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Background: Anti-drug antibodies are associated with treatment failure to anti-TNF agents in patients with inflammatory bowel disease (IBD)., Aim: To assess whether immunogenicity to a patient's first anti-TNF agent would be associated with immunogenicity to the second, irrespective of drug sequence METHODS: We conducted a UK-wide, multicentre, retrospective cohort study to report rates of immunogenicity and treatment failure of second anti-TNF therapies in 1058 patients with IBD who underwent therapeutic drug monitoring for both infliximab and adalimumab. The primary outcome was immunogenicity to the second anti-TNF agent, defined at any timepoint as an anti-TNF antibody concentration ≥9 AU/ml for infliximab and ≥6 AU/ml for adalimumab., Results: In patients treated with infliximab and then adalimumab, those who developed antibodies to infliximab were more likely to develop antibodies to adalimumab, than patients who did not develop antibodies to infliximab (OR 1.99, 95%CI 1.27-3.20, p = 0.002). Similarly, in patients treated with adalimumab and then infliximab, immunogenicity to adalimumab was associated with subsequent immunogenicity to infliximab (OR 2.63, 95%CI 1.46-4.80, p < 0.001). For each 10-fold increase in anti-infliximab and anti-adalimumab antibody concentration, the odds of subsequently developing antibodies to adalimumab and infliximab increased by 1.73 (95% CI 1.38-2.17, p < 0.001) and 1.99 (95%CI 1.34-2.99, p < 0.001), respectively. Patients who developed immunogenicity with undetectable drug levels to infliximab were more likely to develop immunogenicity with undetectable drug levels to adalimumab (OR 2.37, 95% CI 1.39-4.19, p < 0.001). Commencing an immunomodulator at the time of switching to the second anti-TNF was associated with improved drug persistence in patients with immunogenic, but not pharmacodynamic failure., Conclusion: Irrespective of drug sequence, immunogenicity to the first anti-TNF agent was associated with immunogenicity to the second, which was mitigated by the introduction of an immunomodulator in patients with immunogenic, but not pharmacodynamic treatment failure., (© 2022 The Authors. Alimentary Pharmacology & Therapeutics published by John Wiley & Sons Ltd.)

Bromocriptine is a sympatholytic dopamine D2 receptor agonist with remarkable bioactivities. It has been used clinically as a prescription drug for more than 30 years to treat hyperprolactinemia associated conditions, Parkinson's disease, acromegaly, prolactinomas and other pituitary hormone dependent adenomas and recently, diabetes mellitus as well as various other disorders. Long-term treatment with bromocriptine has minimal or no harmful effects on renal, hepatic, cardiac or hematologic functions. This review article was planned to study the hypothetical and proposed mechanism of action as well as provide a brief discussion about its safety issues and tolerability. Bromocriptine represents an attractive option with high efficacy and safety profile for hyperprolactinemia-associated conditions, acromegaly, parkinsonism, type 2 diabetes mellitus and various other diseases in a variety of dosage forms for best possible beneficial effects. It appeared to be an effective and safe addition to the pharmacopoeia of drugs for the treatment of a vast variety of diseases as monotherapy or in combination with other drugs., (© 2022 John Wiley & Sons Australia, Ltd.)

Hantaviruses are enveloped negative (-) single-stranded RNA viruses belongs to Hantaviridae family, hosted by small rodents and entering into the human body through inhalation, causing haemorrhagic fever with renal syndrome (HFRS) and hantavirus pulmonary syndrome (HPS) also known as hantavirus cardiopulmonary syndrome (HCPS). Hantaviruses infect approximately more than 200 000 people annually all around the world and its mortality rate is about 35%-40%. Hantaviruses play significant role in affecting the target cells as these inhibit the apoptotic factor in these cells. These viruses impair the integrity of endothelial barrier due to an excessive innate immune response that is proposed to be central in the pathogenesis and is a hallmark of hantavirus disease. A wide range of different diagnostic tools including polymerase chain reaction (PCR), focus reduction neutralization test (FRNT), enzyme-linked immunosorbent assay (ELISA), immunoblot assay (IBA), immunofluorescence assay (IFA), and other molecular techniques are used as detection tools for hantavirus in the human body. Now the availability of therapeutic modalities is the major challenge to control this deadly virus because still no FDA approved drug or vaccine is available. Antiviral agents, DNA-based vaccines, polyclonal and monoclonal antibodies neutralized the viruses so these techniques are considered as the hope for the treatment of hantavirus disease. This review has been compiled to provide a comprehensive overview of hantaviruses disease, its pathophysiology, diagnostic tools and the treatment approaches to control the hantavirus infection., (© 2020 John Wiley & Sons Australia, Ltd.)

Naegleria fowleri, a thermophilic flagellate amoeba known as a "brain-eating" amoeba, is the aetiological agent of a perilous and devastating waterborne disease known as primary amoebic meningoencephalitis (PAM), both in humans as well as in animals. PAM is a rare but fatal disease affecting young adults all around the world, particularly in the developed world but recently reported from developing countries, with 95%-99% mortality rate. Swimmers and divers are at high risk of PAM as the warm water is the most propitious environment adapted by N. fowleri to cause this infection. Infective amoeba in the trophozoite phase enter the victim's body through the nose, crossing the cribriform plate to reach the human brain and cause severe destruction of the central nervous system (CNS). The brain damage leads to brain haemorrhage and death occurs within 3-7 days in undiagnosed cases and maltreated cases. Though the exact pathogenesis of N. fowleri is still not known, it has exhibited two primary mechanisms, contact-independent (brain damage through different proteins) and contact-dependent (brain damage through surface structures food cups), that predominantly contribute to the pathogen invading the host CNS. For the management of this life-threatening infection different treatment regimens have been applied but still the survival rate is only 5% which is ascribed to its misdiagnosis, as the PAM symptoms closely resembled bacterial meningitis. The main objectives of this review article are to compile data to explore the sources and routes of N. fowleri infection, its association in causing PAM along with its pathophysiology; latest techniques used for accurate diagnosis, management options along with challenges for Pakistan to control this drastic disorder., (© 2019 John Wiley & Sons Australia, Ltd.)

In the title compound, C(10)H(10)N(2)O(2)S, the thia-zine ring approximates to an envelope form with the S atom in the flap position. The amide group attached to the acetate group is almost perpendicular to the mean plane of the thia-zine ring [dihedral angle = 88.83 (8)°]. In the crystal, inversion dimers linked by pairs of N-H⋯O hydrogen bonds occur. Further N-H⋯O and C-H⋯O hydrogen bonds link the dimers into a three-dimensional network.

In the title compound, C(10)H(11)N(3)O(2)S, the thia-zine ring exists in a conformation inter-mediate between twist-boat and half-chair. The dihedral angle between the mean plane of the thia-zine ring and the hydrazide group is 89.45 (13)°. In the crystal, N-H⋯O hydrogen bonds link the mol-ecules into (100) sheets and weak C-H⋯O inter-actions further consolidate the packing.

The conformation of the title compound, C(12)H(17)N(3)O, is consolidated by an intra-molecular N-H⋯O hydrogen bond, generating an S(5) ring. In the crystal, inversion dimers linked by pairs of N-H⋯O inter-actions occur, resulting in R(2) (2)(8) ring motifs.

The title compound, C(10)H(15)N(3)O, crystallizes in an infinite two-dimensional polymeric network due to inter-molecular N-H⋯O hydrogen bonding. Intra-molecular N-H⋯N and inter-molecular C-H⋯N inter-actions are also present. The 3,4-dimethyl-phenyl unit is disordered over two sites with an occupancy ratio of 0.677 (5):0.323 (5). The dihedral angle between the benzene rings of the disordered components is 2.6 (6)°.

Of 49 schizophrenic patients followed up 2 years after their first admission to hospital, 37% were well, 47% had been readmitted to hospital at some time over the 2 years, and 38% showed schizophrenic symptoms at follow-up. A poor outcome at 2 years was associated with male sex, poor outcome after the first 5 weeks of the first admission, negative schizophrenic symptoms on first admission, and a diagnosis of definite or probable schizophrenia using the Feighner criteria. Only 23% were in employment. A small double-blind discontinuation study of maintenance antipsychotic medication during the second year found more relapses in those switched to placebo medication. Repeat psychometric assessment at 2 years confirmed modest improvements found at 12 months; that is, there was no evidence of intellectual decline. Relatives showed no more psychosocial distress than that found in a normal community sample; what distress there was correlated with patients' schizophrenic symptoms.