science, Scopus, PubMed and Cochrane Central Register of Controlled Trials. English language clinical trials comparing the patient and clinical reported outcomes between RCT and pulpotomy were included. The meta-analysis was performed on a fixed-effect model and the quality of evidence assessed by the Grading of Recommendations, Assessment, Development and Evaluations (GRADE) approach.
RESULTS: Two randomized clinical trials were included. Amongst two trials, one has published four reports at different time points involving the same cohorts. The meta-analysis revealed no difference in postoperative pain (Day 7) between RCT and pulpotomy (OR = 0.99, 95% CI 0.63-1.55, I2 = 0%) and quality of evidence was graded as 'High'. Clinical success was high at year 1, 98% for both interventions, however, decreased over time to 78.1% (pulpotomy) and 75.3% (RCT) at 5 years.
DISCUSSION: Pulpotomy is a definitive treatment modality that is as effective as RCT. This could have a significant impact on treatment of such patients affording the advantages of retaining a vital pulp and preventing the need for RCT.
CONCLUSION: This review could only include two trials, hence there is insufficient evidence to draw robust conclusions. The clinical data accumulated so far suggests no difference in pain between RCT and pulpotomy at Day 7 postoperatively and a single randomized control trial suggests that the clinical success rate for both treatment modalities is similar long term. There is a need for more well-designed trials by different research groups to develop a stronger evidence base in this area.
REGISTRATION: PROSPERO database (CRD42021259744).
OBJECTIVE: This article reviews the association between CYP3A4/5 genetic variations and response to atorvastatin therapy globally, which includes atorvastatin PK, and the risk for adverse reactions, with a hint to the Egyptians.
METHODS: Up to March 30, 2022, electronic medical databases like PubMed, Web of Science, MEDLINE, and Egyptian Knowledge Bank (EKB) were searched. All articles that highlighted the relationship between CYP3A4/5 genetic polymorphisms and atorvastatin efficacy/safety profile were included in this review.
RESULTS: Initially, 492 articles were retrieved after an exhaustive search. There were 24 articles included according to the inclusion criteria. Findings of association studies of CYP3A4/5 genetic polymorphisms with response to atorvastatin varied among different ethnicities. CYP3A4*1B was associated with better therapeutic outcomes after atorvastatin therapy in Chileans and vice versa in Americans. Caucasians with myalgia while using atorvastatin were at significant risk of suffering severe muscle damage if they were carriers of CYP3A5*3/*3. As far as we can report for the Egyptian population, the impact of CYP3A4/5 genetic variations on the response to atorvastatin therapy was understudied.
CONCLUSION: More pharmacogenetic studies amongst diverse populations worldwide, like the Egyptian population, are necessary to detect further atorvastatin-gene interactions.
METHOD: A modified Delphi approach with three rounds of questionnaire was adopted. A total of 29 international experts from 11 countries were recruited for this study. Six domains with a total of 37 statements were examined, including anatomical definition; definition of intersphincteric dissection, intersphincteric resection (ISR) and ultra-low anterior resection (uLAR); indication for ISR; surgical technique of ISR; specimen description of ISR; and functional outcome assessment protocol.
RESULTS: Three rounds of questionnaire were performed (response rate 100%, 89.6%, 89.6%). Agreement (≥80%) reached standardization on 36 statements.
CONCLUSION: This study provides an international expert consensus-based definition and standardization of ISR. This is the first study standardizing terminology and definition of deep pelvis/anal canal anatomy from a surgical point of view. Intersphincteric dissection, ISR and uLAR were specifically defined for precise surgical description. Indication for ISR was determined by the rectal tumour's maximal radial infiltration (T stage) below the levator ani. A new surgical definition of T3isp was reached by consensus to define T3 low rectal tumours infiltrating the intersphincteric plane. A practical flowchart for surgical indication for uLAR/ISR/abdominoperineal resection was developed. A standardized ISR surgical technique and functional outcome assessment protocol was defined.
MATERIALS AND METHODS: We reviewed the medical records of all patients that underwent bullectomy from 1st June 2017 to 31st May 2022. Mann Whitney U-test was completed for all variables. Primary objective was to compare operating time (OT), global operating time (GOT), post-operative length of stay (LOS) and complication rate.
RESULTS: A total of 90 bullectomies performed in which 36 were approached via iVATS and 54 NiVATS. It was found that the post-operative LOS, GOT, and OT were significantly shorter in the NiVATS as compared to iVATS. Complication rate between both groups showed no significant difference.
CONCLUSION: NiVATS bullectomy demonstrated a safe and reliable alternative surgical approach with superior surgical outcome than iVATS bullectomy.
MATERIALS AND METHODS: We conducted a descriptive, retrospective study among epilepsy patients treated with perampanel. We aimed to assess the efficacy and safety of perampanel as an adjunctive in our hospital.
RESULTS AND CONCLUSIONS: From our cohort of 25 patients, most of the patients were either on one or three anti-seizure medications (ASMs) prior to initiation of perampanel. Perampanel was added in 88% of them due to persistent seizures. Twenty-two (88%) patients experienced reduction in seizure frequency. 12% experienced mild side effects, which were leg cramps, hyponatremia and drowsiness. Only 1 patient stopped perampanel due to its side effects.
CONCLUSION: Perampanel is a well-tolerated ASM that should be widely used as an adjunctive. More studies with regards to its efficacy and safety involving more centres are encouraged in Malaysia.
METHODS: A systematic review of EMBASE, MEDLINE, PubMed, and Cochrane Register from inception to April 1, 2022 was performed. Articles were assessed using the methodological index for non-randomized studies instrument. The primary outcome was to assess and compare the major surgical outcomes of partial or total flap failure, reoperation, and amputation rates.
RESULTS: Seventeen studies were included. All studies were retrospective in nature, of level three evidence, and published between 1986 and 2021. The most common muscle and fasciocutaneous free flaps used were latissimus dorsi flap (38.1%) and anterolateral thigh (ALT) flap (64.8%), respectively. Meta-analysis found no significance difference in rates of total flap failure, takeback operations, or limb salvage, whereas partial flap failure rate was significantly lower for fasciocutaneous flaps. The majority of studies found no significant difference in complication rates, osteomyelitis, time to fracture union, or time to functional recovery. Most, 82.4% (14/17), of the included studies were of high methodological quality.
CONCLUSION: The rate of total flap failure, reoperation, or limb salvage is not significantly different between muscle and fasciocutaneous free flaps after lower limb reconstruction following trauma. Partial flap failure rates appear to be lower with fasciocutaneous free flaps. Outcomes traditionally thought to be managed better with muscle free flaps, such as osteomyelitis and rates of fracture union, were comparable.
PATIENTS AND METHODS: Patients with mCRPC were prospectively identified as HRR+ with/without BRCA1/2 alterations and randomized 1 : 1 to niraparib (200 mg orally) plus AAP (1000 mg/10 mg orally) or placebo plus AAP. At IA2, secondary endpoints [time to symptomatic progression, time to initiation of cytotoxic chemotherapy, overall survival (OS)] were assessed.
RESULTS: Overall, 212 HRR+ patients received niraparib plus AAP (BRCA1/2 subgroup, n = 113). At IA2 with 24.8 months of median follow-up in the BRCA1/2 subgroup, niraparib plus AAP significantly prolonged radiographic progression-free survival {rPFS; blinded independent central review; median rPFS 19.5 versus 10.9 months; hazard ratio (HR) = 0.55 [95% confidence interval (CI) 0.39-0.78]; nominal P = 0.0007} consistent with the first prespecified interim analysis. rPFS was also prolonged in the total HRR+ population [HR = 0.76 (95% CI 0.60-0.97); nominal P = 0.0280; median follow-up 26.8 months]. Improvements in time to symptomatic progression and time to initiation of cytotoxic chemotherapy were observed with niraparib plus AAP. In the BRCA1/2 subgroup, the analysis of OS with niraparib plus AAP demonstrated an HR of 0.88 (95% CI 0.58-1.34; nominal P = 0.5505); the prespecified inverse probability censoring weighting analysis of OS, accounting for imbalances in subsequent use of poly adenosine diphosphate-ribose polymerase inhibitors and other life-prolonging therapies, demonstrated an HR of 0.54 (95% CI 0.33-0.90; nominal P = 0.0181). No new safety signals were observed.
CONCLUSIONS: MAGNITUDE, enrolling the largest BRCA1/2 cohort in first-line mCRPC to date, demonstrated improved rPFS and other clinically relevant outcomes with niraparib plus AAP in patients with BRCA1/2-altered mCRPC, emphasizing the importance of identifying this molecular subset of patients.
METHODS: We searched PubMed/Medline, Web of Science, and Cochrane Library from the inception of the database to November 2022. All studies that compared LBBP with BVP in patients with HFrEF and indications for CRT were included. Two reviewers performed study selection, data abstraction, and risk of bias assessment. We calculated risk ratios (RRs) with the Mantel-Haenszel method and mean difference (MD) with inverse variance using random effect models. We assessed heterogeneity using the I2 index, with I2 > 50% indicating significant heterogeneity.
RESULTS: Ten studies (9 observational studies and 1 randomized controlled trial; 616 patients; 15 centers) published between 2020 and 2022 were included. We observed a shorter fluoroscopy time (MD: 9.68, 95% confidence interval [CI]: 4.49-14.87, I2 = 95%, p
MATERIAL AND METHODS: This is a retrospective observational study done in Hospital Sg Buloh (HSB), a tertiary referral centre in an urban area located north of Kuala Lumpur, Malaysia's capital city, from January until December 2018, involving 289 patients. All cases with CPR and a sustained return of spontaneous circulation (ROSC) were included in the study and followed up until discharged or died in the hospital.
RESULTS: Out of 236 patients recruited, 25.8% achieved ROSC, 15.7% survived on admission, and 4.2% of patients were discharged alive. Of 74.1% of witnessed OHCA, only 17.5% received bystander CPR. Factors with favourable outcomes include CA in ED (p<0.001), the initial rhythm of ventricular fibrillation (p=0.003), defibrillation (p=0.024), OHCA witnessed by emergency medical services (EMS) (p=0.024) and intravenous adrenaline administration (p=0.001). When using multivariate regression analysis, positive outcomes were associated with the cardiac and respiratory cause of CA (Adjusted Odd Ratio (AOR) 3.66; 95% Confidence Intervals, 95%CI: 2.52 - 12.61 and AOR 8.76; 95%CI: 5.76- 15.46, respectively) as well as OHCA witnessed by EMS (AOR 10.81; 95%CI: 1.84- 19.52).
CONCLUSIONS: Despite being an upper-middle-income country and having advancements in the healthcare system, a relatively lower STD rate among survivors of CA in the ED was observed in this study. There was underutilization of the EMS among patients with CA. The bystander CPR rate among patients with CA in Malaysia is also worryingly low. Aggressive community participation in cardiac arrest awareness programmes is much required. Additionally, in achieving better outcomes, implementing standardized post-resuscitation care protocols with existing resources will be a challenge for physicians managing cardiac arrest cases.