Stakeholders' Perspectives Regarding Supply Chain System of Pharmaceuticals and Vaccines in Pakistan: A Qualitative Study.

The present study was undertaken to assess the current supply chain system of pharmaceuticals and vaccines in Pakistan in terms of structure, process, and outcomes, as well as related barriers and solutions for an effective supply chain system. A qualitative study was designed to explore stakeholders' perceptions selected using the snowball sampling technique. A semi-structured interview guide was used to interview these respondents at a convenient time and place. After data collection, recorded interviews were transcribed verbatim and subjected to thematic analysis. The results highlighted that the standard operating procedures (SOPs), checklists, and government guidelines were available at different levels, except for community pharmacies. Timely delivery of quality products and services along with market reputation, experience, and authorization were the key criteria used for supplier selection and evaluation. Good inventory management, financial models, effective coordination, training, and skill development programs were identified as key factors responsible for an efficient supply chain process. Availability of vaccines, their appropriate temperature monitoring, and transportation are also highly compromised in Pakistan. The results of the present study concluded that the current supply chain system in Pakistan is not up to the mark; major factors include poor forecasting and inventory control, delayed order placement, lack of training, inadequate involvement of professionally qualified staff, inadequate financing and procurement processes, and poor coordination and integration among all stakeholders.

Healthcare Professionals' Practice of HIV Post-Exposure Prophylaxis in Clinical Settings in Karachi, Pakistan.

The human immunodeficiency virus (HIV) is an important public health concern that has become more prevalent in Pakistan in recent decades. Healthcare professionals (HCPs) are frequently exposed to many HIV-infected patients; as a result, they are more vulnerable to HIV infection due to occupational exposure. Hence, the current study was executed to evaluate HCPs' knowledge, attitude and practice in terms of post-exposure prophylaxis (PEP) for HIV. This cross-sectional study was carried out in several clinical and laboratory settings of Karachi and the HCPs involved in treating patients were surveyed using a structured questionnaire. The Shapiro-Wilk test was performed to establish the normality of the variables. Pearson correlation was employed to identify the relationship between the independent variables considering p-values < 0.05 as statistically significant. A total of 578 filled forms were incorporated in the study with a response rate of 72.2%. Physicians and medical students (OR = 1.68; 95% CI = 1.16-2.24; p = 0.001) belonging to private work settings (OR = 1.84; 95% CI = 1.33-2.35; p < 0.003) indicated better knowledge. The majority, 407 (70.4%), of the respondents reported having been exposed to risky occupational circumstances during their professional life; however, 65.7% took PEP for HIV after exposure and only 56.8% completed the entire course. A statistically significant association was observed between experience (p = 0.004, CI = 0.14-0.72), job category (p = 0.0001, CI = 0.16-0.62) and frequency of exposure (p = 0.003, CI = 0.42-11.31) and reporting of occupational exposure. More than half (53.8%) of respondents stated that their institute has a policy for the management of HIV exposures; however, their response was significantly associated with their organization (p = 0.004). The current study shows adequate knowledge revealing a positive attitude among respondents; however, there was a gap between the knowledge and its practical application. Even though many of the HCPs had experienced risky HIV exposure, a lack of reporting was noted in the study.

Accuracy of digitally planned, guided apicoectomy with a conventional trephine and a custom-made endodontic trephine: An in vitro comparative study.

PURPOSE: Static guided trephine apicoectomy has been developed as a less invasive and more accurate alternative to conventional freehand apicoectomy with drills. Overpenetration is a frequent issue with this procedure, which deteriorates accuracy and raises safety concerns. A safety improvement to address this problem is presented. MATERIALS AND METHODS: Guided apicoectomies were performed in porcine mandibles with either a conventional bone trephine or a custom-made endo-trephine with built-in depth control. The deviation of the apical endpoint of the trephine from the digital surgical plan was analyzed. Overpenetration frequency was recorded. RESULTS: Procedures performed with the custom trephine were significantly more accurate both along the x-axis and globally, but no significant difference was found for the y and z axes. Overpenetration frequency was 70% in the conventional trephine group versus 38% in the stop trephine group. CONCLUSION: The results indicate that the lack of physical depth control can interfere with the accuracy (and safety) of these procedures to a significant extent, as visual cues (such as the depth markings on a conventional trephine) are insufficient to prevent overpenetration. Our results show that custom-made trephines with a built-in stop offer an optimal solution for this problem.

Correlation Between Biofilm-Formation and the Antibiotic Resistant Phenotype in Staphylococcus aureus Isolates: A Laboratory-Based Study in Hungary and a Review of the Literature.

INTRODUCTION: Staphylococcus aureus (S. aureus) is an important causative pathogen in human infections. The production of biofilms by bacteria is an important factor, leading to treatment failures. There has been significant interest in assessing the possible relationship between the multidrug-resistant (MDR) status and the biofilm-producer phenotype in bacteria. The aim of our present study was to assess the biofilm-production rates in clinical methicillin-susceptible S. aureus [MSSA] and methicillin-resistant S. aureus [MRSA] isolates from Hungarian hospitals and the correlation between resistance characteristics and their biofilm-forming capacity. METHODS: A total of three hundred (n=300) S. aureus isolates (corresponding to MSSA and MRSA isolates in equal measure) were included in this study. Identification of the isolates was carried out using the VITEK 2 ID/AST system and matrix-assisted laser desorption/ionization time-of-flight mass spectrometry (MALDI-TOF MS). Antimicrobial susceptibility testing was performed using the Kirby-Bauer disk diffusion method and E-tests, confirmation of MRSA status was carried out using PBP2a agglutination assay. Biofilm-production was assessed using the crystal violet (CV) tube-adherence method and the Congo red agar (CRA) plate method. RESULTS: There were significant differences among MSSA and MRSA isolates regarding susceptibility-levels to commonly used antibiotics (in case of erythromycin, clindamycin and ciprofloxacin: p<0.001, gentamicin: p=0.023, sulfamethoxazole/trimethoprim: p=0.027, rifampin: p=0.037). In the CV tube adherence-assay, 37% (n=56) of MSSA and 39% (n=58) of MRSA isolates were positive for biofilm-production, while during the use of CRA plates, 41% (n=61) of MSSA and 44% (n=66) of MRSA were positive; no associations were found between methicillin-resistance and biofilm-production. On the other hand, erythromycin, clindamycin and rifampin resistance was associated with biofilm-positivity (p=0.004, p<0.001 and p<0.001, respectively). Biofilm-positive isolates were most common from catheter-associated infections. DISCUSSION: Our study emphasizes the need for additional experiments to assess the role biofilms have in the pathogenesis of implant-associated and chronic S. aureus infections.

Small, but smelly: the importance of Solobacterium moorei in halitosis and other human infections.

Solobacterium moorei (S. moorei) has been described as Gram-positive, non spore forming, obligate anaerobic bacillus from human feces. The traditional culture and identification of these strains is very difficult (as the strains are often not cultivable or they grow only relatively slowly, in addition to producing only a very few positive biochemical reactions in commercially available identification kits); thus, reliable identification may only be carried out using methods, such as matrix-assisted laser desorption/ionization time-of-flight mass spectrometry and DNA sequencing. Regarding its pathogenic role, the relevance of S. moorei in halitosis (oral malodor) has a good standing, as it has been suggested by multiple studies, while the isolation of these bacteria from invasive infections is very rare; there are only a few reports available in the literature, regarding infections outside the oral cavity. Based on these reports, affected patients are predominantly characterized compromised immunity and are frequently associated with a dental focus of infection. The aim of our present review is to summarize the currently available knowledge on the pathogenic role of S. moorei in halitosis and other infections and to emphasize the relevance of this neglected anaerobic pathogen.

Effects of different decontaminating solutions used for the treatment of peri-implantitis on the growth of Porphyromonas gingivalis-an in vitro study.

Implants have been considered the treatment of choice to replace missing teeth, unfortunately, peri-implant disease is still an unresolved issue. Contaminated implants may be decontaminated by physical debridement and chemical disinfectants; however, there is a lack of consensus regarding the ideal techniques/agents to be used for the decontamination. The objective of our study was to compare the decontaminating efficacy of different chemical agents on a titanium surface contaminated with Porphyromonas gingivalis, a typical representative of the bacterial flora associated with peri-implantitis. Commercially pure Ti grade 4 discs with a polished surface were treated with a mouthwash containing chlorhexidine digluconate (0.1%), povidone-iodine (PVP-iodine) solution (10%) or citric acid monohydrate (40%). Qualitative and quantitative assessment of cellular growth and survival were assessed by a 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyl tetrazolium bromide (MTT) assay and scanning electron microscopy (SEM). Significant differences in the quantity of P. gingivalis could be observed after 6 days of incubation. A numerical, but not statistically significant (P = 0.066) decrease in the amount of living bacteria was observed in the group treated with the PVP-iodine solution as compared to the control group. The chlorhexidine (CHX)-treated group presented with significantly higher cell counts, as compared to the PVP-iodine-treated group (P = 0.032), while this was not observed compared to the control group and citric acid-treated group. Our results have also been verified by SEM measurements. Our results suggest that for P. gingivalis contamination on a titanium surface in vitro, PVP-iodine is a superior decontaminant, compared to citric acid and chlorhexidine-digulconate solution.

Streptococcus suis: An Underestimated Emerging Pathogen in Hungary?

Streptococcus suis (S. suis) is an emerging zoonotic pathogen, demonstrated as an etiological agent in human infections in increasing frequency, including diseases like purulent meningitis, sepsis, uveitis-endophtalmitis and arthritis. Due to the increased availability and utility of novel diagnostic technologies in clinical microbiology, more studies have been published on the epidemiology of S. suis, both in veterinary and human medicine; however, there are no comprehensive data available regarding human S. suis infections from East-Central European countries. As a part of our study, data were collected from the National Bacteriological Surveillance (NBS) system on patients who had at least one positive microbiological result for S. suis, corresponding to an 18-year study period (2002-2019). n = 74 S. suis strains were isolated from invasive human infections, corresponding to 34 patients. The number of affected patients was 1.89 ± 1.53/year (range: 0-5). Most isolates originated from blood culture (63.5%) and cerebrospinal fluid (18.9%) samples. Additionally, we present detailed documentation of three instructive cases from three regions of the country and with three distinctly different outcomes. Hungary has traditional agriculture, the significant portion of which includes the production and consumption of pork meat, with characteristic preparation and consumption customs and unfavorable epidemiological characteristics (alcohol consumption, prevalence of malignant diseases or diabetes), which have all been described as important predisposing factors for the development of serious infections. Clinicians and microbiologist need to be vigilant even in nonendemic areas, especially if the patients have a history of occupational hazards or having close contact with infected pigs.

Heat Generation During Guided and Freehand Implant Site Preparation at Drilling Speeds of 1500 and 2000 RPM at Different Irrigation Temperatures: An In Vitro Study.

PURPOSE: The purpose of our study was to evaluate the impact of different irrigation fluid temperatures on intraosseous temperature increment during guided and freehand implant site preparation. MATERIALS AND METHODS: Bovine rib segments were used. Temperature was detected using K-type thermocouples. The studied groups were defined as combinations of the following: drilling speed (1500, 2000 RPM), drill diameter (2.0, 2.5, 3.0, 3.5 mm), surgical method (guided, freehand), and irrigation fluid temperature (10°C, 15°C, 20°C). The data were analysed with Kruskal-Wallis analysis of variance (ANOVA) and ANOVA, as appropriate. RESULTS: At 1500 RPM, guided drilling with 20°C irrigation fluid yielded temperature values exceeding the necrotic threshold (47°C) when performed with bits of 3.0 and 3.5 mm diameters. Meanwhile, 15°C irrigation managed to keep the mean increment below 8.0°C at the diameter of 3.5 mm for both guided and freehand surgery. However, 10°C irrigation cancelled every statistically significant difference between guided and freehand groups. At 2000 RPM and with 20°C irrigation, mean peak temperatures exceeded the necrotic threshold at the diameters 3.0 and 3.5 mm (guided) and 3.5 mm (freehand). When applying 10°C irrigation, though, all measurements indicated peak temperatures in the safe zone. CONCLUSION: Drillings at 1500 and 2000 RPM, in a guided setting, cause temperature elevations that exceed the necrotic threshold. A speed of 2000 RPM drilling may produce potentially harmful temperatures also in a freehand setting. 10°C and 15°C irrigation kept temperature increments in the safe zone at 2000 RPM and 1500 RPM, respectively.

Intraosseous Heat Generation During Osteotomy Performed Freehand and Through Template With an Integrated Metal Guide Sleeve: An In Vitro Study.

OBJECTIVE: To investigate drill wear and consequent intraosseous temperature elevation during freehand and guided bone drilling, with attention to the effect of metal-on-metal contact during guided drilling. MATERIALS AND METHODS: Osteotomies were performed on bovine ribs, with 2.0 mm diameter stainless steel drill bits of the SMART Guide System, under 3 sterilization protocols, at 800, 1200, 1500, and 2000 rpm. Sterilization was performed after every 3 drilling. Temperature was measured after every 30 drilling. RESULTS: The studied contributing factors had a cumulative effect, and each contributed significantly to temperature elevation. Whether guide use led to a near-necrotic (47°C) temperature increment depended largely on the applied sterilization protocol. CONCLUSION: The metal sleeve is a significant contributing factor to heat generation during guided osteotomy, but its effect can be offset by keeping the other studied factors under control.

Effect of the Combination of Low-Speed Drilling and Cooled Irrigation Fluid on Intraosseous Heat Generation During Guided Surgical Implant Site Preparation: An In Vitro Study.

PURPOSE: Investigating the effect of the combination of low-speed drilling and cooled irrigation fluid on intraosseous temperature rise during guided and freehand implant surgery. MATERIALS AND METHODS: Bovine ribs were used as bone specimens. Grouping determinants were as follows: drill diameter (2.0, 2.5, 3.0, and 3.5 mm), irrigation fluid temperature (10°C, 15°C, and 20°C), and surgical method (guided and freehand). Drilling speed was 800 rpm. Results were compared with previous ones using 1200 rpm. Temperature measurements were conducted using K-type thermocouples. RESULTS: No mean temperature change exceeded 1.0°C if irrigation fluid cooled to 10°C was used, regardless of the drill diameter or the surgical method, with the highest elevation being 2.10°C. No significant reduction was measured when comparing groups using 15°C and 20°C irrigation fluids, regardless of both drill diameter and surgical method. CONCLUSION: The use of irrigation fluid being cooled to 10°C combined with low-speed drilling (800 rpm) seems to be a safe method for implant site preparation and drilling through a drilling guide in terms of temperature control.

Comparison of effects of different fluoride containing prophylactics on the growth of Streptococcus mutans on titanium surfaces - an in vitro study.

The combined use of high fluoride (F-) concentration and acidic pH can weaken the corrosion resistance of titanium (Ti). Caries prophylactic products contain high amounts of F- and are applied at a low pH. The aim of our study was to determine whether the different forms of applied flouride has different effects on the growth of Streptococcus mutans on different titanium surfaces. Titanium with polished surface were treated with a gel (pH: 4,8) containing 1,25% olaflur, a rinse (pH: 4,4) containing 0,025% olaflur or a 1% aqueous solution of NaF at a pH of 4,5. Control discs were not treated. All discs were incubated with S. mutans for 21 days. To assess the amount of S. mutans protein assay analysis was performed at 5, 10 and 21 days. Scanning electron microscopic (SEM) investigations were also executed. By the 21st day significant differences could be observed in the bacterial protein quantity. The between group- comparisons showed that the rinse and gel were superior to NaF or control group (p < 0,01 and p < 0,05). Furthermore signs of corrosion could be observed in the group of gel treated discs. The results suggest that amine-fluoride content mouthwashes might be a suitable choice for prevention to the patients with dental implants.

[Navigation in implantology: Accuracy assessment regarding the literature]. / Navigáció alkalmazása az implantológiában: Összefoglaló áttekintés a pontossági adatok alapján.

Our objective was to assess the literature regarding the accuracy of the different static guided systems. After applying electronic literature search we found 661 articles. After reviewing 139 articles, the authors chose 52 articles for full-text evaluation. 24 studies involved accuracy measurements. Fourteen of our selected references were clinical and ten of them were in vitro (modell or cadaver). Variance-analysis (Tukey's post-hoc test; p < 0.05) was conducted to summarize the selected publications. Regarding 2819 results the average mean error at the entry point was 0.98 mm. At the level of the apex the average deviation was 1.29 mm while the mean of the angular deviation was 3,96 degrees. Significant difference could be observed between the two methods of implant placement (partially and fully guided sequence) in terms of deviation at the entry point, apex and angular deviation. Different levels of quality and quantity of evidence were available for assessing the accuracy of the different computer-assisted implant placement. The rapidly evolving field of digital dentistry and the new developments will further improve the accuracy of guided implant placement. In the interest of being able to draw dependable conclusions and for the further evaluation of the parameters used for accuracy measurements, randomized, controlled single or multi-centered clinical trials are necessary.

Intraosseous generation of heat during guided surgical drilling: an ex vivo study of the effect of the temperature of the irrigating fluid.

We measured the rise in the intraosseous temperature caused by freehand drilling or drilling through a surgical guide, by comparing different temperatures of irrigation fluid (10°C, 15°C, and 20°C), for every step of the drilling sequence (diameters 2.0, 2.5, 3.0, and 3.5mm) and using a constant drilling speed of 1200rpm. The axial load was controlled at 2.0kg. Bovine ribs were used as test models. In the guided group we used 3-dimensional printed surgical guides and temperature was measured with a thermocouple. The significance of differences was assessed with the Kruskal-Wallis analysis of variance. Guided drilling with 10°C irrigation yielded a significantly lower increment in temperature than the 20°C-guided group. When compared with the 20°C freehand group, the reduction in temperature in the 10°C guided group was significantly more pronounced at all diameters except 3.5mm. Finally, when the 10°C-guided group was compared with the 15°C groups, the temperature rise was significantly less at 2.5 and 3.0mm than with the guided technique, and at 3.0mm compared with the freehand technique. We suggest that the use of 10°C pre-cooled irrigation fluid is superior to warmer fluid for keeping temperature down, and this reduces the difference between guided and freehand drilling.

Short- and Long-Term Influence of Fluoride-Containing Prophylactics on the Growth of Streptococcus mutans on Titanium Surface.

OBJECTIVES: Acidic pH and high fluoride (F(-)) concentration impair the corrosion resistance of titanium (Ti). Caries-preventive products contain high amounts of F(-) and are applied at low pH. The purpose of this study was to evaluate whether fluoride applied in different forms has different short-, mid-, and long-term effects on the growth of the bacteria Streptococcus mutans. MATERIALS AND METHODS: Ti discs with polished surface were treated with a rinse containing 0.025% olaflur, a gel containing 1.25% olaflur, or a 1% aqueous solution of NaF (pH 4.5), and they were incubated with S mutans for 21 days. Control discs did not get prophylactic treatment. Protein assay analysis was performed at regular intervals to estimate the amount of S mutans. Scanning electron microscopic (SEM) images were also taken. RESULTS: Bacterial protein quantity became significantly different only by the 21st day. Fluoride in rinse and gel proved to be superior to NaF in aqueous solution or no treatment (P < 0.01 and P < 0.05, respectively). However, the discs treated with fluoride in gel showed signs of corrosion in SEM images. CONCLUSION: The results suggest that the use of fluoride-containing mouthwashes might be the best and safest oral hygienic choice for patients with oral implants. Furthermore, olaflur seems to be superior to NaF for long-term use at low pH.