I always advocate carrying a full sized fighting handgun in an effective caliber. Almost three decades as a cop, trainer at two academies, and thirty years as a competitive shooter....until you can't. The advantage, for your wife, seems to be a pistol she is willing to carry, willing to shoot, and doesn't cause her pain. No one will really argue that a 22lr, even in it's most "effective" loading is not ideal for defensive use. That said, for some it IS effective for self defense because they CAN employ it more effectively than a larger caliber. If she can empty a whole swarm of those angry little bees into an aggressor to stop an attack, create separation, break contact and get away....then, they ARE as effective as a larger caliber. It's a strange Catch 22 (pun intended), but there ya have it.