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Graphical Abstract In 2006, the induced pluripotent stem cell (iPSC) was presented to the world, paving the way for the development of a magnitude of novel therapeutic alternatives, addressing a diverse range of diseases. However, despite the immense cell therapy potential, relatively few clinical trials evaluating iPSC-technology have actually translated into interventional, clinically applied treatment regimens. Herein, our aim was to determine trends in globally conducted clinical trials involving iPSCs. Data were derived both from well-known registries recording clinical trials from across the globe, and databases from individual countries. Comparisons were firstly drawn between observational and interventional studies before the latter was further analyzed in terms of therapeutic and nontherapeutic trials. Our main observations included global distribution, purpose, target size, and types of disorder relevant to evaluated trials. In terms of nontherapeutic trials, the USA conducted the majority, a large average number of participants—187—was included in the trials, and studies on circulatory system disorders comprised a slightly higher proportion of total studies. Conversely, Japan was the frontrunner in terms of conducting therapeutic trials, and the average number of participants was much lower, at roughly 29. Disorders of the circulatory, as well as nervous and visual systems, were all studied in equal measure. This review highlights the impact that iPSC-based cell therapies can have, should development thereof gain more traction. We lastly considered a few companies that are actively utilizing iPSCs in the development of therapies for various diseases, for whom the global trends in clinical trials could become increasingly important. Supplementary Information The online version contains supplementary material available at 10.1007/s12015-021-10262-3.

Patient compliance with treatment regimens remains a serious problem in the treatment of tuberculosis (TB) patients. In the decades after the advent of anti-TB drugs in the late 1940s, Directly Observed Therapy (DOT) gradually became a widely accepted and recommended staple of TB treatment management, resulting in the evolution of DOT-based systems worldwide that attempt to ensure patient compliance with their treatment schedules. Most of these DOT programs involve selecting and training supervisors to monitor, record, and enforce patient treatment regimens. Although widely used, DOT programs face many challenges today, especially in low-resource areas such as rural China. In response to these problems, current developments in treatment management involve utilizing new technology and research to discover more effective and efficient ways of ensuring that patients take their medication.

Ocular drug delivery is one of the most fascinating and challenging area of research due to its distinctive anatomical and physiological barriers. These barriers cause significant challenge for the drug delivery which is compounded by new therapeutic entities such as antibodies and oligonucleotides. Therefore, recently much attention has been focused towards the development of an accurate and sustained drug delivery system having efficient therapeutic efficacy. In this regard, nanotechnology plays a crucial role in the development of different drug delivery vehicles which can revolutionize the treatment regime of various ocular diseases. In this chapter we have discussed various nanotechnology-based drug delivery systems for the ophthalmic therapy.

Adherence-improvement strategies can be broadly classified as educational, organizational, and behavioral (Dunbar, Marshall, & Hovell, 1979). Educational strategies primarily rely on verbal, written, computer-based, or Web-based information designed to enlighten patients and their families about diseases, treatment regimens, potential negative side effects of treatment, and the importance of consistent adherence. Organizational strategies target ways in which health care is delivered, including increasing access to health-care services, simplifying regimens, and increasing provider supervision of regimens. Behavioral strategies refer to behavior-change techniques to alter specific adherence behaviors such as patient and parental monitoring of regimens, problem-solving, contracting, and token reinforcement programs.

We present a semi-parametric, semi-Markov, multi-state model for quality of life data measured in continuous time with right censoring. The model is based on the same principles as the Cox proportional hazards model. The states are defined by categorizing a quality of life score as measured using a standard instrument. Death is considered as a separate state in the model. Transitions between the states represent changes in quality of life (or death) and follow a competing risk framework. We describe the model and derive relevant estimators. We illustrate the methodology using data from a cancer clinical trial comparing quality of life for two treatment regimens.

Parental and patient adherence to therapeutic regimens prescribed by health care providers is essential to positive treatment outcomes for children and adolescents with chronic renal failure (CRF). Adherence or compliance is defined as the extent to which the behavior of patients or parents (if the patient is very young) coincides with the health care providers’ prescribed treatment regimen (taking medications, following diets, keeping medical appointments) (1). This chapter focuses on the problems of adherence to therapeutic regimens for the treatment of CRF with hemodialysis, chronic ambulatory peritoneal dialysis, and chronic cycling peritoneal dialysis.

For nearly 20 years, evidence has been accumulating that behavior therapy can be integrated with psychotherapy to create a powerful treatment regimen for troubled individuals (Goldfried & Castonguay, 1992; Beitman, Goldfried, & Norcross, 1989; London & Palmer, 1988; Marmor & Woods, 1980). The past decade has witnessed a growing eclectic orientation among mental health practitioners and efforts toward theoretical integration by psychotherapy researchers (Garfield & Bergin, 1986). During this period an interdisciplinary group of mental health practitioners and clinical researchers formed an organization for eclectically oriented clinicians: the Society for the Exploration of Psychotherapy Integration. Their Journal of Psychotherapy Integration is now over 10 years old and serves as a forum for those using multimodal therapies.

Inositol (Ins) and inositol hexaphosphate (InsP6 or phytic acid), are components of cereals. InsP6 is particularly abundant in rice, and wheat bran. Both InsP6 and Ins have been shown to inhibit experimentally induced colon cancers, in both rats and mice; Ins potentiating the action of InsP6. The effect of InsP6 and Ins on 7,12-dimethylbenz(a)anthracene (DMBA)-induced mammary carcinoma has been examined in female Sprague-Dawley rats. The rats were started on a treatment regimen of either Na-InsP6, Ins or Na-InSP66+Ins (15 mM each) in drinking water one week prior to intragastric administration of a single dose of 20 mg DMBA. After 17 weeks of treatment our results were as follows

Our experience with aphasia therapy has developed in the Neurology Department of the Technical University in Aachen under the direction of Klaus Poeck. Aphasia therapy is provided for both in- and outpatients. Inpatients stay either on acute wards, including intensive care, or on a special aphasia ward. Outpatients are seen either for extensive neurolinguistic and neuropsychological diagnosis at the neurological clinic or for aphasia therapy administered at the school of logopedics. The aphasia therapists cooperate with an interdisciplinary group of researchers including linguists, psychologists, and neurologists. Research on therapy has developed from clinical, diagnostic, and theoretical interests. In the past, we have made several attempts to combine different approaches to a comprehensive treatment regimen (cf. Huber, 1988; Huber, 1991, 1992; Huber, Poeck, & Springer, 1991; Huber & Springer, 1989; Poeck, 1982; Poeck, Huber, Stachowiak, & Weniger, 1977; Springer, 1986; Springer & Weniger, 1980; Weniger,Huber, Stachowiak, & Poeck, 1980; Weniger & Springer, 1989). Furthermore, we have been concerned with methodological issues of therapy research using either single case or group designs (Willmes, 1985, 1990).

Predicting the clinical course of a primary breast tumor is very problematic. Some patients are cured by local therapy and survive for many years. Other patients experience a rapid deterioration with early recurrence of their disease, followed shortly by death. It would obviously be useful to be able to identify individual patients who are at high or low risk for relapse in order to plan the appropriate management of the patient’s breast cancer. Patients with a low probability of recurrence could be spared the potential toxicities associated with therapeutic regimens, while patients who are likely to recur could be given the option of aggressive adjuvant therapy. However, before optimal treatment strategies can be initiated, it is also necessary to know which patients are likely to benefit from specific treatment regimens.

Chapter 12 reviews the basis in biology and pharmacology for a different approach to elderly people when prescribing medication. Repeatedly, we concluded that the outcome is less certain in the elderly than it is in younger adults. This chapter presents ten simple rules, to be used as a first-order guide to the difficult juggling act of geriatric pharma-cotherapeutics. Traditionally, treatment regime rules consist of drug names, doses, and schedules; here the rules are necessarily more general. Practice makes perfect, and an intuition for pitfalls and safe practice develops with experience.

Before about 15 years ago, psychological consultation in medical settings was primarily service-oriented under the aegis of departments of psychiatry. Thus, its main function was seen as providing psychometric services in support of psychiatric interests, both in terms of clinical services and in terms of research. An ancillary service was brief intervention consultation, usually behavioral in nature, designed to alter specific patient or staff behaviors to encourage compliance with varying treatment regimens. The psychologist in such a setting was, by necessity, relegated to such interests, and most effort was directed to issues of psychopathology and interventions with psychiatric patients.

During 1974, the Charing Cross Clinic for Drug and Alcohol Problems: one of Glasgow’s largest out-patient substance abuse treatment facilities, developed the first program within the National Health Service, for the treatment of young adult (ages 16–30) alcohol and multiple substance abusers (Fischer and Coyle, 1976). The program, called the Young Persons Program, of YPP, was developed to obviate problems brought about by the traditional approach of interspersing younger and older patients in the same treatment regime (Coyle and Fischer, 1977).

The entity (or entities) that we recognize as Hodgkin’s disease has several clinical and pathologic features that set it apart from the non-Hodgkin’s lymphomas and other malignancies in general, and place it in its own unique pathophysiologic group. This tumor was first described by Thomas Hodgkin in 1832 and thus was one of the first malignant tumors to be studied using morbid anatomic techniques. Hodgkin’s disease was also one of the first malignant tumors frequently found to be responsive to the available chemotherapeutic and radiotherapeutic modalities [1, 2]. The potential ability to recognize subgroups of patients capable of being cured stimulated the interests of clinical scientists, including pathologists, to study this disease more intensively [3–6]. Continued efforts in the analysis of the pathology of Hodgkin’s disease gave insights into the patterns of its histopathology and anatomic progression. This accelerated the development of guidelines for the histologic features that were predictive of favorable and unfavorable clinical outcomes in 1966 and of treatment regimens tailored to the disease status of the patient, based on staging guidelines established at Ann Arbor, Michigan, in 1971. Thus, Hodgkin’s disease has been the frontrunner of hematologic malignancies in which the understanding of anatomic and pathologic features plays an important role in designing therapy and predicting the clinical outcome.

The relationship between social competence and psychiatric disorder is well documented in both the psychological and psychiatric literatures (cf. Bellack & Hersen, 1978; Hersen & Bellack, 1976b, 1977; Paul, 1969; Sylph, Ross, & Kedward, 1978). For close to two decades, Zigler and his colleagues (Levine & Zigler, 1973; Phillips & Zigler, 1961, 1964; Zigler & Levine, 1973; Zigler & Phillips, 1960, 1961, 1962) have completed a series of retrospective studies, essentially showing that level of premorbid social competence in a hospitalized psychiatric patient is the best predictor of his posthospital adjustment. This relationship seems to hold irrespective of the patient’s diagnostic label (i.e., schizophrenia, alcoholism, depression) and regardless of the treatment regimen carried out during the course of hospitalization. Indeed, only recently has the relationship between social skill deficits and particular diagnostic entities been carefully evaluated. Among the disorders so considered are: schizophrenia (Bellack & Hersen, 1978; Bellack, Hersen, & Turner, 1976; Hersen & Bellack, 1976a), depression (Libet & Lewinsohn, 1973; Wells, Hersen, Bellack, & Himmelhoch, 1977), alcoholism (Miller & Eisler, 1977; O’Leary, & Donovan, 1976; Van Hasselt, Hersen, & Milliones, 1978), drug addiction (Caliner & Ross, 1976; Van Hasselt et al., 1978), hysterical neurosis (Blanchard & Hersen, 1976), and sexual deviation (Barlow, Abel, Blanchard, Bristow, & Young, 1977). Undoubtedly, as further research evidence is adduced, other disorders will be added to this growing list.

The identification, characterization, and synthesis of luteinizing-hor­mone-releasing hormone (LH-RH) introduced a potential and exciting new approach for the treatment of male and female infertility. This application, which theoretically coincides with the profertility LH-re­leasing role played by endogenous LH-RH, has been and continues to be exhustively pursued, but use of the chemically and biologically identical synthetic LH-RH in a variety of clinical situations has never achieved its anticipated therapeutic promise. Primary responsibility for the inconsis­tency of the results has been attributed to the short half-life of the peptide, and it was hoped that this problem might be circumvented by increased exposure (e.g., through more frequent administration or con­stant infusion) or by employing LH-RH derivatives with prolonged activity. However, despite heroic treatment regimens and the use of a number of LH-RH agonistic analogues with much-increased potency and duration of activity, there has been little improvement in the clinical utility of this approach. In fact, comprehensive reproductive pharmaco­logical evaluation has revealed that the LH-releasing property responsible for the original profertility classification imparts definite correlatable and predictable antireproductive activity. This paradoxical relationship, first evidenced in laboratory animals by the ability of these agents to terminate pregnancy, disrupt cyclicity, retard puberty, and inhibit spermatogenesis, has been extended to humans, in whom LH-RH and its agonistic analogues have been shown to induce luteolysis and premature menstrua­tion. The identification of the antireproductive nature of LH-RH and agonists, aside from providing an explanation for their disappointing performance in treating various hypogonadal states, has, quite ironically, established the concept of these peptides as a novel class of contraceptive agents.

The wx locus assay in maize pollen grains may be conducted using one of two chronic treatment regimens and under in situ conditions. Solutions of a test chemical can be applied to the soil of plants grown in pots or to the nutrient medium of plants grown under hydroponic culture. Under in situ conditions, test plots may be constructed in the field, and various agents may be applied to each test plot. A series of control test plots must also be prepared for comparison.

Phototherapy with ultraviolet (UV) radiation, alone, or as part of a multi-faceted therapy, has been used for Psoriasis with varying degrees of success depending mainly on the radiation source, the treatment regimen used and the type of Psoriasis treated (Goeckermann, 1931; Ingram, 1953; Petrozzi et al, 1978; Levine and Parrish, 1980; Larko, 1982; Morison, 1983; Eells et al, 1984).

Survival of untreated patients with inoperable primary liver neoplasms is approximately 75 days (1,2). Before Adriamycin, both intravenous and intra-arterial chemotherapeutic agents had very little effect upon the survival of these patients despite tumor shrinkage (3,4). Adriamycin given IV as a single agent or in combination with other drugs resulted initially in a response of 78% (5). Later studies reported response rates ranging from 9% to 44% (6–14). In 67% of patients with primary liver neoplasms, disease seems confined to the liver at the time of diagnosis, and even at autopsy disease is still confined to the liver in 44% of the patients (15). A regional approach to a disease with such dismal prognosis seems warranted. A pilot study of hepatic arterial infusion of floxuridine, Adriamycin, and mitomycin C (FUDRAM) resulted in a response rate of 66% in patients with hepatocellular carcinoma (16). We decided, therefore, to explore this treatment regimen further.

Initial research on self-instructional training indicated that the likelihood of obtaining generalization and persistence of treatment effects was increased if we attended to the client’s cognitions. If operant training procedures could be improved by explicitly including in the treatment regimen a client’s thoughts and images, then perhaps other behavior therapy techniques could similarly be improved. In other words, if the Risley and Hart quote that introduces this chapter has any validity, then altering behavior therapy procedures in “reorganizing and restructuring the patient’s verbal statements” should enhance their efficacy. This hypothesis was translated into a program of treatment studies in which we assessed the efficacy of “standard” behavior therapy procedures (such as desensitization, modeling, aversive conditioning) relative to behavior therapy procedures that included self-instructional components (that is, procedures that supplemented the behavior therapy techniques with an explicit concern for the client’s cognitions). This chapter will describe this phase of our research program and summarize the available evidence for the role of cognitions in behavior therapy procedures.

Interferon’s (α and β), produced both by recombinant DNA technology as well as purified from natural sources, have been shown to be efficacious in treating certain cancers and viral diseases. Studies with γ-interferon have more recently been undertaken, and thus definition of their clinical utility is not yet as well defined. The treatment schedules usually involve multiple injections of the Interferon (IFN) over a period of several weeks to many months. Using such treatment regimens, the dose levels of the interferons needed to obtain efficacy can result in toxic side effects. For all these reasons, methods of increasing the ease of administration as well as the therapeutic ratio of interferons are warranted.

A hallmark of melanoma is the multiplicity of prognostic factors that are known to predict the risk of metastatic disease. In fact, the myriad of clinical and pathologic features that appear to affect melanoma survival rates has given the disease a reputation for being very capricious. A prognostic factors analysis of melanoma is therefore essential to identify the dominant variables that can be used for evaluating results of clinical research trials involving adjunctive systemic therapy, and for making certain surgical decisions. When evaluating these treatments, it is important to identify those prognostic variables that can accurately categorize patients into different risk groups for metastatic disease. Otherwise, differences (or lack of differences) between treatment regimens being compared may not be due to the treatments themselves, but may only reflect imbalances of prognostic factors.

Conventional in vitro tests of antibacterial activity offer a simple means of assessing microbial sensitivity in the diagnostic laboratory, but the conditions of exposure of bacteria to antibiotic in such tests are remote from those encountered in vivo. In acknowledgement of this a number of experimental models have been designed utilizing laboratory animals, in which the therapeutic efficacy of new drugs or treatment regimens may be assessed. Unfortunately, animal models of infection also possess inherent limitations in terms of the treatment of human disease. One problem is that, because of anatomical and physiological differences, the conditions in which bacteria and antibiotic interact in the experimental animal differ from those encountered in man. Furthermore, it is difficult to establish the precise factors governing therapeutic efficacy in in vivo models because of their inherent complexity.

Acetaminophen overdosage, taken either as a suicidal gesture or as an accidental poisoning, is a significant clinical entity and one that appears to be growing in incidence. Results from a recent study have shown that the percentage of total drug-related deaths associated with acetaminophen in England and Wales rose dramatically from 3.8% in 1973 to 21% in 1980; further, the number of acetaminophen-associated deaths was the highest of all drug-related deaths for the years 1978 to 1980 (1). Thus there is a need to define more clearly the reasons for differences in patient responsiveness and to develop new treatment regimens to decrease the severity of liver failure.

The aim of this paper is to review the literature on depot-neuroleptics in the acute psychiatry and to report our own experiences with this treatment regimen.

Although irritable bowel syndrome (IBS) has classically been defined with regard to colonic symptoms,1 mounting evidence points to a diffuse motility disturbance in many patients with IBS.2 Further, as discussed elsewhere in this volume, specific functional disorders of esophageal, gastroduodenal, small intestinal, and colonic motility are being recognized as our ability to measure gastrointestinal electrophysiology, motility, and transit has improved. In this chapter, we will summarize the evidence for altered GI transit in IBS and delineate the relationship, if any, between altered transit of luminal contents and symptoms in IBS. Because of its relationship to IBS, we will also summarize the evidence for stress-related changes in normal GI transit. Finally, treatment regimens which may reverse these disturbances in GI transit, and their associated symptoms, will be discussed.