Effectiveness of vaccination against SARS-CoV-2 and the need for alternative preventative approaches in immunocompromised individuals: a narrative review of systematic reviews.

INTRODUCTION: Vaccination against severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), including administration of booster doses, continues to be the most effective method for controlling COVID-19-related complications including progression to severe illness and death. However, there is mounting evidence that more needs to be done to protect individuals with compromised immune function. AREAS COVERED: Here, we review the effectiveness of COVID-19 vaccination in immunocompromised patients, including those with primary immunodeficiencies, HIV, cancer (including hematological malignancies), solid organ transplant recipients, and chronic kidney disease, as reported in systematic reviews/meta-analyses published over a 12-month period in PubMed. Given the varied responses to vaccination in patients with compromised immune function, a major goal of this analysis was to try to identify specific risk-factors related to vaccine failure. EXPERT OPINION: COVID-19 remains a global problem, with new variants of concern emerging at regular intervals. There is an ongoing need for optimal vaccine strategies to combat the pandemic. In addition, alternative treatment approaches are needed for immunocompromised patients who may not mount an adequate immune response to current COVID-19 vaccines. Identification of high-risk patients and the introduction of newer antiviral approaches such as monoclonal antibodies will offer physicians therapeutic options for such vulnerable individuals.

Foscarnet in the management of cytomegalovirus infections in hematopoietic stem cell transplant patients.

Despite significant advances in the day-to-day management of patients receiving hematopoietic stem cell transplantations, including the introduction of new antiviral drugs, cytomegalovirus (CMV) infection continues to be a major cause of morbidity and mortality. The aim of this article is to undertake a literature-based review of foscarnet in this therapeutic setting and to align current best-published evidence with recent recommendations presented at the European Conference on Infections in Leukaemia. Ganciclovir remains the mainstay of CMV infection/disease antiviral management protocols. However, approximately a third of patients develop severe neutropenia and others become resistant to ganciclovir, and thus, a reasonably large proportion of patients are not able to receive and/or continue with this medication. Foscarnet is a suitable option as both pre-emptive therapy or for the treatment of active disease in these patients. Randomized trials have demonstrated that foscarnet is equally effective when compared with ganciclovir for pre-emptive treatment of CMV infections: the outcome was comparable with ganciclovir in terms of control of antigenemia and survival rates. There is a paucity of information for its use in the prophylaxis of CMV, although preliminary data show that it was effective in some patients at high risk of CMV reactivation. The main adverse events associated with foscarnet are renal impairment, serum electrolyte and hemoglobin disturbances, seizures and local genital irritation/ulceration. Foscarnet is a well-established antiviral option in immunocompromised patients, and it is usually administered as a second-line option to ganciclovir. In patients receiving hematopoietic stem cell transplantation, it has proven efficacy when used pre-emptively to treat CMV reactivation, as an alternative to and also in combination with ganciclovir.

Retrospective observational study of the management of multiple sclerosis patients with resistant spasticity in Spain: the '5E' study.

BACKGROUND: Multiple sclerosis spasticity (MSS) is a common and disabling symptom for which a number of antispastic agents are available; however, evidence-based guidelines for optimal management are lacking. OBJECTIVE: This retrospective observational assessment investigated the current management approach for resistant MSS in Spain. Secondary objectives were to evaluate the evolution of MSS and to estimate the social and health-related costs of managing MSS in the Spanish healthcare system. METHODS: A retrospective analysis was performed using case records from 212 MS patients with spasticity that were resistant to ≥ 1 previous therapy. Data were collected over 1-3 years (mean 2.1 years), including: sociodemographics, medical history, clinical scores and all therapy/other resources consumed (e.g., rehabilitation and carers' time). Disease progression was estimated from the evolution of recorded clinical scales, and an analysis of costs from a Spanish healthcare and social perspective was performed. RESULTS: The majority of patients were female and most had secondary progressive MS. Baclofen (76-80%), tizanidine and benzodiazepines were the most common antispastic drugs administered. A variety of spasticity rating scales were employed, and they demonstrated the same general trends. MS progressed, with the composite score for spasticity and mobility deteriorating in 46.4% of patients, and there were no marked differences between antispasticity drugs. The annual healthcare-related cost of treating an MSS resistant patient in the Spanish healthcare system was €15,405, largely attributable to the cost of disease-modifying drugs and care provision. Other aspects, such as medical visits and antispastic treatments, formed only a small portion of cost. CONCLUSIONS: MSS progresses despite treatment with currently available antispastic agents, and it is associated with a high level of disability. Spasticity treatment represents a minor element of the overall cost of managing MSS patients in Spain. The approach to the assessment of spasticity varies between centers.

Urogenital disorders associated with oestrogen deficiency: the role of promestriene as topical oestrogen therapy.

Urogenital disorders associated with oestrogen deficiency affect many women throughout menopausal transition. Symptoms such as vaginal dryness, burning, pruritus, dyspareunia, urinary tract urgency/frequency and incontinence have a significant impact on the individual's quality of life. For younger and healthy menopausal women, systemic oestrogen replacement may improve both vasomotor and urogenital symptoms and will be the treatment of choice. However, a proportion of women on systemic therapy still experience symptoms associated with urogenital atrophy, and patients with oestrogen-dependent cancers may be at risk from systemic oestrogen replacement. For women with mainly urogenital symptoms, local oestrogen is a logical choice and it is often more effective than systemic hormone replacement therapy. Generally speaking, there are no contraindications to local therapy. In terms of which topical preparation to use, a wide range of products are available. Promestriene is an analogue of oestradiol which is minimally absorbed and it has been shown to be effective in reversing atrophic changes caused by oestrogen deficiency in women undergoing natural or surgically induced menopause. Given the absence of systemic activity, promestriene may be a good choice in women requiring purely locally oestrogen, and those who have survived, or who are at risk of breast cancer and who have severe vulvo-vaginal symptoms.

Insulin glargine in the management of diabetes mellitus: an evidence-based assessment of its clinical efficacy and economic value.

INTRODUCTION: Diabetes is a chronic disease associated with high morbidity and mortality, which represents a major public health concern. Interventions that can enhance patient care and reduce clinic visits will not only relieve some of this burden, they will also improve patient QOL and wellbeing. AIMS: This review assesses the evidence for the use of insulin glargine in type 1 and type 2 diabetes mellitus. EVIDENCE REVIEW: Once-daily insulin glargine has a prolonged, peakless activity profile, making it a candidate as a long-acting (basal) insulin. In combination with bolus insulin to cover prandial glucose surges, it facilitates a more physiologic approach to patient management. Evidence from large, randomized, controlled clinical trials in patients with type 1 diabetes has confirmed its effectiveness and tolerability relative to neutral protamine hagedorn (NPH) insulin, with a tendency toward causing less hypoglycemia. In patients with type 2 diabetes requiring insulin therapy, once-daily insulin glargine has proven to be clinically superior to NPH insulin in terms of providing at least as effective glycemic control, but with significantly fewer episodes of nocturnal hypoglycemia. A variety of economic analyses have confirmed the cost effectiveness of insulin glargine in type 1 and type 2 diabetes and in particular it was shown to be significantly superior to NPH insulin. CLINICAL VALUE: Insulin glargine has established itself as a first-line choice in patients with type 1 diabetes, including children (>6 years) and adolescents, and is a recommended treatment option. In patients with type 2 diabetes it is clearly associated with less hypoglycemia than NPH insulin, and this may help overcome one of the major barriers to starting insulin therapy in this class of patient. Thus, insulin glargine is a valuable addition to the therapeutic armamentarium available to physicians and it has the potential to significantly improve the quality of life of patients with diabetes.