Potential drug-drug interactions with phentermine among long-term phentermine consumers: A retrospective analysis.

BACKGROUND: Phentermine is an internationally recognised amphetamine derivative with significant appetite-suppressing properties. The drug is indicated for the short-term management of obesity, as the long-term (LT) use of phentermine may potentially be associated with severe cardiovascular side-effects, abuse and dependence. The LT use hereinafter describes periods exceeding 12 consecutive weeks. This use may also be associated with potential drug-drug interactions (PDDIs), which may result in adverse drug reactions (ADRs). The literature reports that phentermine is often prescribed LT and for several other off-label indications, increasing the risk for individuals to experience adverse drug events (ADEs) and drug-drug interactions (DDIs). There are, to our knowledge, no South African (SA) studies investigating the prevalence of co-prescribing LT phentermine with drugs that may potentially cause DDIs. OBJECTIVE: To determine the prevalence of mild, moderate and severe DDIs with phentermine use when the duration of therapy in private healthcare exceeded 12 consecutive weeks. METHODS: A cross-sectional drug utilisation review (DUR) was done by using data obtained from a SA pharmacy benefit management (PBM) company's database. Retrospective data of medicine claims for phentermine, from 1  January 2015 to 31  December 2019, were extracted for analysis. The number of days phentermine was supplied was used to identify the study population, in other words, those patients who received the drug LT. A drug interaction checker (Drugs.com) was used to identify potential mild, moderate and severe DDIs when using phentermine and co-prescribed drugs concurrently. RESULTS: A total of 889 patients received phentermine LT. The top 20 drugs identified as being frequently co-prescribed in this study population demonstrated no mild PDDI, 15 (75%) moderate PDDIs and 5 (25%) severe PDDIs. The most common co-prescribed drug in the moderate group was dextromethorphan (n=282, 31.72%) and the least co-prescribed was formoterol (n=52, 5.85%). Among the drug group 'severe PDDIs', tramadol (n=416, 46.79%) was most frequently prescribed, whereas phenylpropanolamine (n=69, 7.76%) was the least prescribed to patients in this group. CONCLUSION: There are patients who receive LT phentermine therapy despite the potential severe consequences that may result. These patients may receive concomitant therapy with phentermine and other pharmaceutical constituents, which may potentially cause DDIs, more specifically, moderate and severe DDIs. As such, these patients are not only confronted with the consequences of DDIs but are also at risk to experience ADRs as the residual effect of PDDIs.

Prophylaxis is the new standard of care in patients with haemophilia.

Randomised controlled clinical trial evidence on prophylaxis as optimal care for patients with haemophilia was generated more than a decade ago. However, this knowledge has not translated into clinical practice in South Africa (SA) owing to many barriers to prophylaxis. These include the high treatment burden imposed by prophylaxis (frequent injections two to four times a week), the need for intravenous access to administer replacement clotting factor therapies, and the higher volume of clotting factor required compared with episodic treatment. The recently introduced non-factor therapies in haemophilia care have addressed many of these barriers. For example, emicizumab, which is currently the only globally approved non-factor therapy, can be administered subcutaneously less frequently (weekly, fortnightly or every 4 weeks) and has led to global adoption of prophylaxis as the standard of care in haemophilia by the bleeding disorders community. Haemophilia A is the most prevalent clotting factor deficiency in SA, with >2 000 people diagnosed to date. However, only a few of these patients are currently on prophylaxis. In this 'In Practice' article, we review the rationale for prophylaxis, outline its goals and benefits, and provide evidence-based guidance on which haemophilia patients should be prioritised for emicizumab prophylaxis. This consensus guidance facilitates the adoption of prophylaxis as a national policy and the new standard of care in haemophilia in SA.

The Silk Vista Baby - The UK experience.

BACKGROUND: The Silk Vista Baby (SVB) flow diverter (FDS) is the only FDS deliverable via a 0.017 inch microcatheter and is specifically designed for the distal vasculature. We sought to evaluate the safety and efficacy of the SVB. MATERIALS AND METHODS: We performed a retrospective review to identify SVB cases at 4 tertiary neurosurgical centres within the U.K. Clinical, procedural, angiographic and follow-up data were collected. RESULTS: We identified 60 patients (35 female, 58%) of average age 54 ± 10.5 (range 30-72) with 61 aneurysms, 50 (81.9%) located in the anterior circulation. The majority of the aneurysms treated were unruptured (46, 75.4%) and saccular (46, 75.4%). Dome size was 6.2 ± 6.2 mm (range 1-36mm) and parent vessel diameter was 2.3 ± 0.4 mm (range 1.2-3.3 mm).An average number of 1.07 devices were implanted. Coils or other devices were implanted in 14 aneurysms (23.3%). At last angiographic follow-up (n = 55), 7.5 ± 4.2 months post-procedure, 32 aneurysms (57.1%) were graded as RRC I, 7 (12.5%) RRC II, and 17 RRC III (30.4%).Clinical complications, excluding death, were seen in 4 patients (6.8%) including 1 delayed aneurysm rupture and 3 symptomatic ischaemic events. Only one patient had permanent morbidity (mRS 1). 3 patients died during follow-up (5.1%); 2 deaths were related to the aneurysms (3.4%) - one ruptured dissecting MCA aneurysm, and one giant partially thrombosed posterior circulation aneurysm. 93% of patients were mRS ≤ 2 at last follow-up. CONCLUSION: The SVB has high rates of technical success and an acceptable safety profile. Distal aneurysms may occlude slower due to relative oversizing of the devices.

The Association of Clinical Characteristics and Tumour Markers With Image-Defined Risk Factors in the Management of Neuroblastoma in South Africa.

AIMS: Image-defined risk factors (IDRFs) in neuroblastoma predict surgical complications and management outcomes. As there is a lack of data regarding the association of IDRFs with clinical and pathological factors, this study evaluated the prognostic value of IDRFs to predict neuroblastoma survival outcomes. MATERIALS AND METHODS: This was a retrospective study including 345 patients and reviewed diagnostic imaging for 20 IDRFs, pleural effusions and ascites. The IDRFs were grouped into five 'primary IDRFs' cohorts with vascular encasement, involvement of multiple body compartments, organ infiltration, airway obstruction and intraspinal extension. The association between clinical, histopathological and biological characteristics of neuroblastoma and management was evaluated. RESULTS: More patients without IDRFs had operations compared with patients with IDRFs, with a trend towards significance (64.4% versus 35.6%, P = 0.082). Patients with multiple compartment tumour involvement (P = 0.003) and organ infiltration (P < 0.001) had a higher risk of surgical complications. The 5-year overall survival of the group with more than one IDRF was 0.0% and those with pleural effusions or ascites 6.7%, associated with the worst outcome (P = 0.005). The total number of IDRFs was not predictive of the metastatic remission rate (P = 0.585) or overall survival (P = 0.142), with no conclusive association found between IDRF groups and clinical or biological markers. CONCLUSIONS: Patients with more than one IDRF had the shortest survival time, whereas those with pleural effusions and ascites at diagnosis had a poor outcome. Standardised reporting of IDRFs is crucial for predicting prognosis.

Additive Manufacturing for Occupational Hygiene: A Comprehensive Review of Processes, Emissions, & Exposures.

This comprehensive review introduces occupational (industrial) hygienists and toxicologists to the seven basic additive manufacturing (AM) process categories. Forty-six articles were identified that reported real-world measurements for all AM processes, except sheet lamination. Particles released from powder bed fusion (PBF), material jetting (MJ), material extrusion (ME), and directed energy deposition (DED) processes exhibited nanoscale to submicron scale; real-time particle number (mobility sizers, condensation nuclei counters, miniDiSC, electrical diffusion batteries) and surface area monitors (diffusion chargers) were generally sufficient for these processes. Binder jetting (BJ) machines released particles up to 8.5 µm; optical particle sizers (number) and laser scattering photometers (mass) were sufficient for this process. PBF and DED processes (powdered metallic feedstocks) released particles that contained respiratory irritants (chromium, molybdenum), central nervous system toxicants (manganese), and carcinogens (nickel). All process categories, except those that use metallic feedstocks, released organic gases, including (but not limited to), respiratory irritants (toluene, xylenes), asthmagens (methyl methacrylate, styrene), and carcinogens (benzene, formaldehyde, acetaldehyde). Real-time photoionization detectors for total volatile organics provided useful information for processes that utilize polymer feedstock materials. More research is needed to understand 1) facility-, machine-, and feedstock-related factors that influence emissions and exposures, 2) dermal exposure and biological burden, and 3) task-based exposures. Harmonized emissions monitoring and exposure assessment approaches are needed to facilitate inter-comparison of study results. Improved understanding of AM process emissions and exposures is needed for hygienists to ensure appropriate health and safety conditions for workers and for toxicologists to design experimental protocols that accurately mimic real-world exposure conditions.ABBREVIATIONS ABS : acrylonitrile butadiene styrene; ACGIH® TLV® : American Conference of Governmental Industrial Hygienists Threshold Limit Value; ACH : air change per hour; AM : additive manufacturing; ASA : acrylonitrile styrene acrylate; AVP : acetone vapor polishing; BJ : binder jetting; CAM-LEM : computer-aided manufacturing of laminated engineering materials; CNF : carbon nanofiber; CNT : carbon nanotube; CP : co-polyester; CNC : condensation nuclei counter; CVP : chloroform vapor polishing; DED : directed energy deposition; DLP : digital light processing; EBM : electron beam melting; EELS : electron energy loss spectrometry; EDB : electrical diffusion batteries; EDX : energy dispersive x-ray analyzer; ER : emission rate; FDM™ : fused deposition modeling; FFF : fused filament fabrication; IAQ : indoor air quality; LSP : laser scattering photometer; LCD : liquid crystal display; LDSA : lung deposited particle surface area; LOD : limit of detection; LOM : laminated object manufacturing; LOQ : limit of quantitation; MCE : mixed cellulose ester filter; ME : material extrusion; MJ : material jetting; OEL : occupational exposure limit; OPS : optical particle sizer; PBF : powder bed fusion; PBZ : personal breathing zone; PC : polycarbonate; PEEK : poly ether ether ketone; PET : polyethylene terephthalate; PETG : Polyethylene terephthalate glycol; PID : photoionization detector; PLA : polylactic acid; PM1 : particulate matter with aerodynamic diameter less than 1 µm; PM2.5 : particulate matter with aerodynamic diameter less than 2.5 µm; PM10 : particulate matter with aerodynamic diameter less than 10 µm; PSL : plastic sheet lamination; PVA : polyvinyl alcohol; REL : recommended exposure limit; SDL : selective deposition lamination; SDS : safety data sheet; SEM : scanning electron microscopy; SL : sheet lamination; SLA : stereolithography; SLM : selective laser melting; SMPS : scanning mobility particle sizer; SVOC : semi-volatile organic compound; TEM : transmission electron microscopy; TGA : thermal gravimetric analysis; TPU : thermo polyurethane; UAM : ultrasonic additive manufacturing; UC : ultrasonic consolidation; TVOC : total volatile organic compounds; TWA : time-weighted average; VOC : volatile organic compound; VP : vat photopolymerization.

The Association between Tumour Markers and Meta-iodobenzylguanidine Scans in South African Children with High-risk Neuroblastoma.

AIMS: Diagnostic and post-induction 123I-meta-iodobenzylguanidine (123I-mIBG) scans have prognostic significance in the treatment of neuroblastoma, but data from low- and middle-income countries are limited due to resource constraints. The aim of this study was to determine the association between neuroblastoma-associated tumour markers (lactate dehydrogenase [LDH], ferritin and MYCN amplification) and 123I-mIBG scans (modified Curie scores and metastatic disease patterns) in predicting complete metastatic response rates (mCR) and overall survival. MATERIALS AND METHODS: Two hundred and ninety patients diagnosed with high-risk neuroblastoma in South Africa between January 2000 and May 2018 and a subanalysis of 78 patients with diagnostic 123I-mIBG scans were included. Data collection included LDH, ferritin and MYCN amplification at diagnosis. Two nuclear physicians independently determined the modified Curie scores and pattern of distribution for each diagnostic and post-induction 123I-mIBG scans with high inter-rater agreement (r = 0.952) and reliability (K = 0.805). The cut-off values for the diagnostic and post-induction modified Curie scores of ≥7.0 (P = 0.026) and 3 (P = 0.009), respectively, were generated. The association between the tumour markers and the modified Curie score of the 123I-mIBG scans was determined using post-induction mCR and 2-year overall survival. RESULTS: Diagnostic LDH (P < 0.001), ferritin (P < 0.001) and the diagnostic modified Curie scores (P = 0.019) significantly predicted mCR. Only ferritin correlated with diagnostic modified Curie scores (P = 0.003) but had a low correlation coefficient of 0.353. On multivariable analysis, the only significant covariate for 2-year overall survival at diagnosis was LDH <750 U/l (P = 0.024). A post-induction chemotherapy modified Curie score ≤3.0 had a 2-year overall survival of 46.2% compared with 30.8% for a score >3.0 (P = 0.484). CONCLUSION: LDH, ferritin and the diagnostic 123I-mIBG scans significantly predicted mCR, but only LDH predicted 2-year overall survival. Ferritin and the modified Curie scores correlated with each other. MYCN amplification neither correlated with any aspect of the 123I-mIBG scans nor significantly predicted mCR or 2-year overall survival. LDH and ferritin are therefore appropriate neuroblastoma tumour markers to be used in low- and middle-income countries with limited or no access to mIBG scans and/or MYCN amplification studies.

Reflections on the OECD guidelines for in vitro skin absorption studies.

At the 8th conference of Occupational and Environmental Exposure of the Skin to Chemicals (OEESC) (16-18 September 2019) in Dublin, Ireland, several researchers performing skin permeation assays convened to discuss in vitro skin permeability experiments. We, along with other colleagues, all of us hands-on skin permeation researchers, present here the results from our discussions on the available OECD guidelines. The discussions were especially focused on three OECD skin absorption documents, including a recent revision of one: i) OECD Guidance Document 28 (GD28) for the conduct of skin absorption studies (OECD, 2004), ii) Test Guideline 428 (TGD428) for measuring skin absorption of chemical in vitro (OECD, 2004), and iii) OECD Guidance Notes 156 (GN156) on dermal absorption issued in 2011 (OECD, 2011). GN156 (OECD, 2019) is currently under review but not finalized. A mutual concern was that these guidance documents do not comprehensively address methodological issues or the performance of the test, which might be partially due to the years needed to finalize and update OECD documents with new skin research evidence. Here, we summarize the numerous factors that can influence skin permeation and its measurement, and where guidance on several of these are omitted and often not discussed in published articles. We propose several improvements of these guidelines, which would contribute in harmonizing future in vitro skin permeation experiments.

Evaluation of the use of low-molecular-weight heparin for venous thromboembolism prophylaxis in medical patients.

BACKGROUND: Venous thromboembolism (VTE) complicates a significant proportion of medical admissions. As well as increasing patient morbidity, pulmonary embolism is one of the commonest preventable causes of in-hospital death. An increase in the use of pharmacological preventive measures has been advocated in recent years. South African (SA) and international guidelines have been published in an effort to promote the safe use of VTE prophylaxis. OBJECTIVES: To describe adherence to both local and international recommendations for VTE prophylaxis in an SA hospital with regard to appropriateness of the decision to prescribe or withhold low-molecular-weight heparin (LMWH), and to observe the practice of dose adjustment in special population groups. METHODS: This was a prospective, observational study, and data were collected from consenting adults admitted to the medical wards. We assessed the patients' VTE risk, bleeding risk and the presence of contraindications at the time of LMWH prescription as well as the dose prescribed, specifically taking into consideration adjustment for renal dysfunction and obesity. RESULTS: Three hundred and fifty-two patients were enrolled, of whom 51.4% were male and 58.5% received LMWH. Primary outcomes. The appropriate overall decision according to both SA and international guidelines was made in 254 cases (72.2%). The inappropriate decision according to both guidelines was made in 79 cases (22.4%) and the appropriate decision according to one guideline only was made in 18 cases (5.1%), while 1 case (0.3%) was not categorised. Contraindications to VTE prophylaxis were present in 35 patients (9.9%), but 9 of these patients nevertheless received LMWH. An incorrect dose was prescribed in 36 cases (17.5%), the most common reason being an inappropriate reduction in the dose in mild renal dysfunction. SECONDARY OUTCOMES: Other medications that may have increased bleeding risk were prescribed in 46 patients who received LMWH (22.3%). Mechanical prophylaxis was indicated in 25 (7.1%) of the total sample; however, none received this. CONCLUSIONS: Overall adherence to published guidelines for VTE prophylaxis has improved compared with other published reviews on the topic, but documentation of patients' VTE risk in files is poor. Overuse in low-risk patients may be an unintended consequence of the widespread advocacy of LMWH use in hospital, highlighting the importance of adequate VTE risk stratification. Incorrect dosing in special population groups is an issue that needs to be addressed, as is non-utilisation of mechanical prophylaxis methods.

Evaluation of emissions and exposures at workplaces using desktop 3-dimensional printer.

There is a paucity of data on additive manufacturing process emissions and personal exposures in real-world workplaces. Hence, we evaluated atmospheres in four workplaces utilizing desktop "3-dimensional" (3-d) printers [fused filament fabrication (FFF) and sheer] for production, prototyping, or research. Airborne particle diameter and number concentration and total volatile organic compound concentrations were measured using real-time instruments. Airborne particles and volatile organic compounds were collected using time-integrated sampling techniques for off-line analysis. Personal exposures for metals and volatile organic compounds were measured in the breathing zone of operators. All 3-d printers that were monitored released ultrafine and fine particles and organic vapors into workplace air. Particle number-based emission rates (#/min) ranged from 9.4 × 109 to 4.4 × 1011 (n = 9samples) for FFF3-d printers and from 1.9 to 3.8 × 109 (n = 2 samples) for a sheer 3-d printer. The large variability in emission rate values reflected variability from the printers as well as differences in printer design, operating conditions, and feedstock materials among printers. A custom-built ventilated enclosure evaluated at one facility was capable of reducing particle number and total organic chemical concentrations by 99.7% and 53.2%, respectively. Carbonyl compounds were detected in room air; however, none were specifically attributed to the 3-d printing process. Personal exposure to metals (aluminum, iron) and 12 different organic chemicals were all below applicable NIOSH Recommended Exposure Limit values, but results are not reflective of all possible exposure scenarios. More research is needed to understand 3-d printer emissions, exposures, and efficacy of engineering controls in occupational settings.

Determination of lovastatin, mevastatin, rosuvastatin and simvastatin with HPLC by means of gradient elution.

A novel HPLC method with UV detection was developed and validated in skin penetration (in vitro) studies to identify and quantify lovastatin, mevastatin, rosuvastatin and simvastatin. A Venusil XBP C18 (2), 150 x 4.6 mm, 5 µm column (Agela Technologies, Newark, DE) was used with gradient elution (start at 45 % acetonitrile and increase linearly to 90 % after 1 min; hold at 90 % until 6 min and then re-equilibrate at start conditions) and the mobile phase consisted of (A) Milli-Q ® water and 0.1% orthophosphoric acid, and (B) HPLC grade acetonitrile. The flow rate was set at 1 ml/min, 240 nm UV detection and an injection volume of 10 µl. Linearity was obtained over a range of 0.50-200.00 µg/ml and correlation coefficients ranging from 0.998-1.000 were obtained. Average recovery ranged from 95.9-100.6 %. The LOD and LOQ values obtained from the slope of a calibration curve and the standard deviation of the response ranged from 0.0138-0.0860 µg/ml and 0.0419-0.2615 µg/ml, respectively, where lovastatin and simvastatin could be detected at a concentration similar to the other statins, but could only be quantified at a higher concentration than the remaining statins. The specificity of the method was proved as accurate and quantification of statins was found, even within the incorporation of other compounds.

Migration of etonogestrel contraceptive implants: Implications for difficult removals services need in southern Africa.

The first difficult contraceptive implant removals clinic in sub-Saharan Africa was started 2 years ago at New Somerset Hospital in Cape Town, South Africa, and has seen two cases of implant migration. We report these cases here. The first was a case of fascial migration and the second one of migration via the cephalic vein, both to a site just anterior to the glenohumeral joint. Both implants were removed without complications. Even with correct insertion technique, migrations can occur. Healthcare providers need to know how to manage difficult removals, and how to access and refer to difficult removals services when necessary. These services must therefore be available in all settings where implants are offered, to ensure access to rights-based family planning services for all women in southern Africa.

Insights Into Emissions and Exposures From Use of Industrial-Scale Additive Manufacturing Machines.

BACKGROUND: Emerging reports suggest the potential for adverse health effects from exposure to emissions from some additive manufacturing (AM) processes. There is a paucity of real-world data on emissions from AM machines in industrial workplaces and personal exposures among AM operators. METHODS: Airborne particle and organic chemical emissions and personal exposures were characterized using real-time and time-integrated sampling techniques in four manufacturing facilities using industrial-scale material extrusion and material jetting AM processes. RESULTS: Using a condensation nuclei counter, number-based particle emission rates (ERs) (number/min) from material extrusion AM machines ranged from 4.1 × 1010 (Ultem filament) to 2.2 × 1011 [acrylonitrile butadiene styrene and polycarbonate filaments). For these same machines, total volatile organic compound ERs (µg/min) ranged from 1.9 × 104 (acrylonitrile butadiene styrene and polycarbonate) to 9.4 × 104 (Ultem). For the material jetting machines, the number-based particle ER was higher when the lid was open (2.3 × 1010 number/min) than when the lid was closed (1.5-5.5 × 109 number/min); total volatile organic compound ERs were similar regardless of the lid position. Low levels of acetone, benzene, toluene, and m,p-xylene were common to both AM processes. Carbonyl compounds were detected; however, none were specifically attributed to the AM processes. Personal exposures to metals (aluminum and iron) and eight volatile organic compounds were all below National Institute for Occupational Safety and Health (NIOSH)-recommended exposure levels. CONCLUSION: Industrial-scale AM machines using thermoplastics and resins released particles and organic vapors into workplace air. More research is needed to understand factors influencing real-world industrial-scale AM process emissions and exposures.

Stakeholders' viewpoints on work-integrated learning practices in radiography training in South Africa: Towards improvement of practice.

PURPOSE: The aim of this investigation was to suggest practices to improve the delivery of work-integrated learning (WIL) in radiography training in South Africa (SA). METHODS: An extensive survey was conducted among all universities in SA involved in the training of radiography students, to investigate the current delivery of WIL. Data were collected by means of quantitative questionnaires with open-ended qualitative components. The questionnaire was distributed to lecturers (n = 32), clinical supervisors (n = 44) and final-year students in Radiography (n = 146). RESULTS: The quantitative (closed questions) and qualitative (open-ended comments) findings from the stakeholders with regard to the improvement of practice in the delivery of WIL in radiography training are presented in this article. The main themes discussed relate to curriculum design for WIL, teaching/learning of WIL, assessment of WIL and management and coordination of WIL. CONCLUSION: WIL is a powerful pedagogy if implemented and managed correctly. The results from this study may enable lecturers in radiography programmes in SA to improve the delivery of WIL in the training of high quality, employable graduates.

Assessing a portable, real-time display handheld meter with UV-A and UV-B sensors for potential application in personal sun exposure studies.

BACKGROUND: Observing accurate real-time measurements of solar ultraviolet radiation (UVR) levels is important since personal excess sun exposure is associated with skin cancers. Handheld measurement devices may be helpful but their accuracy is unknown. We compare a portable, science-grade solar UVR monitoring device against two fixed, science-grade solar UVR instruments. METHODS: Instruments were (1) a fixed Solar Light 501 UV-B biometer to measure UV-B; (2) a fixed Kipp and Zonen radiometer used to measure UV-A and UV-B; and (3) Goldilux ultraviolet probes which are commercially available portable devices. Two different probes were used, one measured UV-A and the other UV-B radiation. The Goldilux probes were levelled and secured next to the UV-B biometer. Between 10:00 and 14:40 UTC+2, the UV-B biometer was set to record at 10-minute intervals and measurements by the Goldilux probes were manually taken simultaneously. Results were compared for all data and by solar zenith angle (SZA) ranges. RESULTS: The Goldilux UV-B probe measured UV-B relatively well in its diurnal pattern, however, its readings were ~77% higher than those made by the UV-B biometer. While UV-A measurements from the Goldilux UV-A probe and those from the radiometer were in relatively good agreement in pattern, the radiometer read ~47% higher than the Goldilux UV-A probe. UV-B data from Goldilux UV-B probe had a moderately strong correlation with UV-B biometer data for small SZAs; conversely, for UV-A, the Goldilux UV-A probe had a strong correlation with the UV-A radiometer data for large SZAs. CONCLUSION: Handheld devices may be useful to provide real-time readings of solar UVR patterns, however, to achieve synchronicity in the magnitude of readings to those made by science-grade fixed instruments, devices may need to be used during certain times of the day and in clear-sky conditions which may not be practical in personal exposure studies.

Exploring the potential of T7 bacteriophage protein Gp2 as a novel inhibitor of mycobacterial RNA polymerase.

Over the past six decades, there has been a decline in novel therapies to treat tuberculosis, while the causative agent of this disease has become increasingly resistant to current treatment regimens. Bacteriophages (phages) are able to kill bacterial cells and understanding this process could lead to novel insights for the treatment of mycobacterial infections. Phages inhibit bacterial gene transcription through phage-encoded proteins which bind to RNA polymerase (RNAP), thereby preventing bacterial transcription. Gp2, a T7 phage protein which binds to the beta prime (ß') subunit of RNAP in Escherichia coli, has been well characterized in this regard. Here, we aimed to determine whether Gp2 is able to inhibit RNAP in Mycobacterium tuberculosis as this may provide new possibilities for inhibiting the growth of this deadly pathogen. Results from an electrophoretic mobility shift assay and in vitro transcription assay revealed that Gp2 binds to mycobacterial RNAP and inhibits transcription; however to a much lesser degree than in E. coli. To further understand the molecular basis of these results, a series of in silico techniques were used to assess the interaction between mycobacterial RNAP and Gp2, providing valuable insight into the characteristics of this protein-protein interaction.

Delivery of intracavernosal therapies using needle-free injection devices.

ED affects a significant proportion of males worldwide. With an ever-aging population the prevalence of ED is predicted to double in the next decade. Oral PDE-5 inhibitors are the first-line treatment for ED and have revolutionised its management. These agents are however ineffective in some men. Intracavernosal injection (ICI) of vasoactive agents is an effective second-line therapy for ED. Despite proven efficacy, needle phobia and anxiety with self-needling limit the use of intracavernosal (IC) therapies. Needle-free injection (NFI) devices allow delivery of parenteral therapies through the skin, without a needle. Although these devices have been available for decades, early studies investigating their use for ICI showed inferiority compared to standard needle-tip syringe delivery. Advances in engineering of these systems have lead to functional improvements of many aspects of fluid delivery. Our research demonstrates that modern NFI devices are better equipped to deliver ICI, and, in the cadaver models examined, achieved successful IC delivery. These findings support the potential feasibility of NFI devices to deliver ICI, and may broaden the utility of these devices to patients who refuse or discontinue IC therapy because of needle phobia or other issues with standard needle-tip syringes.

Amniotic band syndrome with pseudoarthrosis of tibia and fibula: A case report.

Constriction of the lower limb by congenital amniotic band has been proposed to explain the development of pseudoarthrosis of tibia and fibula. We report a case of amniotic band syndrome in a preterm infant with pseudoarthrosis of tibia and fibula. Simple release of constriction band with Z-plasty resulted in the growth of mature bone, replacing the pseudoarthrosis and hence did not require surgical amputation. Our case confirms the potential for bone growth in ABS, once the constricting band is released. Early limb preserving surgery with release of the constricting band with an intention to salvage the limb appears appropriate.

Exploratory data analysis of the dependencies between skin permeability, molecular weight and log P.

Molecular weight and log P remain the most frequently used physicochemical properties in models that predict skin permeability. However, several reports over the past two decades have suggested that predictions made by these models may not be sufficiently accurate. In this study, exploratory data analysis of the probabilistic dependencies between molecular weight, log P and log Kp was performed on a dataset constructed from the combination of several popular datasets. The results suggest that, in general, molecular weight and log P are poorly correlated to log Kp. However, after employing several exploratory data analysis techniques, regions within the dataset of statistically significant dependence were identified. As an example of the applicability of the information extracted from the exploratory data analyses, a multiple linear regression model was constructed, bounded by the ranges of dependence. This model gave reasonable approximations to log Kp values obtained from skin permeability studies of selected non-steroidal ant-inflammatory drugs (NSAIDs) administered from a buffer solution and a lipid-based drug delivery system. A method of testing whether a given drug falls within the regions of statistical dependence was also presented. Knowing the ranges within which molecular weight and log P are statistically related to log Kp can supplement existing methods of screening, risk analysis or early drug development decision making to add confidence to predictions made regarding skin permeability.

A novel RP-HPLC method for the detection and quantification of roxithromycin in topical delivery studies.

A novel HPLC method with UV detection for the identification and quantification of roxithromycin (ROX) during in vitro skin penetration studies has been developed and validated. The method proved to be simple and rapid with isocratic elution (flow rate: 1.0 mL/min) of ROX, using a C18 column and UV detection at 205 nm. The mobile phase consisted of 0.06 M potassium di-hydrogen orthophosphate buffer (pH adjusted to 7.4 with sodium hydroxide) and acetonitrile in a 50:50 (v/v) ratio. This method showed linearity across the concentration range of 5 - 1000 µg/mL with a correlation coefficient of 0.9999. An average recovery of 101.78% was obtained. Limit of detection (LOD) and lower limit of quantification (LLOQ) values proved that ROX can still be detected at a concentration level of 0.3 µg/mL and accurately quantified at a concentration of 0.5 µg/mL. The specificity testing during method validation proved that this method is suitable for the accurate detection and quantification of ROX even when combined with different compounds typically used during the formulation of topical delivery systems.