Choosing appropriate pharmacotherapy for drug-resistant HIV

Introduction: Despite the potency of current antiretrovirals, some patients continue to struggle with the management of the treatment of HIV due to drug resistance-associated mutations. The underlying causes of these developments are usually drug adherence and drug availability as well as the economic affordability of those potent drugs in low to middle-income countries as well as in some industrialised countries. Viral replication, despite therapy, varies by region from 5 to 28. Non-adherence includes a variety of behaviours with different clinical implications. Addressing non-adherence and choosing new regimens based on a strategic vision may aid overall treatment strategies in the future.

Areas covered: The authors review the literature derived from Embase, MEDLINE and the main international congresses on transmitted and selected drug resistance to HIV therapeutics. They also consider the pharmacological aspects of antiretroviral therapy including the genetic barrier, convenience, potency, drug-drug interactions and tolerability are discuss prospective randomized or observational clinical trials on salvage therapy.

Expert opinion: Preventive intervention is the most efficient way to reduce the selection and transmission of drug-resistant mutations. While subjects with no current available options may benefit from new compounds (ibalizumab and fostemsavir), strategies should be implemented to spare as many patients as possible from drug resistance.     

An audit of mandibular fractures treated by intermaxillary fixation using intraoral cortical bone screws.

INTRODUCTION: During the last 10 years, intermaxillary fixation using intraoral cortical bone screws has been introduced for the treatment of mandibular fractures. The aim of this work was to evaluate the indications and possible complications of this method. MATERIALS AND METHODS: Sixty-two patients with mandibular fractures, treated by intermaxillary fixation using these screws, were evaluated by preoperative and postoperative panoramic radiographs. Clinical testing was carried out for vitality and abnormal mobility of teeth adjacent to the site of screw insertions. To evaluate the efficacy of this method, different factors were considered such as possible iatrogenic dental injuries, loss, breakage or screw cover by oral mucosa and postoperative occlusion. RESULTS: The most important complication was iatrogenic damage to dental roots (1.5%), 4.9% of the screws were covered by oral mucosa and 1.9% were lost, while none were broken. Malocclusion was observed in one patient (1.6%) and lack of consolidation of a displaced fracture of the mandibular body in another patient. CONCLUSIONS: Use of intraoral cortical bone screws for intermaxillary fixation is a valid alternative to arch bars in the treatment of mandibular fractures. Iatrogenic injury to dental roots is the most important problem of this procedure, but can be minimized by an experienced surgeon.     

Biological factors involved in the osseointegration of oral titanium implants with different surfaces: a pilot study in minipigs

BACKGROUND: The stability of titanium implants is determined by the rigid load-bearing connections that are formed by the bone, a process that involves a complex network of cells, pro- and anti-inflammatory mediators, and growth factors. The osseointegration processes at the interfaces of machined and porous implants were studied using molecular and histological techniques. METHODS: Two machined and two porous titanium implants were inserted into the tibiae of four minipigs. The animals were sacrificed at 15, 30, 60, and 90 days post-implantation. The levels of bone morphogenetic protein (BMP)-4, transforming growth factor (TGF)-beta1, and tumor necrosis factor (TNF)-alpha were quantified in the peri-implant osseous samples. The levels of interleukin (IL)-1beta, IL-6, IL-10, and TNF-alpha in the serum were also assessed. RESULTS: Histomorphological analysis showed evidence of bone ossification around the porous implant at 60 days. Surrounding the machined implants, highly sclerotic fibrous pads started the healing response at 90 days, and the levels of TGF-beta1 and BMP-4 began to increase at 60 days, at which time bone ossification around the porous implants was already evident. TNF-alpha was not present in the bone next to the implants. The serum levels of cytokines IL-1beta, IL-6, and IL-10 were not increased. The serum level of TNF-alpha increased during the healing process. CONCLUSIONS: We observed that the levels of BMP-4 and TGF-beta1, which play essential roles in the osteogenesis process, increased earlier around the porous implants than around the machined implants. Similarly, the ossification process was initiated earlier at the surfaces of the porous implants than at the surfaces of the machined implants.     

The restore rechargeable, implantable neurostimulator: handling and clinical results of a multicenter study

BACKGROUND: Spinal cord stimulation is an effective therapy for chronic, neuropathic pain refractory to medication. Use of a rechargeable neurostimulation system (Restore, Medtronic Inc) could provide greater longevity in the treatment of complex pain. However, patients' ability to successfully recharge a neurostimulation system has not yet been demonstrated. PRIMARY OBJECTIVE: Ability of patients to recharge the neurostimulator. SECONDARY OBJECTIVES: Patient and physician satisfaction with the system, pain relief, quality of life, functional status, adverse events. METHODS: Prospective, open-label, multicenter, European study in patients with long-term refractory neuropathic pain. Recharging ability was assessed 1-month postimplant. Patient and physician satisfaction, pain relief, quality of life, and functional status were assessed at scheduled follow-up visits through 12 months. Adverse events were monitored throughout. RESULTS: Primary end point: 100% of patients (n=41) successfully recharged the neurostimulator. Secondary end points at 1 month: 78.6% of patients found recharging easy. At 12 months: physicians were satisfied with the system for 92.7% of patients; pain intensity decreased significantly (P<0.001); mean self-reported pain relief was 62%; 80.5% of patients had more than 50% pain relief; quality of life and functional status improved significantly (P<0.001); 98% of patients would recommend spinal cord stimulation to others. Overall, 41 device-related complications (23 patients) were observed. CONCLUSIONS: Twelve-month experience indicates that the rechargeable neurostimulation system (Restore) was easy to use, with 100% of patients able to recharge successfully. Patient and physician satisfaction was high, with significant improvements in pain, quality of life, and functional status. Complications were comparable to prior experience with this therapy.     

Impact of an abdominal belt on breathing patterns and scan efficiency in whole-heart coronary magnetic resonance angiography: comparison between the UK and Japan

Background

Long acquisition times and complex breathing motion patterns lead to suboptimal image quality in whole heart coronary magnetic resonance angiography (WHCMRA). To overcome this problem, an abdominal belt (BELT) has been suggested by a Japanese group. However, its applicability in a Western population has not been previously demonstrated. The purpose of this study was to investigate 1) how the application of a BELT alters breathing patterns during MR scanning and 2) whether the BELT has a similar impact on breathing patterns in UK and Japanese patient populations.

Methods

30 patients (15 in the UK and 15 in Japan) were studied at 1.5 Tesla (Achieva, Philips Healthcare). Real time navigator positioned through the right diaphragm in cranio-caudal direction was evaluated. Measurements were performed in the supine position with free breathing for one minute before and after a tight-fitting BELT was positioned around the patient''s abdomen. End expiratory position (EEP), end inspiratory position (EIP), end expiratory duration (EED) for the right diaphragm and respiratory rate (RR) were obtained. Scan efficiency (SE) was calculated as follows; SE = [the duration within 5 mm gating window per minutes]/[RR interval]/[heart rate].

Results

Height and weight of UK patients were significantly larger than in the Japanese population (171.2 ± 10.8 cm vs 160.8 ± 8.5 cm, p = 0.007; 80.5 ± 22.5 kg vs 59.9 ± 7.7 kg, p = 0.004). After fitting the BELT, EEP-EIP decreased (all patients, 14.9 ± 6.2 mm to 9.4 ± 3.8 mm, p < 0.001; UK patients, 15.9 ± 6.0 mm to 9.7 ± 3.1 mm, p = 0.001; Japanese patients, 14.0 ± 6.4 mm to 9.1 ± 4.6 mm, p = 0.001), RR increased (all patients, 10.0 ± 3.1 min^-1 to 11.2 ± 3.0 min^-1, p = 0.003; UK patients, 9.5 ± 2.8 min^-1 to 10.7 ± 2.8 min^-1, p = 0.038; Japanese patients, 10.4 ± 3.5 min^-1 to 11.8 ± 3.1 min^-1, p = 0.036), and calculated scan efficiency increased (all patients, 45.3 ± 11.4% to 58.6 ± 17.0%, p < 0.001; UK patients, 44.2 ± 10.8% to 55.7 ± 16.7%, p = 0.004; Japanese patients, 46.3 ± 32.2% to 61.0 ± 17.6%, p = 0.001). No significant differences were found between UK and Japanese patients before and after administration of the BELT.

Conclusion

Using a BELT significantly increases whole-heart coronary MR angiography scan efficiency in both UK and Japanese patients.     

Therapeutic temperature modulation is associated with pulmonary complications in patients with severe traumatic brain injury

AIM: To examine complications associated with the use of therapeutic temperature modulation(mild hypothermia and normothermia) in patients with severe traumatic brain injury(TBI). METHODS: One hundred and fourteen charts were reviewed. Inclusion criteria were: severe TBI with Glasgow Coma Scale(GCS) 9, intensive care unit(ICU) stay 24 h and non-penetrating TBI. Patients were divided into two cohorts: the treatment group received therapeutic temperature modulation(TTM) with continuous surface cooling and indwelling bladder temperature probes. The control group received standard treatment with intermittent acetaminophen for fever. Information regarding complications during the time in the ICU was collected as follows: Pneumonia was identified using a combination of clinical and laboratory data. Pulmonary embolism, pneumothorax and deep venous thrombosis were identified based onimaging results. Cardiac arrhythmias and renal failure were extracted from the clinical documentation. acute respiratory distress syndrome and acute lung injury were determined based on chest imaging and arterial blood gas results. A logistic regression was conducted to predict hospital mortality and a multiple regression was used to assess number and type of clinical complications. RESULTS: One hundred and fourteen patients were included in the analysis(mean age = 41.4, SD = 19.1, 93 males), admitted to the Jackson Memorial Hospital Neuroscience ICU and Ryder Trauma Center(mean GCS = 4.67, range 3-9), were identified and included in the analysis. Method of injury included motor vehicle accident(n = 29), motor cycle crash(n = 220), blunt head trauma(n = 212), fall(n = 229), pedestrian hit by car(n = 216), and gunshot wound to the head(n = 27). Ethnicity was primarily Caucasian(n = 260), as well as Hispanic(n = 227) and African American(n = 223); four patients had unknown ethnicity. Patients received either TTM(43) or standard therapy(71). Within the TTM group eight patients were treated with normothermia after TBI and 35 patients were treated with hypothermia. A logistic regression predicting in hospital mortality with age, GCS, and TM demonstrated that GCS(Beta = 0.572, P 0.01) and age(Beta =-0.029) but not temperature modulation(Beta = 0.797, ns) were significant predictors of in-hospital mortality [χ2(3) = 22.27, P 0.01] A multiple regression predicting number of complications demonstrated that receiving TTM was the main contributor and was associated with a higher number of pulmonary complications(t =-3.425, P = 0.001). CONCLUSION: Exposure to TTM is associated with an increase in pulmonary complications. These findings support more attention to these complications in studies of TTM in TBI patients.     

No evidence of a role for cystatin B gene in juvenile myoclonic epilepsy

Genetic factors play a major role in the etiology of juvenile myoclonic epilepsy (JME), a common form of idiopathic generalized epilepsy, but so far, genes related to JME remain largely unknown. JME shares electroclinical features with Unverricht‐Lundborg disease (progressive myoclonic epilepsy type 1; EPM1), a form of progressive myoclonus epilepsy characterized by myoclonus, epilepsy, and gradual neurologic deterioration. EPM1 is caused by mutations in the gene that codes for cystatin B (CSTB), an inhibitor of cysteine protease. In the present study, we wished to investigate the role of the CSTB gene in patients with JME. Fifty‐seven unrelated patients (35 women; mean age ± standard deviation [SD], 24.1 ± 7.7; mean age ± SD at onset, 15.3 ± 2.4) with JME were enrolled. Twenty‐three of 57 patients were the probands of families with JME. The molecular diagnosis was carried out to identify the common dodecamer repeat expansion mutation or other disease‐causing mutations in the CSTB gene. The molecular analysis did not depict mutations in any of the 57 patients with JME. Our study did not support a role for the CSTB gene in patients with familial or sporadic JME.