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WHO has launched updated cervical screening guidelines, including provisions for primary HPV screen-and-treat. Papua New Guinea (PNG) has a high burden of cervical cancer, but no national cervical screening programme. We recently completed the first field trials of a screen-and-treat algorithm using point-of-care self-collected HPV and same-day treatment (hereafter self-collected HPV S&T) and showed this had superior clinical performance and acceptability to visual inspection of the cervix with acetic acid (VIA). We, therefore, evaluated the effectiveness, cost-effectiveness and resource implications of a national cervical screening programme using self-collected HPV S&T compared with VIA in PNG.
An extensively validated platform ('Policy1-Cervix') was calibrated to PNG. A total of 38 strategies were selected for investigation, and these incorporated variations in age ranges and screening frequencies and allowed for the identification of the optimal strategy across a wide range of possibilities. Aext 50 years, if scale-up reached 70% coverage from 2023.
Self-collected HPV S&T was effective and cost-effective in the high-burden, low-resource setting of PNG, and, if scaled-up rapidly, could prevent over 20 000 deaths over the next 50 years. VIA screening was not effective or cost-effective. These findings support, at a country level, WHO updated cervical screening guidelines and indicate that similar approaches could be appropriate for other low-resource settings.
Self-collected HPV S&T was effective and cost-effective in the high-burden, low-resource setting of PNG, and, if scaled-up rapidly, could prevent over 20 000 deaths over the next 50 years. VIA screening was not effective or cost-effective. These findings support, at a country level, WHO updated cervical screening guidelines and indicate that similar approaches could be appropriate for other low-resource settings.Glucuronidation is the most common phase II metabolic pathway to eliminate small molecule drugs from the body. However, determination of glucuronide structure is quite challenging by mass spectrometry due to its inability to generate structure-informative fragments about the site of glucuronidation. In this article, we describe a simple method to differentiate acyl-, O-, and N-glucuronides using chemical derivatization. The idea is that derivatization of acyl-, O-, or N-glucuronides of a molecule results in predictable and different numbers of derivatized functional groups, which can be determined by the mass shift using mass spectrometry. The following two reactions were applied to specifically derivatize carboxyl and hydroxyl groups that are present on the aglycone and its glucuronide metabolite Carboxyl groups were activated by thionyl chloride followed by esterification with ethanol. Hydroxyl groups were derivatized via silylation by 1-(trimethylsilyl)imidazole. The mass shift per derivatized carboxyl andon of glucuronide structures when multiple glucuronidation possibilities exist. The type of glucuronidation information is particularly useful for a drug candidate containing carboxyl groups, which can form reactive acyl-glucuronides. Additionally, the method can potentially be used for definitive structure elucidation for a glucuronide with its aglycone containing a single carboxyl, hydroxyl, or amino group even when multiple types of functional groups are present for glucuronidation.Incubation of craving refers to the intensification of drug-seeking behavior in response to reward-paired cues over the course of abstinence. In rodents, craving and drug-seeking behaviors have been measured by an increase in lever pressing in the absence of reinforcer availability in response to cue presentations. However, craving in rodents is difficult to define and little is known about the behavioral signatures that accompany increased drug-seeking behavior measured by lever pressing. The affective components of relapse are also important, but understudied in rodents. Hormonal fluctuations influence craving for psychostimulants, but little is known about the impact of the estrous cycle on opioid-seeking behavior. This study sought to delineate the behavioral and affective signatures associated with craving, and to examine the influence of the female estrous cycle on craving. this website Male and female rats underwent 10 d of intravenous opioid self-administration. Separate cohorts of control rats self-administered oral sucrose, a natural nondrug reward. Cue-induced seeking tests were conducted after 1 or 30d of forced abstinence. These sessions were recorded and scored for overall locomotion, instances of sniffing, grooming, or hyperactivity. Ultrasonic vocalizations (USVs) were also recorded to determine affective profiles that accompany opioid seeking. Although active lever presses and overall locomotion increased unanimously over extended abstinence from heroin and sucrose, a sex- and reinforcer-specific behavioral and affective signature of craving emerged. Furthermore, although the female estrous cycle did not affect taking or seeking, it appears to influence more granular behaviors.A postpartum woman presented with sudden-onset left eyelid swelling and severe pain. Clinical examination revealed left exophthalmos and ophthalmoplegia with marked resistance to retropulsion of the left globe. The patient was not able to perceive light in the affected left eye and a relative afferent pupillary defect was present. CT orbits showed an enhancing lesion in the left retrobulbar space, suggestive of a lateral rectus haemorrhage. An emergency left lateral canthotomy and inferior cantholysis was performed. A day later, an MRI showed expansion of the left lateral rectus with significant mass effect on the globe. As the visual acuity remained reduced at counting fingers and there was a persistent relative afferent pupillary defect (RAPD), an exploratory orbitotomy and haematoma evacuation was performed. Three days postoperatively, the visual acuity had returned to 6/6. Eye movements normalised within 2 weeks and follow-up imaging revealed near complete resolution of the haematoma.Fibromuscular dysplasia (FMD) is an arteriopathy of medium-sized vessels causing pathological arterial wall fragility. However, only minimal data exist on evaluating the risk of transradial access (TRA) in these patients. We describe the case of a woman in her 70s who underwent left middle meningeal artery embolisation for an acute-on-chronic subdural haematoma via right TRA. Radial angiography demonstrated significant FMD throughout the entire right upper extremity. To prevent radial spasm, a 23 cm sheath was placed without difficulty. However, follow-up angiography demonstrated the presence of a new radial arteriovenous fistula (AVF) just distal to the brachial bifurcation. Since no forearm haematoma or limb ischaemia developed, the procedure was continued transradially. After embolisation, the guide catheter was removed and follow-up angiography demonstrated resolution of the fistula. This case illustrates that, in the absence of concerning clinical signs, compression from the guide catheter alone may facilitate thrombosis of an acutely identified iatrogenic radial AVF.Polymyositis is an immune-mediated inflammatory myopathy usually presenting with weakness of proximal muscles in a symmetric pattern. Generalised subcutaneous oedema as presenting feature of inflammatory myopathy, especially polymyositis, has rarely been reported. We report here a case of a young woman who was admitted to our facility with generalised severe subcutaneous oedema. During hospital stay, she gradually developed significant proximal muscle weakness with bulbar symptoms. The initial presentation of the patient masqueraded with other causes of anasarca. However, detailed clinical features, laboratory evaluation, electromyography and muscle biopsy clinched the diagnosis of polymyositis. She was treated with systemic corticosteroids and azathioprine. The patient responded well to treatment and the swelling gradually subsided.Neuraxial anaesthesia is an essential technique in obstetric anaesthesia practice. Cerebrospinal fluid (CSF) fistula is a rare complication and there is no consensus about its clinical approach. We present a case of a 28-year-old nulliparous woman that developed a cutaneous CSF fistula following combined spinal and epidural block for caesarean delivery. After multidisciplinary discussion it was decided that hydration, absolute bed-rest and compressive dressing with abdominal binder was the best option and the patient fully recovered without any sequelae.Based on literature, symptoms of intracranial hypotension and leakage of clear fluid surrounding the puncture site usually motivate referral to anaesthesia. Management strategies can be both conservative and invasive, including direct suture of the skin puncture site and epidural blood patch.Regarding the anaesthesia practice on this topic, most of the available evidence is based on case reports, rendering the decision-making process challenging.Pulmonary lymphangitis carcinomatosis is a complication of malignancy with a poor prognosis. We describe an unusual case in which it caused ventilatory failure and unfortunately death in a previously well male in his 70s. Abnormal chest imaging led to a wide differential diagnosis with Bronchoscopy confirming malignant cells. MRI of his pelvis and biopsy was done diagnosis of metastatic leiomyosarcoma, a particularly aggressive malignancy. Sarcoma-related lymphangitis carcinomatosis is rarely described in the literature and this is the first case to our knowledge of its association with leiomyosarcoma.Jejunocolic fistula, a late complication of intestinal lymphoma, is a rare entity with only five reported cases in the literature. We report a young male presenting with a left lateral neck mass 5 years ago which then progressed to superior vena cava syndrome. Despite receiving radiotherapy and two cycles of chemotherapy, there was still tumour progression. He presented with a 2-week history of diarrhoea, haematochezia and weight loss for which antibiotics provided no relief. Esophagogastroduodenoscopy and colonoscopy showed a jejunocolic fistula. After discussion with the multidisciplinary team, nutritional upbuilding was initiated followed by exploratory laparotomy with segmental resection and anastomosis. On histopathology, diffuse large B-cell lymphoma involving the jejunum and colon was noted. Despite receiving palliative chemotherapy, he still succumbed to disease progression. This case highlights the importance of early recognition of jejunocolic fistulas among patients with intestinal lymphomas to facilitate early multidisciplinary intervention.This report discusses the case of a male refugee from East Africa who presented with persistent right shoulder pain and was found to have a periscapular mass, whose diagnostic and therapeutic delay was due not only to fragmentation of care, but also a lack of awareness of musculoskeletal manifestations of extrapulmonary tuberculosis. This case underscores the importance of including tuberculosis in the differential diagnosis for a variety of symptoms in patients with risk factors, even if they report previous negative screening.
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