Genotypic Diversity among Salmonella Typhi Isolated from Children Living in Informal Settlements in Nairobi, Kenya.

The persistence of multidrug-resistant (MDR) Salmonella Typhi (S. Typhi) is a challenge especially in regions where typhoid is endemic. Surveillance of circulating genotypes of MDR S. Typhi is crucial in typhoid acute cases and carriers. This study aimed to investigate genotypic diversity of S. Typhi from symptomatic and asymptomatic children in endemic settings in Nairobi, Kenya. Symptomatic and asymptomatic individuals' ≤ 16 years were recruited at four health facilities and tested for typhoid through stool cultures. The S. Typhi isolates were subjected to antibiotic susceptibility testing to investigate multidrug resistance. The MDR S. Typhi isolates' DNA was extracted and illumina sequenced. Raw reads were de novo assembled and analyzed by pathogen-watch. From the 90 sequenced isolates, 60 (67%) were confirmed to be S. Typhi (sequence Type 1 and genotype 4.3.1). Out of the 60 S. Typhi strains; 39 (65%) had plasmids, from these 38 (97%) had IncHI1 plasmids alone. Out of the 60, 59 (98%) S. Typhi isolates had bla TEM-1D . Point mutations conferring reduced susceptibility to quinolones were detected in 42 (70%) of S. Typhi isolates, from these; 14 (33%) had gyrA S83Y, and 28 (67%) gyrB S464F genes, respectively. This study reports 4.3.1 (H58) as the most dominant S. Typhi genotype responsible for spread of MDR phenotypes carried on IncHI1 plasmids. Presence of MDR S. Typhi with resistance genes such as bla TEM-1D and reduced susceptibility to ciprofloxacin especially among asymptomatic individuals, reiterates the need for use of typhoid conjugate vaccine among vulnerable children as a control and prevention measure against typhoid.

The impact of loneliness and social relationship dissatisfaction on clinical and functional outcomes in Dutch mental health service users.

The relationship between reduced social connectedness and mental health outcomes is increasingly acknowledged. Yet, relatively little is known about how two crucial subjective aspects of social disconnectedness - loneliness and social relationship dissatisfaction (SRD) - are related to clinical and functional recovery. This cohort study aimed to investigate the associations of loneliness and SRD with various mental health outcomes among 15,512 outpatients from a Dutch mental health service. Demographics and data on loneliness, SRD, symptomatic distress, suicidal ideation, and role functioning, as well as treatment duration, and mortality, were collected. The study analyzed the associations between these factors overall and by diagnostic group, gender, and age, using cross-sectional and longitudinal regression, while controlling for relevant covariates. Findings revealed significant, independent, associations between loneliness, SRD, symptomatic distress, and role functioning across different diagnostic groups. Particularly strong associations were noted in bipolar and psychosis-related disorders. Gender did not significantly influence the strength of associations. In older patients, lower levels of loneliness and SRD were observed, but the impact on clinical and functional outcomes was consistent across ages. Higher loneliness and SRD were associated with longer treatment durations, regardless of age, gender or diagnosis. This study indicates the wide-reaching effects of perceived social disconnectedness on recovery and emphasizes interventions targeting loneliness and SRD to enhance outcomes.

Identifying factors strongest associated with clinical, societal and personal recovery in people with psychosis with a long duration of illness.

INTRODUCTION: Most studies on recovery of psychotic disorders focus on first-episode populations using premorbid and baseline data to predict recovery. However, many patients experience a long duration of illness and many factors are dynamic and change during life. AIMS: To investigate factors strongest associated with clinical, societal and personal recovery, and recovery change scores in people with a long duration of illness using current data measured at the same assessment. METHODS: Least absolute shrinkage and selection operator regression analyses with cross-validation were used to identify the correlates of (changes in) clinical (N = 1054), societal (N = 1145) and personal recovery (N = 1187) in people with psychotic disorders. Subsequently, the identified associated factors were included in separate linear regression models, examining the associative strength of the identified variables and overall fit of the models. RESULTS: Better clinical recovery was associated with better societal and personal recovery, experiencing fewer problems with daily functioning and social relations. Participants had a better societal recovery when they were employed, had fewer problems in daily life, less negative symptoms, had a life partner and better clinical recovery. Personal recovery was associated with greater satisfaction with life in general, no depressive mood and increased clinical recovery. Change scores were small with minimal fluctuation and no significant associations with change scores were detected. CONCLUSIONS: Recovery domains strongly influence each other in people with a long illness duration of psychosis and should therefore have an equally important focus during treatment.

Serum and mucosal antibody-mediated protection and identification of asymptomatic respiratory syncytial virus infection in community-dwelling older adults in Europe.

Introduction: Respiratory syncytial virus (RSV) causes acute respiratory tract infection (ARTI) and reinfects adults throughout life, posing a risk for hospitalization in older adults (>60 years) with frailty and comorbidities. Methods: To investigate serum and mucosal antibodies for protection against RSV infections, baseline serum samples were compared for RSV-pre- and -post-fusion (F) binding, and RSV-A2 neutralizing IgG antibodies between symptomatic RSV-ARTI (N = 30), non-RSV (RSV negative) ARTI (N = 386), and no ARTI (N = 338). Mucosal RSV-pre-F IgA and IgG levels, as well as serum RSV-G IgG antibodies, were analyzed to determine their association with protection from symptomatic RSV-ARTI in a subset study. Results: Using a receiver operating characteristic (ROC) analysis, we established thresholds of 1.4- to 1.6-fold change (FC) for RSV-pre-F and -post-F, and RSV-A2 neutralizing IgG antibodies, respectively, enabling the identification of asymptomatic RSV cases with high sensitivity and specificity (>80% and >90%, respectively). As a result, serum RSV-pre-F, RSV-G IgG, and mucosal pre-F binding IgA antibodies showed correlations with protection against symptomatic RSV infection. RSV-pre-F IgG antibodies were correlated with protection from RSV infections irrespective of the symptoms. Discussion: This study provides insights into antibody-mediated protection for symptomatic RSV infection in a community-dwelling older-adult population and establishes a threshold to identify asymptomatic RSV infection using a data-driven approach.

Management of intracavitary bleeding during ultra-early minimally invasive intracerebral hemorrhage evacuation.

OBJECTIVE: Surgical evacuation of intracerebral hemorrhage (ICH) at early time points contributes to improved functional outcomes. However, ultra-early evacuation has been associated with postoperative rebleeding, a devastating complication that contributes to worse outcomes. Minimally invasive endoscopic techniques allow for intraoperative management of active bleeding, potentially allowing for safe and effective hemostasis at ultra-early time points. The authors proposed and prospectively assigned an intraoperative grading scale that quantified the severity of bleeding encountered intraoperatively. They hypothesized that ultra-early evacuation would correlate to increased intraoperative bleeding but not postoperative rebleeding or worse long-term clinical outcomes in a cohort of patients undergoing minimally invasive endoscopic evacuation. METHODS: Patients presenting to a large healthcare system with spontaneous supratentorial ICH were triaged to a central hospital for potential surgical evacuation. Inclusion criteria for evacuation included age ≥ 18 years, premorbid mRS score ≤ 3, hematoma volume ≥ 15 mL, and presenting National Institutes of Health Stroke Scale score ≥ 6. A 5-point scale was developed and prospectively applied to grade the severity of bleeding encountered intraoperatively. A score of 1 indicated no active intraoperative bleeding. A score of 2 indicated minimal bleeding treated with irrigation alone. A score of 3 indicated bleeding that required cauterization to control. A score of 4 indicated bleeding that required irrigation or cauterization for at least 15 minutes to achieve hemostasis. A score of 5 indicated bleeding that required irrigation or cauterization for at least 1 hour. RESULTS: The authors evaluated 142 consecutive patients. The median bleeding score was 2 (IQR 2-4). Greater preoperative volume, concomitant intraventricular hemorrhage, and earlier time to evacuation were independently associated with increased bleeding score. Specifically, ultra-early evacuation within 5 hours was independently associated with a 2.4-point greater bleeding score as compared with evacuation thereafter (ß = 2.41, 95% CI 1.44-3.38; p < 0.0001). Despite having higher intraoperative bleeding scores, patients undergoing ultra-early evacuation did not have an increased likelihood of postoperative rebleeding (14% vs 3%, p = 0.23), 30-day mortality (0% vs 6%, p = 0.99), or worse median 6-month mRS scores (4 [IQR 2-5] vs 4 [IQR 3-5], p = 0.51). CONCLUSIONS: Ultra-early evacuation within 5 hours of ictus is associated with increased intraoperative bleeding but not postoperative rebleeding or worse clinical outcomes. These findings suggest that the benefits of ultra-early evacuation can be explored without an increased risk of postoperative rebleeding when utilizing a minimally invasive endoscopic technique with good intraoperative visualization, active irrigation for targeted tamponade, and direct cauterization of bleeding vessels.

A new angiographic scoring for grading the difficulty of recanalization for symptomatic non-acute middle cerebral artery occlusions.

Background: Endovascular recanalization is a feasible option for treating symptomatic non-acute middle cerebral artery occlusion (MCAO) patients. Hence, we aimed to establish a new angiographic scoring to grade the recanalization difficulty of MCAO to determine the suitable patients for endovascular treatment. Methods: We retrospectively analyzed a total of 113 consecutive recurrent symptomatic non-acute MCAO patients who underwent endovascular recanalization from July 2015 to August 2021 in four Chinese comprehensive stroke centers. All patients were reappraised using a new angiographic scoring based on the stump morphology, the MCA occlusion length, MCA bend, and the distal vascular bed of MCAO. We used the final results to establish the patients' outcomes. Results: The total successful recanalization and perioperative complication rates were 83.2% (94/113) and 15.9% (18/113), respectively. No deaths occurred within 30 days. Moreover, 96.9, 90, 87.5, 52.6, and 50% of the patients achieved recanalization with scores of 0, 1, 2, 3, and 4 (p < 0.001), respectively. However, the perioperative complication rate showed the opposite trend. (3.1% vs. 7.5% vs. 6.3% vs. 52.6% vs. 50%; p < 0.001). The median time of successful microwire crossing of the occlusion lesion (TMO) in the score 0 group was shorter than the other groups (2 min, 9 min, 8.5 min, 14 min, and 20 min; p < 0.001). When a score of 2 was used as the optimal cut-off point, the sensitivity and specificity were 86.2 and 63.2%, respectively. Conclusion: The new angiographic scoring can effectively predict the successful recanalization rate, perioperative complication rate, and TMO of endovascular recanalization for non-acute MCAO. It can also be used as an effective clinical evaluation tool to determine the suitable non-acute MCAO patients for recanalization, especially with a score ≤ 2.

Cognitive Behavioral Therapy for Paroxysmal Atrial Fibrillation: Heart Rate Variability, Physical Activity, and Sleep.

Background: Cognitive behavioral therapy for symptom preoccupation in paroxysmal atrial fibrillation (AF-CBT) significantly improved AF-specific quality of life in a recent trial. To what extent this may this may be associated with changes in physiological parameters is yet to be determined. Objectives: The purpose of this study was to assess the effects of AF-CBT on heart rate variability (HRV), physical activity, and sleep. Methods: Patients with symptomatic paroxysmal AF on optimal medical therapy (mean ± standard deviation 65.4 ± 8.3 years, 58% females, 61% on beta-blockers) were randomized to a 10-week online AF-CBT (n = 65) or AF education (n = 62). AF-CBT was therapist-led and focused on social and physical avoidance. A 5-day Patch-Holter with an integrated accelerometer was applied at baseline, post-treatment, and at 3-month follow-up to assess AF burden, HRV, physical activity, and sleep duration. Subjective assessments were made by the International Physical Activity (IPAQ) and Insomnia Severity Index questionnaires. Results: At baseline, participants walked on average 8040 ± 2600 steps/day and slept 8.0 ± 1.1 hours. Objective and subjective physical activity and sleep duration remained unchanged after treatment, with no significant difference between the groups. The Insomnia Severity Index score went from subclinical insomnia (12.2 ± 6.7) to near normal values (8.1 ± 5.6), a significant change compared to controls (P = 0.032). No changes were found in AF burden or HRV indices at rest during the day or at night. Conclusions: In this select cohort, AF-CBT decreased insomnia severity but had no impact on HRV or physical activity. Thus, AF-CBT may operate through psychological and behavioral factors that are not targeted by current medical and lifestyle interventions.

Frontoparietal network integrity supports cognitive function in pre-symptomatic frontotemporal dementia: Multimodal analysis of brain function, structure, and perfusion.

INTRODUCTION: Genetic mutation carriers of frontotemporal dementia can remain cognitively well despite neurodegeneration. A better understanding of brain structural, perfusion, and functional patterns in the pre-symptomatic stage could inform accurate staging and potential mechanisms. METHODS: We included 207 pre-symptomatic genetic mutation carriers and 188 relatives without mutations. The gray matter volume, cerebral perfusion, and resting-state functional network maps were co-analyzed using linked independent component analysis (LICA). Multiple regression analysis was used to investigate the relationship of LICA components to genetic status and cognition. RESULTS: Pre-symptomatic mutation carriers showed an age-related decrease in the left frontoparietal network integrity, while non-carriers did not. Executive functions of mutation carriers became dependent on the left frontoparietal network integrity in older age. DISCUSSION: The frontoparietal network integrity of pre-symptomatic mutation carriers showed a distinctive relationship to age and cognition compared to non-carriers, suggesting a contribution of the network integrity to brain resilience. HIGHLIGHTS: A multimodal analysis of structure, perfusion, and functional networks. The frontoparietal network integrity decreases with age in pre-symptomatic carriers only. Executive functions of pre-symptomatic carriers dissociated from non-carriers.

Major clinical outcomes in symptomatic vs. asymptomatic atrial fibrillation: a meta-analysis.

BACKGROUND AND AIMS: Current guidelines suggest that asymptomatic atrial fibrillation (AF) is independently associated with increased risks of stroke and mortality compared with symptomatic AF. Considering that recent investigations have provided conflicting results, the present study aimed to evaluate the association between symptom status and clinical outcomes in patients with AF. METHODS: Medline, Cochrane Library, and Scopus were searched until 25 March 2024. Triple-independent study selection, data extraction and quality assessment were performed. Evidence was pooled using random-effects meta-analyses. RESULTS: Thirty-six studies (217 850 participants) were included. Based on the frequentist analysis, symptomatic individuals had no significant difference in the risk of all-cause mortality [hazard ratio (HR) .97, 95% confidence interval (CI) .80-1.17], cardiovascular mortality (HR 1.04, 95% CI .72-1.49), thromboembolism (HR 1.06, 95% CI .87-1.28), stroke (HR 1.06, 95% CI .84-1.34), hospitalization (HR 1.34, 95% CI .89-2.02), and myocardial infarction (HR .98, 95% CI .70-1.36), compared to the asymptomatic group. Symptomatic patients had a 33% increased risk of new-onset heart failure (HR 1.33, 95% CI 1.19-1.49) and a 30% lower risk of progression to permanent AF (HR .70, 95% CI .54-.89). The Bayesian analysis yielded comparable results, yet the association between symptom status and new-onset heart failure was not significant (HR 1.27, 95% credible interval .76-1.93; Bayes factor = 1.2). Symptomatic patients had higher odds of receiving antiarrhythmic drugs (odds ratio [OR] 1.64, 95% CI 1.33-2.03) and ablation therapy (OR 1.47, 95% CI 1.06-2.05) compared to asymptomatic cases. CONCLUSIONS: The risk of major clinical outcomes did not differ between individuals with and without AF-related symptoms. Asymptomatic patients had a greater hazard of progression to permanent AF.

mRNA expression of vitamin D receptor, calcium-sensing receptor, cyclin D1, and PTH in symptomatic and asymptomatic primary hyperparathyroidism.

BACKGROUND AND OBJECTIVE: The exact underlying mechanism for the differential clinical profiles of symptomatic and asymptomatic primary hyperparathyroidism (PHPT) patients has not been fully elucidated, and efforts to define the molecular mechanisms underlying the phenotypic heterogeneity of PHPT have been limited. The aim of this study was to explore the underlying molecular mechanisms involved in the pathogenesis of symptomatic and asymptomatic sporadic PHPT in Asian Indians. METHODS: A prospective cohort study was conducted at a tertiary care hospital in North India. PHPT patients who underwent parathyroidectomy were included. The main outcome was the comparison of vitamin D receptor (VDR), calcium-sensing receptor (CaSR), cyclin D 1 (CD1), and parathyroid hormone (PTH) mRNA levels between symptomatic and asymptomatic PHPT patients and controls determined via quantitative real-time polymerase chain reaction (qRT-PCR). RESULTS: Forty-two PHPT patients were studied. The mean (SD) age was 49.7 (12.8) years. Twenty patients were asymptomatic. The median PTH levels were significantly greater in the symptomatic group than in the asymptomatic group (878 vs 653 pg/mL). CaSR and VDR mRNAs were significantly lower in both symptomatic and asymptomatic patients than in controls. CD1 and PTH mRNAs were significantly increased in symptomatic patients, but not in asymptomatic PHPT patients compared with controls. Symptomatic PHPT patients had significantly greater CD1 mRNA expression and reduced CaSR expression than asymptomatic patients. CONCLUSION: Symptomatic PHPT patients had significantly greater CD1 mRNA expression and lower CaSR expression than asymptomatic patients, underscoring the importance of the molecular mechanisms underlying the phenotypic heterogeneity of PHPT.

Transcarotid arterial revascularization for symptomatic carotid web.

OBJECTIVES: Symptomatic carotid web is an increasingly recognized cause of acute ischemic stroke with a high risk of recurrent ischemic events despite aggressive medical interventions. Surgical interventions including transfemoral carotid artery stenting (TFCAS) and carotid endarterectomy have been described to reduce this risk, but transcarotid arterial revascularization (TCAR) has not been evaluated for this purpose. MATERIALS AND METHODS: Patients with cerebral ischemia from carotid web underwent TCAR with flow reversal. Patients were monitored for periprocedural complications and assessed at follow-up for clinical evidence of recurrent ischemia. RESULTS: Six cases over the course of 21 months were identified, 2 males and 4 females with a median age of 59.5 (interquartile range of 39). All underwent technically successful TCAR without periprocedural complications no post-procedural cerebral ischemia over a median follow-up time of 21 months. CONCLUSIONS: In this small series of patients, TCAR provided a safe and effective treatment of carotid webs that had previously caused cerebral ischemia.

Understanding long COVID: prevalence, characteristics, and risk factors in the Eastern Province of Saudi Arabia.

Background: The COVID-19 pandemic has significantly raised public health concerns and efforts to limit its spread, impacting societies and health systems worldwide. As challenges persist, the emergence of Long COVID (LC) marks a turning point in understanding the pandemic's long-term effects. Aim: This study aimed to determine the prevalence of LC in the Eastern Province of the Kingdom of Saudi Arabia (KSA) and explore factors contributing to its persistence. Methods: This descriptive, cross-sectional, questionnaire-based study was carried out between December 1, 2023, and March 1, 2024, involving 1,355 patients who recovered from COVID-19. Participants were conveniently chosen and information was gathered through in-person interviews in public settings after obtaining consent. Results: A majority of the patients (N = 1,355; 47.5% female; 93.8% Saudis; mean Age ± SD 33.13 ± 12.60 years) had received three COVID-19 vaccine doses (89.5%). Women experienced 17.4% more LC symptoms than men (p < 0.001). The risk of having a higher symptom count increased by 42.5% 12 months after acute COVID-19 infection compared with baseline (<3 months, p < 0.001). A higher body mass index (BMI) was associated with more symptoms (1.1% increase per unit, p = 0.004). More acute-phase symptoms correlated with more LC symptoms (p < 0.001). Higher educational attainment reduced LC risk by 33% (p < 0.001). Finally, age and vaccination status had no effect on LC symptoms count (p > 0.05). Conclusion: Sociodemographic and clinical factors contribute differently to the chances of having LC and the count of symptoms. Awareness of such factors could provide insight into improving management, leading to better health outcomes.

Immune response to viscerotropic Leishmania: a comprehensive review.

L. donovani and L. infantum infections are associated with a broad clinical spectrum, ranging from asymptomatic cases to visceral leishmaniasis (VL) with high mortality rates. Clinical manifestations such as post-kala-azar dermal leishmaniasis (PKDL) and visceral leishmaniasis-associated hemophagocytic lymphohistiocytosis-mimic (VL-associated HLH-mimic) further contribute to the diversity of clinical manifestations. These clinical variations are intricately influenced by the complex interplay between the host's immune response and the parasite's escape mechanisms. This narrative review aims to elucidate the underlying immunological mechanisms associated with each clinical manifestation, drawing from published literature within the last 5 years. Specific attention is directed toward viscerotropic Leishmania sinfection in patients with inborn errors of immunity and acquired immunodeficiencies. In VL, parasites exploit various immune evasion mechanisms, including immune checkpoints, leading to a predominantly anti-inflammatory environment that favors parasite survival. Conversely, nearly 70% of individuals are capable of mounting an effective pro-inflammatory immune response, forming granulomas that contain the parasites. Despite this, some patients may experience reactivation of the disease upon immunosuppression, challenging current understandings of parasite eradication. Individuals living with HIV and those with inborn errors of immunity present a more severe course of infection, often with higher relapse rates. Therefore, it is crucial to exclude both primary and acquired immune deficiencies in patients presenting disease relapse and VL-associated HLH-mimic. The distinction between VL and HLH can be challenging due to clinical similarities, suggesting that the nosological entity known as VL-associated HLH may represent a severe presentation of symptomatic VL and it should be considered more accurate referring to this condition as VL-associated HLH-mimic. Consequently, excluding VL in patients presenting with HLH is essential, as appropriate antimicrobial therapy can reverse immune dysregulation. A comprehensive understanding of the immune-host interaction underlying Leishmania infection is crucial for formulating effective treatment and preventive strategies to mitigate the disease burden.

Seizure recurrence following the first unprovoked seizure: Risk factors among children in UAE.

In a retrospective study of paediatric and adolescent patients in Abu Dhabi, UAE, who experienced their first unprovoked seizure between March 2016 and March 2020, with a minimum one-year follow-up, we identified significant risk factors associated with seizure recurrence. Among 317 patients, 96.2% experienced seizure recurrence, with the majority (68.8%) occurring within the first 6-month follow-up period. Notable risk factors for recurrence included focal seizures, symptomatic seizure causes, abnormal initial electroencephalogram (EEG) findings, abnormal brain magnetic resonance imaging results, and the presence of neurological disorders. Interestingly, the type of epileptiform activity in the initial EEG did not predict recurrence risk. Over a 3-year period, the overall recurrence risk was 98.4%, particularly higher in cases with symptomatic seizures compared to idiopathic (genetic) ones. These findings underscore the importance of vigilant monitoring, particularly in the early post-seizure follow-up period, and advocate for initial EEG assessments, especially in cases of remote symptomatic first unprovoked seizures.

Knee Osteoarthritis-Current Diagnosis and Treatment Options-A Narrative Review.

Knee osteoarthritis (KOA) represents a progressive and painful disease that in time can lead to loss of function and disability. Early diagnosis and correct treatment are essential in preventing the advancement of the condition to a stage where it can affect the quality of life. The development of new imagistic methods and devices can help detect changes in the structure of the join before the onset of symptoms. At the moment there are no disease- modifying drugs approved, so the current treatment is symptomatic, focusing on pain reduction, improving function and trying to prevent progression towards disability.

The effect of empagliflozin (sodium-glucose cotransporter-2 inhibitor) on osteoporosis and glycemic parameters in patients with type 2 diabetes: a quasi-experimental study.

OBJECTIVE: Diabetic osteoporosis (DOP) is a metabolic disease that occurs in patients with diabetes due to insufficient insulin secretion. This condition can lead to sensory neuropathy, nephropathy, retinopathy, and hypoglycemic events, which can increase the risk of fractures. This study aimed to assess the effectiveness of Empagliflozin, a sodium-glucose cotransporter-2 (SGLT-2) inhibitor, in treating diabetic osteoporosis (DOP) and preventing fractures. METHODS: This quasi-experimental study enrolled 100 patients with diabetic osteoporosis from February 2023 to February 2024. Participants were randomly assigned to an intervention group (n = 50) and a control group (n = 50). The intervention group received Empagliflozin in combination with symptomatic treatment, while the control group received only symptomatic treatment. The treatment duration was six months. Fasting blood glucose (FBG), 2-hour postprandial blood glucose (2 h PG), glycosylated hemoglobin A1c (Hb A1c), bone mineral density (BMD), serum phosphorus and calcium concentration were measured after the intervention and the incidence of fracture was followed up for 12 months. The data were analyzed using SPSS 23. Descriptive statistics (mean, standard deviation, and percentage) and analytical methods (t test, Chi square) were also used to analyze the data. RESULTS: After six months of treatment, the intervention group exhibited significantly lower levels of FBG (P < 0.001), 2 h-PG (P = 0.001), and HbA1c (P < 0.001) than the control group. Additionally, bone mineral density, serum phosphorus, and calcium levels were significantly higher in the intervention group (P < 0.001). After a 12-months follow-up, the incidence of fractures in the intervention group was 2%, while it was 16.33% in the control group (P < 0.05). CONCLUSION: Empagliflozin, when combined with symptomatic treatment, demonstrates a positive clinical effect in patients with diabetic osteoporosis. The treatment effectively improves blood glucose metabolism, bone mineral density, and phosphorus and calcium metabolism, ultimately leading to a significant reduction in the incidence of fracture.

An overview on disease modifying and symptomatic drug treatments for multiple sclerosis.

INTRODUCTION: Multiple sclerosis (MS) is an inflammatory and degenerative autoimmune condition, resulting frequently in a disabling condition. Significant improvements of long-term prognosis have been recently achieved with an early and more aggressive use of disease modifying therapies (DMTs). Addressing the complexity of managing its progressive forms remains a significant challenge. AREAS COVERED: This review provides an update on DMTs for relapsing-remitting MS (RRMS) and progressive MS and their efficacy, safety, and mechanism of action, emphasizing the critical role of biomarkers in optimizing treatment decisions. Moreover, some key information on drugs used to manage symptoms such as pain, fatigue, spasticity and urinary problems will be provided. The literature search was conducted using PubMed, Embase, and Cochrane Library databases covering the period from January 2000 to January 2024. EXPERT OPINION: Major advances have been achieved in the treatment of RRMS. Treatment should start immediately as soon as the neurologist is confident with the diagnosis and its choice should be based on the prognostic profile and on the patient's propensity to accept drug-related risks. The therapeutic landscape for progressive MS is quite disappointing and necessitates further innovation. Personalized medicine, leveraging biomarker insights, holds promise for refining treatment efficacy and patient outcomes.

Photobiomodulation by soft laser irradiation with and without ibuprofen improves success rate of inferior alveolar nerve block using 2% lignocaine with adrenaline in symptomatic irreversible pulpitis of mandibular molar teeth: a double-blind, randomized placebo-controlled trial.

Background: Achieving successful pain control and adequate anesthesia through an inferior alveolar nerve block for endodontic treatment in cases with symptomatic irreversible pulpitis (SIP) is difficult, especially in mandibular molars. This study was designed to compare the effect of oral medication with ibuprofen and soft laser therapy on inferior alveolar nerve block during endodontic treatment. Methods: The trial comprised 180 patients (45 each group) with SIP. Four groups of patients were created: group 1 received 400 mg of ibuprofen; group 2 received soft laser irradiation; group 3 received a combination of soft laser and ibuprofen 400 mg; and group 4 received a placebo 1 h prior to local anesthesia. Patients recorded their pain scores on the Heft-Parker visual analog scale (VAS) before the start of intervention, 15 min after anesthesia, during access cavity preparation, and ultimately during root canal instrumentation. Each patient also rated their level of discomfort on a VAS. Every stage with no or minimal discomfort was deemed successful. The chi-square, Kruskal-Wallis, and one-way analysis of variance tests were used to evaluate the data. Results: The best success rate was achieved for soft laser ibuprofen combination, ibuprofen and soft laser groups reported similar success results, and control group recorded the least pain scores. The mean pain scores were lowest for group 3 and highest for group 4 (P < 0.001). Ibuprofen and soft laser combination was significantly better than control group (P < 0.001). There was no significant difference between ibuprofen and laser groups (P = 0.24). Conclusion: For teeth with irreversible pulpitis, preoperative ibuprofen treatment combined with soft laser irradiation greatly improved the success rates of inferior alveolar nerve block anesthesia.

Symptomatic Vitreous Opacities: Exploring the Mismatch between Clinical Observation of Vitreous Alterations and Self-Reported Symptoms.

Objectives: To assess the mismatch between the clinical observation of vitreous alterations and self-reported symptoms in young patients complaining of symptomatic vitreous opacities (SVO). Methods: The ophthalmic medical records of young patients presenting primarily with SVO were retrospectively evaluated. Symptoms severity was assessed using a questionnaire. The status of the vitreous body was examined with indirect ophthalmoscopy at the slit-lamp and classified according to an ad hoc severity scale. Results: Sixty eyes of thirty otherwise healthy patients (median age: 32.5 (IQR: 29.0-37.0) years old) complaining of SVO (median duration: 38 months; interquartile range: 18-84 months) were enrolled. SVO was rated as severe by 50% of participants, affecting all the activities explored in the questionnaire. Twenty-three patients (76.6%) reported SVO-related depression and/or anxiety, for which eleven patients (36.6%) were or had been using medication. Fifty-eight eyes (96.6%) showed no evidence of (or minimal) vitreous opacity, while two eyes (3.3%) were found to have significant vitreous opacity. No significant inter-gender differences (p > 0.05) and no significant differences (p > 0.05) were found between the severity of vitreous opacity and patients' reported symptoms nor with their psychological status and medication use. Conclusions: Severe discomfort related to the perception of vitreous floaters exists in young patients whose vitreous gel examination is unremarkable or shows only minor alterations. We believe this discrepancy can be explained by optical anisotropy; significant forward-scattering of light, which results in floater symptoms; and reduced back reflection, which limits the clinical observation.

The effect of COVID-19 vaccination on symptomatic infection and related symptoms among preterm-born children aged 3-7 years in China.

Vaccination plays a crucial role in preventing and controlling SARS-CoV-2 infections as well as their associated adverse outcomes. But there is a notable lack of research on the effectiveness of COVID-19 vaccination in children, particularly those young preterm-born children, who are more vulnerable to severe outcomes from SARS-CoV-2 infection. We aimed to determine the effect of vaccination with inactivated vaccines BBIBP-CorV and CoronaVac on symptomatic COVID-19 infection and related symptoms in preterm-born children aged 3-7 years after relaxation of the COVID-19 prevention and control measures in December 2022 in China. We performed a retrospective cohort study involving 242 preterm-born children aged 3-7 years and the data were collected in March 2023. Logistic regression models and modified Poisson regression models combined with entropy balancing were used to explore the associations of vaccination against SARS-CoV-2 with symptomatic COVID-19, specific symptoms, and persistent symptoms one month after recovery from COVID-19. Of the 242 recruited preterm-born children, 156 (64.5%) were vaccinated with inactivated vaccines BBIBP-CorV and CoronaVac. After entropy balancing, the covariates were balanced between the vaccinated and the unvaccinated groups, with standardized mean difference < 0.001. Vaccination with the said SARS-CoV-2 vaccines lowered the risk of developing symptomatic COVID-19 in preterm-born children (risk ratio [RR] = 0.783; 95% confidence interval [CI]: (0.711, 0.861). Likewise, COVID-19 vaccination was associated with a decline in the risk of pneumonia (odds ratio [OR] = 0.318; 95% CI 0.110, 0.913), fever (RR = 0.710; 95% CI 0.635, 0.794), high fever (RR = 0.542; 95% CI 0.297, 0.988), sore throat (OR = 0.304; 95% CI 0.139, 0.664), and persistent symptoms (RR = 0.425; 95% CI 0.182, 0.993). Immunization with inactivated vaccines BBIBP-CorV and CoronaVac provides protection against symptomatic COVID-19 for preterm-born children 3-7 years.