Clinical standards for the diagnosis and management of asthma in low- and middle-income countries.

BACKGROUND: The aim of these clinical standards is to aid the diagnosis and management of asthma in low-resource settings in low- and middle-income countries (LMICs).METHODS: A panel of 52 experts in the field of asthma in LMICs participated in a two-stage Delphi process to establish and reach a consensus on the clinical standards.RESULTS: Eighteen clinical standards were defined: Standard 1, Every individual with symptoms and signs compatible with asthma should undergo a clinical assessment; Standard 2, In individuals (>6 years) with a clinical assessment supportive of a diagnosis of asthma, a hand-held spirometry measurement should be used to confirm variable expiratory airflow limitation by demonstrating an acute response to a bronchodilator; Standard 3, Pre- and post-bronchodilator spirometry should be performed in individuals (>6 years) to support diagnosis before treatment is commenced if there is diagnostic uncertainty; Standard 4, Individuals with an acute exacerbation of asthma and clinical signs of hypoxaemia or increased work of breathing should be given supplementary oxygen to maintain saturation at 94-98%; Standard 5, Inhaled short-acting beta-2 agonists (SABAs) should be used as an emergency reliever in individuals with asthma via an appropriate spacer device for metered-dose inhalers; Standard 6, Short-course oral corticosteroids should be administered in appropriate doses to individuals having moderate to severe acute asthma exacerbations (minimum 3-5 days); Standard 7, Individuals having a severe asthma exacerbation should receive emergency care, including oxygen therapy, systemic corticosteroids, inhaled bronchodilators (e.g., salbutamol with or without ipratropium bromide) and a single dose of intravenous magnesium sulphate should be considered; Standard 8, All individuals with asthma should receive education about asthma and a personalised action plan; Standard 9, Inhaled medications (excluding dry-powder devices) should be administered via an appropriate spacer device in both adults and children. Children aged 0-3 years will require the spacer to be coupled to a face mask; Standard 10, Children aged <5 years with asthma should receive a SABA as-needed at step 1 and an inhaled corticosteroid (ICS) to cover periods of wheezing due to respiratory viral infections, and SABA as-needed and daily ICS from step 2 upwards; Standard 11, Children aged 6-11 years with asthma should receive an ICS taken whenever an inhaled SABA is used; Standard 12, All adolescents aged 12-18 years and adults with asthma should receive a combination inhaler (ICS and rapid onset of action long-acting beta-agonist [LABA] such as budesonide-formoterol), where available, to be used either as-needed (for mild asthma) or as both maintenance and reliever therapy, for moderate to severe asthma; Standard 13, Inhaled SABA alone for the management of patients aged >12 years is not recommended as it is associated with increased risk of morbidity and mortality. It should only be used where there is no access to ICS.The following standards (14-18) are for settings where there is no access to inhaled medicines. Standard 14, Patients without access to corticosteroids should be provided with a single short course of emergency oral prednisolone; Standard 15, Oral SABA for symptomatic relief should be used only if no inhaled SABA is available. Adjust to the individual's lowest beneficial dose to minimise adverse effects; Standard 16, Oral leukotriene receptor antagonists (LTRA) can be used as a preventive medication and is preferable to the use of long-term oral systemic corticosteroids; Standard 17, In exceptional circumstances, when there is a high risk of mortality from exacerbations, low-dose oral prednisolone daily or on alternate days may be considered on a case-by-case basis; Standard 18. Oral theophylline should be restricted for use in situations where it is the only bronchodilator treatment option available.CONCLUSION: These first consensus-based clinical standards for asthma management in LMICs are intended to help clinicians provide the most effective care for people in resource-limited settings.

Transient Right-Sided Hemiparesis and Diplopia in the Setting of a Migrated Cervical Spinal Cord Stimulator Lead: A Case Report.

A 36-year-old man with a history of cervical spinal cord stimulator (SCS) lead placement presented with transient right-sided hemiparesis and diplopia that began 2 days after a coughing episode. Imaging revealed lateral and cranial migration of one of the patient's SCS leads. Deactivation of the SCS resulted in rapid improvement of his nonmotor symptoms but did not resolve his motor deficits. The SCS system was surgically explanted, resulting in resolution of the patient's motor symptoms. The unique neurologic symptomatology demonstrated by this patient is a previously undescribed complication of SCS placement and lead migration.

Patient-derived functional organoids as a personalized approach for drug screening against hepatobiliary cancers.

Patient-derived organoids (PDOs) established from hepatobiliary cancers are seen as valuable models of the cancer of origin. More precisely, PDOs have the ability to retain the original cancer genetic, epigenetic and phenotypic features. By extension, hepatobiliary cancer PDOs have the potential to (1) increase our understanding of cancer biology; (2) allow high-throughput drug screening for more efficient identification and testing of small molecule therapeutics, and (3) permit the design of personalized drug choice approaches for patients with liver cancer. Here, we review general principles for PDO establishment from hepatocellular carcinoma and cholangiocarcinoma, their utilization in drug screening strategies, and last, the establishment of complex PDOs to include tumor stroma. We conclude that PDOs represent a promising and important development in investigating interaction between liver cancer cell types and their microenvironment, as well as for positioning PDOs for high throughput drug screening for hepatobiliary cancers, and that further work is now needed to fully realize their potential.

[Transcutaneous stimulation of the posterior tibial nerve modifies the sympathetic skin response and improves overactive bladder syndrome: Case series and possible diagnostic test]. / La estimulación transcutánea del nervio tibial posterior modifica la respuesta simpática cutánea y mejora el síndrome de vejiga hiperactiva: serie de casos y posible prueba diagnóstica.

OBJECTIVE: (a) To assess the effect of transcutaneous neuromodulation (TNM) of the posterior tibial nerve plus biofeedback on the sympathetic skin response (SSR). (b) Evaluate its effect on clinical symptoms. (c) Consider SSR as a probable neurophysiological test useful both for diagnosis and for follow-up in patients with overactive bladder (OAB). (d) Evaluate its cost compared to other techniques. MATERIAL AND METHODS: A prospective quasi-experimental before and after study in 10 OAB patients. OUTCOME VARIABLES: daytime (DUF) and nighttime (NUF) urinary frequency, strength of the pelvic floor muscles measured by manometry (maximum and mean pressure) and sympathetic skin response (SSR). RESULTS: DUF improved from 10.3±5.45 to 5.9±2.42 episodes (P=.0050). The NUF improved from 2.4±1.5 to 0.6±0.69 episodes (P=.0012). The maximum pressure ranged from 34.7±16.51 to 39.7±3.65mmHg (P=.0195). The mean pressure of the pelvic floor muscles improved from 6.6±3.65 to 9.3±5.43mmHg (P=.0333). SSR changed from 100% hyperexcitability prior to treatment to 50±14.14% (P=.0000). CONCLUSION: TNM plus biofeedback could modify SSR and improve clinical and manometry variables in a series of patients with OAB. The probable diagnostic and prognostic utility of this neurophysiological test in OAB and detrusor hyperactivity is reported for the first time. A larger sample study is needed to confirm the promising findings seen in this preliminary study.

Electroacupuncture at ST36 Relieves Visceral Hypersensitivity via the NGF/TrkA/TRPV1 Peripheral Afferent Pathway in a Rodent Model of Post-Inflammation Rectal Hypersensitivity.

PURPOSE: The aim of the study was to investigate the effects of electroacupuncture (EA) at ST36 on rectal hypersensitivity and compliance in DSS-treated post-inflammation rats. In addition, we explored the involvement of mast cells-triggered NGF/TrkA/TRPV1 peripheral afferent pathway. METHODS: Rats were provided water with 5% dextran sulphate sodium (DSS) for 7 days. Two weeks after the DSS treatment they were subjected to initial and repetitive EA. Different sets of parameters were compared in the initial test and then EA with the selected parameters were performed for 2 weeks. Rectal compliance was assessed by colorectal distension while visceral sensitivity was evaluated by abdominal withdraw reflexes (AWR) and electromyogram (EMG). Masson's trichrome staining was performed to stain collagen and toluidine blue staining was applied to assess the degranulation of mast cells. Nerve growth factor (NGF), tryptase, TrkA and TRPV1 were measured by Western blot or immunofluorescence staining. RESULTS: EA at 100 Hz was more effective in improving rectal compliance and visceral hypersensitivity. Daily EA improved visceral hypersensitivity but not rectal compliance. Five weeks after DSS treatment, fibrosis was noted in both sham-EA and EA groups. The expression and activation of mast cells were significantly reduced after the 2-week EA treatment with a concurrent decrease in the expression of colonic NGF/TrkA and TRPV1 in both colon and dorsal root ganglions. CONCLUSION: EA at ST36 with a special set of parameters has no effect on reduced rectal compliance but relieves visceral hypersensitivity via the mast cells-triggered NGF/TrkA/TRPV1 peripheral afferent pathway in DSS-treated post-inflammation rats.

[Effectiveness of multimodal rehabilitation (biofeedback plus capacitive-resistive radiofrequency) on chronic pelvic pain and dyspareunia: prospective study and literature review]. / Efectividad de la rehabilitación multimodal (biofeedback más radiofrecuencia capacitiva-resistiva) sobre el dolor pélvico crónico y la dispareunia: estudio prospectivo y revisión de la bibliografía.

OBJECTIVE: To determine whether a multimodal rehabilitation protocol (Biofeedback [BFB] plus capacitive-resistive [INDIBA®] radiofrequency [RF]) reduces pain and increases muscular strength in patients with chronic pelvic pain (CPP) and dyspareunia. MATERIAL AND METHODS: We performed a prospective, quasi-experimental, before-after study in 37 patients with CPP and/or dyspareunia referred to the Rehabilitation Department of Hospital Universitario Santa Cristina (January 2016 to December 2018). The protocol consisted of 8 sessions of pelvic floor exercises assisted by manometric BFB (15min of tonic/phasic exercises each) supervised by a physiotherapist, followed by suprapubic and perineovaginal bipolar RF [capacitive(5 min)/resistive(10 min)]. The variables evaluated were pain (VAS 0-10) and strength (mmHg) of the pelvic floor musculature and the start/end of the treatment. RESULTS: The mean age was 41.5±12.65 years. The prevalence was higher among women aged 21-40 years (n=20, 54%) and those aged 41-60 years (n=12; 32.4%). Dyspareunia was present in 34 patients (91.8%), and non-specific CPP in 3 (8.2%). The protocol improved pain (from 7.27±1.34 to 3.75±2.21 points), maximal muscular strength (from 25.56±15.9mmHg to 35.35±20.4mmHg) and mean muscular strength (from 4.86±3.53mmHg to 7.18±4.46mmHg) respectively (p<0.0001). CONCLUSION: CPP and dyspareunia are a diagnostic challenge that requires multidisciplinary management. Treatment should be started early and should consist of distinct therapeutic modalities. The protocol of multimodal rehabilitation including BFB and capacitive-resistive RF reduces pain and improves strength in patients with CPP and dyspareunia.